@article{FeketeKulpokTaurinesetal.2023, author = {Fekete, Stefanie and Kulpok, Christine and Taurines, Regina and Egberts, Karin and Geissler, Julia and Gerlach, Manfred and Malonga Makosi, Doroth{\´e}e and K{\"o}nig, Jochem and Urschitz, Michael S. and Toni, Irmgard and Neubert, Antje and Romanos, Marcel}, title = {Value of a web-based pediatric drug information system to prevent serious adverse drug reactions in child and adolescent psychiatry}, series = {Journal of Neural Transmission}, volume = {130}, journal = {Journal of Neural Transmission}, number = {1}, doi = {10.1007/s00702-022-02563-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324817}, pages = {53-63}, year = {2023}, abstract = {Psychotropic drugs are frequently prescribed 'off-label' to children and adolescents and carry the risk of serious adverse drug reactions (sADR). We examined the frequency of sADRs of psychotropic drugs in pediatric inpatients and explored their potential preventability through following the recommendations of a web-based pediatric drug information system (PDIS). The potential socio-economic impacts of using this online system is also addressed. Routine clinical data from all inpatients treated in a child and adolescent psychiatry department between January 2017 and December 2018 were retrospectively examined for the occurrence of sADRs as defined by the European Medicines Agency. The preventability of the sADRs was assessed based on the information of the PDIS. Furthermore, the expected prolongation of the hospital stay due to sADRs was calculated as well as the associated treatment costs. The study was supported by the Innovation Fund of the Joint Federal Committee, grant number 01NVF16021. In total, 1036 patients were screened of whom 658 (63.5\%) received psychopharmacological treatment. In 53 (8.1\%) of these patients 54 sADRs were documented, of which 37 sADRs were identified as potentially preventable through PDIS. Mitigating sADR through PDIS would likely have prevented prolonged hospital stays and conferred considerable savings for health insurance companies. PDIS provides systematic and evidence-based information about pediatric psychopharmacotherapy and helps to prevent prescribing errors. Therefore, PDIS is a useful tool to increase drug therapy safety in child and adolescent psychiatry. Further prospective studies are needed to confirm the results.}, language = {en} } @article{FrankeConzelmannGruenblattetal.2019, author = {Franke, Maximilian and Conzelmann, Annette and Gr{\"u}nblatt, Edna and Werling, Anna M. and Spieles, Helen and Wewetzer, Christoph and Warnke, Andreas and Romanos, Marcel and Walitza, Susanne and Renner, Tobias J.}, title = {No Association of Variants of the NPY-System With Obsessive-Compulsive Disorder in Children and Adolescents}, series = {Frontiers in Molecular Neuroscience}, volume = {12}, journal = {Frontiers in Molecular Neuroscience}, doi = {10.3389/fnmol.2019.00112}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229051}, year = {2019}, abstract = {Obsessive-compulsive disorder (OCD) causes severe distress and is therefore counted by the World Health Organisation (WHO) as one of the 10 most impairing illnesses. There is evidence for a strong genetic underpinning especially in early onset OCD (eoOCD). Though several genes involved in neurotransmission have been reported as candidates, there is still a need to identify new pathways. In this study, we focussed on genetic variants of the Neuropeptide Y (NPY) system. NPY is one of the most abundant neuropeptides in the human brain with emerging evidence of capacity to modulate stress response, which is of high relevance in OCD. We focussed on tag-SNPs of NPY and its receptor gene NPY1R in a family-based approach. The sample comprised 86 patients (children and adolescents) with eoOCD with both their biological parents. However, this first study on genetic variants of the NPY-system could not confirm the association between the investigated SNPs and eoOCD. Based on the small sample size results have to be interpreted as preliminary and should be replicated in larger samples. However, also in an additional GWAS analysis in a large sample, we could not observe an associations between NPY and OCD. Overall, these preliminary results point to a minor role of NPY on the stress response of OCD.}, language = {en} } @phdthesis{Frey2022, author = {Frey, Lillien Mara}, title = {Furchtgeneralisierung und Attentional Bias bei Kindern und Jugendlichen mit einer St{\"o}rung des Sozialverhaltens}, doi = {10.25972/OPUS-25974}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259746}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Bereits vorangegangene Studien haben zeigen k{\"o}nnen, dass eine verst{\"a}rke Generali- sierung von Furcht sowohl bei Erwachsenen, bei denen beispielsweise eine Angstst{\"o}rung oder eine PTSB diagnostiziert wurde, aber auch bei gesunden Kindern eine Rolle spielt. In unserer Studie untersuchten wir eine Gruppe Kinder und Jugendliche (n = 31, m = 25, w = 6; Alter = 13.35 ± 2.03), die eine St{\"o}rung des Sozialverhaltens aufwiesen, auf die Konditionierbarkeit von Furcht und eine m{\"o}gliche Furchtgeneralisierung. Diese Gruppe verglichen wir mit einer gesunden Kontrollgruppe (n = 29, m = 11, w = 18; Alter = 14.28 ± 2.43). Als Generalisierungsstimuli verwendeten wir ein Furchtgeneralisierungsparadigma mit zwei Frauengesichtern, die in vier Schritten aneinander angeglichen wurden. Zus{\"a}tzlich f{\"u}hrten wir mit beiden Probandengruppen ein Dot-Probe-Paradigma zur Objektivierung von Aufmerksamkeitsprozessen im Sinne eines Attentional Bias oder Attentional Avoidance mit emotionalen Gesichtern durch. Wir konnten eine erfolgreiche Furchtkonditionierung f{\"u}r beide Gruppen erreichen. Im Vergleich mit der gesunden Kontrollgruppe zeigte die externalisierende Probandengruppe eine verst{\"a}rke Furchtgeneralisierung. Hinsichtlich der subjektiven Valenz- und Kontingenzratings wurden die Unterschiede besonders deutlich. Eine verst{\"a}rkte Generalisierungsneigung bei erh{\"o}hter Trait-Angst konnten wir nicht finden. Die externalisierende Gruppe zeigte im Vergleich mit neutralen Gesichtern bei den emotionalen Gesichtern insgesamt einen Attentional Bias. Am deutlichsten war dabei eine verst{\"a}rkte Aufmerksamkeitslenkung hin zu gl{\"u}cklichen Gesichtern festzustellen. F{\"u}r die gesunde Kontrollgruppe konnten wir keine Besonderheiten bez{\"u}glich der Aufmerksamkeitsrichtung finden. Weiterf{\"u}hrende Studien sollten mit gr{\"o}ß- eren Probandengruppen und nach Geschlecht und Alter gepaarten Probanden durch- gef{\"u}hrt werden. Mit externalisierenden Probanden sollte ein Furchtgeneralisierungs- paradigma mit neutralen Stimuli (z.B. Ringe) gew{\"a}hlt werden, um eine subjektive Wertung emotionaler Gesichter bei den Ratings als St{\"o}rfaktor auszuschließen. F{\"u}r externalisierende Probanden sollte außerdem die Auspr{\"a}gung von CU-Traits erfasst und die Dauer der Testung verk{\"u}rzt oder auf zwei Termine aufgeteilt werden, um eine ausreichende Konzentrationsf{\"a}higkeit zu erm{\"o}glichen.}, subject = {Psychische St{\"o}rung}, language = {de} } @article{FoeckerTimmesfeldBuehlmeieretal.2021, author = {F{\"o}cker, Manuel and Timmesfeld, Nina and B{\"u}hlmeier, Judith and Zwanziger, Denise and F{\"u}hrer, Dagmar and Grasemann, Corinna and Ehrlich, Stefan and Egberts, Karin and Fleischhaker, Christian and Wewetzer, Christoph and Wessing, Ida and Seitz, Jochen and Herpertz-Dahlmann, Beate and Hebebrand, Johannes and Libuda, Lars}, title = {Vitamin D level trajectories of adolescent patients with anorexia nervosa at inpatient admission, during treatment, and at one year follow up: association with depressive symptoms}, series = {Nutrients}, volume = {13}, journal = {Nutrients}, number = {7}, issn = {2072-6643}, doi = {10.3390/nu13072356}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242662}, year = {2021}, abstract = {(1) Background: Evidence has accumulated that patients with anorexia nervosa (AN) are at higher risk for vitamin D deficiency than healthy controls. In epidemiologic studies, low 25(OH) vitamin D (25(OH)D) levels were associated with depression. This study analyzed the relationship between 25(OH)D serum levels in adolescent patients and AN and depressive symptoms over the course of treatment. (2) Methods: 25(OH)D levels and depressive symptoms were analyzed in 93 adolescent (in-)patients with AN from the Anorexia Nervosa Day patient versus Inpatient (ANDI) multicenter trial at clinic admission, discharge, and 1 year follow up. Mixed regression models were used to analyze the relationship between 25(OH)D levels and depressive symptoms assessed by the Beck Depression Inventory (BDI-II). (3) Results: Although mean 25(OH)D levels constantly remained in recommended ranges (≥50 nmol/L) during AN treatment, levels decreased from (in)patient admission to 1 year follow up. Levels of 25(OH)D were neither cross-sectionally, prospectively, nor longitudinally associated with the BDI-II score. (4) Conclusions: This study did not confirm that 25(OH)D levels are associated with depressive symptoms in patients with AN. However, increasing risks of vitamin D deficiency over the course of AN treatment indicate that clinicians should monitor 25(OH)D levels.}, language = {en} } @article{GeisslerJansBanaschewskietal.2018, author = {Geissler, Julia and Jans, Thomas and Banaschewski, Tobias and Becker, Katja and Renner, Tobias and Brandeis, Daniel and D{\"o}pfner, Manfred and Dose, Christina and Hautmann, Christopher and Holtmann, Martin and Jenkner, Carolin and Millenet, Sabina and Romanos, Marcel}, title = {Individualised short-term therapy for adolescents impaired by attention-deficit/hyperactivity disorder despite previous routine care treatment (ESCAadol)-Study protocol of a randomised controlled trial within the consortium ESCAlife}, series = {Trials}, volume = {19}, journal = {Trials}, number = {254}, doi = {10.1186/s13063-018-2635-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176061}, year = {2018}, abstract = {Background: Despite the high persistence rate of attention-deficit/hyperactivity disorder (ADHD) throughout the lifespan, there is a considerable gap in knowledge regarding effective treatment strategies for adolescents with ADHD. This group in particular often shows substantial psychosocial impairment, low compliance and insufficient response to psychopharmacological interventions. Effective and feasible treatments should further consider the developmental shift in ADHD symptoms, comorbidity and psychosocial adversity as well as family dysfunction. Thus, individualised interventions for adolescent ADHD should comprise a multimodal treatment strategy. The randomised controlled ESCAadol study addresses the needs of this patient group and compares the outcome of short-term cognitive behavioural therapy with parent-based telephone-assisted self-help. Methods/design: In step 1, 160 adolescents aged 12 to 17 years with a diagnosis of ADHD will undergo a treatment as usual (TAU) observation phase of 1 month. In step 2, those still severely affected are randomised to the intervention group with an Individualised Modular Treatment Programme (IMTP) or a telephone-assisted self-help programme for parents (TASH) as an active control condition. The IMTP was specifically designed for the needs of adolescent ADHD. It comprises 10 sessions of individual cognitive behavioural therapy with the adolescents and/or the parents, for which participants choose three out of 10 available focus modules (e.g. organisational skills and planning, emotion regulation, problem solving and stress management, dysfunctional family communication). TASH combines a bibliotherapeutic component with 10 counselling sessions for the parents via telephone. Primary outcome is the change in ADHD symptoms in a clinician-rated diagnostic interview. Outcomes are assessed at inclusion into the study, after the TAU phase, after the intervention phase and after a further 12-week follow-up period. The primary statistical analysis will be by intention-to-treat, using linear regression models. Additionally, we will analyse psychometric and biological predictors and moderators of treatment response. Discussion: ESCAadol compares two short-term non-pharmacological interventions as cost-efficient and feasible treatment options for adolescent ADHD, addressing the specific needs and obstacles to treatment success in this group. We aim to contribute to personalised medicine for adolescent ADHD intended to be implemented in routine clinical care.}, language = {en} } @article{GeisslerWernerDworschaketal.2021, author = {Geissler, Julia M. and Werner, Elisabeth and Dworschak, Wolfgang and Romanos, Marcel and Ratz, Christoph}, title = {German Law Reform Does Not Reduce the Prevalence of Coercive Measures in Residential Institutions for Children, Adolescents, and Young Adults With Intellectual and Developmental Disabilities}, series = {Frontiers in Psychiatry}, volume = {12}, journal = {Frontiers in Psychiatry}, issn = {1664-0640}, doi = {10.3389/fpsyt.2021.765830}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-249030}, year = {2021}, abstract = {Background: Approximately 10\% of children, adolescents and young adults with an intellectual and developmental disability (IDD) in Bavaria live in residential institutions. 2015 saw media reports raising suspicions about excessive use of coercive measures (cM) in those institutions. Until a law reform at the end of 2017 made permission from family courts mandatory for cM, their use was governed by parental consent. The REDUGIA project conducted a representative survey comparing cM and their relation to challenging behaviour (cB) and employee stress in Bavaria pre and post reform. Methods: We sent questionnaires to 65 residential institutions for children, adolescents and young adults with IDD in 2017 (pre reform, T1) and 2019 (post reform, T2). To assess changes, we analysed data from all available questionnaire pairs (T1 and T2, N = 43). We calculated paired t-test and correlative analyses concerning the relationship between cB, cM, and employee stress. Results: The number of residents overall (T1: N = 1,661; T2: N = 1,673) and per institution (T1: m = 38.6 ± 32.0; T2: m = 38.9 ± 34.5, p = 0.920) remained stable. We did not see any changes in the Index cB (p = 0.508) or the proportion of residents per institution displaying various types of challenging behaviour (all ps>0.220). There was no change in the Index cM (p = 0.089) or any indicator of employee stress, all ps > 0.323. At follow-up, the Index cB correlated positively with the Index cM (r = 0.519 p < 0.001). Regarding employee stress, the Index cB correlated positively with the frequency of sick leave (r = 0.322, p = 0.037) and physical attacks on employees (r = 0.552, p < 0.001). The Index cM also correlated positively with the frequency of sick leave (r = 0.340, p = 0.028) and physical attacks on employees (r = 0.492, p = 0.001). Discussion: Coercive measures are not a general phenomenon, but are focused on specialised institutions. The law reform did not lead to changes in the number of children, adolescents and young adults with IDD affected by coercive measures in residential institutions in Bavaria. There were still large discrepancies between institutions in the prevalence of challenging behaviour and coercive measures. Coercive measures were associated with challenging behaviour and employee stress. Taken together, findings from REDUGIA emphasise the need to prevent challenging behaviour and thus coercive measures.}, language = {en} } @article{GeisslerWernerDworschaketal.2021, author = {Geissler, Julia and Werner, Elisabeth and Dworschak, Wolfgang and Romanos, Marcel and Ratz, Christoph}, title = {Freiheitsentziehende Maßnahmen in bayerischen Heimeinrichtungen f{\"u}r Kinder, Jugendliche und junge Vollj{\"a}hrige mit Intelligenzminderung}, series = {Zeitschrift f{\"u}r Kinder- und Jugendpsychiatrie und Psychotherapie}, volume = {49}, journal = {Zeitschrift f{\"u}r Kinder- und Jugendpsychiatrie und Psychotherapie}, number = {4}, issn = {1422-4917}, doi = {10.1024/1422-4917/a000808}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244859}, pages = {273-283}, year = {2021}, abstract = {Fragestellung: In Bayern leben etwa 10 \% aller jungen Menschen mit Intelligenzminderung in Heimeinrichtungen. 2016 wurde in Presseberichten der Vorwurf unzul{\"a}ssiger freiheitsentziehender Maßnahmen formuliert. Im Rahmen des Projekts REDUGIA wurde in bayerischen Heimeinrichtungen eine repr{\"a}sentative Erhebung zu freiheitsentziehenden Maßnahmen (FeM), herausforderndem Verhalten (hfV) und der Mitarbeiterbelastung (MaB) durchgef{\"u}hrt. Methodik: 65 Einrichtungen f{\"u}r junge Menschen mit Intelligenzminderung in Bayern wurde ein Fragebogen zu strukturellen Gegebenheiten sowie MaB, hfV und FeM zugesendet. Neben deskriptiven Auswertungen wurden korrelative Analysen bzw. Regressionsanalysen zum Zusammenhang zwischen hfV, FeM und MaB durchgef{\"u}hrt. Ergebnisse: Es wurden Daten zu 1839 Personen in 61 Einrichtungen erhoben. 84.3 \% der Einrichtungen berichteten geringe Raten an hfV und FeM, w{\"a}hrend 15.7 \% ein geh{\"a}uftes Vorkommen von hfV und FeM angaben. Auf n = 1809 Vollzeit{\"a}quivalente kam es innerhalb von 14 Tagen zu 639 k{\"o}rperlichen Angriffen durch Bewohner_innen. In 12 Monaten wurden problemverhaltensassoziiert 85 Krankmeldungen sowie 33 Versetzungsantr{\"a}ge/K{\"u}ndigungen berichtet. Es zeigte sich ein signifikant positiver Zusammenhang zwischen hfV und FeM (R² = .307, F = 21.719, p < .001). Die Mitarbeiterbelastung korrelierte positiv mit hfV (r = .507, p < .001). Schlussfolgerungen: Die Studienbefunde weisen darauf hin, dass hfV sowie FeM bei jungen Menschen mit Intelligenzminderung kein fl{\"a}chendeckendes Ph{\"a}nomen darstellen, sondern sich auf wenige spezialisierte Einrichtungen fokussieren. M{\"o}gliche Maßnahmen zur Pr{\"a}vention von Problemverhalten und Freiheitsentzug werden diskutiert.}, language = {de} } @article{GerlachMaetzlerBroichetal.2012, author = {Gerlach, Manfred and Maetzler, Walter and Broich, Karl and Hampel, Harald and Rems, Lucas and Reum, Torsten and Riederer, Peter and St{\"a}ffler, Albrecht and Streffer, Johannes and Berg, Daniela}, title = {Biomarker candidates of neurodegeneration in Parkinson's disease for the evaluation of disease-modifying therapeutics}, series = {Journal of Neural Transmission}, volume = {119}, journal = {Journal of Neural Transmission}, number = {1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125375}, pages = {39-52}, year = {2012}, abstract = {Reliable biomarkers that can be used for early diagnosis and tracking disease progression are the cornerstone of the development of disease-modifying treatments for Parkinson's disease (PD). The German Society of Experimental and Clinical Neurotherapeutics (GESENT) has convened a Working Group to review the current status of proposed biomarkers of neurodegeneration according to the following criteria and to develop a consensus statement on biomarker candidates for evaluation of disease-modifying therapeutics in PD. The criteria proposed are that the biomarker should be linked to fundamental features of PD neuropathology and mechanisms underlying neurodegeneration in PD, should be correlated to disease progression assessed by clinical rating scales, should monitor the actual disease status, should be pre-clinically validated, and confirmed by at least two independent studies conducted by qualified investigators with the results published in peer-reviewed journals. To date, available data have not yet revealed one reliable biomarker to detect early neurodegeneration in PD and to detect and monitor effects of drug candidates on the disease process, but some promising biomarker candidates, such as antibodies against neuromelanin, pathological forms of α-synuclein, DJ-1, and patterns of gene expression, metabolomic and protein profiling exist. Almost all of the biomarker candidates were not investigated in relation to effects of treatment, validated in experimental models of PD and confirmed in independent studies.}, language = {en} } @article{GerlachMaetzlerBroichetal.2011, author = {Gerlach, Manfred and Maetzler, Walter and Broich, Karl and Hampel, Harald and Rems, Lucas and Reum, Torsten and Riederer, Peter and St{\"o}ffler, Albrecht and Streffer, Johannes and Berg, Daniela}, title = {Biomarker candidates of neurodegeneration in Parkinson's disease for the evaluation of disease-modifying therapeutics}, series = {Journal of Neural Transmission}, volume = {119}, journal = {Journal of Neural Transmission}, number = {1}, doi = {10.1007/s00702-011-0682-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133856}, pages = {39-52}, year = {2011}, abstract = {Reliable biomarkers that can be used for early diagnosis and tracking disease progression are the cornerstone of the development of disease-modifying treatments for Parkinson's disease (PD). The German Society of Experimental and Clinical Neurotherapeutics (GESENT) has convened a Working Group to review the current status of proposed biomarkers of neurodegeneration according to the following criteria and to develop a consensus statement on biomarker candidates for evaluation of disease-modifying therapeutics in PD. The criteria proposed are that the biomarker should be linked to fundamental features of PD neuropathology and mechanisms underlying neurodegeneration in PD, should be correlated to disease progression assessed by clinical rating scales, should monitor the actual disease status, should be pre-clinically validated, and confirmed by at least two independent studies conducted by qualified investigators with the results published in peer-reviewed journals. To date, available data have not yet revealed one reliable biomarker to detect early neurodegeneration in PD and to detect and monitor effects of drug candidates on the disease process, but some promising biomarker candidates, such as antibodies against neuromelanin, pathological forms of α-synuclein, DJ-1, and patterns of gene expression, metabolomic and protein profiling exist. Almost all of the biomarker candidates were not investigated in relation to effects of treatment, validated in experimental models of PD and confirmed in independent studies.}, language = {en} } @phdthesis{GernertgebBaranski2017, author = {Gernert [geb. Baranski], Stefanie}, title = {Assoziationsuntersuchung zu Neuropeptid Y-Polymorphismen bei Kindern und Jugendlichen mit Aufmerksamkeitsdefizit-/Hyperaktivit{\"a}tsst{\"o}rung}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-155692}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Die Aufmerksamkeitsdefizit-/Hyperaktivit{\"a}tsst{\"o}rung ist eine der h{\"a}ufigsten psychiatrischen Erkrankung des Kindesalters, die eine hohe Heritabilit{\"a}t aufweist und h{\"a}ufig bis ins Erwachsenenalter persistiert und lebenslang zu sozialen, gesundheitlichen und {\"o}konomischen Problemen f{\"u}hrt. Die ADHS tritt bei vielen Patienten in Kombina-tion mit anderen psychiatrischen und nicht-psychiatrischen Erkrankungen auf. In den letzten Jahren r{\"u}ckte zunehmend die h{\"a}ufig zur ADHS komorbid auftretende Adipositas in den Fokus der Forschung. Auf der Suche nach copy number variations in Zusammenhang mit ADHS, wurde eine Duplikation auf Chromosom 7p15 - dem Genlocus des NPY - entdeckt. NPY, ist ein endogenes orexigenes Peptid, welches physiologischerweise die Nahrungsaufnahme stimuliert und neben zahlreichen Effekten, wie Blutdruck- und Knochenregulation, auch in Zusammenhang mit neuropsychiatrischen Erkrankungen gebracht werden konnte. Diese Duplikation auf einem Genort, dessen Produkt f{\"u}r die Regulation von Energiehaushalt und K{\"o}rpergewicht zust{\"a}ndig ist, bildete die Grundlage, eine Assoziationsuntersuchung zu NPY-Genvarianten und dem K{\"o}rpergewicht bei Kindern durchzuf{\"u}hren. Untersucht wurden bei 269 an ADHS erkrankten Kindern und 142 gesunden Kontrollkindern die Assoziation zwischen NPY-Genvarianten (rs16147, rs16139, rs5574, rs16124) und ADHS, sowie die Assoziation zwischen NPY-Genvarianten und BMI-Perzentilen bei ADHS. Es ergab sich keine signifikante Assoziation bez{\"u}glich der aufgestellten Hypothesen.}, subject = {{\"U}bergewicht}, language = {de} } @article{GottschalkRichterZiegleretal.2019, author = {Gottschalk, Michael G. and Richter, Jan and Ziegler, Christiane and Schiele, Miriam A. and Mann, Julia and Geiger, Maximilian J. and Schartner, Christoph and Homola, Gy{\"o}rgy A. and Alpers, Georg W. and B{\"u}chel, Christian and Fehm, Lydia and Fydrich, Thomas and Gerlach, Alexander L. and Gloster, Andrew T. and Helbig-Lang, Sylvia and Kalisch, Raffael and Kircher, Tilo and Lang, Thomas and Lonsdorf, Tina B. and Pan{\´e}-Farr{\´e}, Christiane A. and Str{\"o}hle, Andreas and Weber, Heike and Zwanzger, Peter and Arolt, Volker and Romanos, Marcel and Wittchen, Hans-Ulrich and Hamm, Alfons and Pauli, Paul and Reif, Andreas and Deckert, J{\"u}rgen and Neufang, Susanne and H{\"o}fler, Michael and Domschke, Katharina}, title = {Orexin in the anxiety spectrum: association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes}, series = {Translational Psychiatry}, volume = {9}, journal = {Translational Psychiatry}, doi = {10.1038/s41398-019-0415-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227479}, year = {2019}, abstract = {Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10-7), particularly in the female subsample (p = 9.8 × 10-9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10-4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.}, language = {en} } @phdthesis{Graefe2011, author = {Gr{\"a}fe, Catherin}, title = {Familienuntersuchung bei Kindern und Jugendlichen mit ADHS - Unterschiede der DSM-IV Subtypen bez{\"u}glich Komorbidit{\"a}t, famili{\"a}rer Belastung und Krankheitsbeginn}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-57370}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2011}, abstract = {Im Rahmen der vorliegenden Arbeit wurden Unterschiede zwischen dem vorwiegend unaufmerksamen und dem kombinierten Subtyp nach DSM-IV anhand von Familien, in denen mindestens zwei Kinder von ADHS betroffen sind, untersucht. Die famili{\"a}re Betroffenheit, Art und Anzahl der komorbiden St{\"o}rungen sowie der Diagnosezeitpunkt wurden bez{\"u}glich der Unterschiede zwischen den Subtypen analysiert. Weiterhin wurden epidemiologische und soziodemographische Merkmale beschrieben. Methodik: Im Rahmen einer Multicenterstudie wurden 250 Kinder sowie deren Eltern aus 116 Familien untersucht. ADHS und Komorbidit{\"a}ten wurden anhand des K-SADS-PL und DIKJ erhoben. Bei den Eltern wurde ADHS anhand der Wender-Utah-Rating-Scale (WURS) und der Barkley-Skalen ermittelt. Ergebnisse: Bei 39\% der an ADHS erkrankten Kinder und Jugendlichen lag zus{\"a}tzlich mindestens eine komorbide St{\"o}rung zum Zeitpunkt der Untersuchung vor. Die Annahme, dass der kombinierte Subtyp mit einer h{\"o}heren famili{\"a}ren Belastung einhergeht, konnte im Rahmen der Studie nicht best{\"a}tigt werden. Verglichen mit den einfachen Subtypen zeigte sich keine st{\"a}rkere Betroffenheit von Komorbidit{\"a}ten beim kombinierten Subtyp. Patienten, die vom kombinierten Subtyp betroffen waren, hatten signifikant h{\"a}ufiger komorbide externalisierende St{\"o}rungen als Patienten, bei denen ein einfacher Subtyp diagnostiziert worden war. Diese Studie best{\"a}tigte die Annahme, dass Patienten, bei denen ein unaufmerksamer Subtyp diagnostiziert worden war, signifikant h{\"a}ufiger an komorbiden internalisierenden St{\"o}rungen litten und sich verglichen mit den anderen Subtypen durch einen sp{\"a}teren Diagnosezeitpunkt auszeichneten.}, subject = {ADHS}, language = {de} } @article{GruenblattOnedaEkicietal.2017, author = {Gr{\"u}nblatt, Edna and Oneda, Beatrice and Ekici, Arif B. and Ball, Juliane and Geissler, Julia and Uebe, Steffen and Romanos, Marcel and Rauch, Anita and Walitza, Susanne}, title = {High resolution chromosomal microarray analysis in paediatric obsessive-compulsive disorder}, series = {BMC Medical Genomics}, volume = {10}, journal = {BMC Medical Genomics}, number = {68}, doi = {10.1186/s12920-017-0299-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172791}, year = {2017}, abstract = {Background Obsessive-Compulsive Disorder (OCD) is a common and chronic disorder in which a person has uncontrollable, reoccurring thoughts and behaviours. It is a complex genetic condition and, in case of early onset (EO), the patients manifest a more severe phenotype, and an increased heritability. Large (>500 kb) copy number variations (CNVs) previously associated with autism and schizophrenia have been reported in OCD. Recently, rare CNVs smaller than 500 kb overlapping risk loci for other neurodevelopmental conditions have also been reported in OCD, stressing the importance of examining CNVs of any size range. The aim of this study was to further investigate the role of rare and small CNVs in the aetiology of EO-OCD. Methods We performed high-resolution chromosomal microarray analysis in 121 paediatric OCD patients and in 124 random controls to identify rare CNVs (>50 kb) which might contribute to EO-OCD. Results The frequencies and the size of the observed rare CNVs in the patients did not differ from the controls. However, we observed a significantly higher frequency of rare CNVs affecting brain related genes, especially deletions, in the patients (OR = 1.98, 95\% CI 1.02-3.84; OR = 3.61, 95\% CI 1.14-11.41, respectively). Similarly, enrichment-analysis of CNVs gene content, performed with three independent methods, confirmed significant clustering of predefined genes involved in synaptic/brain related functional pathways in the patients but not in the controls. In two patients we detected \(de-novo\) CNVs encompassing genes previously associated with different neurodevelopmental disorders \(\textit{NRXN1, ANKS1B, UHRF1BP1}\)). Conclusions Our results further strengthen the role of small rare CNVs, particularly deletions, as susceptibility factors for paediatric OCD.}, language = {en} } @article{GschmackMonoranuMaroufetal.2022, author = {Gschmack, Eva and Monoranu, Camelia-Maria and Marouf, Hecham and Meyer, Sarah and Lessel, Lena and Idris, Raja and Berg, Daniela and Maetzler, Walter and Steigerwald, Frank and Volkmann, Jens and Gerlach, Manfred and Riederer, Peter and Koutsilieri, Eleni and Scheller, Carsten}, title = {Plasma autoantibodies to glial fibrillary acidic protein (GFAP) react with brain areas according to Braak staging of Parkinson's disease}, series = {Journal of Neural Transmission}, volume = {129}, journal = {Journal of Neural Transmission}, number = {5-6}, doi = {10.1007/s00702-022-02495-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325161}, pages = {545-555}, year = {2022}, abstract = {Idiopathic Parkinson's disease (PD) is characterized by a progredient degeneration of the brain, starting at deep subcortical areas such as the dorsal motor nucleus of the glossopharyngeal and vagal nerves (DM) (stage 1), followed by the coeruleus-subcoeruleus complex; (stage 2), the substantia nigra (SN) (stage 3), the anteromedial temporal mesocortex (MC) (stage 4), high-order sensory association areas and prefrontal fields (HC) (stage 5) and finally first-order sensory association areas, premotor areas, as well as primary sensory and motor field (FC) (stage 6). Autoimmunity might play a role in PD pathogenesis. Here we analyzed whether anti-brain autoantibodies differentially recognize different human brain areas and identified autoantigens that correlate with the above-described dissemination of PD pathology in the brain. Brain tissue was obtained from deceased individuals with no history of neurological or psychiatric disease and no neuropathological abnormalities. Tissue homogenates from different brain regions (DM, SN, MC, HC, FC) were subjected to SDS-PAGE and Western blot. Blots were incubated with plasma samples from 30 PD patients and 30 control subjects and stained with anti-IgG antibodies to detect anti-brain autoantibodies. Signals were quantified. Prominent autoantigens were identified by 2D-gel-coupled mass spectrometry sequencing. Anti-brain autoantibodies are frequent and occur both in healthy controls and individuals with PD. Glial fibrillary acidic protein (GFAP) was identified as a prominent autoantigen recognized in all plasma samples. GFAP immunoreactivity was highest in DM areas and lowest in FC areas with no significant differences in anti-GFAP autoantibody titers between healthy controls and individuals with PD. The anti-GFAP autoimmunoreactivity of different brain areas correlates with the dissemination of histopathological neurodegeneration in PD. We hypothesize that GFAP autoantibodies are physiological but might be involved as a cofactor in PD pathogenesis secondary to a leakage of the blood-brain barrier.}, language = {en} } @phdthesis{Goessler2007, author = {G{\"o}ßler, Michael}, title = {Molekulargenetische Untersuchungen serotonerger Kandidatengene bei Zwangsst{\"o}rungen im Kindes- und Jugendalter}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-23773}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2007}, abstract = {Zwangsst{\"o}rungen, im englischen als Obsessive Compulsive Disorder (OCD) bezeichnet, sind sowohl in der Erwachsenen- als auch in der Kinder- und Jugendpsychiatrie bekannte Krankheitsbilder, die mit einer Lebenszeitpr{\"a}valenz von 2,5 - 3\% zu den h{\"a}ufigsten psychiatrischen Erkrankungen im Kindes- und Jugendalter geh{\"o}ren. Sie stellen in der Regel eine erhebliche Belastung sowohl f{\"u}r die betroffenen Kinder als auch f{\"u}r deren Familie dar und schr{\"a}nken den allt{\"a}glichen Lebensablauf je nach Auspr{\"a}gung erheblich ein. Familien- und Zwillingsuntersuchungen zeigen, dass bei Zwangsst{\"o}rungen eine deutliche famili{\"a}re Belastung vorliegt. Gerade bei einer fr{\"u}hen Manifestation im Kindesalter (auf englisch als early onset bezeichnet) konnten Familienstudien zeigen, dass genetische Faktoren eine besonders ausgepr{\"a}gte Rolle spielen. Diese formalgenetischen Studien legen weitere Untersuchungen auf molekulargenetischer Ebene f{\"u}r Zwangsst{\"o}rungen im Kindes- und Jugendalter nahe. Pharmakologische Studien und erste molekulargenetische Studien verweisen zudem auf einen Zusammenhang zwischen Zwangs- und Angstsymptomen und dem Serotoninstoffwechsel. Selektive Serotonin Wiederaufnahme-Hemmer (Selective Serotonine Reuptake Inhibitors, SSRI) und tricyclische Antidepressiva sind bei der Behandlung von Zwangsst{\"o}rungen besonders wirksam. Auch im Kindes- und Jugendalter sind diese Medikamente aufgrund ihrer positiven Wirkung bei Zwangsst{\"o}rungen Mittel der ersten Wahl. Insgesamt wird die Pathogenese der Zwangsst{\"o}rungen nach aktuellem Forschungsstand als multifaktoriell angenommen. Dabei bezieht sich bisher die {\"u}berwiegende Zahl der Untersuchungen auf Zwangsst{\"o}rungen erwachsener Patienten. Nach aktuellem Kenntnisstand handelt es sich bei der vorliegenden Arbeit um die ersten familienbasierten Assoziationsstudien bei Kindern und Jugendlichen mit Zwangsst{\"o}rungen. Zielsetzung dieser Arbeit war die Untersuchung einer Assoziation von Varianten in ausgew{\"a}hlten Genen des serotonergen Systems und juvenilen Zwangsst{\"o}rungen. Die Auswahl der Kandidatengene f{\"u}r Zwangsst{\"o}rungen erfolgte auf patho-physiologischen {\"U}berlegungen: Die Tryptophanhydroxylase als geschwindigkeits-bestimmendes Enzym in der Synthese von Serotonin, der Serotonin-1B-Rezeptor als Zielorgan mit autoregulierender Funktion auf das serotonerge System, sowie der Serotonintransporter, der, therapeutisch genutzt, von SSRIs blockiert wird. Untersuchungen zu den genannten Kandidatengenen liegen bei erwachsenen Patienten mit Zwangsst{\"o}rungen vor, die Ergebnisse sollten in unserer Studie repliziert werden. 64 Kinder und Jugendliche, sowie deren leibliche Eltern wurden in die Untersuchung eingeschlossen. In den vorliegenden molekulargenetischen Untersuchungen konnten f{\"u}r Varianten im Tryptophanhydroxylase-1-Gen und dem Serotonin-1B-Rezeptor-Gen kein Zusammenhang mit Zwangsst{\"o}rungen bei Kindern und Jugendlichen gesehen werden. Die funktionelle Variante des Serotonintransporter-Gens, die zu einer h{\"o}heren Aktivit{\"a}t des Transporters f{\"u}hrt, wurde tendenziell h{\"a}ufiger bei den Patienten mit Zwangsst{\"o}rungen beobachtet. Der Befund entspricht damit in der Richtung den fr{\"u}heren Befunden von erwachsenen Patienten.}, language = {de} } @article{HammerleHussErnstetal.2016, author = {Hammerle, Florian and Huss, Michael and Ernst, Verena and B{\"u}rger, Arne}, title = {Thinking dimensional: prevalence of DSM-5 early adolescent full syndrome, partial and subthreshold eating disorders in a cross-sectional survey in German schools}, series = {BMJ Open}, volume = {6}, journal = {BMJ Open}, number = {e010843}, doi = {10.1136/bmjopen-2015-010843}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164734}, year = {2016}, abstract = {Objectives Investigating for the first time in Germany Diagnostic and Statistical Manual Fifth Edition (DSM-5) prevalences of adolescent full syndrome, Other Specified Feeding or Eating Disorder (OSFED), partial and subthreshold anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED). Method A national school-based cross-sectional survey with nine schools in Germany was undertaken that was aimed at students from grades 7 and 8. Of the 1775 students who were contacted to participate in the study, 1654 participated (participation rate: 93.2\%). The sample consisted of 873 female and 781 male adolescents (mean age=13.4 years). Prevalence rates were established using direct symptom criteria with a structured inventory (SIAB-S) and an additional self-report questionnaire (Eating Disorder Inventory 2 (EDI-2)). Results Prevalences for full syndrome were 0.3\% for AN, 0.4\% for BN, 0.5\% for BED and 3.6\% for OSFED-atypical AN, 0\% for BN (low frequency/limited duration), 0\% for BED (low frequency/limited duration) and 1.9\% for purging disorder (PD). Prevalences of partial syndrome were 10.9\% for AN (7.1\% established with cognitive symptoms only, excluding weight criteria), 0.2\% for BN and 2.1\% for BED, and of subthreshold syndrome were 0.8\% for AN, 0.3\% for BN and 0.2\% for BED. Cases on EDI-2 scales were much more pronounced with 12.6-21.1\% of the participants with significant sex differences. Conclusions The findings were in accordance with corresponding international studies but were in contrast to other German studies showing much higher prevalence rates. The study provides, for the first time, estimates for DSM-5 prevalences of eating disorders in adolescents for Germany, and evidence in favour of using valid measures for improving prevalence estimates."}, language = {en} } @article{HautmannDoepfnerKatzmannetal.2018, author = {Hautmann, Christopher and D{\"o}pfner, Manfred and Katzmann, Josepha and Sch{\"u}rmann, Stephanie and Wolff Metternich-Kaizman, Tanja and Jaite, Charlotte and Kappel, Viola and Geissler, Julia and Warnke, Andreas and Jacob, Christian and Hennighausen, Klaus and Haack-Dees, Barbara and Schneider-Momm, Katja and Philipsen, Alexandra and Matthies, Swantje and R{\"o}sler, Michael and Retz, Wolfgang and Gontard, Alexander von and Sobanski, Esther and Alm, Barbara and Hohmann, Sarah and H{\"a}ge, Alexander and Poustka, Luise and Colla, Michael and Gentschow, Laura and Freitag, Christine M. and Becker, Katja and Jans, Thomas}, title = {Sequential treatment of ADHD in mother and child (AIMAC study): importance of the treatment phases for intervention success in a randomized trial}, series = {BMC Psychiatry}, volume = {18}, journal = {BMC Psychiatry}, doi = {10.1186/s12888-018-1963-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227930}, year = {2018}, abstract = {Background The efficacy of parent-child training (PCT) regarding child symptoms may be reduced if the mother has attention-deficit/hyperactivity disorder (ADHD). The AIMAC study (ADHD in Mothers and Children) aimed to compensate for the deteriorating effect of parental psychopathology by treating the mother (Step 1) before the beginning of PCT (Step 2). This secondary analysis was particularly concerned with the additional effect of the Step 2 PCT on child symptoms after the Step 1 treatment. Methods The analysis included 143 mothers and children (aged 6-12 years) both diagnosed with ADHD. The study design was a two-stage, two-arm parallel group trial (Step 1 treatment group [TG]: intensive treatment of the mother including psychotherapy and pharmacotherapy; Step 1 control group [CG]: supportive counseling only for mother; Step 2 TG and CG: PCT). Single- and multi-group analyses with piecewise linear latent growth curve models were applied to test for the effects of group and phase. Child symptoms (e.g., ADHD symptoms, disruptive behavior) were rated by three informants (blinded clinician, mother, teacher). Results Children in the TG showed a stronger improvement of their disruptive behavior as rated by mothers than those in the CG during Step 1 (Step 1: TG vs. CG). In the CG, according to reports of the blinded clinician and the mother, the reduction of children's disruptive behavior was stronger during Step 2 than during Step 1 (CG: Step 1 vs. Step 2). In the TG, improvement of child outcome did not differ across treatment steps (TG: Step 1 vs. Step 2). Conclusions Intensive treatment of the mother including pharmacotherapy and psychotherapy may have small positive effects on the child's disruptive behavior. PCT may be a valid treatment option for children with ADHD regarding disruptive behavior, even if mothers are not intensively treated beforehand. Trial registration ISRCTN registry ISRCTN73911400. Registered 29 March 2007.}, language = {en} } @article{HavikDegenhardtJohanssonetal.2012, author = {Havik, Bjarte and Degenhardt, Franziska A. and Johansson, Stefan and Fernandes, Carla P. D. and Hinney, Anke and Scherag, Andr{\´e} and Lybaek, Helle and Djurovic, Srdjan and Christoforou, Andrea and Ersland, Kari M. and Giddaluru, Sudheer and O'Donovan, Michael C. and Owen, Michael J. and Craddock, Nick and M{\"u}hleisen, Thomas W. and Mattheisen, Manuel and Schimmelmann, Benno G. and Renner, Tobias and Warnke, Andreas and Herpertz-Dahlmann, Beate and Sinzig, Judith and Albayrak, {\"O}zg{\"u}r and Rietschel, Marcella and N{\"o}then, Markus M. and Bramham, Clive R. and Werge, Thomas and Hebebrand, Johannes and Haavik, Jan and Andreassen, Ole A. and Cichon, Sven and Steen, Vidar M. and Le Hellard, Stephanie}, title = {DCLK1 Variants Are Associated across Schizophrenia and Attention Deficit/Hyperactivity Disorder}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {4}, doi = {10.1371/journal.pone.0035424}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135285}, pages = {e35424}, year = {2012}, abstract = {Doublecortin and calmodulin like kinase 1 (DCLK1) is implicated in synaptic plasticity and neurodevelopment. Genetic variants in DCLK1 are associated with cognitive traits, specifically verbal memory and general cognition. We investigated the role of DCLK1 variants in three psychiatric disorders that have neuro-cognitive dysfunctions: schizophrenia (SCZ), bipolar affective disorder (BP) and attention deficit/hyperactivity disorder (ADHD). We mined six genome wide association studies (GWASs) that were available publically or through collaboration; three for BP, two for SCZ and one for ADHD. We also genotyped the DCLK1 region in additional samples of cases with SCZ, BP or ADHD and controls that had not been whole-genome typed. In total, 9895 subjects were analysed, including 5308 normal controls and 4,587 patients (1,125 with SCZ, 2,496 with BP and 966 with ADHD). Several DCLK1 variants were associated with disease phenotypes in the different samples. The main effect was observed for rs7989807 in intron 3, which was strongly associated with SCZ alone and even more so when cases with SCZ and ADHD were combined (P-value = 4x10\(^{-5}\) and 4x10\(^{-6}\), respectively). Associations were also observed with additional markers in intron 3 (combination of SCZ, ADHD and BP), intron 19 (SCZ+BP) and the 3'UTR (SCZ+BP). Our results suggest that genetic variants in DCLK1 are associated with SCZ and, to a lesser extent, with ADHD and BP. Interestingly the association is strongest when SCZ and ADHD are considered together, suggesting common genetic susceptibility. Given that DCLK1 variants were previously found to be associated with cognitive traits, these results are consistent with the role of DCLK1 in neurodevelopment and synaptic plasticity.}, language = {en} } @article{HebestreitZeidlerSchippersetal.2022, author = {Hebestreit, Helge and Zeidler, Cornelia and Schippers, Christopher and de Zwaan, Martina and Deckert, J{\"u}rgen and Heuschmann, Peter and Krauth, Christian and Bullinger, Monika and Berger, Alexandra and Berneburg, Mark and Brandstetter, Lilly and Deibele, Anna and Dieris-Hirche, Jan and Graessner, Holm and G{\"u}ndel, Harald and Herpertz, Stephan and Heuft, Gereon and Lapstich, Anne-Marie and L{\"u}cke, Thomas and Maisch, Tim and Mundlos, Christine and Petermann-Meyer, Andrea and M{\"u}ller, Susanne and Ott, Stephan and Pfister, Lisa and Quitmann, Julia and Romanos, Marcel and Rutsch, Frank and Schaubert, Kristina and Schubert, Katharina and Schulz, J{\"o}rg B. and Schweiger, Susann and T{\"u}scher, Oliver and Ungeth{\"u}m, Kathrin and Wagner, Thomas O. F. and Haas, Kirsten}, title = {Dual guidance structure for evaluation of patients with unclear diagnosis in centers for rare diseases (ZSE-DUO): study protocol for a controlled multi-center cohort study}, series = {Orphanet Journal of Rare Diseases}, volume = {17}, journal = {Orphanet Journal of Rare Diseases}, number = {1}, doi = {10.1186/s13023-022-02176-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300440}, year = {2022}, abstract = {Background In individuals suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis often extends over many years. Factors contributing to delayed diagnosis include health care professionals' limited knowledge of rare diseases and frequent (co-)occurrence of mental disorders that may complicate and delay the diagnostic process. The ZSE-DUO study aims to assess the benefits of a combination of a physician focusing on somatic aspects with a mental health expert working side by side as a tandem in the diagnostic process. Study design This multi-center, prospective controlled study has a two-phase cohort design. Methods Two cohorts of 682 patients each are sequentially recruited from 11 university-based German Centers for Rare Diseases (CRD): the standard care cohort (control, somatic expertise only) and the innovative care cohort (experimental, combined somatic and mental health expertise). Individuals aged 12 years and older presenting with symptoms and signs which are not explained by current diagnoses will be included. Data will be collected prior to the first visit to the CRD's outpatient clinic (T0), at the first visit (T1) and 12 months thereafter (T2). Outcomes Primary outcome is the percentage of patients with one or more confirmed diagnoses covering the symptomatic spectrum presented. Sample size is calculated to detect a 10 percent increase from 30\% in standard care to 40\% in the innovative dual expert cohort. Secondary outcomes are (a) time to diagnosis/diagnoses explaining the symptomatology; (b) proportion of patients successfully referred from CRD to standard care; (c) costs of diagnosis including incremental cost effectiveness ratios; (d) predictive value of screening instruments administered at T0 to identify patients with mental disorders; (e) patients' quality of life and evaluation of care; and f) physicians' satisfaction with the innovative care approach. Conclusions This is the first multi-center study to investigate the effects of a mental health specialist working in tandem with a somatic expert physician in CRDs. If this innovative approach proves successful, it will be made available on a larger scale nationally and promoted internationally. In the best case, ZSE-DUO can significantly shorten the time to diagnosis for a suspected rare disease.}, language = {en} } @phdthesis{Hench2007, author = {Hench, Franz}, title = {Familienuntersuchung bei Kindern und Jugendlichen mit Aufmerksamkeitsdefizit-/ Hyperaktivit{\"a}tsst{\"o}rung (ADHS): Komorbidit{\"a}ten und famili{\"a}re Belastung}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-35494}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2007}, abstract = {Die Aufmerksamkeitsdefizit- /Hyperaktivit{\"a}tsst{\"o}rung (ADHS) gilt heute als eine der h{\"a}ufigsten Erkrankungen, die in der Kinder- und Jugendpsychiatrie bzw. in der Kinder- und Jugendmedizin behandelt werden. Bei diesem St{\"o}rungsbild spielen genetische Faktoren eine wichtige Rolle. Erblichkeitssch{\"a}tzungen liegen bei bis zu 80\% und damit h{\"o}her als bei den meisten kinder- und jugendpsychiatrischen Erkrankungen. Das Ziel der vorliegenden Arbeit war die Erhebung epidemiologischer und soziodemographischer Daten, komorbider St{\"o}rungen in Abh{\"a}ngigkeit von vorliegenden Subtypen bei ADHS nach DSM-IV sowie die Untersuchung der Pr{\"a}valenz f{\"u}r eine ADHS bei Eltern in Familien mit mindestens zwei an ADHS erkrankten Kindern. Methode: Es wurde N = 64 Patienten aus 25 Familien mit mindestens zwei an ADHS erkrankten Kindern untersucht. Die Stichprobe wurde im Rahmen einer multizentrischen Familienuntersuchung zu genetischen Faktoren ADHS (Nationales Genomforschungsnetz) erhoben. Die Diagnose der ADHS und Erhebung komorbider St{\"o}rungen der betroffenen Kinder erfolgte nach DSM-IV-Kriterien unter Zuhilfenahme des K-SADS-PL. Bei den Eltern wurde die Wender-Utah-Rating-Scale (WURS) verwendet. Ergebnis: Bei Patienten mit kombiniertem Subtyp einer ADHS nach DSM-IV wurden signifikant h{\"a}ufiger externalisierende St{\"o}rungen diagnostiziert. Betroffene Kinder mit {\"u}berwiegend unaufmerksamen Subtyp litten h{\"a}ufiger an internalisierenden St{\"o}rungen und bei ihnen wurde die Diagnose signifikant sp{\"a}ter gestellt als bei Kindern mit einem anderen Subtyp nach DSM-IV. Im Vergleich mit Studien in denen Familien mit nur einem betroffenen Kind untersucht wurden zeigten sich im wesentlichen keine signifikanten Unterschiede in der Verteilung der h{\"a}ufigsten komorbiden St{\"o}rungen bei den betroffenen Kindern. Insgesamt fanden wir, dass 48\% der M{\"u}tter und 43\% der V{\"a}ter im Kindesalter von einer ADHS betroffen waren. Auf alle Familien verteilt, ergab sich eine mindestens einfache Belastung der Eltern von ca. 78\%.}, subject = {ADHS}, language = {de} } @phdthesis{Herhaus2015, author = {Herhaus, Gabriele}, title = {Besteht ein Zusammenhang zwischen Symptomen der Aufmerksamkeitsdefizit-/Hyperaktivit{\"a}tsst{\"o}rung in der Kindheit sowie ihrer Pharmakotherapie und dem sp{\"a}teren Auftreten eines Parkinson-Syndroms?}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126191}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Die ADHS und die Parkinson-Krankheit gehen beide mit Ver{\"a}nderungen des dopaminergen Systems einher. Methylphenidat (MPH) ist ein zentralwirkendes Psychostimulans, das den Dopamin-Wiederaufnahme-Transporter reversibel hemmt. Obwohl MPH seit {\"u}ber 50 Jahren in der symptomatischen Therapie der ADHS angewandt wird, ist die Datenlage zu den Langzeiteffekten und Risiken dieses Medikaments relativ d{\"u}nn. Basierend auf den Ergebnissen von Versuchen an Ratten wurde die Theorie aufgestellt, dass MPH die Ausreifung des zentralen dopaminergen Systems beeinflusst und dadurch ein Risikofaktor f{\"u}r die Entwicklung eines Parkinson-Syndroms sein k{\"o}nnte. Ziel dieser Pilotstudie war zum einen zu untersuchen, ob bei Patienten mit Parkinson ADHS-{\"a}hnliche Symptome in der Kindheit auftraten und zum anderen zu ermitteln, ob Parkinson-Patienten in ihrer Kindheit Psychostimulanzien eingenommen haben. Als Instrumentarium dienten die deutsche Kurzform der Wenda Utah Rating Scale (WURS-k) sowie der 'Fragebogen zu Kindheit und Entwicklung U40'. Insgesamt f{\"u}llten 88 Parkinson-Patienten die Frageb{\"o}gen vollst{\"a}ndig aus. Die Daten dieser Patienten sowie einer ebenso großen, randomisierten Kontrollgruppe wurden in die Auswertung einbezogen. Im Fragebogen WURS-k fanden sich in der Gruppe der Parkinson-Patienten signifikant h{\"o}here Summenscores im Vergleich zur Kontrollgruppe. Zus{\"a}tzlich zeigten sich bei den Parkinson-Patienten h{\"o}here Scores bez{\"u}glich der Faktoren „Aufmerksamkeitsdefizit/Hyperaktivit{\"a}t" sowie „{\"a}ngstlich-depressive Symptomatik", nicht aber bei den Faktoren „Impulsivit{\"a}t", „Protestverhalten" und „St{\"o}rung der sozialen Adaptation". Auch die Auswertung des Fragebogens U40 ergab signifikant h{\"o}here Punktwerte bez{\"u}glich der Items „Aufmerksamkeitsdefizit" und „Hyperaktivit{\"a}t" bei den Parkinson-Patienten. Dennoch kann aus diesen Ergebnissen nicht geschlossen werden, dass die in unserer Studie untersuchten Parkinson-Patienten in ihrer Kindheit an einer ADHS litten, da die durchschnittlichen Summenscores der WURS-k deutlich unter dem festgelegten Cut-Off-Wert von gr{\"o}ßer oder gleich 30 lagen. Es ist aber m{\"o}glich, dass einzelne ADHS-{\"a}hnliche Symptome den motorischen Symptomen einer Parkinson-Erkrankung vorausgehen k{\"o}nnen. Letztlich fanden wir keinen Anhalt daf{\"u}r, dass die Parkinson-Patienten in ihrer Kindheit Psychostimulanzien wie MPH eingenommen hatten.}, subject = {ADHS}, language = {de} } @article{HerzogAndreattaSchneideretal.2021, author = {Herzog, Katharina and Andreatta, Marta and Schneider, Kristina and Schiele, Miriam A. and Domschke, Katharina and Romanos, Marcel and Deckert, J{\"u}rgen and Pauli, Paul}, title = {Reducing Generalization of Conditioned Fear: Beneficial Impact of Fear Relevance and Feedback in Discrimination Training}, series = {Frontiers in Psychology}, volume = {12}, journal = {Frontiers in Psychology}, issn = {1664-1078}, doi = {10.3389/fpsyg.2021.665711}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239970}, year = {2021}, abstract = {Anxiety patients over-generalize fear, possibly because of an incapacity to discriminate threat and safety signals. Discrimination trainings are promising approaches for reducing such fear over-generalization. Here we investigated the efficacy of a fear-relevant vs. a fear-irrelevant discrimination training on fear generalization and whether the effects are increased with feedback during training. Eighty participants underwent two fear acquisition blocks, during which one face (conditioned stimulus, CS+), but not another face (CS-), was associated with a female scream (unconditioned stimulus, US). During two generalization blocks, both CSs plus four morphs (generalization stimuli, GS1-GS4) were presented. Between these generalization blocks, half of the participants underwent a fear-relevant discrimination training (discrimination between CS+ and the other faces) with or without feedback and the other half a fear-irrelevant discrimination training (discrimination between the width of lines) with or without feedback. US expectancy, arousal, valence ratings, and skin conductance responses (SCR) indicated successful fear acquisition. Importantly, fear-relevant vs. fear-irrelevant discrimination trainings and feedback vs. no feedback reduced generalization as reflected in US expectancy ratings independently from one another. No effects of training condition were found for arousal and valence ratings or SCR. In summary, this is a first indication that fear-relevant discrimination training and feedback can improve the discrimination between threat and safety signals in healthy individuals, at least for learning-related evaluations, but not evaluations of valence or (physiological) arousal.}, language = {en} } @phdthesis{Hohage2012, author = {Hohage, Amelie}, title = {{\"U}berpr{\"u}fung der Eignung des Kiddie-SADS-Interviews zur dimensionalen Erfassung der externalen Symptomatik bei Kindern und Jugendlichen mit Aufmerksamkeitsdefizit-/Hyperaktivit{\"a}tsst{\"o}rung - Eine empirische Untersuchung}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-73984}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2012}, abstract = {In der vorliegenden Arbeit sollte ein Interview auf die G{\"u}tekriterien Objektivit{\"a}t, Validit{\"a}t und Reliabilit{\"a}t {\"u}berpr{\"u}ft werden. Es sollte untersucht werden, ob das Interview geeignet ist, aktuell vorhandene Symptome der ADHS und der ODD dimensional zu erfassen. Dabei wurden 61 Patienten der Klinik und Poliklinik f{\"u}r Kinder- und Jugendpsychiatrie und Psychotherapie der Universit{\"a}t W{\"u}rzburg mit ihren M{\"u}ttern befragt. Die Objektivit{\"a}t wurde {\"u}berpr{\"u}ft, indem das Interview auf Video aufgezeichnet und nochmals von einem zweiten Beurteiler ausgewertet wurde. Die Summenwerte der beiden Interviewer wurden miteinander korreliert. Die Korrelation war signifikant und ergab einen Wert von rk= ,98. Die Objektivit{\"a}t im Sinne der Beurteiler{\"u}bereinstimmung kann somit als hoch angesehen werden. Es konnte gezeigt werden, dass die zusammenfassende Beurteilung des Interviewers h{\"o}her mit der Einsch{\"a}tzung aufgrund der Angaben der M{\"u}tter korreliert als mit der Einsch{\"a}tzung aufgrund der Angaben der Kinder. Die Korrelation zwischen der zusammenfassenden Beurteilung und der Einsch{\"a}tzung aufgrund der Angaben der M{\"u}ttern ergab einen Wert von r= ,98, die Korrelation zwischen der zusammenfassenden Beurteilung und der Einsch{\"a}tzung aufgrund der Angaben der Kindern einen Wert von r= ,57. Die zusammenfassende Beurteilung des Interviewers gr{\"u}ndet demnach im Wesentlichen auf den Angaben der M{\"u}tter. Die Konstruktvalidit{\"a}t wurde ermittelt, indem das Interview mit anderen diagnostischen Verfahren verglichen wurde. Die Korrelation des Interviews mit ADHS-nahen Konstrukten war signifikant und ergab Werte zwischen rtc= ,48 und rtc= ,70. Die diskriminante Validit{\"a}t wurde durch Korrelation mit ADHS-fernen Konstrukten ermittelt. Der Korrelationskoeffizient betrug rtc= ,27. Die Validit{\"a}t liegt somit im mittleren bis oberen Bereich. Ebenfalls wurde belegt, dass Kinder mit zus{\"a}tzlicher St{\"o}rung des Sozialverhaltens einen h{\"o}heren Gesamtscore im Interview erreichen. Das Interview diskriminiert demnach erwartungsgem{\"a}ß zwischen ADHS-Patienten mit zus{\"a}tzlicher St{\"o}rung des Sozialverhaltens und ADHS-Patienten ohne zus{\"a}tzliche St{\"o}rung. Die {\"U}berpr{\"u}fung der G{\"u}tekriterien erzielte gute Ergebnisse f{\"u}r Objektivit{\"a}t und Validit{\"a}t. Demnach werden Symptome der ADHS und der oppositionellen St{\"o}rung des Sozialverhaltens mit dem untersuchten Verfahren in hinreichender G{\"u}te erfasst.}, subject = {Aufmerksamkeits-Defizit-Syndrom}, language = {de} } @phdthesis{Holweck2022, author = {Holweck, Julia}, title = {Putative Biomarker neuropsychiatrischer Entwicklungskomorbidit{\"a}ten beim Deletionssyndrom 22q11.2}, doi = {10.25972/OPUS-29291}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-292915}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Vom Deletionssyndrom 22q11.2 Betroffene sind einem {\"u}berdurchschnittlich hohen Risiko ausgesetzt im Entwicklungsverlauf psychisch zu erkranken. H{\"a}ufige St{\"o}rungsbilder sind unter anderem ADHS, Angsterkrankungen, affektive St{\"o}rungen, Erkrankungen aus dem schizophrenen Formenkreis und Morbus Parkinson. Ziel der Studie war es, ph{\"a}notypische Auff{\"a}lligkeiten beim DS22q11 zu identifizieren, die dabei helfen k{\"o}nnten, Hochrisikogruppen innerhalb des Syndroms fr{\"u}hzeitig identifizieren zu k{\"o}nnen und in Form von Biomarkern messbar sind. Hierzu wurden die bereits in Forschung und teilweise auch in der Klinik etablierten Verfahren der transkraniellen Sonographie und der standardisierten Riechtestung eingesetzt.}, subject = {Mikrodeletionssyndrom 22q11}, language = {de} } @article{HommersRichterYangetal.2018, author = {Hommers, L. G. and Richter, J. and Yang, Y. and Raab, A. and Baumann, C. and Lang, K. and Schiele, M. A. and Weber, H. and Wittmann, A. and Wolf, C. and Alpers, G. W. and Arolt, V. and Domschke, K. and Fehm, L. and Fydrich, T. and Gerlach, A. and Gloster, A. T. and Hamm, A. O. and Helbig-Lang, S. and Kircher, T. and Lang, T. and Pan{\´e}-Farr{\´e}, C. A. and Pauli, P. and Pfleiderer, B. and Reif, A. and Romanos, M. and Straube, B. and Str{\"o}hle, A. and Wittchen, H.-U. and Frantz, S. and Ertl, G. and Lohse, M. J. and Lueken, U. and Deckert, J.}, title = {A functional genetic variation of SLC6A2 repressor hsa-miR-579-3p upregulates sympathetic noradrenergic processes of fear and anxiety}, series = {Translational Psychiatry}, volume = {8}, journal = {Translational Psychiatry}, doi = {10.1038/s41398-018-0278-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-322497}, year = {2018}, abstract = {Increased sympathetic noradrenergic signaling is crucially involved in fear and anxiety as defensive states. MicroRNAs regulate dynamic gene expression during synaptic plasticity and genetic variation of microRNAs modulating noradrenaline transporter gene (SLC6A2) expression may thus lead to altered central and peripheral processing of fear and anxiety. In silico prediction of microRNA regulation of SLC6A2 was confirmed by luciferase reporter assays and identified hsa-miR-579-3p as a regulating microRNA. The minor (T)-allele of rs2910931 (MAFcases = 0.431, MAFcontrols = 0.368) upstream of MIR579 was associated with panic disorder in patients (pallelic = 0.004, ncases = 506, ncontrols = 506) and with higher trait anxiety in healthy individuals (pASI = 0.029, pACQ = 0.047, n = 3112). Compared to the major (A)-allele, increased promoter activity was observed in luciferase reporter assays in vitro suggesting more effective MIR579 expression and SLC6A2 repression in vivo (p = 0.041). Healthy individuals carrying at least one (T)-allele showed a brain activation pattern suggesting increased defensive responding and sympathetic noradrenergic activation in midbrain and limbic areas during the extinction of conditioned fear. Panic disorder patients carrying two (T)-alleles showed elevated heart rates in an anxiety-provoking behavioral avoidance test (F(2, 270) = 5.47, p = 0.005). Fine-tuning of noradrenaline homeostasis by a MIR579 genetic variation modulated central and peripheral sympathetic noradrenergic activation during fear processing and anxiety. This study opens new perspectives on the role of microRNAs in the etiopathogenesis of anxiety disorders, particularly their cardiovascular symptoms and comorbidities.}, language = {en} } @article{HaertelSpieglerFortmannetal.2020, author = {H{\"a}rtel, Christoph and Spiegler, Juliane and Fortmann, Ingmar and Astiz, Mariana and Oster, Henrik and Siller, Bastian and Viemann, Dorothee and Keil, Thomas and Banaschewski, Tobias and Romanos, Marcel and Herting, Egbert and G{\"o}pel, Wolfgang}, title = {Breastfeeding for 3 months or longer but not probiotics is associated with reduced risk for inattention/hyperactivity and conduct problems in very-low-birth-weight children at early primary school age}, series = {Nutrients}, volume = {12}, journal = {Nutrients}, number = {11}, issn = {2072-6643}, doi = {10.3390/nu12113278}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216319}, year = {2020}, abstract = {(1) Background: We aimed to evaluate the effect of proposed "microbiome-stabilising interventions", i.e., breastfeeding for ≥3 months and prophylactic use of Lactobacillus acidophilus/ Bifidobacterium infantis probiotics on neurocognitive and behavioral outcomes of very-low-birthweight (VLBW) children aged 5-6 years. (2) Methods: We performed a 5-year-follow-up assessment including a strength and difficulties questionnaire (SDQ) and an intelligence quotient (IQ) assessment using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI)-III test in preterm children previously enrolled in the German Neonatal Network (GNN). The analysis was restricted to children exposed to antenatal corticosteroids and postnatal antibiotics. (3) Results: 2467 primary school-aged children fulfilled the inclusion criteria. In multivariable linear regression models breastfeeding ≥3 months was associated with lower conduct disorders (B (95\% confidence intervals (CI)): -0.25 (-0.47 to -0.03)) and inattention/hyperactivity (-0.46 (-0.81 to -0.10)) as measured by SDQ. Probiotic treatment during the neonatal period had no effect on SDQ scores or intelligence. (4) Conclusions: Prolonged breastfeeding of highly vulnerable infants may promote their mental health later in childhood, particularly by reducing risk for inattention/hyperactivity and conduct disorders. Future studies need to disentangle the underlying mechanisms during a critical time frame of development.}, language = {en} } @phdthesis{Haeussler2019, author = {H{\"a}ußler, Marie}, title = {Untersuchung der kardialen autonomen Regulation anhand der Herzfrequenzvariabilit{\"a}t bei depressiven Kindern und Jugendlichen im Vergleich zu gesunden Kontrollen - eine Pilotstudie mit Querschnitts- und L{\"a}ngsschnittanalysen}, doi = {10.25972/OPUS-16875}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168750}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {Bei Erwachsenen ist ein Zusammenhang zwischen Depressionen und Herzerkrankungen bekannt. Als m{\"o}glicher Mechanismus hierf{\"u}r gilt eine Ver{\"a}nderung der kardialen autonomen Funktion, messbar {\"u}ber eine verminderte Herzfrequenzvariabilit{\"a}t (HRV) und eine h{\"o}here Herzfrequenz. Es finden sich in der Literatur erste Hinweise, dass auch bei Kindern und Jugendlichen mit Depressionen Ver{\"a}nderungen der kardialen autonomen Regulation zu beobachten sind. In der vorliegenden Studie an der Klinik und Poliklinik f{\"u}r Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie W{\"u}rzburg wurde erstmals die kardiale autonome Funktion bei depressiven Kindern und Jugendlichen mit Hilfe von Langzeit-EKGs untersucht. Gepr{\"u}ft wurde hierbei, ob depressive St{\"o}rungen im Kindes- und Jugendalter mit einer gest{\"o}rten kardialen autonomen Regulation in Form einer verminderten HRV und einer erh{\"o}hten Herzfrequenz vergesellschaftet sind. Zudem wurde der Einfluss einer antidepressiven Therapie untersucht. Die Ergebnisse der Studie zeigen, dass depressive Kinder und Jugendliche im Vergleich zu gesunden eine signifikant h{\"o}here mittlere Herzfrequenz im Langzeit-EKG aufweisen. Zudem hatten sie leicht verminderte HRV-Parameter, wobei dieser Unterschied nicht statistisch signifikant war. Eine Ver{\"a}nderung der HRV oder der Herzfrequenz im Therapieverlauf konnte nicht belegt werden. Weitere gr{\"o}ßere Studien sind n{\"o}tig, um die Zusammenh{\"a}nge zwischen Depressionen und Ver{\"a}nderungen der kardialen autonomen Funktion im Kindes- und Jugendalter zu erforschen.}, subject = {Herzfrequenzvariabilit{\"a}t}, language = {de} } @phdthesis{Huettl2023, author = {H{\"u}ttl, Fabian}, title = {Motorische Fertigkeiten von Kindern und Jugendlichen mit psychischen St{\"o}rungen - eine retrospektive Analyse}, doi = {10.25972/OPUS-32190}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321905}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Durch die vorliegende Arbeit konnte st{\"o}rungs{\"u}bergreifend ein Zusammenhang zwischen dem Tag der Motorik-Testung und dem IQ einerseits und den Testbefunden zur Motorik andererseits gezeigt werden. Es gelang nicht, den vermuteten negativen Einfluss von psychosozialen Faktoren auf motorische F{\"a}higkeiten zu demonstrieren. Bez{\"u}glich der ADHS-Medikation konnte aufgrund des Studiendesigns als Querschnittstudie keine klare Aussage getroffen werden, ob ein positiver Einfluss auf motorische F{\"a}higkeiten vorliegt. Bei den Patient-/innen mit Hyperkinetischer St{\"o}rung des Sozialverhaltens (F90.1) fanden sich zwar bei bestehender ADHS-Medikation signifikant bessere Testbefunde der Balance, es konnte jedoch nicht gekl{\"a}rt werden, warum der positive Effekt der ADHS-Medikation nur auf diese St{\"o}rungsgruppe und den Balance-Untertest der M-ABC II begrenzt war. Im Gruppenvergleich konnten signifikant bessere motorische F{\"a}higkeiten der Patient-/innen mit internalisierender St{\"o}rung als jener mit externalisierender St{\"o}rung festgestellt werden. Damit kongruent kam die Diagnose einer UEMF (F82) in der Gruppe der externalisierenden St{\"o}rungen h{\"a}ufiger vor. Da ein Großteil der Patient-/innen der externalisierenden St{\"o}rungsgruppe an Defiziten der Aufmerksamkeit, Impulskontrolle und der Motivation litt, ist davon auszugehen, dass diese Symptome zu schwerwiegenden Beeintr{\"a}chtigungen der motorischen F{\"a}higkeiten und damit auch zu weiteren Problemen im Alltag oder bei der Schullaufbahn f{\"u}hren. Innerhalb der Gruppe der externalisierenden St{\"o}rungen konnte hinsichtlich der motorischen F{\"a}higkeiten kein Unterschied zwischen Patient-/innen mit Hyperkinetischen St{\"o}rungen (F90.-) und solchen mit St{\"o}rung des Sozialverhaltens (F91) gefunden werden. Ein solcher Unterschied h{\"a}tte einen Hinweis geben k{\"o}nnen, ob eher Defizite der Aufmerksamkeit und Impulskontrolle oder ein Motivationsdefizit mit motorischen Einschr{\"a}nkungen verbunden sind. Hierbei ist anzumerken, dass die Gruppengr{\"o}ßen f{\"u}r einen validen Vergleich dieser St{\"o}rungsgruppen nicht ausreichend waren. Der Vergleich motorischer F{\"a}higkeiten sowie der H{\"a}ufigkeit einer UEMF (F82) zwischen Patient-/innen mit umschriebener Entwicklungsst{\"o}rung des Sprechens und der Sprache (F80) einerseits und Patient-/innen mit umschriebener Entwicklungsst{\"o}rung der schulischen Fertigkeiten (F81) andererseits best{\"a}tigte die Vermutung, dass bei Patient-/innen der St{\"o}rungsgruppe F80 schlechtere motorische F{\"a}higkeiten und signifikant mehr motorische Defizite vorlagen. Ein Teil dieses Unterschieds l{\"a}sst sich jedoch durch den signifikant niedrigeren IQ der St{\"o}rungsgruppe F80 erkl{\"a}ren. Es muss dar{\"u}ber hinaus ber{\"u}cksichtigt werden, dass bei den umschriebenen Entwicklungsst{\"o}rungen F80 und F81 eine h{\"a}ufige Komorbidit{\"a}t mit externalisierenden St{\"o}rungen bestand, sodass motorische Defizite auch durch ein urs{\"a}chliches Defizit der Aufmerksamkeit und Impulskontrolle erkl{\"a}rt werden k{\"o}nnten.}, subject = {Motorische F{\"a}higkeit}, language = {de} } @phdthesis{Huetz2021, author = {H{\"u}tz, Barbara}, title = {Substantia Nigra-Echogenit{\"a}t als Biomarker f{\"u}r Erkrankungen aus dem psychotischen Formenkreis und Korrelat psychopharmakologischer Nebenwirkungen bei Jugendlichen und jungen Erwachsenen}, doi = {10.25972/OPUS-23171}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231713}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Hintergrund: Bei erwachsenen Patient*innen mit Erkrankungen aus dem Schizophrenie-Spektrum konnte im transkraniellen Ultraschall im Vergleich zu gesunden Proband*innen eine signifikant erh{\"o}hte Echogenit{\"a}t der Substantia Nigra (SN) nachgewiesen werden. Zudem bestand ein Zusammenhang zwischen der SN-Fl{\"a}che und st{\"a}rker ausgepr{\"a}gten extrapyramidalmotorischen Bewegungsst{\"o}rungen unter Antipsychotikatherapie. In der vorliegenden Arbeit wurde {\"u}berpr{\"u}ft, inwiefern die Echogenit{\"a}t der SN auch bei Jugendlichen und jungen Erwachsenen als Biomarker f{\"u}r Erkrankungen aus dem psychotischen Formenkreis und als Korrelat psychopharmakologischer Nebenwirkungen herangezogen werden kann. Des Weiteren wurde der Einfluss von Alter, Krankheitsdauer sowie Antipsychotika-Lebenszeitdosis auf die SN-Echogenit{\"a}t untersucht sowie Zusammenh{\"a}nge mit peripheren Eisenparametern. Methoden: Hierf{\"u}r wurden insgesamt 16 station{\"a}r behandelte Patient*innen zwischen 14 - 22 Jahren mit Erkrankungen aus dem schizophrenen Formenkreis sowie nach Alter und Geschlecht gematchte gesunde Kontrollen mittels TCS untersucht. Aus peripher entnommenem Blut wurden Parameter des Eisenhaushalts bestimmt. Ergebnisse: Es konnten entgegen der Hypothese keine signifikanten Unterschiede in Bezug auf die Echogenit{\"a}t der SN im Vergleich zur gesunden Kontrollgruppe festgestellt werden. Bez{\"u}glich der Schwere der beobachteten EPMS ergab sich entgegen der Hypothese und im Kontrast zu Befunden bei Erwachsenen kein Zusammenhang mit der SN-Echogenit{\"a}t. Das Alter der Proband*innen, die Krankheitsdauer sowie die Dosis der eingenommenen Antipsychotika zeigten keine Zusammenh{\"a}nge mit der SN-Echogenit{\"a}t. Interessanterweise zeigte sich eine signifikant negative Korrelation zwischen der echogenen Fl{\"a}che der SN und Eisen sowie Transferrin. Schlussfolgerung: Im Jugend- und jungen Erwachsenenalter eignet sich die SN-Echogenit{\"a}t vermutlich nicht als Biomarker f{\"u}r Erkrankungen aus dem Schizophrenie-Spektrum oder f{\"u}r die Pr{\"a}diktion von Nebenwirkungen antipsychotischer Medikation. M{\"o}glicherweise manifestiert sich eine erh{\"o}hte Echogenit{\"a}t der SN, welche als Zeichen f{\"u}r eine Sch{\"a}digung der dopaminergen Neurone gesehen wird, bei schizophrenen Psychosen erst im Verlauf der Krankheit. Da wir die Studienteilnehmer*innen nur zu einem einzigen Zeitpunkt im Laufe ihrer Krankheitsgeschichte untersuchten, kann keine Aussage {\"u}ber den weiteren Verlauf der SN-Echogenit{\"a}t getroffen werden. Hierf{\"u}r w{\"a}ren longitudinale Untersuchungen zielf{\"u}hrend, da nur so m{\"o}gliche entwicklungsbedingte Ver{\"a}nderungen festgestellt werden k{\"o}nnen.}, subject = {Substantia nigra}, language = {de} } @article{JaiteBuehrenDahmenetal.2019, author = {Jaite, Charlotte and B{\"u}hren, Katharina and Dahmen, Brigitte and Dempfle, Astrid and Becker, Katja and Correll, Christoph U. and Egberts, Karin M. and Ehrlich, Stefan and Fleischhaker, Christian and von Gontard, Alexander and Hahn, Freia and Kolar, David and Kaess, Michael and Legenbauer, Tanja and Renner, Tobias J. and Schulze, Ulrike and Sinzig, Judith and Thomae, Ellen and Weber, Linda and Wessing, Ida and Antony, Gisela and Hebebrand, Johannes and F{\"o}cker, Manuel and Herpertz-Dahlmann, Beate}, title = {Clinical Characteristics of Inpatients with Childhood vs. Adolescent Anorexia Nervosa}, series = {Nutrients}, volume = {11}, journal = {Nutrients}, number = {11}, issn = {2072-6643}, doi = {10.3390/nu11112593}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193160}, pages = {2593}, year = {2019}, abstract = {We aimed to compare the clinical data at first presentation to inpatient treatment of children (<14 years) vs. adolescents (≥14 years) with anorexia nervosa (AN), focusing on duration of illness before hospital admission and body mass index (BMI) at admission and discharge, proven predictors of the outcomes of adolescent AN. Clinical data at first admission and at discharge in 289 inpatients with AN (children: n = 72; adolescents: n = 217) from a German multicenter, web-based registry for consecutively enrolled patients with childhood and adolescent AN were analyzed. Inclusion criteria were a maximum age of 18 years, first inpatient treatment due to AN, and a BMI <10th BMI percentile at admission. Compared to adolescents, children with AN had a shorter duration of illness before admission (median: 6.0 months vs. 8.0 months, p = 0.004) and higher BMI percentiles at admission (median: 0.7 vs. 0.2, p = 0.004) as well as at discharge (median: 19.3 vs. 15.1, p = 0.011). Thus, in our study, children with AN exhibited clinical characteristics that have been associated with better outcomes, including higher admission and discharge BMI percentile. Future studies should examine whether these factors are actually associated with positive long-term outcomes in children.}, language = {en} } @article{JarickVolckmarPuetteretal.2014, author = {Jarick, I. and Volckmar, A. L. and P{\"u}tter, C. and Pechlivanis, S. and Nguyen, T. T. and Dauvermann, M. R. and Beck, S. and Albayrak, {\"O}. and Scherag, S. and Gilsbach, S. and Cichon, S. and Hoffmann, P. and Degenhardt, F. and N{\"o}then, M. M. and Schreiber, S. and Wichmann, H. E. and J{\"o}ckel, K. H. and Heinrich, J. and Tiesler, C. M. T. and Faraone, S. V. and Walitza, S. and Sinzig, J. and Freitag, C. and Meyer, J. and Herpertz-Dahlmann, B. and Lehmkuhl, G. and Renner, T. J. and Warnke, A. and Romanos, M. and Lesch, K. P. and Reif, A. and Schimmelmann, B. G. and Hebebrand, J. and Scherag, A. and Hinney, A.}, title = {Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder}, series = {Molecular Psychiatry}, volume = {19}, journal = {Molecular Psychiatry}, number = {19}, doi = {10.1038/mp.2012.161}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121131}, pages = {115-21}, year = {2014}, abstract = {Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder. Genetic loci have not yet been identified by genome-wide association studies. Rare copy number variations (CNVs), such as chromosomal deletions or duplications, have been implicated in ADHD and other neurodevelopmental disorders. To identify rare (frequency ≤1\%) CNVs that increase the risk of ADHD, we performed a whole-genome CNV analysis based on 489 young ADHD patients and 1285 adult population-based controls and identified one significantly associated CNV region. In tests for a global burden of large (>500 kb) rare CNVs, we observed a nonsignificant (P=0.271) 1.126-fold enriched rate of subjects carrying at least one such CNV in the group of ADHD cases. Locus-specific tests of association were used to assess if there were more rare CNVs in cases compared with controls. Detected CNVs, which were significantly enriched in the ADHD group, were validated by quantitative (q)PCR. Findings were replicated in an independent sample of 386 young patients with ADHD and 781 young population-based healthy controls. We identified rare CNVs within the parkinson protein 2 gene (PARK2) with a significantly higher prevalence in ADHD patients than in controls \((P=2.8 × 10^{-4})\) after empirical correction for genome-wide testing). In total, the PARK2 locus (chr 6: 162 659 756-162 767 019) harboured three deletions and nine duplications in the ADHD patients and two deletions and two duplications in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD patients \((P=1.2 × 10^{-3})\) after empirical correction for genome-wide testing). In the replication sample, CNVs at the PARK2 locus were found in four additional ADHD patients and one additional control \((P=4.3 × 10^{-2})\). Our results suggest that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated with Parkinson disease.}, language = {en} } @article{KaiserAggensteinerHoltmannetal.2021, author = {Kaiser, Anna and Aggensteiner, Pascal-M. and Holtmann, Martin and Fallgatter, Andreas and Romanos, Marcel and Abenova, Karina and Alm, Barbara and Becker, Katja and D{\"o}pfner, Manfred and Ethofer, Thomas and Freitag, Christine M. and Geissler, Julia and Hebebrand, Johannes and Huss, Michael and Jans, Thomas and Jendreizik, Lea Teresa and Ketter, Johanna and Legenbauer, Tanja and Philipsen, Alexandra and Poustka, Luise and Renner, Tobias and Retz, Wolfgang and R{\"o}sler, Michael and Thome, Johannes and Uebel-von Sandersleben, Henrik and von Wirth, Elena and Zinnow, Toivo and Hohmann, Sarah and Millenet, Sabina and Holz, Nathalie E. and Banaschewski, Tobias and Brandeis, Daniel}, title = {EEG data quality: determinants and impact in a multicenter study of children, adolescents, and adults with attention-deficit/hyperactivity disorder (ADHD)}, series = {Brain Sciences}, volume = {11}, journal = {Brain Sciences}, number = {2}, issn = {2076-3425}, doi = {10.3390/brainsci11020214}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228788}, year = {2021}, abstract = {Electroencephalography (EEG) represents a widely established method for assessing altered and typically developing brain function. However, systematic studies on EEG data quality, its correlates, and consequences are scarce. To address this research gap, the current study focused on the percentage of artifact-free segments after standard EEG pre-processing as a data quality index. We analyzed participant-related and methodological influences, and validity by replicating landmark EEG effects. Further, effects of data quality on spectral power analyses beyond participant-related characteristics were explored. EEG data from a multicenter ADHD-cohort (age range 6 to 45 years), and a non-ADHD school-age control group were analyzed (n\(_{total}\) = 305). Resting-state data during eyes open, and eyes closed conditions, and task-related data during a cued Continuous Performance Task (CPT) were collected. After pre-processing, general linear models, and stepwise regression models were fitted to the data. We found that EEG data quality was strongly related to demographic characteristics, but not to methodological factors. We were able to replicate maturational, task, and ADHD effects reported in the EEG literature, establishing a link with EEG-landmark effects. Furthermore, we showed that poor data quality significantly increases spectral power beyond effects of maturation and symptom severity. Taken together, the current results indicate that with a careful design and systematic quality control, informative large-scale multicenter trials characterizing neurophysiological mechanisms in neurodevelopmental disorders across the lifespan are feasible. Nevertheless, results are restricted to the limitations reported. Future work will clarify predictive value.}, language = {en} } @phdthesis{Kipp2019, author = {Kipp, Ellen}, title = {Therapeutisches Drug Monitoring von Clozapin und Olanzapin bei Kindern und Jugendlichen mit Erkrankungen aus dem schizophrenen Formenkreis}, doi = {10.25972/OPUS-18269}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-182699}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {Derzeit gibt es nur wenige Informationen zu konzentrationsabh{\"a}ngigen klinischen Effekten von Clozapin und Olanzapin in der Behandlung von Kindern und Jugendlichen mit schizophrenen St{\"o}rungen. Es existieren keine altersspezifisch-definierte therapeutische Zielbereiche f{\"u}r die H{\"o}he der Serumkonzentration in dieser Altersklasse. Das Ziel dieser retrospektiven, naturalistischen Studie ist die Untersuchung der Zusammenh{\"a}nge zwischen Dosis, Serumkonzentration und klinischen Effekten (Therapieeffekt und unerw{\"u}nschte Arzneimittelwirkungen) sowie die Untersuchung m{\"o}glicher Einflussfaktoren darauf. Des Weiteren sollen Erkenntnisse zu therapeutischen Konzentrationsbereichen von Clozapin und Olanzapin bei Kindern und Jugendlichen gewonnen werden. Ausgewertet wurden multizentrische Daten von 32 (Clozapin) bzw. 17 (Olanzapin) Patienten, bei denen routinem{\"a}ßig Therapeutisches Drug Monitoring im Zeitraum von Februar 2004 bis Dezember 2007 durchgef{\"u}hrt wurde. Die psychopathologische Befundeinsch{\"a}tzung erfolgte mittels der Clinical Global Impression Scale und der Brief Psychiatric Rating Scale, die der unerw{\"u}nschten Arzneimittelwirkungen mithilfe der Dose Record and Treatment Emergent Symptom Scale bzw. der Udvalg for Kliniske Unders{\o}gelser Side Effect Rating Scale. Bei beiden untersuchten Wirkstoffen zeigte sich eine signifikant positive Korrelation zwischen der (gewichtskorrigierten) Tagesdosis und der Serumkonzentration sowie eine hohe interindividuelle Variabilit{\"a}t der Serumkonzentrationen bei gleicher Dosierung. Als weiterer m{\"o}glicher Einflussfaktor auf die H{\"o}he der Serumkonzentration konnte in der Olanzapin-Stichprobe eine signifikante Assoziation zwischen dem Geschlecht und der Serumkonzentration nachgewiesen werden: M{\"a}dchen scheinen unter gleicher klinischer Dosierung h{\"o}here Serumkonzentrationen aufzubauen als Jungen. In beiden Stichproben gab es eine hohe Rate dokumentierter unerw{\"u}nschter Arzneimittelwirkungen. Ein Zusammenhang zwischen der H{\"o}he der Serumkonzentration und dem Auftreten unerw{\"u}nschter Arzneimittelwirkungen ließ sich nicht nachweisen. In der Clozapin-Stichprobe zeigte sich ein signifikanter Zusammenhang zwischen der Serumkonzentration und dem Therapieeffekt: Im untersuchten Sample war der Therapieeffekt besser bei niedrigeren (< 350 ng/ml) Serumkonzentrationen. Zudem zeigte sich eine Tendenz zu einem niedrigeren unteren Schwellenwert f{\"u}r einen empfohlenen therapeutischen Bereich der Serumkonzentration verglichen mit dem Bereich der f{\"u}r Erwachsene definiert wurde. In der Olanzapin-Stichprobe ließ sich mit dem gew{\"a}hlten Studiendesign keine signifikante Korrelation zwischen der Serumkonzentration und dem Therapieeffekt nachweisen. Die Mehrheit der p{\"a}diatrischen Patienten hatte eine Serumkonzentration innerhalb des empfohlenen Zielbereichs f{\"u}r Erwachsene. Dieses Ergebnis k{\"o}nnte auf eine {\"U}bereinstimmung des zu empfehlenden Zielbereichs der Serumkonzentration von Olanzapin in beiden Altersklassen hinweisen. Aufgrund der Limitationen des naturalistischen Studiendesigns sind weitere Studien mit kontrolliertem Design und gr{\"o}ßerer Stichprobe notwendig, um die Ergebnisse zu replizieren.}, subject = {Arzneimittel{\"u}berwachung}, language = {de} } @phdthesis{Klampfl2003, author = {Klampfl, Karin Maria}, title = {Komorbidit{\"a}t bei Kindern und Jugendlichen mit einer Zwangsst{\"o}rung}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-8139}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2003}, abstract = {Thema der vorliegenden Arbeit war die Erfassung und Beschreibung der psychiatrischen Komorbidit{\"a}t bei Kindern und Jugendlichen mit einer Zwangsst{\"o}rung. An vier deutschen Universit{\"a}tskliniken f{\"u}r Kinder- und Jugendpsychiatrie wurden konsekutiv 55 Kinder und Jugendliche mit juveniler Zwangsst{\"o}rung im Hinblick auf Art und Auspr{\"a}gung ihrer Zwangssymptomatik sowie hinsichtlich komorbid vorliegender psychiatrischer St{\"o}rungen mit standardisierten Instrumenten untersucht. Die beschriebene Patientenstichprobe zeigte bez{\"u}glich klinischer und epidemiologischer Merkmale große {\"U}bereinstimmung mit den bisher epirisch gewonnenen Daten. Es konnte gezeigt werden, dass bei Kindern un Jugendlichen mit Zwangsst{\"o}rung von einer hohen Zahl komorbider psychischer St{\"o}rungen auszugehen ist, wobei Angstst{\"o}rungen, affektive St{\"o}rungen und expansive St{\"o}rungen (Hyperkinetisches Syndrom, St{\"o}rung des Sozialverhaltens)am h{\"a}ufigsten zu diagnostizieren waren, gefolgt von Essst{\"o}rungen und Tics. Die genaue Erhebung des Verteilungsmusters der komorbiden St{\"o}rungen ist nicht nur von therapeutischer Relevanz, sondern kann auch einen Beitrag leisten, Untergruppen der juvenilen Zwangsst{\"o}rung zu identifizieren und m{\"o}glicherweise R{\"u}ckschl{\"u}sse auf die Entstehung der Erkrankung zu ziehen.}, language = {de} } @phdthesis{Kneer2022, author = {Kneer, Katharina Johanna}, title = {The association of three anxiety dimensions in children and adolescents: their influence on the brain and malleability by a prevention program}, doi = {10.25972/OPUS-25746}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257468}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Anxiety disorders are the most prevalent group of neuropsychiatric disorders and go along with high personal suffering. They often arise during childhood and show a progression across the life span, thus making this age a specific vulnerable period during development. Still most research about these disorders is done in adults. In light of this, it seems of utmost importance to identify predictive factors of anxiety disorders in children and adolescents. Temperament or personality traits have been proclaimed as risk markers for the development of subsequent anxiety disorders, but their exact interplay is not clear. In this dissertation an effort is made to contribute to the understanding of how risk markers of early temperamental traits, in this case Trait Anxiety, Anxiety Sensitivity and Separation Anxiety are interplaying. While Trait Anxiety is regarded as a more general tendency to react anxiously to threatening situations or stimuli (Unnewehr, Joormann, Schneider, \& Margraf, 1992), Anxiety Sensitivity is the tendency to react with fear to one's own anxious sensations (Allan et al., 2014; S. Reiss, Peterson, Gursky, \& McNally, 1986), and Separation Anxiety is referring to the extent to which the child is avoiding certain situations because of the fear of being separated from primary care givers (In-Albon \& Schneider, 2011). In addition, it will be addressed how these measurements are associated with negative life events, as well as brain functioning and if they are malleable by a prevention program in children and adolescents. In study 1 the aim was to extend the knowledge about the interrelations of this anxiety dimensions and negative life events. Results indicated positive correlations of all three anxiety traits as well as with negative life events. Thus, a close connection of all three anxiety measures as well as with negative life events could be indicated. The closest association was found between Anxiety Sensitivity and Trait Anxiety and between Separation Anxiety and Anxiety Sensitivity. Furthermore, negative life events functioned as mediator between Anxiety Sensitivity and Trait Anxiety, indicating that a part of the association was explained by negative life events. In study 2 we extended the findings from study 1 with neurobiological parameters and examined the influence of anxiety traits on emotional brain activation by administering the "emotional face matching task". This task activated bilateral prefrontal regions as well as both hippocampi and the right amygdala. Further analyses indicated dimension-specific brain activations: Trait Anxiety was associated with a hyperactivation of the left inferior frontal gyrus (IFG) and Separation Anxiety with a lower activation bilaterally in the IFG and the right middle frontal gyrus (MFG). Furthermore, the association between Separation Anxiety and Anxiety Sensitivity was moderated by bi-hemispheric Separation-Anxiety-related IFG activation. Thus, we could identify distinct brain activation patterns for the anxiety dimensions (Trait Anxiety and Separation Anxiety) and their associations (Separation Anxiety and Anxiety Sensitivity). The aim of study 3 was to probe the selective malleability of the anxiety dimensions via a prevention program in an at-risk population. We could identify a reduction of all three anxiety traits from pre- to post-prevention-assessment and that this effect was significant in Anxiety Sensitivity and Trait Anxiety scores. Furthermore, we found that pre-intervention Separation Anxiety and Anxiety Sensitivity post-intervention were associated. In addition, pre-interventive scores were correlated with the intervention-induced change within the measure (i.e., the higher the score before the intervention the higher the prevention-induced change) and pre-intervention Anxiety Sensitivity correlated with the change in Separation Anxiety scores. All relations, seemed to be direct, as mediation/moderation analyses with negative life events did not reveal any significant effect. These results are very promising, because research about anxiety prevention in children and adolescents is still rare and our results are indicating that cognitive-behavioural-therapy based prevention is gilding significant results in an indicated sample even when samples sizes are small like in our study. In sum the present findings hint towards distinct mechanisms underlying the three different anxiety dimensions on a phenomenological and neurobiological level, though they are highly overlapping (Higa-McMillan, Francis, Rith-Najarian, \& Chorpita, 2016; Taylor, 1998). Furthermore, the closest associations were found between Anxiety Sensitivity and Trait Anxiety, as well as between Separation Anxiety and Anxiety Sensitivity. Specifically, we were able to find a neuronal manifestation of the association between Separation Anxiety and Anxiety Sensitivity (Separation Anxiety-specific IFG activation) and a predictive potential on prevention influence. The results of these studies lead to a better understanding of the etiology of anxiety disorders and the interplay between different anxiety-related temperamental traits and could lead to further valuable knowledge about the intervention as well as further prevention strategies.}, subject = {Pr{\"a}vention}, language = {en} } @article{KolarHammerleJenetzkyetal.2016, author = {Kolar, David R. and Hammerle, Florian and Jenetzky, Ekkehart and Huss, Michael and B{\"u}rger, Arne}, title = {Aversive tension in female adolescents with Anorexia Nervosa: a controlled ecological momentary assessment using smartphones}, series = {BMC Psychiatry}, volume = {16}, journal = {BMC Psychiatry}, number = {97}, doi = {10.1186/s12888-016-0807-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164720}, year = {2016}, abstract = {Background Current models of Anorexia Nervosa (AN) emphasize the role of emotion regulation. Aversive tension, described as a state of intense arousal and negative valence, is considered to be a link between emotional events and disordered eating. Recent research focused only on adult patients, and mainly general emotion regulation traits were studied. However, the momentary occurrence of aversive tension, particularly in adolescents with AN, has not been previously studied. Method 20 female adolescents with AN in outpatient treatment and 20 healthy adolescents aged 12 to 19 years participated in an ecological momentary assessment using their smartphones. Current states of aversive tension and events were assessed hourly for two consecutive weekdays. Mean and maximum values of aversive tension were compared. Multilevel analyses were computed to test the influence of time and reported events on aversive tension. The effect of reported events on subsequent changes of aversive tension in patients with AN were additionally tested in a multilevel model. Results AN patients showed higher mean and maximum levels of aversive tension. In a multilevel model, reported food intake was associated with higher levels of aversive tension in the AN group, whereas reported school or sport-related events were not linked to specific states of aversive tension. After food intake, subsequent increases of aversive tension were diminished and decreases of aversive tension were induced in adolescents with AN. Conclusions Aversive tension may play a substantial role in the psychopathology of AN, particular in relation with food intake. Therefore, treatment should consider aversive tension as a possible intervening variable during refeeding. Our findings encourage further research on aversive tension and its link to disordered eating.}, language = {en} } @article{KuhlmannHussBuergeretal.2016, author = {Kuhlmann, S.M. and Huss, M. and B{\"u}rger, A. and Hammerle, F.}, title = {Coping with stress in medical students: results of a randomized controlled trial using a mindfulness-based stress prevention training (MediMind) in Germany}, series = {BMC Medical Education}, volume = {16}, journal = {BMC Medical Education}, doi = {10.1186/s12909-016-0833-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164593}, pages = {316}, year = {2016}, abstract = {Background High prevalence rates of psychological distress in medical training and later professional life indicate a need for prevention. Different types of intervention were shown to have good effects, but little is known about the relative efficacy of different types of stress management interventions, and methodological limitations have been reported. In order to overcome some of these limitations, the present study aimed at evaluating the effect of a specifically developed mindfulness-based stress prevention training for medical students (MediMind) on measures of distress, coping and psychological morbidity. Methods We report on a prospective randomized controlled trial with three study conditions: experimental treatment (MediMind), standard treatment (Autogenic Training) and a control group without treatment. The sample consisted of medical or dental students in the second or eighth semester. They completed self-report questionnaires at baseline, after the training and at one year follow-up. Distress (Trier Inventory for the Assessment of Chronic Stress, TICS) was assessed as the primary outcome and coping (Brief COPE) as a co-primary outcome. Effects on the psychological morbidity (Brief Symptom Inventory, BSI) as a secondary outcome were expected one year after the trainings. Results Initially, N = 183 students were randomly allocated to the study groups. At one year follow-up N = 80 could be included into the per-protocol analysis: MediMind (n =31), Autogenic Training (n = 32) and control group (n = 17). A selective drop-out for students who suffered more often from psychological symptoms was detected (p = .020). MANCOVA's on TICS and Brief COPE revealed no significant interaction effects. On the BSI, a significant overall interaction effect became apparent (p = .002, η2partial = .382), but post hoc analyses were not significant. Means of the Global Severity Index (BSI) indicated that MediMind may contribute to a decrease in psychological morbidity. Conclusion Due to the high and selective dropout rates, the results cannot be generalized and further research is necessary. Since the participation rate of the trainings was high, a need for further prevention programs is indicated. The study gives important suggestions on further implementation and evaluation of stress prevention in medical schools.}, language = {en} } @article{KuhnScharfenortSchuemannetal.2016, author = {Kuhn, Manuel and Scharfenort, Robert and Sch{\"u}mann, Dirk and Schiele, Miriam A. and M{\"u}nsterk{\"o}tter, Anna L. and Deckert, J{\"u}rgen and Domschke, Katharina and Haaker, Jan and Kalisch, Raffael and Pauli, Paul and Reif, Andreas and Romanos, Marcel and Zwanzger, Peter and Lonsdorf, Tina B.}, title = {Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament}, series = {Social Cognitive and Affective Neuroscience}, volume = {11}, journal = {Social Cognitive and Affective Neuroscience}, number = {4}, doi = {10.1093/scan/nsv137}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189645}, pages = {537-547}, year = {2016}, abstract = {Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences.}, language = {en} } @phdthesis{Kaempf2012, author = {K{\"a}mpf, Anne Kristina}, title = {Does methylphenidate cause a cytogenetic effect in children with attention deficit hyperactivity disorder?}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-77652}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2012}, abstract = {MPH wird seit {\"u}ber 50 Jahren zur Therapie des ADHS eingesetzt. Gerade in den letzten Jahren wurde deutlich, dass der Einsatz ohne fundierte Kenntnis {\"u}ber m{\"o}gliche Langzeit-effekte erfolgte, da zum Zeitpunkt der Zulassung aufgrund der begrenzten technischen M{\"o}glichkeiten weniger strenge und weniger umfassende Einschr{\"a}nkungen beachtet wer-den mussten (Walitza, Werner et al. 2007). Da in den letzten Jahren die Anzahl der verschrieben Tagesdosen MPH sprunghaft anstiegen, ist es wichtig, auch die langfristigen Nebenwirkungen von MPH zu untersuchen (Janhsen 2007). Eine Studie von El-Zein et al. von 2005 brachte die Frage auf, ob MPH eventuell Genomsch{\"a}den hervorrufe. Bei 11 von 12 untersuchten Kindern wurde unter der Therapie mit MPH um das 2,4fache erh{\"o}hte Mikrokernfrequenzen gefunden (El-Zein, Abdel-Rahman et al. 2005). Dies beunruhig-te vor allem im Hinblick auf das mit erh{\"o}hten Mikrokernfrequenzen korrelierte erh{\"o}hte Karzinomrisiko. Eine daraufhin von Walitza et al. durchgef{\"u}hrte Studie, die ebenfalls Mikrokernfrequenzen in peripheren Blutzellen untersuchte (Walitza, Werner et al. 2007), konnte keine Hinweise auf eine Genomsch{\"a}digung durch MPH erbringen. Zahlreiche weitere Untersuchungen zur potentiellen Genomsch{\"a}digung durch MPH konnten die Ergebnisse durch in vivo- oder in vitro-Studien nicht best{\"a}tigen und kritisierten die ge-ringe Stichprobengr{\"o}ße sowie mangelnde Transparenz der Arbeit von El-Zein (Preston, Kollins et al. 2005; El-Zein, Hay et al. 2006; Holtmann, Kaina et al. 2006; Suter, Martus et al. 2006). Da jedoch keine weitere Studie sich konkret mit zytogenetischen Effekten in peripheren Blutzellen befasste, soll die vorliegende Arbeit dazu dienen, den Verdacht einer Genomsch{\"a}digung endg{\"u}ltig auszur{\"a}umen (Walitza, Kampf et al. 2009). Dazu wurde eine gr{\"o}ßere Gruppe von Kindern eingeschlossen, sowie Untersuchungen zu verschiedenen Zeitpunkten w{\"a}hrend der MPH-Einnahme, bis hin zu Untersuchungen nach einem Zeitraum von 12 Monaten der MPH- Einnahme, durchgef{\"u}hrt. Mit Hilfe eines Mikrokerntestes wurden in der vorliegenden Studie versucht, DNS-Sch{\"a}den an periphe-ren Lymphozyten zu bestimmen, um daraus auf ein potentiell erh{\"o}htes Krebsrisiko schließen zu k{\"o}nnen. Im Vergleich mit einer gesunden Kontrollgruppe waren die Werte von ADHS-Kindern ohne MPH-Therapie sowie nach 3 und 12 Monaten MPH-Therapie zwar signifikant er-h{\"o}ht, diese gesunde Kontrollgruppe wies jedoch im Vergleich mit internationalen Refe-renzwerten eine extrem niedrige Mikrokernfrequenz auf, so dass davon ausgegangen werden muss, dass diese Vergleiche nur begrenzte Aussagekraft haben. In keiner der verschiedenen mit MPH therapierten Gruppen konnten {\"u}ber die Dauer der Einnahme eine signifikant Erh{\"o}hung der Mikrokernfrequenzen im Vergleich zu den Werten vor Einnahmebeginn nachgewiesen werden, was den Schluss zul{\"a}sst, dass eine Therapie mit Methylphenidat in therapie{\"u}blichen Dosen bei Kindern das Erbgut nicht zu sch{\"a}digen scheint. Dieses Ergebnis best{\"a}tigen inzwischen auch weitere Studien. Der Mikrokerntest erfasst Genomsch{\"a}den, nicht jedoch etwaige tumorpromovierende Eigenschaften des verabreichten Medikaments. Damit ist unklar, ob MPH auf andere Art als {\"u}ber eine Sch{\"a}digung des Genoms das Karzinomrisiko erh{\"o}hen k{\"o}nnte. Erste epidemiologische Studien sehen jedoch keinen Hinweis auf eine wie auch immer entstandene erh{\"o}hte Karzinominzidenz unter der Therapie mit MPH (Selby, Friedman et al. 1989; Oestreicher, Friedman et al. 2007). Hier scheinen jedoch weitere epidemiologische Studien, die m{\"o}g-lichst große Zeitspannen umfassen, n{\"o}tig zu sein}, subject = {Methylphenidat}, language = {en} } @article{LechermeierZimmerLueffeetal.2019, author = {Lechermeier, Carina G. and Zimmer, Frederic and L{\"u}ffe, Teresa M. and Lesch, Klaus-Peter and Romanos, Marcel and Lillesaar, Christina and Drepper, Carsten}, title = {Transcript analysis of zebrafish GLUT3 genes, slc2a3a and slc2a3b, define overlapping as well as distinct expression domains in the zebrafish (Danio rerio) central nervous system}, series = {Frontiers in Molecular Neuroscience}, volume = {12}, journal = {Frontiers in Molecular Neuroscience}, number = {199}, doi = {10.3389/fnmol.2019.00199}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201797}, year = {2019}, abstract = {The transport of glucose across the cell plasma membrane is vital to most mammalian cells. The glucose transporter (GLUT; also called SLC2A) family of transmembrane solute carriers is responsible for this function in vivo. GLUT proteins encompass 14 different isoforms in humans with different cell type-specific expression patterns and activities. Central to glucose utilization and delivery in the brain is the neuronally expressed GLUT3. Recent research has shown an involvement of GLUT3 genetic variation or altered expression in several different brain disorders, including Huntington's and Alzheimer's diseases. Furthermore, GLUT3 was identified as a potential risk gene for multiple psychiatric disorders. To study the role of GLUT3 in brain function and disease a more detailed knowledge of its expression in model organisms is needed. Zebrafish (Danio rerio) has in recent years gained popularity as a model organism for brain research and is now well-established for modeling psychiatric disorders. Here, we have analyzed the sequence of GLUT3 orthologs and identified two paralogous genes in the zebrafish, slc2a3a and slc2a3b. Interestingly, the Glut3b protein sequence contains a unique stretch of amino acids, which may be important for functional regulation. The slc2a3a transcript is detectable in the central nervous system including distinct cellular populations in telencephalon, diencephalon, mesencephalon and rhombencephalon at embryonic and larval stages. Conversely, the slc2a3b transcript shows a rather diffuse expression pattern at different embryonic stages and brain regions. Expression of slc2a3a is maintained in the adult brain and is found in the telencephalon, diencephalon, mesencephalon, cerebellum and medulla oblongata. The slc2a3b transcripts are present in overlapping as well as distinct regions compared to slc2a3a. Double in situ hybridizations were used to demonstrate that slc2a3a is expressed by some GABAergic neurons at embryonic stages. This detailed description of zebrafish slc2a3a and slc2a3b expression at developmental and adult stages paves the way for further investigations of normal GLUT3 function and its role in brain disorders.}, language = {en} } @article{LudwigSaemannAlexanderetal.2013, author = {Ludwig, K. U. and S{\"a}mann, P. and Alexander, M. and Becker, J. and Bruder, J. and Moll, K. and Spieler, D. and Czisch, M. and Warnke, A. and Docherty, S. J. and Davis, O. S. P. and Plomin, R. and N{\"o}then, M. M. and Landerl, K. and M{\"u}ller-Myhsok, B. and Hoffmann, P. and Schumacher, J. and Schulte-K{\"o}rne, G. and Czamara, D.}, title = {A common variant in Myosin-18B contributes to mathematical abilities in children with dyslexia and intraparietal sulcus variability in adults}, series = {Translational Psychiatry}, volume = {3}, journal = {Translational Psychiatry}, number = {e229}, doi = {10.1038/tp.2012.148}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131513}, year = {2013}, abstract = {The ability to perform mathematical tasks is required in everyday life. Although heritability estimates suggest a genetic contribution, no previous study has conclusively identified a genetic risk variant for mathematical performance. Research has shown that the prevalence of mathematical disabilities is increased in children with dyslexia. We therefore correlated genome-wide data of 200 German children with spelling disability, with available quantitative data on mathematic ability. Replication of the top findings in additional dyslexia samples revealed that rs133885 was a genome-wide significant marker for mathematical abilities\((P_{comb}=7.71 x 10^{-10}, n=699)\), with an effect size of 4.87\%. This association was also found in a sample from the general population (P=0.048, n=1080), albeit with a lower effect size. The identified variant encodes an amino-acid substitution in MYO18B, a protein with as yet unknown functions in the brain. As areas of the parietal cortex, in particular the intraparietal sulcus (IPS), are involved in numerical processing in humans, we investigated whether rs133885 was associated with IPS morphology using structural magnetic resonance imaging data from 79 neuropsychiatrically healthy adults. Carriers of the MYO18B risk-genotype displayed a significantly lower depth of the right IPS. This validates the identified association between rs133885 and mathematical disability at the level of a specific intermediate phenotype.}, language = {en} } @phdthesis{LopezdeMiguel2024, author = {L{\´o}pez de Miguel, Pilar}, title = {Patientenzufriedenheit mit dem Aufkl{\"a}rungsgespr{\"a}ch}, doi = {10.25972/OPUS-34720}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-347201}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {Ziele: Das Ziel der vorliegenden Arbeit ist eine standardisierte Analyse der Patientenzufriedenheit mit dem Aufkl{\"a}rungsgespr{\"a}ch und die m{\"o}gliche Einflussfaktoren, die hier eine Rolle spielen k{\"o}nnen, zu bieten. Methodik: Es wurden 189 Frageb{\"o}gen bzw. Aufkl{\"a}rungsgespr{\"a}che in den Kliniken f{\"u}r An{\"a}sthesie und Innere Medizin im St. Josef Krankenhaus und Chirurgie und Kinder- und Jugendpsychiatrie im Leopoldina Krankenhaus in Schweinfurt untersucht. Ergebnisse: Der Fragebogen, der verwendet wurde, war reliabel. Es zeigte sich eine schlechte Item-Selektivit{\"a}t. Die Kriteriumsvalidit{\"a}t konnte best{\"a}tigt werden jedoch nicht die diskriminante Validit{\"a}t. Die Patienten waren zufriedener mit {\"A}rzten, die Deutsch als Muttersprache angaben, mit l{\"a}ngeren Aufkl{\"a}rungsgespr{\"a}chen und mit Fach{\"a}rzten im Vergleich zu Assistenz{\"a}rzten. Eine h{\"o}here allgemeine Lebenszufriedenheit war mit h{\"o}herer Patientenzufriedenheit mit dem Aufkl{\"a}rungsgespr{\"a}ch assoziiert. Der moralistische Bias kann einen St{\"o}rfaktor der Validit{\"a}t der Messungen darstellen. Zusammenfassung: Eine angemessene Gespr{\"a}chdauer, die deutsche Muttersprache und der Facharztstatus des aufkl{\"a}renden Arztes haben einen positiven Einfluss auf die Patientenzufriedenheit mit dem Aufkl{\"a}rungsgespr{\"a}ch. Um sicher zu stellen, welche von diesen drei Faktoren besondere Wichtigkeit besitzt, werden weitere Untersuchungen ben{\"o}tigt.}, subject = {Zufriedenheit}, language = {de} } @article{LueffeBauerGiogaetal.2022, author = {L{\"u}ffe, Teresa M. and Bauer, Moritz and Gioga, Zoi and {\"O}zbay, Duru and Romanos, Marcel and Lillesaar, Christina and Drepper, Carsten}, title = {Loss-of-Function Models of the Metabotropic Glutamate Receptor Genes Grm8a and Grm8b Display Distinct Behavioral Phenotypes in Zebrafish Larvae (Danio rerio)}, series = {Frontiers in Molecular Neuroscience}, volume = {15}, journal = {Frontiers in Molecular Neuroscience}, issn = {1662-5099}, doi = {10.3389/fnmol.2022.901309}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-277429}, year = {2022}, abstract = {Members of the family of metabotropic glutamate receptors are involved in the pathomechanism of several disorders of the nervous system. Besides the well-investigated function of dysfunctional glutamate receptor signaling in neurodegenerative diseases, neurodevelopmental disorders (NDD), like autism spectrum disorders (ASD) and attention-deficit and hyperactivity disorder (ADHD) might also be partly caused by disturbed glutamate signaling during development. However, the underlying mechanism of the type III metabotropic glutamate receptor 8 (mGluR8 or GRM8) involvement in neurodevelopment and disease mechanism is largely unknown. Here we show that the expression pattern of the two orthologs of human GRM8, grm8a and grm8b, have evolved partially distinct expression patterns in the brain of zebrafish (Danio rerio), especially at adult stages, suggesting sub-functionalization of these two genes during evolution. Using double in situ hybridization staining in the developing brain we demonstrate that grm8a is expressed in a subset of gad1a-positive cells, pointing towards glutamatergic modulation of GABAergic signaling. Building on this result we generated loss-of-function models of both genes using CRISPR/Cas9. Both mutant lines are viable and display no obvious gross morphological phenotypes making them suitable for further analysis. Initial behavioral characterization revealed distinct phenotypes in larvae. Whereas grm8a mutant animals display reduced swimming velocity, grm8b mutant animals show increased thigmotaxis behavior, suggesting an anxiety-like phenotype. We anticipate that our two novel metabotropic glutamate receptor 8 zebrafish models may contribute to a deeper understanding of its function in normal development and its role in the pathomechanism of disorders of the central nervous system.}, language = {en} } @article{LueffeD'OrazioBaueretal.2021, author = {L{\"u}ffe, Teresa M. and D'Orazio, Andrea and Bauer, Moritz and Gioga, Zoi and Schoeffler, Victoria and Lesch, Klaus-Peter and Romanos, Marcel and Drepper, Carsten and Lillesaar, Christina}, title = {Increased locomotor activity via regulation of GABAergic signalling in foxp2 mutant zebrafish - implications for neurodevelopmental disorders}, series = {Translational Psychiatry}, volume = {11}, journal = {Translational Psychiatry}, doi = {10.1038/s41398-021-01651-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264713}, year = {2021}, abstract = {Recent advances in the genetics of neurodevelopmental disorders (NDDs) have identified the transcription factor FOXP2 as one of numerous risk genes, e.g. in autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). FOXP2 function is suggested to be involved in GABAergic signalling and numerous studies demonstrate that GABAergic function is altered in NDDs, thus disrupting the excitation/inhibition balance. Interestingly, GABAergic signalling components, including glutamate-decarboxylase 1 (Gad1) and GABA receptors, are putative transcriptional targets of FOXP2. However, the specific role of FOXP2 in the pathomechanism of NDDs remains elusive. Here we test the hypothesis that Foxp2 affects behavioural dimensions via GABAergic signalling using zebrafish as model organism. We demonstrate that foxp2 is expressed by a subset of GABAergic neurons located in brain regions involved in motor functions, including the subpallium, posterior tuberculum, thalamus and medulla oblongata. Using CRISPR/Cas9 gene-editing we generated a novel foxp2 zebrafish loss-of-function mutant that exhibits increased locomotor activity. Further, genetic and/or pharmacological disruption of Gad1 or GABA-A receptors causes increased locomotor activity, resembling the phenotype of foxp2 mutants. Application of muscimol, a GABA-A receptor agonist, rescues the hyperactive phenotype induced by the foxp2 loss-of-function. By reverse translation of the therapeutic effect on hyperactive behaviour exerted by methylphenidate, we note that application of methylphenidate evokes different responses in wildtype compared to foxp2 or gad1b loss-of-function animals. Together, our findings support the hypothesis that foxp2 regulates locomotor activity via GABAergic signalling. This provides one targetable mechanism, which may contribute to behavioural phenotypes commonly observed in NDDs.}, language = {en} } @phdthesis{Lueffe2023, author = {L{\"u}ffe, Teresa Magdalena}, title = {Behavioral and pharmacological validation of genetic zebrafish models for ADHD}, doi = {10.25972/OPUS-25716}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257168}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Attention-deficit/hyperactivity disorder (ADHD) is the most prevalent neurodevelopmental disorder described in psychiatry today. ADHD arises during early childhood and is characterized by an age-inappropriate level of inattention, hyperactivity, impulsivity, and partially emotional dysregulation. Besides, substantial psychiatric comorbidity further broadens the symptomatic spectrum. Despite advances in ADHD research by genetic- and imaging studies, the etiopathogenesis of ADHD remains largely unclear. Twin studies suggest a heritability of 70-80 \% that, based on genome-wide investigations, is assumed to be polygenic and a mixed composite of small and large, common and rare genetic variants. In recent years the number of genetic risk candidates is continuously increased. However, for most, a biological link to neuropathology and symptomatology of the patient is still missing. Uncovering this link is vital for a better understanding of the disorder, the identification of new treatment targets, and therefore the development of a more targeted and possibly personalized therapy. The present thesis addresses the issue for the ADHD risk candidates GRM8, FOXP2, and GAD1. By establishing loss of function zebrafish models, using CRISPR/Cas9 derived mutagenesis and antisense oligonucleotides, and studying them for morphological, functional, and behavioral alterations, it provides novel insights into the candidate's contribution to neuropathology and ADHD associated phenotypes. Using locomotor activity as behavioral read-out, the present work identified a genetic and functional implication of Grm8a, Grm8b, Foxp2, and Gad1b in ADHD associated hyperactivity. Further, it provides substantial evidence that the function of Grm8a, Grm8b, Foxp2, and Gad1b in activity regulation involves GABAergic signaling. Preliminary indications suggest that the three candidates interfere with GABAergic signaling in the ventral forebrain/striatum. However, according to present and previous data, via different biological mechanisms such as GABA synthesis, transmitter release regulation, synapse formation and/or transcriptional regulation of synaptic components. Intriguingly, this work further demonstrates that the activity regulating circuit, affected upon Foxp2 and Gad1b loss of function, is involved in the therapeutic effect mechanism of methylphenidate. Altogether, the present thesis identified altered GABAergic signaling in activity regulating circuits in, presumably, the ventral forebrain as neuropathological underpinning of ADHD associated hyperactivity. Further, it demonstrates altered GABAergic signaling as mechanistic link between the genetic disruption of Grm8a, Grm8b, Foxp2, and Gad1b and ADHD symptomatology like hyperactivity. Thus, this thesis highlights GABAergic signaling in activity regulating circuits and, in this context, Grm8a, Grm8b, Foxp2, and Gad1b as exciting targets for future investigations on ADHD etiopathogenesis and the development of novel therapeutic interventions for ADHD related hyperactivity. Additionally, thigmotaxis measurements suggest Grm8a, Grm8b, and Gad1b as interesting candidates for prospective studies on comorbid anxiety in ADHD. Furthermore, expression analysis in foxp2 mutants demonstrates Foxp2 as regulator of ADHD associated gene sets and neurodevelopmental disorder (NDD) overarching genetic and functional networks with possible implications for ADHD polygenicity and comorbidity. Finally, with the characterization of gene expression patterns and the generation and validation of genetic zebrafish models for Grm8a, Grm8b, Foxp2, and Gad1b, the present thesis laid the groundwork for future research efforts, for instance, the identification of the functional circuit(s) and biological mechanism(s) by which Grm8a, Grm8b, Foxp2, and Gad1b loss of function interfere with GABAergic signaling and ultimately induce hyperactivity.}, language = {en} } @phdthesis{Mai2005, author = {Mai, Marion}, title = {Mutationsanalyse der Gene Connexin 36 (CX36) und Tyrosinkinase 3 (TYRO3) als Kandidatengene f{\"u}r periodische Katatonie}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-18046}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2005}, abstract = {Das humane Chromosom 15 wurde bereits im Zusammenhang mit anderen Erkrankungen wie dem Marfan Syndrom und der Tay Sachs Erkrankung erw{\"a}hnt. F{\"u}r deren Genese wurden auf dem Chromosom gelegene Gene verantwortlich gemacht (Richard et al. 1994). Aufbauend auf den Vorarbeiten der W{\"u}rzburger Arbeitsgruppe (St{\"o}ber et al. 2000, 2002; Meyer et al. 2002) wurden auf Chromosom 15 anhand der Lokalisation, der Funktion und dem Vorhandensein im Zentralnervensystem die Gene Cx36 und TYRO3 f{\"u}r die Mutationsanalyse ausgew{\"a}hlt, um sie nach der Methode von Sanger (Sanger et al. 1977) zu sequenzieren. Sowohl Cx36 als auch TYRO3 spielen eine zentrale Rolle in der Entwicklung und Zellinteraktion im ZNS. Es w{\"a}re denkbar, daß ein Defekt w{\"a}hrend der Synaptogenese im ZNS an der Krankheitsentstehung beteiligt ist, ebenso wie eine unzureichende Ausbildung von Gap junctions, an denen Cx36 maßgeblich beteiligt ist. Die Patienten-DNA wurde aus Blutproben von Probanden mit periodischer Katatonie gewonnen. Diese wurden aus der Familie 11 der bereits erw{\"a}hnten Studie rekrutiert, die in drei Generationen von der Erkrankung betroffen ist und zehn gesunde, sowie 7 kranke Mitglieder z{\"a}hlt. Die Proben wurden zusammen mit solchen von gesunden Kontrollpersonen vergleichend sequenziert und auf {\"U}bereinstimmung mit den Eintr{\"a}gen der GenBank {\"u}berpr{\"u}ft mit dem Ziel, Mutationen zu finden, die zu einem Defekt im Protein f{\"u}hren und zur Auspr{\"a}gung der Krankheit beitragen, bzw. die Gene als Kandidaten auszuschließen.}, language = {de} } @article{McNeillZieglerRadtkeetal.2020, author = {McNeill, Rhiannon V. and Ziegler, Georg C. and Radtke, Franziska and Nieberler, Matthias and Lesch, Klaus‑Peter and Kittel‑Schneider, Sarah}, title = {Mental health dished up — the use of iPSC models in neuropsychiatric research}, series = {Journal of Neural Transmission}, volume = {127}, journal = {Journal of Neural Transmission}, issn = {0300-9564}, doi = {10.1007/s00702-020-02197-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235666}, pages = {1547-1568}, year = {2020}, abstract = {Genetic and molecular mechanisms that play a causal role in mental illnesses are challenging to elucidate, particularly as there is a lack of relevant in vitro and in vivo models. However, the advent of induced pluripotent stem cell (iPSC) technology has provided researchers with a novel toolbox. We conducted a systematic review using the PRISMA statement. A PubMed and Web of Science online search was performed (studies published between 2006-2020) using the following search strategy: hiPSC OR iPSC OR iPS OR stem cells AND schizophrenia disorder OR personality disorder OR antisocial personality disorder OR psychopathy OR bipolar disorder OR major depressive disorder OR obsessive compulsive disorder OR anxiety disorder OR substance use disorder OR alcohol use disorder OR nicotine use disorder OR opioid use disorder OR eating disorder OR anorexia nervosa OR attention-deficit/hyperactivity disorder OR gaming disorder. Using the above search criteria, a total of 3515 studies were found. After screening, a final total of 56 studies were deemed eligible for inclusion in our study. Using iPSC technology, psychiatric disease can be studied in the context of a patient's own unique genetic background. This has allowed great strides to be made into uncovering the etiology of psychiatric disease, as well as providing a unique paradigm for drug testing. However, there is a lack of data for certain psychiatric disorders and several limitations to present iPSC-based studies, leading us to discuss how this field may progress in the next years to increase its utility in the battle to understand psychiatric disease.}, language = {en} } @article{MelfsenJansRomanosetal.2022, author = {Melfsen, Siebke and Jans, Thomas and Romanos, Marcel and Walitza, Susanne}, title = {Family relationships in selective mutism — a comparison group study of children and adolescents}, series = {Children}, volume = {9}, journal = {Children}, number = {11}, issn = {2227-9067}, doi = {10.3390/children9111634}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290386}, year = {2022}, abstract = {Selective mutism (SM) mostly develops early in childhood and this has led to interest into whether there could be differences in relationships in families with SM compared to a control group without SM. Currently, there are merely few empirical studies examining family relationships in SM. A sample of 28 children and adolescents with SM was compared to 33 controls without SM. The groups were investigated using self-report questionnaires (Selective Mutism Questionnaire, Child-Parent Relationship Test—Child Version) for the assessment of SM and family relationships. Children with SM did not report a significantly different relationship to their mothers compared with the control group without SM. However, the scores in respect to the relationship to their fathers were significantly lower in cohesion, identification and autonomy compared with children without SM. Relationships in families with SM should be considered more in therapy.}, language = {en} } @article{MelfsenKuehnemundSchwiegeretal.2011, author = {Melfsen, Siebke and K{\"u}hnemund, Martina and Schwieger, Judith and Warnke, Andreas and Stadler, Christina and Poustka, Fritz and Stangier, Ulrich}, title = {Cognitive behavioral therapy of socially phobic children focusing on cognition: a randomised wait-list control study}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68747}, year = {2011}, abstract = {Background: Although literature provides support for cognitive behavioral therapy (CBT) as an efficacious intervention for social phobia, more research is needed to improve treatments for children. Methods: Forty four Caucasian children (ages 8-14) meeting diagnostic criteria of social phobia according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; APA, 1994) were randomly allocated to either a newly developed CBT program focusing on cognition according to the model of Clark and Wells (n = 21) or a wait-list control group (n = 23). The primary outcome measure was clinical improvement. Secondary outcomes included improvements in anxiety coping, dysfunctional cognitions, interaction frequency and comorbid symptoms. Outcome measures included child report and clinican completed measures as well as a diagnostic interview. Results: Significant differences between treatment participants (4 dropouts) and controls (2 dropouts) were observed at post test on the German version of the Social Phobia and Anxiety Inventory for Children. Furthermore, in the treatment group, significantly more children were free of diagnosis than in wait-list group at post-test. Additional child completed and clinician completed measures support the results. Discussion: The study is a first step towards investigating whether CBT focusing on cognition is efficacious in treating children with social phobia. Future research will need to compare this treatment to an active treatment group. There remain the questions of whether the effect of the treatment is specific to the disorder and whether the underlying theoretical model is adequate. Conclusion: Preliminary support is provided for the efficacy of the cognitive behavioral treatment focusing on cognition in socially phobic children. Active comparators should be established with other evidence-based CBT programs for anxiety disorders, which differ significantly in their dosage and type of cognitive interventions from those of the manual under evaluation (e.g. Coping Cat).}, subject = {Verhaltenstherapie}, language = {en} } @phdthesis{Mittermeier2023, author = {Mittermeier, Anna Barbara}, title = {Furchtgeneralisierung bei Kindern und Jugendlichen mit internalisierenden St{\"o}rungen}, doi = {10.25972/OPUS-28265}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-282658}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {In vorgegangenen Studien wurde bei erwachsenen Patienten mit Angstst{\"o}rungen eine verst{\"a}rkte Furchtgeneralisierung, eine eingeschr{\"a}nkte F{\"a}higkeit zur Reizdiskrimination sowie eine ver{\"a}nderte Aufmerksamkeitsverteilung nachgewiesen. In einer gesunden Studienpopulation konnte bei Kindern eine st{\"a}rkere Furchtgeneralisierung nachgewiesen werden als bei Erwachsenen. Ihre Generalisierungsgradienten gleichen denen von Erwachsenen mit Angstst{\"o}rung. M{\"o}glicherweise haben gest{\"o}rte Lernprozesse in der Kindheit somit langfristige Effekte auf die Entwicklung von Angstst{\"o}rungen. Obwohl die Vorg{\"a}nge des Furchtlernens im Kindesalter entscheidend f{\"u}r das Verst{\"a}ndnis von Angstst{\"o}rungen sind, gibt es kaum Studien in dieser Altersgruppe. Die vorliegende Studie untersucht die Zusammenh{\"a}nge von Furchtgeneralisierung und Aufmerksamkeitsprozessen in einer klinischen Population mit internalisierender St{\"o}rung im Kindes- und Jugendalter. Hierzu durchliefen Kinder und Jugendliche mit internalisierender St{\"o}rung (n= 49) sowie gesunde Kontrollen (n=48) im Alter von 9 bis 17 Jahre ein Furcht-generalisierungsparadigma mit Diskriminationstraining sowie einen modifizierten Dotprobe mit integriertem Eyetracking. Die {\"A}ngstlichkeit wurde mittels verschiedener Angstfrageb{\"o}gen gemessen. Im Generalisierungsparadigma wurden zwei weibliche Gesichter mit neutralem Gesichtsausdruck als Stimuli verwendet, die entweder mit (CS+) oder ohne (CS-) einem 95dB lauten Schrei sowie einem angsterf{\"u}llten Gesichtsausdruck gezeigt wurden. Zur Messung der Furchtreaktion wurden subjektive Ratings f{\"u}r Arousal, Valenz und Kontingenz erfasst, zudem wurde die Hautleitf{\"a}higkeit gemessen. Zur Auswertung des Dotprobes wurden die Reaktionszeiten und die Initialsakkade erfasst. Die statistische Analyse des Furchtgeneralisierungsparadigmas sowie des Dotprobe-Paradigmas wurde mittels Multivarianzanalysen mit Messwiederholung durchgef{\"u}hrt, gefolgt von t-Tests zur weiterf{\"u}hrenden Analyse. Desweiteren wurden die Aufmerksamkeitsreaktionen von nicht-{\"a}ngstlichen und {\"a}ngstlichen Teilnehmern in Kategorien eingeteilt und mittels Chi-Quadrat Analysen verglichen. Zur Analyse des Zusammenhangs zwischen Furchtgeneralisierung und Aufmerksamkeitsprozessen erfolgte eine Regressionsanalyse mit einem GS Mittelwert als abh{\"a}ngiger Variable und der {\"A}ngstlichkeit und den Aufmerk-samkeitsprozessen als Pr{\"a}diktoren. Die Ergebnisse best{\"a}tigten eine solide Furchtkonditionierung anhand des „Screaming Lady"-Paradigmas in einer klinischen Population, dies war erkennbar an h{\"o}heren Ratings f{\"u}r den aversiven Stimulus im Vergleich zum sicheren Stimulus in beiden Gruppen. Grunds{\"a}tzlich h{\"o}here Furchtratings sowie h{\"o}here Ratings der Generalisierungsstimuli im Vergleich zum sicheren Stimulus wiesen auf eine st{\"a}rkere Generalisierung in der Untergruppe mit h{\"o}herem Angst-Trait innerhalb der internalisierenden Probandengruppe hin. Die Analyse der Dotprobe Daten ergab schnellere Reaktionszeiten sowie h{\"a}ufigere Initialsakkaden gegen{\"u}ber furchteinfl{\"o}ßenden Stimuli bei Patienten mit internalisierender St{\"o}rung. Des Weiteren zeigten sehr {\"a}ngstliche Probanden h{\"a}ufiger einen Attentional bias im Chi Quadrat Test als nicht-{\"a}ngstliche Probanden. Dies wies daraufhin, dass sowohl bei Patienten mit internalisierender St{\"o}rung als auch bei sehr {\"a}ngstlichen Probanden ein Attentional bias gegen{\"u}ber furchtrelevanten Stimuli vorliegt. Vor allem bei Kindern mit internalisierender St{\"o}rung sagten die {\"A}ngstlichkeit und ver{\"a}nderte Aufmerksamkeitsprozesse die Auspr{\"a}gung der Furchtgeneralisierung voraus. Somit kann ein Zusammenhang von ver{\"a}nderten Aufmerksamkeitsprozessen und Furchtgeneralisierung vermutet werden.}, subject = {Kinderpsychiatrie}, language = {de} } @article{MittermeierSeidelScheineretal.2024, author = {Mittermeier, Sabrina and Seidel, Alexandra and Scheiner, Christin and Kleindienst, Nikolaus and Romanos, Marcel and Buerger, Arne}, title = {Emotional dysregulation and its pathways to suicidality in a community-based sample of adolescents}, series = {Child and Adolescent Psychiatry and Mental Health}, volume = {18}, journal = {Child and Adolescent Psychiatry and Mental Health}, issn = {1753-2000}, doi = {10.1186/s13034-023-00699-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357501}, year = {2024}, abstract = {Objective Effective suicide prevention for adolescents is urgently needed but difficult, as suicide models lack a focus on age-specific influencing factors such as emotional dysregulation. Moreover, examined predictors often do not specifically consider the contribution to the severity of suicidality. To determine which adolescents are at high risk of more severe suicidality, we examined the association between emotional dysregulation and severity of suicidality directly as well as indirectly via depressiveness and nonsuicidal self-injury. Method Adolescents from 18 high schools in Bavaria were included in this cross-sectional and questionnaire-based study as part of a larger prevention study. Data were collected between November 2021 and March 2022 and were analyzed from January 2023 to April 2023. Students in the 6th or 7th grade of high school (11-14 years) were eligible to participate. A total of 2350 adolescents were surveyed and data from 2117 students were used for the analyses after excluding incomplete data sets. Our main outcome variable was severity of suicidality (Paykel Suicide Scale, PSS). Additionally, we assessed emotional dysregulation (Difficulties in Emotion Regulation Scale, DERS-SF), depressiveness (Patient Health Questionnaire, PHQ-9) and nonsuicidal self-injury (Deliberate Self-Harm Inventory, DSHI). Results In total, 2117 adolescents (51.6\% female; mean age, 12.31 years [standard deviation: 0.67]) were included in the structural equation model (SEM). Due to a clear gender-specific influence, the model was calculated separately for male and female adolescents. For male adolescents, there was a significant indirect association between emotional dysregulation and severity of suicidality, mediated by depressiveness (β = 0.15, SE = .03, p = .008). For female adolescents, there was a significant direct path from emotional dysregulation to severity of suicidality and also indirect paths via depressiveness (β = 0.12, SE = .05, p = 0.02) and NSSI (β = 0.18, SE = .04, p < .001). Conclusions Our results suggest that gender-related risk markers in 11-14-year-olds need to be included in future suicide models to increase their predictive power. According to our findings, early detection and prevention interventions based on emotion regulation skills might be enhanced by including gender-specific adjustments for the co-occurrence of emotional dysregulation, depressiveness, and nonsuicidal self-injury in girls and the co-occurrence of emotional dysregulation and depressiveness in boys.}, language = {en} } @phdthesis{Mueller2007, author = {M{\"u}ller, Frauke}, title = {Serotonerges System und elektophysiologische Korrelate der motorischen Hemmung sowie der emotionalen Verarbeitung}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-23307}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2007}, abstract = {Untersuchung der Verarbeitungsprozesse im Gehirn mittels EEG. Daf{\"u}r wurden 2 Versuche durchgef{\"u}hrt: der CPT (Continous Performance Test) zur Erfassung von motorischer Aktivierung und Hemmung einer Bewegung und der EMO (Test zur Erfassung des emotionalen Paradigmas), bei welchem den Probaden 200 Bilder gezeigt wurden, die streng nach Arousel (Hoch/Niedrigerregend) sowie Bildcharakter( Positiv/Negativ) unterschieden wurden. Die Versuche wurden an 54 M{\"a}nnern/Frauen durchgef{\"u}hrt, die nach ihren Genotyp (nach COM sowie 5-HTTLPR) ausgesucht wurden. Es wurde untersucht, ob sich elekrtophysiologisch Unterschiede zwischen den einzelnen Genotypen des COMT/ 5-HTTLPR ergeben, die eine genetische Pr{\"a}disposition f{\"u}r Erkrankungen aus dem psychiatrischen Formenkreis, die diesen Genen zugesprochen wird, best{\"a}tigt. Es konnte keine statistisch signifikanten Ver{\"a}nderungen erkannt werden.}, language = {de} } @phdthesis{Nachtigall2022, author = {Nachtigall, Lea}, title = {Vergleichende Untersuchung der Beeintr{\"a}chtigung der Gesundheit und Arbeitsf{\"a}higkeit von Eltern mit Kindern, welche an ADHS leiden, gegen{\"u}ber einer Stichprobe von Eltern mit unauff{\"a}lligen Kindern}, doi = {10.25972/OPUS-25949}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259495}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {In der dargestellten Arbeit wurden verschiedene Hypothesen im Hinblick auf die berufliche und gesundheitliche Belastung von Eltern mit Kindern, die an ADHS leiden, untersucht. So wurde zun{\"a}chst der Fragestellung nachgegangen, in wieweit das von ADHS betroffene Kind in der Familie selbst zu einer erh{\"o}hten Belastung der Eltern am Arbeitsplatz und somit zu einer gesteigerten gesundheitlichen Einschr{\"a}nkung f{\"u}hrt. Zudem untersuchten wir die Auswirkungen einer m{\"o}glichen eigenen ADHS-Symptomatik in der Kindheit laut WURS auf die gesundheitliche Verfassung und die Leistungsf{\"a}higkeit am Arbeitsplatz. Schließlich wurde in der dritten Hypothese die Frage untersucht, in wieweit ein Effekt der Anzahl betroffener Kinder mit ADHS innerhalb einer Familie feststellbar ist. Entsprechend wurde eine vergleichende Untersuchung mit einer klinischen Stichprobe (n=91) und einer gesunden Vergleichsstichprobe (n=198) durchgef{\"u}hrt. Um die verschiedenen Einflussfaktoren verifizierbar zu machen, wurden verschiedene Untersuchungsinstrumente in Form von Frageb{\"o}gen sowohl an die klinische Stichprobe als auch an die Vergleichsstichprobe (Familien, deren Kinder als gesund beschrieben wurden) verteilt. Zur allgemeinen Einsch{\"a}tzung von Verhaltensauff{\"a}lligkeiten der Kinder in den jeweiligen Familien wurde die Child-Behavior-Checklist von den Eltern ausgef{\"u}llt. Zudem sch{\"a}tzten die Eltern {\"u}ber den Fremdbeurteilungsbogen f{\"u}r hyperkinetische St{\"o}rungen die ADHS-Symptomatik ihrer Kinder ein. Dar{\"u}ber hinaus beurteilten die Eltern eine m{\"o}gliche eigene ADHS-Symptomatik in der Kindheit {\"u}ber die retrospektiv ausgelegte Wender Utah Rating Scale. Der individuelle Gesundheitszustand der V{\"a}ter und M{\"u}tter wurde {\"u}ber den „EQ-5D" erfragt, w{\"a}hrend die Belastung am Arbeitsplatz mittels der Work Limitation Questionnaire ermittelt wurde. Schließlich f{\"u}llten alle teilnehmenden Eltern einen sozio{\"o}konomischen Fragebogen aus, in dem Alter, Geschlecht, Familienstand, Schulabschluss und das Haushaltsnettoeinkommen ber{\"u}cksichtigt wurden. In zahlreichen, im Diskussionsteil bereits erw{\"a}hnten Studien wurde eine Mehrbelastung der Eltern festgestellt. In der vorliegenden Arbeit wurden dar{\"u}ber hinaus die konkreten Auswirkungen dieser bereits festgestellten Mehrbelastung auf den Gesundheitszustand und das berufliche Umfeld untersucht. Die Untersuchung dieser Auswirkungen auf das allt{\"a}gliche Leben der betroffenen Eltern geriet bislang kaum in den Fokus wissenschaftlicher Arbeiten. Um zuk{\"u}nftig betroffene Familien gezielter in unterschiedlichen Lebensbereichen unterst{\"u}tzen zu k{\"o}nnen ist es jedoch von eminenter Bedeutung, diese Auswirkungen zu kennen und besser zu verstehen. In den Ergebnissen konnte konkret gezeigt werden, dass bez{\"u}glich der Hypothese 1 die Anwesenheit eines ADHS-Kindes innerhalb einer Familie den Gesundheitszustand der Eltern laut Selbsturteil im EQ-5D signifikant beeinflusst. Im Rahmen der beruflichen Belastung war feststellbar, dass ein ADHS-Kind sich signifikant auf die physische Konstitution laut WLQ der Eltern auswirkt. Die Untersuchung der Hypothese II ergab, dass eine m{\"o}gliche eigene ADHS-Symptomatik in der Kindheit sich auf unterschiedliche Dimensionen im beruflichen Umfeld auswirkt, jedoch nicht signifikant auf den individuellen Gesundheitszustand. V{\"a}ter und M{\"u}tter, die selbst in ihrer Kindheit ADHS-Symptome angaben, geben eine signifikante Beeintr{\"a}chtigung bez{\"u}glich der mentalen F{\"a}higkeiten, des Zeitmanagements und der allgemeinen Arbeitsproduktivit{\"a}t laut Selbsteinsch{\"a}tzung im WLQ an. Eine physische Einschr{\"a}nkung am Arbeitsplatz laut WLQ war bei den V{\"a}tern signifikant feststellbar, nicht jedoch bei den M{\"u}ttern. Die Ergebnisse der Hypothese III ergaben, dass bez{\"u}glich der Arbeitsf{\"a}higkeit bereits bei einem oder mehr Kindern mit ADHS die kognitiven F{\"a}higkeiten der Eltern am Arbeitsplatz laut WLQ beeintr{\"a}chtigt sind. Gleichermaßen wird die Arbeitsproduktivit{\"a}t bereits bei einem oder mehr von ADHS betroffenen Kindern signifikant beeinflusst. Auf die physische Konstitution der Eltern laut Selbsteinsch{\"a}tzung im WLQ haben ein oder auch mehrere von ADHS betroffene Kinder jedoch keinen signifikanten Einfluss. Die zeitliche Organisation der Eltern am Arbeitsplatz laut WLQ ist folglich bei einem Kind mit ADHS noch nicht signifikant beeintr{\"a}chtigt, wohl aber, wenn mehr als ein Kind betroffen ist. Ebenso ist der Gesundheitszustand der Eltern laut EQ-5D erst ab zwei betroffenen Kindern in einer Familie durch diesen Umstand beeinflusst. Zusammenfassend l{\"a}sst sich also feststellen, dass durch die Anwesenheit eines Kindes mit ADHS in einer Familie eher der Gesundheitszustand der Eltern signifikant beeinflusst wird, wohingegen die eigene ADHS-Symptomatik der Eltern in der Kindheit viel mehr zu einer signifikanten und mehrdimensionalen Beeintr{\"a}chtigung am Arbeitsplatz f{\"u}hrt. Diese Erkenntnis zeigt, dass die eigene ADHS-Symptomatik der Eltern in der Kindheit neben der Anwesenheit eines ADHS - Kindes nicht unerhebliche Auswirkungen auf die allt{\"a}glichen Aufgaben der Betroffenen hat. Die Erkenntnis dieser neuen Zusammenh{\"a}nge sollte in zuk{\"u}nftigen Forschungsvorhaben ber{\"u}cksichtigt werden.}, subject = {Aufmerksamkeitsdefizit-Syndrom}, language = {de} } @article{NeufangAkhrifHerrmannetal.2016, author = {Neufang, S. and Akhrif, A. and Herrmann, C.G. and Drepper, C. and Homola, G.A. and Nowak, J. and Waider, J. and Schmitt, A.G. and Lesch, K.-P. and Romanos, M.}, title = {Serotonergic modulation of 'waiting impulsivity' is mediated by the impulsivity phenotype in humans}, series = {Translational Psychiatry}, journal = {Translational Psychiatry}, number = {6}, doi = {10.1038/tp.2016.210}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164418}, pages = {e940}, year = {2016}, abstract = {In rodents, the five-choice serial reaction time task (5-CSRTT) has been established as a reliable measure of waiting impulsivity being defined as the ability to regulate a response in anticipation of reinforcement. Key brain structures are the nucleus accumbens (NAcc) and prefrontal regions (for example, pre- and infralimbic cortex), which are, together with other transmitters, modulated by serotonin. In this functional magnetic resonance imaging study, we examined 103 healthy males while performing the 5-CSRTT measuring brain activation in humans by means of a paradigm that has been widely applied in rodents. Subjects were genotyped for the tryptophan hydroxylase-2 (TPH2; G-703T; rs4570625) variant, an enzyme specific for brain serotonin synthesis. We addressed neural activation patterns of waiting impulsivity and the interaction between the NAcc and the ventromedial prefrontal cortex (vmPFC) using dynamic causal modeling. Genetic influence was examined via interaction analyses between the TPH2 genotype (GG homozygotes vs T allele carriers) and the degree of impulsivity as measured by the 5-CSRTT. We found that the driving input of the vmPFC was reduced in highly impulsive T allele carriers (reflecting a reduced top-down control) in combination with an enhanced response in the NAcc after correct target processing (reflecting an augmented response to monetary reward). Taken together, we found a high overlap of our findings with reports from animal studies in regard to the underlying cognitive processes, the brain regions associated with waiting impulsivity and the neural interplay between the NAcc and vmPFC. Therefore, we conclude that the 5-CSRTT is a promising tool for translational studies.}, language = {en} } @article{NeuhoffBruderBartlingetal.2012, author = {Neuhoff, Nina and Bruder, Jennifer and Bartling, J{\"u}rgen and Warnke, Andreas and Remschmidt, Helmut and M{\"u}ller-Myhsok, Bertram and Schulte-K{\"o}rne, Gerd}, title = {Evidence for the Late MMN as a Neurophysiological Endophenotype for Dyslexia}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {5}, doi = {10.1371/journal.pone.0034909}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133686}, pages = {e34909}, year = {2012}, abstract = {Dyslexia affects 5-10\% of school-aged children and is therefore one of the most common learning disorders. Research on auditory event related potentials (AERP), particularly the mismatch negativity (MMN) component, has revealed anomalies in individuals with dyslexia to speech stimuli. Furthermore, candidate genes for this disorder were found through molecular genetic studies. A current challenge for dyslexia research is to understand the interaction between molecular genetics and brain function, and to promote the identification of relevant endophenotypes for dyslexia. The present study examines MMN, a neurophysiological correlate of speech perception, and its potential as an endophenotype for dyslexia in three groups of children. The first group of children was clinically diagnosed with dyslexia, whereas the second group of children was comprised of their siblings who had average reading and spelling skills and were therefore "unaffected'' despite having a genetic risk for dyslexia. The third group consisted of control children who were not related to the other groups and were also unaffected. In total, 225 children were included in the study. All children showed clear MMN activity to/da/-/ba/ contrasts that could be separated into three distinct MMN components. Whilst the first two MMN components did not differentiate the groups, the late MMN component (300-700 ms) revealed significant group differences. The mean area of the late MMN was attenuated in both the dyslexic children and their unaffected siblings in comparison to the control children. This finding is indicative of analogous alterations of neurophysiological processes in children with dyslexia and those with a genetic risk for dyslexia, without a manifestation of the disorder. The present results therefore further suggest that the late MMN might be a potential endophenotype for dyslexia.}, language = {en} } @phdthesis{Neumann2017, author = {Neumann, Maria Johanna}, title = {Chronische Effekte von Methylphenidat auf die Riechfunktion von Kindern mit Aufmerksamkeitsdefizit-/Hyperaktivit{\"a}tsst{\"o}rung}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150795}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Bei der Aufmerksamkeitsdefizit-/ Hyperaktivit{\"a}tsst{\"o}rung (ADHS) handelt es sich um ein weltweit verbreitetes St{\"o}rungsbild mit Beginn in der Kindheit, das sich anhand der Symptome Unaufmerksamkeit, Impulsivit{\"a}t und Hyperaktivit{\"a}t manifestiert. Ein Fortbestehen der St{\"o}rung in das Jugend- und Erwachsenenalter ist nicht selten. Die Auswirkungen sind dabei vielf{\"a}ltig und f{\"u}hren bei fehlender Behandlung zu psychosozialen Beeintr{\"a}chtigungen der Betroffenen. Obwohl ADHS mittels multimodaler Therapie behandelbar ist, werden die Diagnose und vor allem die medikament{\"o}se Behandlung weiterhin kontrovers diskutiert. Bei einer zu Grunde liegenden komplexen, multifaktoriellen Genese der St{\"o}rung ist die Erforschung objektiver Diagnosekriterien, wie es zum Beispiel Biomarker sein k{\"o}nnten, in den Fokus der Forschung ger{\"u}ckt. F{\"u}r andere neurologische und psychiatrische Erkrankungen, wie zum Beispiel Morbus Parkinson, ist eine Ver{\"a}nderung der Geruchsfunktion bekannt. Auch f{\"u}r die ADHS existieren Studien, die sich mit der Geruchsleistung von Patienten befassen. Eine verbesserte Geruchsensitivit{\"a}t bei Kindern mit ADHS ohne Medikation konnte bereits gezeigt werden. Mit Methylphenidat (MPH) behandelte Patienten zeigten aber keine Verbesserung in der Geruchsleistung. Daher ist es Gegenstand dieser Studie die Geruchsfunktion f{\"u}r die Leistungen Sensitivit{\"a}t (Schwellenwahrnehmung eines Geruchs), Diskrimination (Unterscheidung zweier Ger{\"u}che) und Identifikation (Erkennen und Benennen von Ger{\"u}chen) bei ADHS- Patienten zu untersuchen, sowie verschiedene Medikationsstatus zu ber{\"u}cksichtigen. Die Geruchsleistung wurde mittels Sniffin´ Sticks, einer klinischen Geruchstestungsbatterie zur Erhebung der genannten Parameter, durchgef{\"u}hrt. Eingeschlossen wurden 112 Kinder zwischen 6 und 12 Jahren mit ADHS sowie 86 Kontrollprobanden zwischen 6 und 12 Jahren. Die Patienten wurden eingeteilt in solche, die noch nie Stimulanzienmedikation erhalten hatten (medikationsnaiv), solche, die aktuell MPH erhielten und solche, die ihre Medikation zu unterschiedlichen Zeitpunkten abgesetzt hatten (vor maximal 6 Tagen, vor maximal 31 Tagen, vor mehr als 30 Tagen). Es konnte eine signifikant bessere Sensitivit{\"a}tsleistung bei Patienten, welche ihre Medikation l{\"a}nger als 30 Tage abgesetzt hatten, im Vergleich zu Kontrollprobanden und allen medizierten Patienten gezeigt werden. Des Weiteren konnte eine verbesserte Sensitivit{\"a}tsleistung bei ADHS-Patienten, welche ihre Medikation seit einem l{\"a}ngeren Zeitraum abgesetzt hatten, im Vergleich zu Kontrollprobanden gefunden werden. Dies ist ein Hinweis f{\"u}r eine m{\"o}gliche Anpassung der Sensitvit{\"a}tsleistung an das urspr{\"u}nglich verbesserte Niveau nach einer gewissen Medikationskarenz. Bei der ADHS liegt unter anderem eine dopaminerge Dysregulation als krankheitsurs{\"a}chlich zu Grunde. Aufgrund eines erh{\"o}hten dopaminergen Tonus beim AHDS in mesolimbischen Bereichen k{\"o}nnte es zu einer verminderten Proliferation von adulten Stammzellen und somit zur Verminderung der Anzahl nachr{\"u}ckender Interneurone, mit daraus resultierender verbesserter Geruchsfunktion bei geringerer dopaminerger Hemmung kommen. F{\"u}r die Auswirkung der unterschiedlichen Absetzzeitr{\"a}ume auf die Sensitivit{\"a}tsleistung k{\"o}nnten kurzfristige Mechanismen, wie eine Erh{\"o}hung der Durchblutung, und langfristige Mechanismen, die sich durch Ver{\"a}nderungen von Rezeptorprofilen ergeben, bei MPH-Einnahme verantwortlich sein. F{\"u}r die Diskriminationsleistung ergab sich in dieser Arbeit eine Verbesserung allein in der medikationsnaiven Patientengruppe, jedoch nur unter Ber{\"u}cksichtigung potentieller Einflussfaktoren wie IQ, Alter und Geschlecht. Daher m{\"u}ssen diese Erkenntnisse mit Vorsicht interpretiert werden. Auch im Fall der verbesserten Diskriminationsleistung gibt es Hinweise, dass eine ver{\"a}nderte Stammzellproliferation verantwortlich sein k{\"o}nnte. Bez{\"u}glich der Identifikationsleistung ergab sich in der vorliegenden Arbeit eine Verschlechterung der Leistung allein in der Patientengruppe, welche ihre Medikation seit kurzem abgesetzt hatte. Im Gegensatz zur Sensitivit{\"a}t unterliegen Diskrimination und Identifikation noch weiterer zentraler Prozessierung zum Beispiel im orbitofrontalen Kortex. Die Zusammenh{\"a}nge sind hier also komplexer. Dennoch unterliegt auch der Hippocampus adulter Neurogenese, so dass Zusammenh{\"a}nge zwischen dopaminerger Dysregulation und Identifikationsleistung diskutiert werden k{\"o}nnen. Die Erkenntnisse der vorliegenden Studie sind ein weiterer Schritt in der Etablierung der Sensitvit{\"a}tsleistung als Biomarker f{\"u}r ADHS im Kindesalter. Weitere bildgebende Studien k{\"o}nnten die Erkenntnisse erweitern beziehungsweise die genauen Hintergr{\"u}nde bez{\"u}glich Diskriminations- und Identifikationsleistung verifizieren. Methodische Unterschiede scheinen f{\"u}r die heterogene Studienlage bez{\"u}glich Diskriminations- und Identifikationsleistung verantwortlich.}, subject = {Geruchsschwelle}, language = {de} } @article{OezkurMagyarThomasetal.2018, author = {Oezkur, Mehmet and Magyar, Atilla and Thomas, Phillip and Reif, Andreas and St{\"o}rk, Stefan and Heuschmann, Peter U. and Leyh, Rainer G. and Wagner, Martin}, title = {The COMT-polymorphism is not associated with the incidence of acute kidney injury after cardiac surgery - a prospective cohort study}, series = {BMC Nephrology}, volume = {19}, journal = {BMC Nephrology}, number = {34}, doi = {10.1186/s12882-018-0820-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175529}, year = {2018}, abstract = {Background: The Catechol-O-methyltransferase (COMT) represents the key enzyme in catecholamine degradation. Recent studies suggest that the COMT rs4680 polymorphism is associated with the response to endogenous and exogenous catecholamines. There are, however, conflicting data regarding the COMT Met/Met phenotype being associated with an increased risk of acute kidney injury (AKI) after cardiac surgery. The aim of the current study is to prospectively investigate the impact of the COMT rs4680 polymorphism on the incidence of AKI in patients undergoing cardiac surgery. Methods: In this prospective single center cohort study consecutive patients hospitalized for elective cardiac surgery including cardiopulmonary-bypass (CPB) were screened for participation. Demographic clinical data, blood, urine and tissue samples were collected at predefined time points throughout the clinical stay. AKI was defined according to recent recommendations of the Kidney Disease Improving Global Outcome (KDIGO) group. Genetic analysis was performed after patient enrolment was completed. Results: Between April and December 2014, 150 patients were recruited. The COMT genotypes were distributed as follows: Val/Met 48.7\%, Met/Met 29.3\%, Val/Val 21.3\%. No significant differences were found for demography, comorbidities, or operative strategy according to the underlying COMT genotype. AKI occurred in 35 patients (23.5\%) of the total cohort, and no differences were evident between the COMT genotypes (20.5\% Met/Met, 24.7\% Val/Met, 25.0\% Val/Val, p = 0.66). There were also no differences in the post-operative period, including ICU or in-hospital stay. Conclusions: We did not find statistically significant variations in the risk for postoperative AKI, length of ICU or in-hospital stay according to the underlying COMT genotype.}, language = {en} } @article{PalladinoChiocchettiFranketal.2020, author = {Palladino, Viola Stella and Chiocchetti, Andreas G. and Frank, Lukas and Haslinger, Denise and McNeill, Rhiannon and Radtke, Franziska and Till, Andreas and Haupt, Simone and Br{\"u}stle, Oliver and G{\"u}nther, Katharina and Edenhofer, Frank and Hoffmann, Per and Reif, Andreas and Kittel-Schneider, Sarah}, title = {Energy metabolism disturbances in cell models of PARK2 CNV carriers with ADHD}, series = {Journal of Clinical Medicine}, volume = {9}, journal = {Journal of Clinical Medicine}, number = {12}, issn = {2077-0383}, doi = {10.3390/jcm9124092}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220074}, year = {2020}, abstract = {The main goal of the present study was the identification of cellular phenotypes in attention-deficit-/hyperactivity disorder (ADHD) patient-derived cellular models from carriers of rare copy number variants (CNVs) in the PARK2 locus that have been previously associated with ADHD. Human-derived fibroblasts (HDF) were cultured and human-induced pluripotent stem cells (hiPSC) were reprogrammed and differentiated into dopaminergic neuronal cells (mDANs). A series of assays in baseline condition and in different stress paradigms (nutrient deprivation, carbonyl cyanide m-chlorophenyl hydrazine (CCCP)) focusing on mitochondrial function and energy metabolism (ATP production, basal oxygen consumption rates, reactive oxygen species (ROS) abundance) were performed and changes in mitochondrial network morphology evaluated. We found changes in PARK2 CNV deletion and duplication carriers with ADHD in PARK2 gene and protein expression, ATP production and basal oxygen consumption rates compared to healthy and ADHD wildtype control cell lines, partly differing between HDF and mDANs and to some extent enhanced in stress paradigms. The generation of ROS was not influenced by the genotype. Our preliminary work suggests an energy impairment in HDF and mDAN cells of PARK2 CNV deletion and duplication carriers with ADHD. The energy impairment could be associated with the role of PARK2 dysregulation in mitochondrial dynamics.}, language = {en} } @phdthesis{Peters2023, author = {Peters, Katharina}, title = {Biological Substrates of Waiting Impulsivity in Children and Adolescents with and without ADHD}, doi = {10.25972/OPUS-24636}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246368}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Focus of the present work were the questions whether and how the concept of waiting impulsivity (WI), defined as the ability to regulate a response in anticipation of reward and measured by the 4-choice serial reaction time task (4-CSRTT), may contribute to our understanding of Attention-Deficit/Hyperactivity Disorder (ADHD) and its neurobiological underpinnings. To address this topic, two studies were conducted: in a first study, the relationship be-tween 4-CSRTT behavioral measures, neural correlates and ADHD symptom domains, i.e. inattention (IA) and hyperactivity/impulsivity (H/I) was explored in a pooled sample of 90 children and adolescents with (n=44) and without (n=46) ADHD diagnosis. As ex-pected, IA was associated with dorsolateral prefrontal brain regions linked with executive functions and attentional control, which was evident on the structural and the functional level. Higher levels of both IA and H/I covaried with decreased activity in the right ven-trolateral prefrontal cortex (PFC), a central structure for response inhibition. Moderation analyses revealed that H/I-related decreased activation in this region did not map linearly on difficulties on the behavioral level: brain activation was a significant predictor of task accuracy only, when H/I symptoms were low/absent but not for clinically relevant ADHD symptoms. Further, H/I was implicated in dysfunctional top-down control of reward eval-uation. Both symptom domains correlated positively with hippocampus (HC) activity in anticipation of reward. In addition, for high H/I symptoms, greater activation in the HC was found to correlate with higher motivation on the behavioral level, indicating that rein-forcement-learning and/or contingency awareness may contribute to altered reward pro-cessing in ADHD patients. In a second study, the possible serotonergic modulation of WI and the ADHD-WI relation-ship was addressed in a sub-sample comprising 86 children and adolescents of study I. The effects of a functional variant in the gene coding for the rate-limiting enzyme in the synthesis of brain serotonin on behavior and structure or function of the WI-network was investigated. Moderation analyses revealed that on the behavioral level, a negative corre-lation between accuracy and IA was found only in GG-homozygotes, whereas no signifi-cant relationship emerged for carriers of the T-allele. This is in line with previous reports of differential effects of serotonergic modulation on attentional performance depending on the presence of ADHD symptoms. A trend-wise interaction effect of genotype and IA for regional volume of the right middle frontal gyrus was interpreted as a hint towards an involvement of the PFC in this relationship, although a more complex mechanism includ-ing developmental effects can be assumed. In addition, interaction effects of genotype and IA were found for brain activation in the amygdala (AMY) und HC during perfor-mance of the 4-CSRTT, while another interaction was found for H/I symptoms and geno-type for right AMY volume. These findings indicate a serotonergic modulation of coding of the emotional value of reward during performance of the 4-CSRTT that varies de-pending on the extent of psychopathology-associated traits. Taken together, it was shown that the 4-CSRTT taps distinct domains of impulsivity with relevance to ADHD symptomatology: (proactive) response inhibition difficulties in relation with anticipation of reward. Furthermore, the two symptom domains, IA and H/I, contrib-ute differently to WI, which emphasizes the need to distinguish both in the research of ADHD. The results of study II emphasized the relevance of serotonergic transmission especially for attentional control and emotional processing. Although the present findings need replication and further refinement in more homogenous age groups, the use of the 4-CSRTT with a dimensional approach is a very promising strategy, which will hopefully extend our understanding of impulsivity-related mental disorders in the future.}, subject = {Aufmerksamkeitsdefizit-Syndrom}, language = {en} } @article{PlumEggersHellingetal.2020, author = {Plum, Sarah and Eggers, Britta and Helling, Stefan and Stepath, Markus and Theiss, Carsten and Leite, Renata E. P. and Molina, Mariana and Grinberg, Lea T. and Riederer, Peter and Gerlach, Manfred and May, Caroline and Marcus, Katrin}, title = {Proteomic characterization of synaptosomes from human substantia nigra indicates altered mitochondrial translation in Parkinson's disease}, series = {Cells}, volume = {9}, journal = {Cells}, number = {12}, issn = {2073-4409}, doi = {10.3390/cells9122580}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219978}, year = {2020}, abstract = {The pathological hallmark of Parkinson's disease (PD) is the loss of neuromelanin-containing dopaminergic neurons within the substantia nigra pars compacta (SNpc). Additionally, numerous studies indicate an altered synaptic function during disease progression. To gain new insights into the molecular processes underlying the alteration of synaptic function in PD, a proteomic study was performed. Therefore, synaptosomes were isolated by density gradient centrifugation from SNpc tissue of individuals at advanced PD stages (N = 5) as well as control subjects free of pathology (N = 5) followed by mass spectrometry-based analysis. In total, 362 proteins were identified and assigned to the synaptosomal core proteome. This core proteome comprised all proteins expressed within the synapses without regard to data analysis software, gender, age, or disease. The differential analysis between control subjects and PD cases revealed that CD9 antigen was overrepresented and fourteen proteins, among them Thymidine kinase 2 (TK2), mitochondrial, 39S ribosomal protein L37, neurolysin, and Methionine-tRNA ligase (MARS2) were underrepresented in PD suggesting an alteration in mitochondrial translation within synaptosomes.}, language = {en} } @phdthesis{Pollerhoff2024, author = {Pollerhoff, Lena Katharina}, title = {Age differences in prosociality across the adult lifespan: Insights from self-reports, experimental paradigms, and meta-analyses}, doi = {10.25972/OPUS-35944}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-359445}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {Human prosociality, encompassing generosity, cooperation, and volunteering, holds a vital role in our daily lives. Over the last decades, the question of whether prosociality undergoes changes over the adult lifespan has gained increased research attention. Earlier studies suggested increased prosociality in older compared to younger individuals. However, recent meta-analyses revealed that this age effect might be heterogeneous and modest. Moreover, the contributing factors and mechanisms behind these age-related variations remain to be identified. To unravel age-related differences in prosociality, the first study of this dissertation employed a meta-analytical approach to summarize existing findings and provide insight into their heterogeneity by exploring linear and quadratic age effects on self-reported and behavioral prosociality. Additionally, two empirical research studies investigated whether these age-related differences in prosociality were observed in real life, assessed through ecological momentary assessment (Study 2), and in a controlled laboratory setting by applying a modified dictator game (Study 3). Throughout these three studies, potential underlying behavioral and computational mechanisms were explored. The outcome of the meta-analysis (Study 1) revealed small linear age effects on prosociality and significant age group differences between younger and older adults, with higher levels of prosociality in older adults. Explorative evidence emerged in favor of a quadratic age effect on behavioral prosociality, indicating the highest levels in midlife. Additionally, heightened prosocial behavior among middle-aged adults was observed compared to younger adults, whereas no significant differences in prosocial behavior were noted between middle-aged and older adults. Situational and contextual features, such as the setting of the study and specific paradigm characteristics, moderated the age-prosociality relationship, highlighting the importance of the (social) context when studying prosociality. For Study 2, no significant age effect on real-life prosocial behavior was observed. However, evidence for a significant linear and quadratic age effect on experiencing empathy in real life emerged, indicating a midlife peak. Additionally, across all age groups, the link between an opportunity to empathize and age significantly predicted real-life prosocial behavior. This effect, indicating higher levels of prosocial behavior when there was a situation possibly evoking empathy, was most pronounced in midlife. Study 3 presented age differences in how older and younger adults integrate values related to monetary gains for self and others to make a potential prosocial decision. Younger individuals effectively combined both values in a multiplicative fashion, enhancing decision-making efficiency. Older adults showed an additive effect of values for self and other and displayed increased decision-making efficiency when considering the values separately. However, among older adults, individuals with better inhibitory control were better able to integrate information about both values in their decisions. Taken together, the findings of this dissertation offer new insights into the multi-faceted nature of prosociality across adulthood and the mechanisms that help explain these age-related disparities. While this dissertation observed increasing prosociality across the adult lifespan, it also questions the assumption that older adults are inherently more prosocial. The studies highlight midlife as a potential peak period in social development but also emphasize the importance of the (social) context and that different operationalizations might capture distinct facets of prosociality. This underpins the need for a comprehensive framework to understand age effects of prosociality better and guide potential interventions.}, subject = {Altersunterschied}, language = {en} } @phdthesis{Popp2017, author = {Popp, Hanna Margitta}, title = {Ver{\"a}nderung der Emotionsverarbeitung depressiver Patienten - eine EEG-Studie -}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-155211}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {In der vorliegenden Studie soll die Ver{\"a}nderung emotionaler Verarbeitung depressiver Patienten im Vergleich zu einer gesunden Kontrollgruppe untersucht werden. Als Messinstrument dient uns das EEG, welches als eine nicht invasive, sensitive Methode, die Ver{\"a}nderung der emotionalen Reaktion mittels EKPs darstellbar macht. So soll in dieser Studie ein Paradigma entwickelt werden, welches die Ver{\"a}nderung der emotionalen Verarbeitung von depressiven Patienten erfassen kann, um zuk{\"u}nftig die Effektivit{\"a}t von Psychotherapie anhand objektivierbarer Maße zu evaluieren.}, subject = {Elektroencephalogramm}, language = {de} } @phdthesis{Posch2022, author = {Posch, Ines Juliane}, title = {Die retrospektive Beurteilung station{\"a}rer kinder- und jugendpsychiatrischer Behandlung nach 10 Jahren - Eine Nachbefragung ehemaliger Patienten der Klinik f{\"u}r Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie des Universit{\"a}tsklinikums W{\"u}rzburg}, doi = {10.25972/OPUS-28313}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-283135}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Fragestellung: P{\"a}dagogische und medizinische Institutionen betreuen Kinder und Jugendliche, um Aufsicht, Beschulung, Erziehung, Therapie und Schutz sicherzustellen. Gleichwohl sind Kinder in institutioneller Betreuung potentiellen Gef{\"a}hrdungsmomenten bez{\"u}glich Misshandlung und Missbrauch ausgesetzt. Methodik: Im Rahmen der Etablierung des Schutzkonzeptes der Klinik f{\"u}r Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie am Universit{\"a}tsklinikum W{\"u}rzburg wurde eine retrospektive Patientenbefragung durchgef{\"u}hrt. Das Untersuchungskollektiv bildeten alle ehemaligen station{\"a}ren Patientinnen und Patienten der Jahre 2006 und 2007, die zum Katamnesezeitpunkt vollj{\"a}hrig waren. Die Befragung erfolgte postalisch. Der Fragebogen umfasste neben Items zum Kontext von Gewalterfahrungen etablierte Skalen zur Erfassung von Behandlungszufriedenheit und Lebensqualit{\"a}t (FBB-K, WHO-BREF). Ergebnisse: Von 568 ehemaligen Patientinnen und Patienten gaben 87 (15.3 \%) eine g{\"u}ltige R{\"u}ckantwort (59 weiblich, durchschnittliches Alter zum Befragungszeitpunkt: 24.5 Jahre). 35 ehemalige Patientinnen und Patienten (40.2 \% der Teilnehmenden) gaben an, Gewalt w{\"a}hrend der station{\"a}ren Behandlung erlebt (n=26) oder erlebt und ausge{\"u}bt (n=7) oder ausschließlich ausge{\"u}bt (n=2) zu haben. Gewalterfahrungen beinhalteten in den meisten F{\"a}llen emotionale Gewalt (34.5 \%), aber auch k{\"o}rperliche (5.7 \%) und sexuelle Gewalt (10.3 \%). Schlussfolgerung: Es zeigt sich ein signifikanter Zusammenhang zwischen Gewalterfahrungen einerseits sowie retrospektiver Behandlungszufriedenheit und aktueller Lebensqualit{\"a}t andererseits. Die Ergebnisse der Befragung unterstreichen die Bedeutung der Etablierung von Schutzkonzepten in Kliniken und anderen Institutionen.}, subject = {Kinder- und Jugendpsychiatrie}, language = {de} } @phdthesis{PreussWiedenhoff2017, author = {Preuß-Wiedenhoff, Andrea}, title = {Therapeutisches Drug Monitoring bei an Schizophrenie erkrankten Kindern und Jugendlichen unter Pharmakotherapie mit Risperidon}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-156176}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Ziel: Das Ziel dieser retrospektiven, naturalistischen Studie ist zum einen die Untersuchung der Zusammenh{\"a}nge von Dosierung und Serumkonzentration, Serumkonzentration und Therapieeffekt sowie von Serumkonzentration und unerw{\"u}nschten Arzneimittel-Wirkungen (UAW) bei an Schizophrenie erkrankten Kindern und Jugendlichen unter Risperidon-Therapie. Zum anderen soll die Anwendbarkeit des therapeutischen Serumkonzentrations-Referenzbereichs von Erwachsenen f{\"u}r Kinder und Jugendliche untersucht werden. Methode: Die von mehreren Kliniken in den Jahren 2005 - 2009 erhobenen Daten von 40 Kindern und Jugendlichen, die mittels des Therapeutischen Drug Monitorings {\"u}berwacht wurden, wurden retrospektiv ausgewertet. Die gemessenen Serumkonzentrationen erfolgten im Steady State und beziehen sich auf die Summe von Risperidon und 9-hydroxy-Risperidon (aktive Menge). Die Beurteilung der Therapieeffekte erfolgte mittels der CGI-C-Unterskala (Clinical Global Impression of Change), die der UAW mithilfe der UKU-Skala (Udvalg for Kliniske Unders{\o}gelser). Ergebnis und Fazit: Es zeigt sich eine signifikante, positive Korrelation zwischen der Tagesdosierung und der Serumkonzentration und keine signifikante Korrelation zwischen der Serumkonzentration und dem Therapieeffekt bzw. den UAW. Die Ergebnisse dieser Arbeit liefern erste Hinweise f{\"u}r einen m{\"o}glicherweise niedrigeren therapeutischen Referenzbereich f{\"u}r an Schizophrenie erkrankten Kindern und Jugendlichen unter Risperidon-Behandlung. Aufgrund der Limitationen des naturalistischen Studiendesigns ist der vorgeschlagene Referenzbereich eine richtungsweisende Empfehlung. Weitere Studien mit gr{\"o}ßeren Stichprobenzahlen sind n{\"o}tig um diese Ergebnisse zu validieren.}, subject = {Arzneimittel{\"u}berwachung}, language = {de} } @phdthesis{Reefschlaeger2018, author = {Reefschl{\"a}ger, Lennart Gunnar}, title = {Expressionsanalysen monoaminerger Kandidatengene bei der Aufmerksamkeitsdefizit-/Hyperaktivit{\"a}tsst{\"o}rung und Autismusspektrumsst{\"o}rung}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162371}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Objectives. In absence of objective clinical characteristics the identification of peripheral biomarkers in neuropsychiatric disorders is highly relevant for the diagnostic process and an individualized therapy. We analyzed mRNA-expression of monoaminergic candidate genes (DRD4, DRD5, TPH1) in peripheral tissue of patients with attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD), highly comorbid with ADHD, searching for possible molecular markers for these disorders. Methods. mRNA was obtained from children and adolescents with ADHD (n = 51) and ASD (n = 26), diagnosed according to ICD-10 criteria, as well as healthy controls (n = 39). mRNA expression was determined via quantitative realtime PCR (qRT-PCR) from whole blood cells. Results. The concentrations of DRD4-mRNA in the whole blood were significantly lower in ADHD and ASD children (19 of 26 comorbid with ADHD) compared to healthy controls. ASD patients revealed a significantly decreased DRD5 mRNA expression in comparison to the two other groups. Conclusions. Alterations in mRNA expression patterns provide further evidence for a relevant effect of the respective candidate genes in the pathophysiology of ADHD. Given their potential as biomarkers mRNA expression patterns may be useful tools in (differential-) diagnostic procedures of ADHD and ASD. Future studies may determine the sensitivity and specificity of these putative biomarkers in larger samples including further neuropsychiatric diagnoses.}, language = {de} } @phdthesis{Renner2007, author = {Renner, Tobias Johann}, title = {Die Nogo-Anteriorisierung bei gesunden und zwangserkrankten Kindern und Jugendlichen}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-22778}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2007}, abstract = {In der vorliegenden Studie wurden erstmals Kinder und Jugendliche mit Zwangsst{\"o}rungen in Hinblick auf eine ver{\"a}nderte Aktivierung von anteriorem cingul{\"a}rem Cortex (ACC) und pr{\"a}frontalen Arealen elektrophysiologisch untersucht. Zur Durchf{\"u}hrung der Studie wurde als Paradigma ein cued Continuous Performance Test (cCPT) mit Aufgabenstellung zu Exekution und Inhibition vorbereiteter motorischer Reaktionen gew{\"a}hlt. In der Auswertung der Daten lag ein besonderer Schwerpunkt auf der Nogo-Anteriorisierung (NGA), die in der topographischen Analyse des ereigniskorrelierten Potentials P300 speziell die Aktivierung von ACC und pr{\"a}frontalen Arealen erfasst. Um Vergleichswerte von gesunden Kindern und Jugendlichen zu erhalten und zugleich die NGA als elektrophysiologischen Parameter f{\"u}r das Kindes- und Jugendalter in Hinblick auf Auftreten und Beeinflussung durch Alter und Geschlecht zu validieren, wurden gesunde Probanden im Alter von 10 bis 17 Jahren mit einem ausgewogenem Verh{\"a}ltnis der Geschlechter mit dem identischen Studiensetting untersucht. Dabei konnte erstmals f{\"u}r ein kontinuierliches Altersspektrum f{\"u}r Kinder und Jugendliche gezeigt werden, dass die NGA bei {\"a}lteren Kindern und Jugendlichen als stabiler elektrophysiologischer Parameter auftritt und zur Untersuchung von hirnelektrischer Aktivierung bei psychiatrisch erkrankten Kindern und Jugendlichen qualifiziert. In {\"U}bereinstimmung mit den Daten von Erwachsenen ergab sich kein geschlechtsspezifischer Einfluss; auch die mit dem Lebensalter zunehmende Frontalisierung der hirnelektrischen Aktivierung konnte f{\"u}r Kinder und Jugendliche nachvollzogen werden. Die Ergebnisse f{\"u}r j{\"u}ngere Kinder, die nicht durchg{\"a}ngig eine NGA aufweisen, sind kongruent zu Vorbefunden und k{\"o}nnten einen Hinweis auf eine entwicklungsabh{\"a}ngige Ausbildung der NGA sein. Der Vergleich der Daten von Kindern und Jugendlichen mit Zwangsst{\"o}rungen mit gesunden Gleichaltrigen zeigte keine signifikanten Unterschiede in der Auspr{\"a}gung der NGA, die Hypothese einer differierenden Aktivierung von ACC und pr{\"a}frontalen Arealen ist demnach nicht best{\"a}tigt. Unterschiede ergaben sich in den Verhaltensdaten, hier wiesen die Kinder und Jugendlichen mit Zwangsst{\"o}rungen mehr falsche positive Fehler auf. Ebenfalls ver{\"a}ndert war die Latenz der P300 f{\"u}r die Bedingung Go, die f{\"u}r die Patientengruppe verl{\"a}ngert war. Aus diesen Daten ergeben sich Hinweise auf eine ver{\"a}nderte initiale Informationsverarbeitung bei Kindern und Jugendlichen mit Zwangsst{\"o}rungen in Aufgaben zu motorischer Reaktion. Eine weitere Schlussfolgerung dieser Studie geht aus den deutlichen Unterschieden zu den Daten von erwachsenen Probanden mit Zwangsst{\"o}rungen hervor. W{\"a}hrend bei den gesunden Kindern und Jugendlichen eine Entwicklung hin zu den Daten gesunder Erwachsener gezeigt werden konnte, weisen die differierenden Daten bei den Patienten mit Zwangsst{\"o}rungen auf abweichende neurophysiologische Abl{\"a}ufe hin, wodurch die Hypothese einer f{\"u}r das Kindes- und Jugendalter spezifischen Pathophysiologie bei Zwangsst{\"o}rungen gest{\"u}tzt und der weitere Bedarf an eigenst{\"a}ndigen Studien mit Kindern und Jugendlichen zu psychiatrischen Erkrankungen unterstrichen wird.}, language = {de} } @article{ReuterJaeckelsKneitzetal.2019, author = {Reuter, Isabel and J{\"a}ckels, Jana and Kneitz, Susanne and Kuper, Jochen and Lesch, Klaus-Peter and Lillesaar, Christina}, title = {Fgf3 is crucial for the generation of monoaminergic cerebrospinal fluid contacting cells in zebrafish}, series = {Biology Open}, volume = {8}, journal = {Biology Open}, doi = {10.1242/bio.040683}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200749}, pages = {bio040683}, year = {2019}, abstract = {In most vertebrates, including zebrafish, the hypothalamic serotonergic cerebrospinal fluid-contacting (CSF-c) cells constitute a prominent population. In contrast to the hindbrain serotonergic neurons, little is known about the development and function of these cells. Here, we identify fibroblast growth factor (Fgf)3 as the main Fgf ligand controlling the ontogeny of serotonergic CSF-c cells. We show that fgf3 positively regulates the number of serotonergic CSF-c cells, as well as a subset of dopaminergic and neuroendocrine cells in the posterior hypothalamus via control of proliferation and cell survival. Further, expression of the ETS-domain transcription factor etv5b is downregulated after fgf3 impairment. Previous findings identified etv5b as critical for the proliferation of serotonergic progenitors in the hypothalamus, and therefore we now suggest that Fgf3 acts via etv5b during early development to ultimately control the number of mature serotonergic CSF-c cells. Moreover, our analysis of the developing hypothalamic transcriptome shows that the expression of fgf3 is upregulated upon fgf3 loss-of-function, suggesting activation of a self-compensatory mechanism. Together, these results highlight Fgf3 in a novel context as part of a signalling pathway of critical importance for hypothalamic development.}, language = {en} } @phdthesis{Schaeff2021, author = {Schaeff, Sulamith}, title = {Correlates of Substantia Nigra Echogenicity in Healthy Children}, doi = {10.25972/OPUS-23074}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230747}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Objective: Substantia nigra hyperechogenicity is found in children with attention- deficit hyperactivity disorder (ADHD). Research with transcranial sonography (TCS) in adults suggests that echogenic alterations are linked to subclinical behavioral deficits and that brain iron homeostasis is involved in the signal genesis. The purpose of this study was to explore substantia nigra echogenicity in healthy children, to assess age-related changes and to investigate whether echogenic signals relate to subclinical alterations in behavior. Furthermore, associations of central nigral neuromelanin measures and peripheral serum iron parameters to echogenic signals of the substantia nigra were evaluated. Methods: In a multimodal study design, neuroimaging of the substantia nigra was conducted with TCS and neuromelanin-sensitive magnetic resonance imaging (MRI) in 28 healthy children (8 - 12 years). Correlations and multiple regression analyses determined associations between the neuroimaging methods, behavioral data from Strength and Difficulties Questionnaire (SDQ) and serum iron-related parameters. Results: Substantia nigra echogenicity correlated inversely with hyperactivity ratings in healthy, non-ADHD children (r = -.602, p = .001). Echogenic sizes did not change as a function of age. Neuromelanin-sensitive MRI measures of the substantia nigra and peripheral serum iron parameters were not associated with nigral TCS signals. Conclusion: In healthy children behavioral differences in hyperactive tendencies are associated with differences in substantia nigra echogenicity. This could help to identify those children who are at risk of subclinical ADHD.}, subject = {Substantia nigra}, language = {en} } @article{ScheinerDaunkeSeideletal.2023, author = {Scheiner, Christin and Daunke, Andrea and Seidel, Alexandra and Mittermeier, Sabrina and Romanos, Marcel and K{\"o}lch, Michael and Buerger, Arne}, title = {LessStress - how to reduce stress in school: evaluation of a universal stress prevention in schools: study protocol of a cluster-randomised controlled trial}, series = {Trials}, volume = {24}, journal = {Trials}, number = {1}, doi = {10.1186/s13063-022-06970-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300393}, year = {2023}, abstract = {Background Chronic stress is detrimental to health, and children and young people have had to cope with significantly more stress since the start of the COVID-19 pandemic. In particular, stress at school and in relation to learning is a major problem in this age group. Studies in Germany have indicated that the pandemic has led to a reduced quality of life (QoL) and an increased risk for psychiatric disorders in children and adolescents. Schools are an ideal setting for interventions against stress, which is one of the strongest predictors for the development of psychosocial problems. The present study seeks to address stress by means of a short prevention training programme in schools, including emotion regulation, mindfulness, and self-compassion. In addition to information material for self-study, students should have the opportunity to actively deal with the topic of stress and develop coping strategies within a short space of time. In contrast to very long stress reduction programmes that often last several weeks, the programme is delivered in just 90 min. Methods The effectiveness of the short and economical prevention programme LessStress will be examined in a cluster-randomised controlled trial (RCT) encompassing 1894 students. At several measurement time points, students from two groups (intervention and control) will be asked about their subjectively perceived stress levels, among other aspects. Due to the clustered nature of the data, mainly multilevel analyses will be performed. Discussion In Germany, there are no nationwide universal prevention programmes for students against stress in schools, and this gap has become more evident since the outbreak of the pandemic. Universal stress prevention in schools may be a starting point to promote resilience. By dealing with stress in a healthy way, mental health can be strengthened and maintained. Moreover, to reach at-risk students at an early stage, we advocate for a stronger networking between child psychiatry and schools.}, language = {en} } @article{ScheinerGrashoffKleindienstetal.2022, author = {Scheiner, Christin and Grashoff, Jan and Kleindienst, Nikolaus and Buerger, Arne}, title = {Mental disorders at the beginning of adolescence: Prevalence estimates in a sample aged 11-14 years}, series = {Public Health in Practice}, volume = {4}, journal = {Public Health in Practice}, doi = {10.1016/j.puhip.2022.100348}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300404}, year = {2022}, abstract = {Objectives This study aims to provide a deeper insight into mental disorders in early adolescence. We report prevalence rates (mental health problems, depressive symptoms, eating disorders, NSSI, STBs) to be used in future studies and clinical ventures. We also expected to find gender differences, with girls being be more affected than boys are. Study design 877 adolescents (M = 12.43, SD = 0.65) from seven German high schools completed a series of questionnaires assessing their mental health (SDQ, PHQ-9, SEED, DSHI-9, Paykel Suicide Scale, FAS III). Methods We calculated cut-off-based prevalence estimates for mental health issues for the whole sample and compared estimates between genders. Results 12.5\% of the sample reported general mental health problems. The estimated prevalence of depressive symptoms lay at of 11.5\%. Additionally, 12.1\% and 1.3\% of the participants displayed relevant symptoms of anorexia or bulimia nervosa, respectively. A total of 10.8\% reported engaging in non-suicidal self-injury (NSSI) at least once in their lifetime, of whom 5.6\% reported repetitive NSSI. 30.1\% of the participants described suicidal thoughts, 9.9\% suicide plans, and 3.5\% at least one suicide attempt. Girls were generally more affected than boys, except for bulimia nervosa, suicidal behavior, and partly NSSI. Conclusion Our findings corroborate the established relevance of early adolescence for the development of mental health problems and suggest that a substantial proportion of young adolescents suffer from such problems early on. Considering the ongoing COVID-19 pandemic and reported negative mental health consequences, the current findings underline the importance of preventive interventions to avoid the manifestation of mental disorders during adolescence.}, language = {en} } @article{ScheinerSeisKleindienstetal.2023, author = {Scheiner, Christin and Seis, Christian and Kleindienst, Nikolaus and Buerger, Arne}, title = {Psychopathology, protective factors, and COVID-19 among adolescents: a structural equation model}, series = {International Journal of Environmental Research and Public Health}, volume = {20}, journal = {International Journal of Environmental Research and Public Health}, number = {3}, issn = {1660-4601}, doi = {10.3390/ijerph20032493}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304475}, year = {2023}, abstract = {Since the outbreak of the COVID-19 pandemic in December 2019 and the associated restrictions, mental health in children and adolescents has been increasingly discussed in the media. Negative impacts of the pandemic, including a sharp increase in psychopathology and, consequently, reduced quality of life, appear to have particularly affected children and young people, who may be especially vulnerable to the adverse effects of isolation. Nevertheless, many children and adolescents have managed to cope well with the restrictions, without deterioration of their mental health. The present study therefore explored the links between COVID-19 infection (in oneself or a family member, as well as the death of a family member due to the virus), protective factors such as self-efficacy, resilience, self-esteem, and health-related quality of life, and measures of psychopathology such as depression scores, internalizing/externalizing problems, emotion dysregulation, and victimization. For this purpose, we examined data from 2129 adolescents (mean age = 12.31, SD = 0.67; 51\% male; 6\% born outside of Germany) using a structural equation model. We found medium to high loadings of the manifest variables with the latent variables (COVID-19, protective factors, and psychopathology). Protective factors showed a significant negative correlation with psychopathology. However, COVID-19 had a weak connection with psychopathology in our sample. External pandemic-related factors (e.g., restrictions) and their interaction with existing psychopathology or individual protective factors appear to have a greater influence on young people's mental health than the impact of the virus per se. Sociopolitical efforts should be undertaken to foster prevention and promote individual resilience, especially in adolescence.}, language = {en} } @article{SchieleReinhardReifetal.2016, author = {Schiele, Miriam A. and Reinhard, Julia and Reif, Andreas and Domschke, Katharina and Romanos, Marcel and Deckert, J{\"u}rgen and Pauli, Paul}, title = {Developmental aspects of fear: Comparing the acquisition and generalization of conditioned fear in children and adults}, series = {Developmental Psychobiology}, volume = {58}, journal = {Developmental Psychobiology}, number = {4}, doi = {10.1002/dev.21393}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189488}, pages = {471-481}, year = {2016}, abstract = {Most research on human fear conditioning and its generalization has focused on adults whereas only little is known about these processes in children. Direct comparisons between child and adult populations are needed to determine developmental risk markers of fear and anxiety. We compared 267 children and 285 adults in a differential fear conditioning paradigm and generalization test. Skin conductance responses (SCR) and ratings of valence and arousal were obtained to indicate fear learning. Both groups displayed robust and similar differential conditioning on subjective and physiological levels. However, children showed heightened fear generalization compared to adults as indexed by higher arousal ratings and SCR to the generalization stimuli. Results indicate overgeneralization of conditioned fear as a developmental correlate of fear learning. The developmental change from a shallow to a steeper generalization gradient is likely related to the maturation of brain structures that modulate efficient discrimination between danger and (ambiguous) safety cues.}, language = {en} } @phdthesis{Schiffczyk2017, author = {Schiffczyk, Eva-Maria}, title = {„Katamnestische Untersuchung der Behandlungszufriedenheit kindlicher Patientinnen und Patienten mit Anorexia nervosa nach station{\"a}rem Klinikaufenthalt"}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-156165}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Summary The aims of the current "Catamnestic examination of treatment satisfaction of patients with anorexia nervosa (AN) in childhood after inpatient treatment" were to extend the low data on AN in childhood in general and treatment satisfaction of this patient group in particular, and to use the knowledge gained to optimize future treatment concepts for patients with AN in childhood. To the best of our knowledge this is the first study retrospectively describing the treatment satisfaction of a patient population consisting exclusively of patients with a former AN in childhood. The central questions of the study were to find out whether and how many patients retrospectively found the treatment to be "satisfactory / unsatisfactory" or "helpful / harmful" and which elements of inpatient therapy produced "satisfaction / dissatisfaction" or subjective "help / harm" through the therapy. Further important aims of the study were to find out whether there is a correlation between the "treatment satisfaction / help / treatment amount" and various patient- and therapy-related parameters. The recent catamnestic study shows that former patients with AN in childhood, as well as other groups of AN patients (children, adolescents, adults) in previous studies, appear to be critical about the medical treatment compared to patients with other mental illnesses, with only 55.8 \% of the total patients who were at least mediocrely satisfied showing rather moderate satisfaction rates in the context of closed questions. Most likely are also in patients with AN in childhood typical disease characteristics (e.g. ambivalence in recovery and treatment, fear of loss of control) and personality traits (e.g. rigidity) frequently observed in AN patients responsible for that. The majority of patients with AN in childhood (65.4 \%) considered the therapy to be helpful retrospectively, in accordance with retrospective evaluations of patients with AN (children, adolescents, adults) on treatment as predominantly helpful. As part of the therapy, socio-emotional therapy components such as one-to-one therapeutic sessions, contact with fellow patients and caregivers were of the utmost importance for the patients with AN in childhood. These treatment elements generated the most satisfaction and were considered by many to be the most helpful. The results are hypothesis-generating that childlike patients with AN seem to have a special care / support need in the context of social relationships during therapy. However, the central role of socio-emotional components in therapy has also been highlighted in many other treatment satisfaction studies with childlike / adolescent and adult AN patients, patients with eating disorders in general, child and adolescent psychiatric and general psychiatric patients and in scientific work about the help of therapy for AN patients of different age groups as well as for other patient groups. As part of the therapeutic relationship, the desire for close contact with the therapist (more one-to-one interviews) was expressed. In addition, some patients wanted a more personalized therapy. The therapeutic relationship also played a key role in comparative studies with childlike and adolescent AN patients and other groups of patients, with sufficient time and individualism in therapy being required by the patients. A certain degree of self-determination, a fixed caregiver, inclusion of the family in the therapy, group therapy, adequate feedback and sufficient follow-up care were also important for the patients in the context of treatment. Treatment elements aimed at overcoming eating disordered behavior and recovering from the disease were partly rated to be satisfactory and helpful, but partly unsatisfactory and unhelpful. The critical evaluation of restrictive therapy elements to overcome the symptoms of eating disorders and ambivalence of patients with regard to their willingness to recover, their motivation to change and the initiation and implementation of a treatment, which has been cited in some studies, is also expressed in a group of patients with AN in childhood. With regard to these essential therapeutic ingredients for the treatment of AN, it is probably the right dosage in the context of the therapy concept. A comprehensible correlation was found in the fact that the former childlike AN patients, who judged the treatment to be satisfactory, also perceived it as more helpful and vice versa. The assumption that socio-cultural comparison variables (age and BMI) correlate with treatment satisfaction could not be proven in the own study for the former childlike study collective. Due to very different previous study results, further research on the relationship between socio-demographic variables and patient satisfaction is necessary in order to be able to draw clearer conclusions in this regard. However, an assumed association between the perceived help of the therapy and patient- / therapy-related variables could be confirmed, as patients with higher discharge BMI found treatment to be more helpful retrospectively than those with lower values. From a retrospective patient's perspective, this confirms the currently valid therapeutic guideline for not discharging patients from inpatient treatment until they achieve a body weight appropriate for their age and height (DGPM 2011). In addition, the perceived help from treatment at the different university hospitals showed significant differences, presumably due to the different specialization of the facilities with regard to eating disorders, as previous study results suggest that the treatment in an eating disorder clinic is more helpful than in a non-specialized hospital. With regard to the assessment of the treatment amount, the present catamnestic study showed contradictory results in relation to the long-term (presence of an eating disorder at the time of the catamnestic examination) or short-term treatment result (BMI at discharge) of the former AN patients. On average, patients who rated the amount of treatment as too low reported a higher BMI at hospital discharge (better short-term treatment outcome) than those who judged the treatment amount to be too high. This means that patients with better treatment results in the short term would have wished to receive more treatment quantitatively in the retrospective, than those with worse results. However, in return, more frequently, patients who still had an eating disorder (worse long-term outcome) at the time of study wished to have more treatment quantitatively, than recovered subjects at the time of the study (better long-term outcome). On this basis, it can be hypothesized that the patient group with lower discharge BMI may have had less disease insight than the group with higher discharge BMI, thus less able to engage in therapy with less benefit from it as a result of a poorer treatment outcome. It can also be speculated that in the meantime patients with a still ongoing eating disorder at the time of catamnesis had sufficient insight into the disease and therefore would have wished for more treatment retrospectively. Another plausible result of the current study is that patients who rated the treatment as satisfactory / helpful would have wanted more treatment quantitatively and patients who rated the treatment as unsatisfactory / harmful also judging the treatment amount to be too high. In summary, it becomes clear from our own results that it is a particular challenge to provide a therapy for patients with AN that finds their acceptance and satisfaction (Gulliksen et al., 2012). Accordingly, it is important to refine existing therapies and provide treatments that are adapted to the needs of the patient population. This requires a systematic knowledge of what generates satisfaction and dissatisfaction in patients with AN (Gulliksen et al., 2012). To our knowledge, the present study is the first study on treatment satisfaction that examined exclusively patients with former AN in childhood as a patient collective. Therefore, the results could only be compared with study data from other groups of patients (general psychiatric, child and adolescent psychiatric, eating disorder, adult and adolescent or partly childlike AN patients). Further studies with patients with AN in childhood are useful and desirable to validate the results presented here and to draw practical conclusions for an individualized treatment that meets the needs of the young patients.}, subject = {Anorexia nervosa}, language = {de} } @phdthesis{Schuler2003, author = {Schuler, Simone}, title = {Verlaufsuntersuchung zu Knochendichtever{\"a}nderungen bei juveniler Anorexia nervosa und Implikationen f{\"u}r ihre Therapie}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-7511}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2003}, abstract = {In der vorliegenden Arbeit konnten 52 von 103 Patientinnen, die in der Zeit von 1989 bis 1995 aufgrund einer Anorexia nervosa an der Universit{\"a}tsklinik f{\"u}r Kinder- und Jugendpsychiatrie W{\"u}rzburg station{\"a}r behandelt worden waren, nach im Mittel 5,3 Jahren pers{\"o}nlich nachuntersucht werden. Schwerpunkte der Studie waren der Langzeitverlauf der Knochendichte nach einer Erkrankung an Anorexia nervosa und m{\"o}gliche Einflussfaktoren auf die Knochendichteentwicklung. Es wurde untersucht, in wieweit sich Krankheitsverlauf, Heilungserfolg, {\"O}strogensubstitution, Amenorrhoedauer sowie sportliche Bet{\"a}tigung auf die Entwicklung der Knochendichteparameter auswirkten. Im Gegensatz zu den meisten vorhergehenden Verlaufsstudien wurde eine relativ große Patientinnengruppe, die alle im Kindes- und Jugendalter erkrankt waren und {\"u}ber Ausgangsdaten bez{\"u}glich der Knochendichte verf{\"u}gten, pers{\"o}nlich nachuntersucht. Neben verschiedenen klinischen Parametern wurde die Knochendichte mittels pQCT und DEXA bestimmt. Es zeigte sich, dass Knochendichteverluste noch ver{\"a}nderbar waren und die jungen Frauen teilweise eine g{\"u}nstige Knochendichteentwicklung aufwiesen. Positiv wirkte sich vor allem ein g{\"u}nstiger Heilungsverlauf aus. Im Gegensatz dazu fand sich bei Patientinnen mit chronischem Krankheitsverlauf eine sehr ung{\"u}nstige Knochendichteentwicklung. Nicht ganz so positiv stellt sich die Restitution der Knochenarchitektur dar. Insgesamt ließ sich kein eindeutiger Einfluss einer {\"O}strogensubstitution nachweisen. Positive Tendenzen waren bez{\"u}glich der Knochendichteentwicklung im Zusammenhang mit sportlicher Aktivit{\"a}t zu beobachten. Die Ergebnisse zeigen, dass eine z{\"u}gige und anhaltende Gesundung der Patientinnen den einzig nachweislich positiven Einflussfaktor auf die Knochendichteentwicklung darstellt. In wieweit die Einflussgr{\"o}ßen sportliche Aktivit{\"a}t und {\"O}strogensubstitution sich g{\"u}nstig auswirken, ließ sich nicht eindeutig kl{\"a}ren. Aus diesem Grund bedarf es weiterf{\"u}hrender prospektiver, randomisierter Studien, um die anorexieassoziierten Knochendichtever{\"a}nderungen und damit verkn{\"u}pfte Einflussfaktoren zu verstehen.}, language = {de} } @phdthesis{Seifert2004, author = {Seifert, J{\"u}rgen}, title = {Elektrophysiologische Untersuchung zur Wirksamkeit von Methylphenidat anhand einer Vergleichsuntersuchung von Kindern mit und ohne ADHS}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-10155}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2004}, abstract = {Ziel der vorliegenden Studie war es, mittels eines weiter entwickelten CPT-Tests (CPT-OX-Paradigma) gewonnener hirnelektrischer Korrelate, die klinische Wirksamkeit von Methylphenidat (MPH) bei Kindern mit Aufmerksamkeitsdefizit-/ Hyperaktivit{\"a}tsst{\"o}rung (ADHS) im Kontrollgruppenvergleich experimentell nachzuweisen. 1) Vorgegeben wurden Aufgaben zur Anregung von „Aufmerksamkeit" und zur „Hemmungskontrolle" bzw. „Impulsivit{\"a}tskontrolle" mittels einer weiter entwickelten Form des Continous- performance- Tests (CPT- OX). Die Kinder mit ADHS wurden unter den entsprechend definierten experimentellen Bedingungen mit und ohne Medikation von je 10 mg MPH untersucht und die evozierten Potentiale mit jenen der Gruppe alters- und geschlechtsgleicher Kontrollkinder verglichen. Als abh{\"a}ngige Variable wurden 21Kanal-ERPs von 17 Jungen mit ADHS, - mit und ohne Methylphenidatmedikation -, sowie von 20 gesunden Kontrollkindern mittels referenzunabh{\"a}ngiger Methoden analysiert. Vier quasi stabile Mikrozust{\"a}nde, welche den Zeitabschnitten der konventionellen ERP-Komponenten P 100, P 200, P 3a und P 3b entsprechen, konnten dabei mittels einer datengetriebenen Segmentierung abgegrenzt werden. Anschließend wurden die P 3a-Amplituden der Kinder mit ADHS - jeweils ohne und mit MPH-Medikation - mit den P 3a-Amplituden der gesunden Kontrollkinder verglichen. Die hypothesengeleitete experimentelle Studie kam zu folgenden wesentlichen Ergebnissen: Im Gruppenvergleich ohne Medikation waren die Amplituden im P 3a-Intervall (257-406 ms post stimulus) sowohl in der Hinweisreiz- als auch in der Hemmreizbedingung, also bei Aufmerksamkeitsanforderung wie auch bei Anforderung zur Impulsivit{\"a}tskontrolle, bei den nicht medizierten hyperkinetischen Kindern jeweils signifikant niedriger als bei den gesunden Kontrollkindern. 2) Im Gruppenvergleich ergab sich ein signifikanter Medikationseffekt. Die Amplituden im Zeitbereich 3 (P 300) bei den mit Methylphenidat medizierten Kindern mit Aufmerksamkeitsdefizit-/ Hyperaktivit{\"a}tsst{\"o}rung unterschieden sich nicht mehr signifikant von den entsprechenden P 3a-Amplituden der gesunden Kontrollkinder. Durch Stimulantienmedikation ließ sich somit eine Normalisierung des hirnelektrischen Korrelats von Aufmerksamkeit und Impulsivit{\"a}tskontrolle erreichen. Die Interpretation der Ergebnisse f{\"u}hrt zu dem Schluss, dass Methylphenidat einen normalisierenden Effekt auf die fr{\"u}he, hirnelektrisch messbare Reizverarbeitung bei der visuellen Orientierung (Aufmerksamkeit) und Stimuluserkennung (Bewertung von Reizunterschieden) aufweist. Mit dem CPT-OX-Paradigma lassen sich damit zuverl{\"a}ssig elektrophysiologische Korrelate der hirnelektrischen Wirksamkeit von Methylphenidat, in verschiedenen Reizbedingungen, messen.}, language = {de} } @phdthesis{Slyschak2022, author = {Slyschak, Anna}, title = {Fear conditioning, its generalization and extinction in children and adolescents under consideration of trait anxiety and anxiety sensitivity}, doi = {10.25972/OPUS-26780}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267806}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {The propounded thesis investigated fear learning including fear conditioning, its generalization as well as its extinction in 133 healthy children and adolescents aged 8 to 17 years. The main goal was to analyze these processes also in the course of childhood and adolescence due to far less research in this age span compared to adults. Of note, childhood is the typical period for the onset of anxiety disorders. To achieve this, an aversive discriminative fear conditioning, generalization and extinction paradigm, which based on the "screaming lady paradigm" from Lau et al. (2008) and was adapted by Schiele \& Reinhard et al. (2016), was applied. All probands traversed the pre-acquisition (4 x CS-, 4 x CS+, no US), the acquisition (12 x CS-, 12 x CS+, reinforcement rate: 83\%), the generalization (12 x CS-, 12 x GS4, 12 x GS3, 12 x GS2, 12 x GS1, 12 x CS+, reinforcement rate: 50\%) and the extinction (18 x CS-, 18 x CS+, no US). The generalization stimuli, i.e. GS1-GS4, were built out of CS- and CS+ in different mixtures on a percentage basis in steps of 20\% from CS- to CS+. Pictures of faces of two actresses with a neutral expression were used for the discriminative conditioning, whereby the CS+ was paired with a 95-dB loud female scream at the same time together with a fearful facial expression (US). CS- and GS1-GS4 were never followed by the US. Subjective ratings (arousal, valence and US expectancy) were collected and further the psychophysiological measure of the skin conductance response (SCR). The hypotheses were 1) that underage probands show a negative correlation between age and overgeneralization and 2) that anxiety is positively correlated with overgeneralization in the same sample. ANOVAs with repeated measures were conducted for all four dependent variables with phase (pre-acquisition phase, 1. + 2. acquisition phase, 1. + 2. generalization phase, 1. - 3. extinction phase) and stimulus type (CS-, CS+, GS1-GS4) as within-subject factors. For the analyses of the modulatory effects of age and anxiety in additional separate ANCOVAs were conducted including a) age, b) the STAIC score for trait anxiety and c) the CASI score for anxiety sensitivity as covariates. Sex was always included as covariate of no interest. On the one hand, findings indicated that the general extent of the reactions (arousal, valence and US expectancy ratings and the SCR) decreased with growing age, i.e. the older the probands the lower their reactions towards the stimuli regardless of the type of dependent variable. On the other hand, ratings of US expectancy, i.e. the likelihood that a stimulus is followed by a US (here: female scream coupled with a fearful facial expression), showed better discrimination skills the older the probands were, resulting in a smaller overgeneralization within older probands. It must be emphasized very clearly that no causality can be derived. Thus, it was only an association revealed between 15 age and generalization of conditioned fear, which is negative. Furthermore, no obvious impact of trait anxiety could be detected on the different processes of fear learning. Especially, no overgeneralization was expressed by the probands linked to higher trait anxiety. In contrast to trait anxiety, for anxiety sensitivity there was an association between its extent and the level of fear reactions. This could be described best with a kind of parallel shifts: the higher the anxiety sensitivity, the stronger the fear reactions. Likewise, for anxiety sensitivity no overgeneralization due to a stronger extent of anxiety sensitivity could be observed. Longitudinal follow-up examinations and, furthermore, neurobiological investigations are needed for replication purposes and purposes of gaining more supporting or opposing insights, but also for the profound exploration of the impact of hormonal changes during puberty and of the maturation processes of different brain structures. Finally, the question whether enhanced generalization of conditioned fear facilitates the development of anxiety disorders or vice versa remains unsolved yet.}, subject = {Furcht}, language = {en} } @phdthesis{Storch2009, author = {Storch, Astrid}, title = {Neurophysiologische Untersuchung der Antwortinhibition w{\"a}hrend des Continuous Performance Test bei dem Deletionssyndrom 22q11.2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-44543}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2009}, abstract = {Bei dem Deletionssyndroms 22q11.2 (DS 22q11.2) als eines der h{\"a}ufigsten menschlichen Mikrodeletionssyndrome wurde in den letzten Jahren zunehmend {\"u}ber Symptome aus dem neuropsychiatrischen Spektrum berichtet, insbesondere Schizophrenie und die Aufmerksamkeitsdefizit-/ Hyperaktivit{\"a}tsst{\"o}rung (ADHS). Eine gest{\"o}rte Inhibitionsf{\"a}higkeit und Aufmerksamkeitsdefizite, wie sie bei ADHS anzutreffen sind, wurden mit einer Funktionsst{\"o}rung des Anterioren Cingul{\"a}ren Cortex (ACC) in Zusammenhang gebracht. Mit einer einfachen und nebenwirkungsfreien computergest{\"u}tzten neurophysiologischen Methode ist es m{\"o}glich, ein elektrophysiologisches Korrelat der ACC-Funktion, die sogenannte NoGo-Anteriorisierung (NGA) zu messen. Eine reduzierte NGA wurde in fr{\"u}heren Untersuchungen u.a. bei Patienten mit ADHS und Schizophrenie als auch DS 22q11.2 als Hinweis auf eine verminderte Aktivit{\"a}t des ACC gefunden. Basierend auf erhobenen Vorbefunden stellten wir die Hypothese auf, dass bei Patienten mit DS 22q11.2 eine pr{\"a}frontale Dysfunktion, untersucht mittels computergest{\"u}tzter elektrophysiologischer CPT-Testung, im Sinne einer verminderten F{\"a}higkeit zur Antwortinhibition durch den neurophysiologischen Parameter NGA nachzuweisen ist. Zus{\"a}tzlich wurde eine Kontrollgruppe gesunder parallelisierter Probanden sowie eine klinische Kontrollgruppe mit ADHS untersucht. Zum Anderen sollte in dieser Doktorarbeit explorativ der Frage nachgegangen werden, inwiefern die NGA die Suszeptibilit{\"a}t f{\"u}r psychische St{\"o}rungen widerspiegelt und langfristig als potentieller Surrogatmarker f{\"u}r die erh{\"o}hte psychiatrische Komorbidit{\"a}t dienen k{\"o}nnte. Obwohl eine hypothesenkonforme NGA-Reduktion bei den Patienten mit DS 22q11.2 nachgewiesen werden konnte, war diese nicht auf eine verminderte Antwortinhibition zur{\"u}ckzuf{\"u}hren. Im Gegensatz zu fr{\"u}heren Befunden bei Schizophrenie und ADHS beruhte die NGA-Reduktion nicht auf einer verminderten Anteriorisierung des NoGo-Centroids, sondern auf einer isolierten Anteriorisierung des Go-Centroids. Die Topographie der Centroide ist bislang als spezifisch f{\"u}r DS 22q11.2 anzusehen und sollte im Weiteren hinsichtlich seiner Relevanz bei der psychiatrischen Disposition untersucht werden. Des Weiteren zeigte sich in der Quellenlokalisation LORETA bei DS 22q11.2 eine unver{\"a}nderte Aktivit{\"a}t des ACC w{\"a}hrend der Antwortinhibition, jedoch eine verminderte linkstemporale Aktivit{\"a}t w{\"a}hrend der Go-Bedingung. Die klinische Kontrollgruppe von ADHS-Patienten, die aufgrund der hohen Komorbidit{\"a}t mit ADHS untersucht wurde, zeigte dieses Aktivierungsmuster nicht. Unterschiedliche Aktivierungsmuster unterst{\"u}tzen die Annahme, dass die beobachteten Ver{\"a}nderungen bei DS 22q11.2 nicht auf das komorbide Vorliegen von ADHS zur{\"u}ckzuf{\"u}hren sind, sondern vielmehr spezifische Defizite widerspiegeln k{\"o}nnten.}, subject = {Elektroencephalogramm}, language = {de} } @article{SusewindWalkowitz2020, author = {Susewind, Moritz and Walkowitz, Gari}, title = {Symbolic Moral Self-Completion - Social Recognition of Prosocial Behavior Reduces Subsequent Moral Striving}, series = {Frontiers in Psychology}, volume = {11}, journal = {Frontiers in Psychology}, issn = {1664-1078}, doi = {10.3389/fpsyg.2020.560188}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211327}, year = {2020}, abstract = {According to theories on moral balancing, a prosocial act can decrease people's motivation to engage in subsequent prosocial behavior, because people feel that they have already achieved a positive moral self-perception. However, there is also empirical evidence showing that people actually need to be recognized by others in order to establish and affirm their self-perception through their prosocial actions. Without social recognition, moral balancing could possibly fail. In this paper, we investigate in two laboratory experiments how social recognition of prosocial behavior influences subsequent moral striving. Building on self-completion theory, we hypothesize that social recognition of prosocial behavior (self-serving behavior) weakens (strengthens) subsequent moral striving. In Study 1, we show that a prosocial act leads to less subsequent helpfulness when it was socially recognized as compared to a situation without social recognition. Conversely, when a self-serving act is socially recognized, it encourages subsequent helpfulness. In Study 2, we replicate the effect of social recognition on moral striving in a more elaborated experimental setting and with a larger participant sample. We again find that a socially recognized prosocial act leads to less subsequent helpfulness compared to an unrecognized prosocial act. Our results shed new light on the boundary conditions of moral balancing effects and underscore the view that these effects can be conceptualized as a dynamic of self-completion.}, language = {en} } @article{TaurinesFeketePreussWiedenhoffetal.2022, author = {Taurines, R. and Fekete, S. and Preuss-Wiedenhoff, A. and Warnke, A. and Wewetzer, C. and Plener, P. and Burger, R. and Gerlach, M. and Romanos, M. and Egberts, K. M.}, title = {Therapeutic drug monitoring in children and adolescents with schizophrenia and other psychotic disorders using risperidone}, series = {Journal of Neural Transmission}, volume = {129}, journal = {Journal of Neural Transmission}, number = {5-6}, doi = {10.1007/s00702-022-02485-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324833}, pages = {689-701}, year = {2022}, abstract = {Risperidone is commonly used to treat different psychiatric disorders worldwide. Knowledge on dose-concentration relationships of risperidone treatment in children and adolescents with schizophrenia or other psychotic disorders is, however, scarce and no age-specific therapeutic ranges have been established yet. Multicenter data of a therapeutic drug monitoring service were analyzed to evaluate the relationship between risperidone dose and serum concentration of the active moiety (risperidone (RIS) plus its main metabolite 9-hydroxyrisperidone (9-OH-RIS)) in children and adolescents with psychotic disorders. Patient characteristics, doses, serum concentrations and therapeutic outcomes were assessed by standardized measures. The study also aimed to evaluate whether the therapeutic reference range for adults (20-60 ng/ml) is applicable for minors. In the 64 patients (aged 11-18 years) included, a positive correlation between daily dose and the active moiety (RIS\(_{am}\)) concentration was found (r\(_s\) = 0.49, p = 0.001) with variation in dose explaining 24\% (r\(_s\)\(^2\) = 0.240) of the variability in serum concentrations. While the RIS\(_{am}\) concentration showed no difference, RIS as well 9-OH-RIS concentrations and the parent to metabolite ratio varied significantly in patients with co-medication of a CYP2D6 inhibitor. Patients with extrapyramidal symptoms (EPS) had on average higher RIS\(_{am}\) concentrations than patients without (p = 0.05). Considering EPS, the upper threshold of the therapeutic range of RIS\(_{am}\) was determined to be 33 ng/ml. A rough estimation method also indicated a possibly decreased lower limit of the preliminary therapeutic range in minors compared to adults. These preliminary data may contribute to the definition of a therapeutic window in children and adolescents with schizophrenic disorders treated with risperidone. TDM is recommended in this vulnerable population to prevent concentration-related adverse drug reactions.}, language = {en} } @article{VloetFetekeGerlachetal.2022, author = {Vloet, Timo D. and Feteke, Stefanie and Gerlach, Manfred and Romanos, Marcel}, title = {Das pharmakologische Management kinder- und jugendpsychiatrischer Notf{\"a}lle : Evidenz und Qualit{\"a}tssicherung}, series = {Zeitschrift f{\"u}r Kinder- und Jugendpsychiatrie und Psychotherapie}, volume = {50}, journal = {Zeitschrift f{\"u}r Kinder- und Jugendpsychiatrie und Psychotherapie}, number = {4}, issn = {1422-4917}, doi = {10.1024/1422-4917/a000833}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-280982}, pages = {262-274}, year = {2022}, abstract = {Kinder- und jugendpsychiatrische Notf{\"a}lle sind h{\"a}ufig und stellen die beteiligten {\"A}rztinnen und {\"A}rzte vor besondere Herausforderungen, da eine erhebliche Gefahr f{\"u}r die Patient_innen oder Dritte unter Anwendung m{\"o}glichst wenig invasiver Mittel abzuwenden ist. In diesem Kontext werden neben haltgebenden, deeskalierenden und psychotherapeutischen Optionen h{\"a}ufig auch pharmakologische Interventionen eingesetzt. Da ein Mangel an systematisch erhobenen Daten besteht, findet die pharmakologische Notfallbehandlung in der Kinder- und Jugendpsychiatrie regelhaft im off-label-Bereich statt. Vor dem Hintergrund der komplexen klinischen und rechtlichen Anforderungen an die {\"A}rztinnen und {\"A}rzte werden im vorliegenden Artikel praxisrelevante Hinweise insbesondere zum pharmakologischen Management von in der Praxis h{\"a}ufig auftretenden kinder- und jugendpsychiatrischen Notf{\"a}llen wie akuter Suizidalit{\"a}t, akut psychotischem Erleben, Delir und Bewusstseinsst{\"o}rungen sowie akuter Intoxikation und Alkoholentzugssyndrom gegeben. Weiterhin werden Maßnahmen zur Qualit{\"a}tssicherung und Arzneimittelsicherheit diskutiert.}, language = {de} } @phdthesis{vonDobschuetz2021, author = {von Dobsch{\"u}tz, Bernadette}, title = {Die Ver{\"a}nderung familienspezifischer Messgr{\"o}ßen unter therapeutischer Intervention bei der Aufmerksamkeitsdefizit-/Hyperaktivit{\"a}tsst{\"o}rung}, doi = {10.25972/OPUS-24376}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-243766}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Die psychosoziale Komponente spielt bei der ADHS v.a. in der Bew{\"a}ltigung von Erziehungsaufgaben eine erhebliche Rolle, da sowohl die Eltern als auch das Kind von der St{\"o}rung betroffen sein k{\"o}nnen. Ziel der vorliegenden Studie war die Untersuchung von Beziehungen und Konfliktpotential in Familien, die von ADHS betroffen sind. Es wurde der Frage nachgegangen, ob eine st{\"o}rungsspezifische Therapie von M{\"u}ttern mit ADHS und deren Kind, das ebenfalls an ADHS litt, bessere familienspezifische Messwerte erreicht als eine {\"u}bliche Standardbehandlung. Die Behandlungsgruppe erhielt eine intensive Gruppenpsychotherapie und begleitende Pharmakotherapie mit Methylphenidat, die Kontrollgruppe wiederholte psychiatrische Beratungen, beide Gruppen erhielten zus{\"a}tzlich ein Mutter-Kind-Training. Die Stichprobe bestand aus 144 Mutter-Kind Paaren mit ADHS, die im Rahmen einer Mutter-Kind Treatment Studie rekrutiert wurden. Es zeigten sich Verbesserungen in den untersuchten familienbezogenen Outcomes (soziales Leben, negative Gef{\"u}hle gegen{\"u}ber der Erziehung), nicht aber in allen erfassten Bereichen. Diese Verbesserungen zeigten jedoch keine signifikanten Gruppenunterschiede im Hinblick auf die beiden Studienbehandlungen zur Therapie der ADHS der M{\"u}tter (Pharmakotherapie plus Verhaltenstherapie vs. alleinige unspezifische Beratung). Bei M{\"u}ttern, die ein Krankheitsverst{\"a}ndnis f{\"u}r die ADHS, sowie eine Behandlungsmotivation hatten, verbesserte das Mutter-Kind-Training die Outcomes der Kinder, auch wenn die Mutter nur eine unterst{\"u}tzende Beratung erhielt. Die multimodale Therapie der M{\"u}tter mit Gruppenpsychotherapie und MPH-Medikation war bez{\"u}glich der Symptomreduktion der M{\"u}tter effektiv. Jedoch beeinflusste die multimodale Therapie im Vergleich zur unterst{\"u}tzenden psychiatrischen Beratung das externalisierende Verhalten des Kindes nach dem Elterntraining nicht zus{\"a}tzlich. Deshalb scheint es vielversprechend, M{\"u}ttern mit ADHS, welche nicht die M{\"o}glichkeit einer Medikation oder spezifischen Psychotherapie haben, auch zuk{\"u}nftig Elterntraining anzubieten.}, subject = {Aufmerksamkeitsdefizit-Syndrom}, language = {de} } @phdthesis{vonSchoenfeld2022, author = {von Sch{\"o}nfeld, Cornelia}, title = {Universal prevention of nonsuicidal self-injury for children and adolescents - A systematic review -}, doi = {10.25972/OPUS-28702}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287020}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {In a synopsis of the current state of research regarding NSSI, there are two key findings of this thesis: Firstly, there is a severe scarcity of studies and currently no evidence base for effective universal prevention of NSSI in youth. Secondly, not only the number but also quality of those few studies found was considered too low to draw wide-ranging conclusions and no meta-analysis could be conducted. This conclusion based - among other factors listed in chapter six - on the application of the EPHPP quality assessment tool (Evans, Lasen et al. 2015), which revealed distinct deficiencies and a weak overall study quality for all seven studies. Even if the high prevalence of NSSI among adolescents and the importance of this field of research is increasingly emphasized in contemporary literature (Muehlenkamp, Walsh et al. 2010, Wasserman, Carli et al. 2010, Brunner, Kaess et al. 2014, Plener, Schumacher et al. 2015), the shortage of concrete programs addressing the issue is manifest. The potential to tackle NSSI via prevention is underlined in view of the fact that many recent studies prove the high potential of primary prevention regarding NSSI incidences (Evans, Hawton et al. 2005, Fortune, Sinclair et al. 2008). From the studies included for this review, it can be concluded that most interventions show positive effects in raising awareness, knowledge, understanding of risk factors and help-seeking attitudes among school staff or students, particularly when starting with low knowledge at baseline (Robinson, Gook et al. 2008). Yet, most studies focus on training of gatekeepers and only two programmes address students directly and primarily measure actual NSSI behaviour. This finding highlights the importance of more investigation into concrete NSSI measurement targeting mainly the group of youth. There is a severe lack of literature on primary prevention with suitable contexts and target groups, while reviews on secondary targeted prevention deliver much more potential in the quantity of research (Kothgassner, Robinson et al. 2020, Kothgassner, Goreis et al. 2021). Until that changes, secondary prevention approaches of NSSI should be relied upon first. Looking into the future, several considerations may help advance universal approaches to NSSI. Regarding study planning, it is crucial for future research to pursue a thorough background research, examine the feasibility of interventions, and evaluate the appropriateness of study samples chosen. Moreover, research groups are expected to ensure a close observation of participants in cases of adverse events, in order to offer support, but also detect potential deficiencies in the study organisation. Additionally - in accordance with other research in this field (Plener, Brunner et al. 2010) - findings of this review highlight the necessity to expand fundamental research on functions of NSSI and its (neurobiological) mechanism of formation in order to enhance the knowledge of correlations and improve effective preventive approaches. As psychoeducational methods have shown risks of iatrogenic effects (e.g. in patients with eating disorders) (Stice, 2007 \#10063), it might be worthwhile to focus on improving emotion regulation in order to strengthen protective factors and improve adolescents' management of their everyday lives rather than on merely mitigating possible risk factors. Regarding intervention costs, it appears indispensable to include more cost calculations in the study planning of future research. In contrast to therapeutic interventions of NSSI, which are usually conducted in an in-patient setting and entail high measurable expenses as compared to preventive interventions, preventive approaches may in case of success result in a reduction of clinical presentation (O'Connell, Boat et al. 2009). A promising outlook is entailed by study protocol presenting a skills-based universal prevention program of NSSI "DUDE", a cluster randomized controlled trial scheduled for 16 German schools with a total of 3.200 adolescents (Buerger, Emser et al. 2022). The program is tailored to decrease the incidence of NSSI and avert potential and associated long-term consequences like suicidality among adolescents. It is aimed to provide easy access for adolescents due to its implementation during lesson time at school and is declared cost-effective. Furthermore, DUDE is a promising approach to effective NSSI prevention, as it is intended to improve mental health through the pathway of emotion regulation. It remains to await the implementation of the protocol, which is currently delayed due to the SARS-CoV-19 pandemic. In sum, initial research is promising and suggests that the approach to tackle NSSI via prevention is meaningful. Yet, high-quality studies on the development and evaluation of universal NSSI prevention in adolescents are urgently needed.}, language = {en} } @article{WalitzaMelfsenJansetal.2011, author = {Walitza, Susanne and Melfsen, Siebke and Jans, Thomas and Zellmann, Henrike and Wewetzer, Christoph and Warnke, Andreas}, title = {Obsessive-Compulsive Disorder in Children and Adolescents}, series = {Deutsches {\"A}rzteblatt International}, volume = {108}, journal = {Deutsches {\"A}rzteblatt International}, number = {11}, doi = {10.3238/arztebl.2011.0173}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141214}, pages = {173-I}, year = {2011}, abstract = {Background: Early-onset obsessive-compulsive disorder (OCD) is one of the more common mental illnesses of children and adolescents, with prevalence of 1\% to 3\%. Its manifestations often lead to severe impairment and to conflict in the family. In this review, we summarize the manifestations, comorbidity, pathophysiology, and course of this disease as well as current modes of diagnosis and treatment. Methods: We selectively review the relevant literature and the German-language guidelines for the diagnosis and treatment of mental illnesses in children and adolescents. Results: Obsessive-compulsive manifestations are of many types and cause severe impairment. Comorbid mental disturbances are present in as many as 70\% of patients. The disease takes a chronic course in more than 40\% of patients. Cognitive behavioral therapy is the treatment of first choice, followed by combination pharmacotherapy including selective serotonin reuptake inhibitors (SSRI) and then by SSRI alone. Conclusion: OCD often begins in childhood or adolescence. There are empirically based neurobiological and cognitive-behavioral models of its pathophysiology. Multiaxial diagnostic evaluation permits early diagnosis. Behavioral therapy and medications are highly effective treatments, but the disorder nonetheless takes a chronic course in a large percentage of patients.}, language = {en} } @phdthesis{Wallem2021, author = {Wallem, Friederike}, title = {Psychometrische Analyse des Fragebogens zur Erfassung der Zufriedenheit mit der Aufkl{\"a}rung im Rahmen der kinder- und jugendpsychiatrischen Behandlung}, doi = {10.25972/OPUS-24710}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-247108}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Ziel der vorliegenden Arbeit war es, eine psychometrische Analyse des von W. Briegel entwickelten Fragebogens durchzuf{\"u}hren , der die Zufriedenheit mit dem Aufkl{\"a}rungsgespr{\"a}ch {\"u}ber eine medikament{\"o}se Therapie multiperspektivisch aus Sicht der Beteiligten erfassen soll. An einer Stichprobe von 63 g{\"u}ltigen F{\"a}llen erfolgte eine Evaluation des Fragebogens im Sinne einer Itemanalyse, sowie die {\"U}berpr{\"u}fung auf Validit{\"a}t und Reliabilit{\"a}t. Zudem wurde untersucht ob im Allgemeinen Zufriedenheit angegeben wurden und ob Einflussfaktoren auf das Antwortverhalten und die Zufriedenheit festgestellt werden konnten Insgesamt wurden die Fragen von allen Beteiligten im Sinne von Zufriedenheit beantwortet. Die Itemanalyse erbrachte hohe Schwierigkeitsindices, hohe Trennsch{\"a}rfewerte und geringe Varianzen. Des Weiteren zeigte der Fragebogen gute Werte f{\"u}r die Interne Konsistenz und f{\"u}r die Pr{\"u}fung auf Kriteriumsvalidit{\"a}t. Aufgrund der sich ergebenden Hinweise, dass die hohen Werte der Zufriedenheitsbefragung durch die Konstruktionsweise des Fragebogens zustande gekommen sein k{\"o}nnten, erscheint es sinnvoll, die Ratingskala des Fragebogens zu modifizieren. Dieser so ver{\"a}nderte Fragebogen sollte dann an einer heterogeneren Stichprobe erneut eingesetzt werden, um herauszufinden, ob die Ergebnisse in diesem Kontext dieselbe Tendenz zeigen.}, language = {de} } @phdthesis{Waltmann2024, author = {Waltmann, Maria}, title = {Neurocognitive mechanisms of loss of control in Binge Eating Disorder}, doi = {10.25972/OPUS-36430}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-364300}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {Binge Eating Disorder (BED) is a common, early-onset mental health condition characterised by uncontrollable episodes of overeating followed by negative emotions such as guilt and shame. An improved understanding of the neurocognitive mechanisms underlying BED is central to the development of more targeted and effective treatments. This thesis comprises a systematic review and three empirical studies contributing to this endeavour. BED can be thought of as a disorder of cognitive-behavioural control. Indeed, self-report evidence points towards enhanced impulsivity and compulsivity in BED. However, retrospective self-reports do not capture the mechanisms underlying impulsive and compulsive lapses of control in the moment. The systematic review therefore focussed on the experimental literature on impulsivity and compulsivity in BED. The evidence was very mixed, although there was some indication of altered goal-directed control and behavioural flexibility in BED. We highlight poor reliability of experimental paradigms and the failure to properly account for weight status as potential reasons for inconsistencies between studies. Moreover, we propose that impulsivity and/or compulsivity may be selectively enhanced in negative mood states in BED and may therefore not be consistently detected in lab-based studies. In the empirical studies, we explored the role of behavioural flexibility in BED using experimental and neuroimaging methods in concert with computational modelling. In the first empirical study, we assessed the reliability of a common measure of behavioural flexibility, the Probabilistic Reversal Learning Task (PRLT). We demonstrate that the behavioural and computational metrics of the PRLT have sufficient reliability to justify past and future applications if calculated using hierarchical modelling. This substantially improves reliability by reducing error variance. The results support the use of the PRLT in the second and third empirical studies on development and BED. Because a majority of patients develop BED as adolescents or young adults, we speculated that it may emerge as a consequence of disrupted or deficient maturation of behavioural flexibility. Little is known about typical development in this domain. We therefore investigated normative development of reversal learning from adolescence to adulthood in the second empirical study. Typically- developing adolescents exhibited less adaptive and more erratic and explorative behaviour than adults. This behaviour was accounted for by reduced sensitivity to positive feedback in a reinforcement learning model, and partially mediated by reduced activation reflecting uncertainty in the medial prefrontal cortex, a region known to mature substantially during adolescence. In the third empirical study, we investigated reversal learning in BED, paying special attention to potential biases associated with learning from wins vs learning from losses. We speculated that negative urgency could make it more difficult for BED patients to learn and make decisions under pressure to avoid losses. To dissociate between effects of excess weight and BED, we collected data from obese individuals with and without BED as well as normal-weight controls. As hypothesised, there were subtle neurocognitive differences between obese participants with and without BED with regard to learning to obtain rewards and to avoid losses. Obese individuals showed relatively impaired learning to obtain rewards, while BED patients showed relatively impaired learning to avoid losses. This was reflected in differential learning signals in the brain and associated with BED symptom severity. In sum, this thesis shows that the evidence on impulsivity and compulsivity in BED is inconsistent and offers potential explanations for this inconsistency. It highlights the need for reliability in interindividual difference research and indicates ways to improve it. Further, it charts the typical development of reversal learning from adolescence to adulthood and underscores the relevance of exploration in the context of learning and decision-making in adolescence. Finally, it demonstrates qualitative differences between BED and obesity, hinting at a pivotal role of aversive states in loss of control in BED.}, subject = {Binge-eating Disorder}, language = {en} } @article{WaltmannSchlagenhaufDeserno2022, author = {Waltmann, Maria and Schlagenhauf, Florian and Deserno, Lorenz}, title = {Sufficient reliability of the behavioral and computational readouts of a probabilistic reversal learning task}, series = {Behavior Research Methods}, volume = {54}, journal = {Behavior Research Methods}, number = {6}, issn = {1554-3528}, doi = {10.3758/s13428-021-01739-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324246}, pages = {2993-3014}, year = {2022}, abstract = {Task-based measures that capture neurocognitive processes can help bridge the gap between brain and behavior. To transfer tasks to clinical application, reliability is a crucial benchmark because it imposes an upper bound to potential correlations with other variables (e.g., symptom or brain data). However, the reliability of many task readouts is low. In this study, we scrutinized the retest reliability of a probabilistic reversal learning task (PRLT) that is frequently used to characterize cognitive flexibility in psychiatric populations. We analyzed data from N = 40 healthy subjects, who completed the PRLT twice. We focused on how individual metrics are derived, i.e., whether data were partially pooled across participants and whether priors were used to inform estimates. We compared the reliability of the resulting indices across sessions, as well as the internal consistency of a selection of indices. We found good to excellent reliability for behavioral indices as derived from mixed-effects models that included data from both sessions. The internal consistency was good to excellent. For indices derived from computational modeling, we found excellent reliability when using hierarchical estimation with empirical priors and including data from both sessions. Our results indicate that the PRLT is well equipped to measure individual differences in cognitive flexibility in reinforcement learning. However, this depends heavily on hierarchical modeling of the longitudinal data (whether sessions are modeled separately or jointly), on estimation methods, and on the combination of parameters included in computational models. We discuss implications for the applicability of PRLT indices in psychiatric research and as diagnostic tools.}, language = {en} } @phdthesis{Weigand2005, author = {Weigand, Tobias}, title = {Das klinische Bild dissoziativer St{\"o}rungen im Kindes- und Jugendalter, ihr Verlauf und Ihre Prognose}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-19519}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2005}, abstract = {Bislang finden sich in der Literatur nur wenige untereinander vergleichbare Studien den langfristigen Verlauf dissoziativer St{\"o}rungen im Kindes- und Jugendalter betreffend. Da diese St{\"o}rungen in den vergangenen Jahrzehnten etliche Male verschiedenen Gruppen psychischer St{\"o}rungen zugeordnet wurden, ziegt sich ein teils sehr heterogenes Krankheitsbild. Ziel der Studie war daher zun{\"a}chst, anhand der aktuellen Krankheitsklassifikation ICD-10 eine einheitliche und vergleichbare Patientengruppe, die an dissoziativen St{\"o}rungen erkrankt war, zu untersuchen, um Erfahrungen {\"u}ber die klinischen Auspr{\"a}gungen der Krankheit im Kindes- und Jugendalter zu gewinnen. Hierzu wurden die Krankengeschichten von 62 Kindern und Jugendlichen, die zwischen 1983 und 1992 in der Klinik f{\"u}r Kinder- und Jugendpsychiatrie der Universit{\"a}t W{\"u}rzburg an dissoziativen St{\"o}rungen behandelt wurden, untersucht und statistisch ausgewertet. Um zus{\"a}tzlich einen Einblick in den langfristigen Krankheitsverlauf gewinnen zu k{\"o}nnen, wurde in den Jahren 2000 und 2001 eine L{\"a}ngsschnitt-Katamnese-Untersuchung mit den ehemaligen Patientinnen und Patienten durchgef{\"u}hrt, in der neben rezidivierenden dissoziativen Symptomen auch andere relevante psychische Erkrankungen und Pers{\"o}nlichkeitsst{\"o}rungen sowohl zum Untersuchungszeitpunkt als auch in der vergangenen Zeitspanne seit Entlassung aus der Klinik untersucht wurden. Hierzu wurde eine Vielzahl klinisch etablierter und hinreichend validierter diagnostischer Interviews in einem pers{\"o}nlichen Untersuchungsgespr{\"a}ch mit den Patienten bearbeitet. Im Rahmen der Untersuchung konnte gezeigt werden, dass die klinischen Symptome der dissoziativen St{\"o}rung im Kindes- und Jugendalter einige Abweichungen vom typischen St{\"o}rungsbild bei Erwachsenen aufweisen. Sehr deutlich zeigte sich zudem, dass im Gegensatz zu mehreren bestehenden Untersuchungen der langfristige Verlauf der Erkrankung von einem hohen Anteil chronisch-rezidivierender St{\"o}rungen und einerseits und komorbiden psychischen St{\"o}rungen andererseits gepr{\"a}gt ist. Auffallend hoch war der Anteil komorbider Angsterkrankungen sowohl w{\"a}hrend der prim{\"a}r klinischen Behandlung als auch im weiteren Krankheitsverlauf; hierbei war zudem eine hohe Zahl depressiver St{\"o}rungen und somatoformer St{\"o}rungen zu beobachten. Die dissoziative St{\"o}rung selbst zeigte bei nahezu jedem dritten Patienten einen rezidivierenden Verlauf. Die Ergebnisse legen die Notwendigkeit einer weiterf{\"u}hrenden und zeitlich ausreichend lange angelegten Nachbehandlung von Patienten mit dissoziativen St{\"o}rungen nahe, gerade bei einem Beginn der Erkrankung in der Kindheit oder Adoleszenz.}, language = {de} } @article{WeselekKeinerFauseretal.2020, author = {Weselek, Grit and Keiner, Silke and Fauser, Mareike and Wagenf{\"u}hr, Lisa and M{\"u}ller, Julia and Kaltschmidt, Barbara and Brandt, Moritz D. and Gerlach, Manfred and Redecker, Christoph and Hermann, Andreas and Storch, Alexander}, title = {Norepinephrine is a negative regulator of the adult periventricular neural stem cell niche}, series = {Stem Cells}, volume = {38}, journal = {Stem Cells}, number = {9}, doi = {10.1002/stem.3232}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218250}, pages = {1188 -- 1201}, year = {2020}, abstract = {The limited proliferative capacity of neuroprogenitor cells (NPCs) within the periventricular germinal niches (PGNs) located caudal of the subventricular zone (SVZ) of the lateral ventricles together with their high proliferation capacity after isolation strongly implicates cell-extrinsic humoral factors restricting NPC proliferation in the hypothalamic and midbrain PGNs. We comparatively examined the effects of norepinephrine (NE) as an endogenous candidate regulator of PGN neurogenesis in the SVZ as well as the periventricular hypothalamus and the periaqueductal midbrain. Histological and neurochemical analyses revealed that the pattern of NE innervation of the adult PGNs is inversely associated with their in vivo NPC proliferation capacity with low NE levels coupled to high NPC proliferation in the SVZ but high NE levels coupled to low NPC proliferation in hypothalamic and midbrain PGNs. Intraventricular infusion of NE decreased NPC proliferation and neurogenesis in the SVZ-olfactory bulb system, while pharmacological NE inhibition increased NPC proliferation and early neurogenesis events in the caudal PGNs. Neurotoxic ablation of NE neurons using the Dsp4-fluoxetine protocol confirmed its inhibitory effects on NPC proliferation. Contrarily, NE depletion largely impairs NPC proliferation within the hippocampus in the same animals. Our data indicate that norepinephrine has opposite effects on the two fundamental neurogenic niches of the adult brain with norepinephrine being a negative regulator of adult periventricular neurogenesis. This knowledge might ultimately lead to new therapeutic approaches to influence neurogenesis in hypothalamus-related metabolic diseases or to stimulate endogenous regenerative potential in neurodegenerative processes such as Parkinson's disease.}, language = {en} } @phdthesis{Wittek2003, author = {Wittek, Nina}, title = {Untersuchungen zur K{\"o}rperschemast{\"o}rung bei Anorexia nervosa}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-8018}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2003}, abstract = {Die Arbeit befasst sich mit dem Symptomkomplex K{\"o}rperschemast{\"o}rung bei Patientinnen mit Anorexia nervosa. Verschiedene Messmethoden zur Erfassung von K{\"o}rperschemast{\"o}rung werden einander gegen{\"u}bergestellt. Die Arbeit analysiert mittels Computer Body Image Test das K{\"o}rperbild jugendlicher Anorexiepatientinnen. Dar{\"u}ber hinaus wird eine Abh{\"a}ngigkeit der K{\"o}rperschemast{\"o}rung von Therapieverlauf und Schweregrad der Erkrankung untersucht.}, language = {de} } @phdthesis{Wohkittel2024, author = {Wohkittel, Christopher Philipp}, title = {Untersuchung der Amphetamin- und Guanfacinkonzentrationen im Speichel als m{\"o}gliche alternative Matrix f{\"u}r Therapeutisches Drug Monitoring}, doi = {10.25972/OPUS-34963}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349635}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {F{\"u}r Kinder und Jugendliche stellt die Blutentnahme im Rahmen des Therapeutischen Drug Monitorings (TDM) aufgrund der Invasivit{\"a}t h{\"a}ufig eine große physische sowie psychische Belastung dar. Diese Stresssituation kann durch Speichelsammlung aufgrund des nicht invasiven Prozederes vermieden und zus{\"a}tzlich der Material-, Personal- und Zeitaufwand im Vergleich zu einer Blutentnahme minimiert werden. Da die therapeutischen Referenzbereiche in der AGNP Konsensus-Leitlinie zum TDM von Psychopharmaka nur f{\"u}r Serum und Plasma validiert sind, sind vergleichende Untersuchungen von alternativen Matrizes mit Serum oder Plasma sowie eine klinische Validierung essenziell f{\"u}r die Implementierung in die klinische Praxis. Die Zielsetzung dieser Arbeit war es daher, den Zusammenhang zwischen Speichel- und Serumkonzentrationen von Amphetamin und Guanfacin zu untersuchen, um zuk{\"u}nftig das Prozedere der Probenahme f{\"u}r TDM bei Kinder und Jugendliche unter ADHS-Pharmakotherapie durch ein nicht invasives Verfahren zu erleichtern. Zur quantitativen Bestimmung wurden zwei unterschiedliche Methoden aus der Literatur weiterentwickelt. So war es m{\"o}glich, aus Speichel- und Serumproben Amphetamin mittels HPLC-FL Analytik sowie Guanfacin mittels LC-MS/MS Analytik zu quantifizieren. Die chromatographischen Methoden wurden in Anlehnung an die Richtlinien der Gesellschaft f{\"u}r toxikologische und forensische Chemie (GTFCh) erfolgreich validiert. Zur Untersuchung des Zusammenhangs zwischen Speichel- und Serumkonzentrationen von Amphetamin und Guanfacin bei Kinder und Jugendlichen wurde eine klinische Studie in der Klinik und Poliklinik f{\"u}r Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie des Universit{\"a}tsklinikum W{\"u}rzburgs initiiert. Von 34 Probanden, die mit Lisdexamphetamin und/oder Guanfacin behandelt wurden, konnte jeweils eine korrespondierende Speichel- und Serumprobe gewonnen und quantifiziert werden. F{\"u}r Amphetamin wurde belegt, dass der Speichel-pH-Wert einen erheblichen Einfluss auf die Wirkstoffverteilung, den Quotienten aus Speichel- und Serumkonzentration, hat (ρ = -0,712; P < 0,001). Dadurch konnte erstmalig unter Ber{\"u}cksichtigung des Speichel-pH-Wertes eine Berechnung der theoretischen Serumkonzentration aus der Speichelkonzentration durchgef{\"u}hrt werden. Es wurde zwar gezeigt, dass sich sowohl der Mittelwert der Differenzen durch die Berechnung theoretischen Serumkonzentration von -343 auf 12 ng/mL als auch die Anzahl der Messwert innerhalb des Akzeptanzintervalls von 20 \% verbessern, jedoch war auch nach der Umrechnung die Differenz der Messwerte zu groß, sodass eine klinische Validierung f{\"u}r Amphetamin nicht m{\"o}glich war. In dieser Studie wurde auch erstmals Guanfacin im Speichel nachgewiesen und quantifiziert, die Konzentrationen lagen zwischen 0,45 und 5,55 ng/mL und waren im Mittel dreifach niedriger als im Serum (2,36 ng/mL vs. 7,47 ng/mL; t (8) = 5,94; P < 0,001).   Die Speichelguanfacinkonzentration wies einen starken Zusammenhang mit der korrespondierenden Serumkonzentration auf (r = 0,758; P = 0,018). Obwohl ein nicht signifikanter Trend f{\"u}r den Einfluss des Speichel-pH-Wertes auf den Quotienten aus Speichel- und Serumkonzentration zu erkennen war, scheint dieser weniger stark ausgepr{\"a}gt zu sein als bei Amphetamin und anderen basischen Arzneistoffen (r = -0,574; P = 0,106). Mit der vorliegenden Arbeit konnte zum einen gezeigt werden, dass sich die Speichelbestimmung von Amphetamin nur zum qualitativen Nachweis f{\"u}r TDM eignet. Zum anderen konnte gezeigt werden, dass der Speichel-pH-Wert einen geringeren Einfluss auf die Speichelkonzentration von Guanfacin zu haben scheint, als es bei Amphetamin der Fall ist, und sich Guanfacin somit potenziell f{\"u}r TDM in Speichel eignet. Zuk{\"u}nftig k{\"o}nnten Speichelproben zur Kontrolle der Adh{\"a}renz sowohl von Amphetamin als auch von Guanfacin verwendet werden und die Probenahme f{\"u}r die Patienten vereinfachen.}, subject = {Pharmakotherapie}, language = {de} } @article{WulfBarkovitsSchorketal.2022, author = {Wulf, Maximilian and Barkovits, Katalin and Schork, Karin and Eisenacher, Martin and Riederer, Peter and Gerlach, Manfred and Eggers, Britta and Marcus, Katrin}, title = {The proteome of neuromelanin granules in dementia with Lewy bodies}, series = {Cells}, volume = {11}, journal = {Cells}, number = {22}, issn = {2073-4409}, doi = {10.3390/cells11223538}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297465}, year = {2022}, abstract = {Neuromelanin granules (NMGs) are organelle-like structures present in the human substantia nigra pars compacta. In addition to neuromelanin, NMGs contain proteins, lipids and metals. As NMG-containing dopaminergic neurons are preferentially lost in Parkinson's disease and dementia with Lewy bodies (DLB), it is assumed that NMGs may play a role in neurodegenerative processes. Until now, this role is not completely understood and needs further investigation. We therefore set up an exploratory proteomic study to identify differences in the proteomic profile of NMGs from DLB patients (n = 5) compared to healthy controls (CTRL, n = 5). We applied a laser microdissection and mass-spectrometry-based approach, in which we used targeted mass spectrometric experiments for validation. In NMG-surrounding (SN\(_{Surr.}\)) tissue of DLB patients, we found evidence for ongoing oxidative damage and an impairment of protein degradation. As a potentially disease-related mechanism, we found α-synuclein and protein S100A9 to be enriched in NMGs of DLB cases, while the abundance of several ribosomal proteins was significantly decreased. As S100A9 is known to be able to enhance the formation of toxic α-synuclein fibrils, this finding points towards an involvement of NMGs in pathogenesis, however the exact role of NMGs as either neuroprotective or neurotoxic needs to be further investigated. Nevertheless, our study provides evidence for an impairment of protein degradation, ongoing oxidative damage and accumulation of potentially neurotoxic protein aggregates to be central mechanisms of neurodegeneration in DLB.}, language = {en} } @article{ZieglerEhlisWeberetal.2021, author = {Ziegler, Georg C. and Ehlis, Ann-Christine and Weber, Heike and Vitale, Maria Rosaria and Z{\"o}ller, Johanna E. M. and Ku, Hsing-Ping and Schiele, Miriam A. and K{\"u}rbitz, Laura I. and Romanos, Marcel and Pauli, Paul and Kalisch, Raffael and Zwanzger, Peter and Domschke, Katharina and Fallgatter, Andreas J. and Reif, Andreas and Lesch, Klaus-Peter}, title = {A Common CDH13 Variant is Associated with Low Agreeableness and Neural Responses to Working Memory Tasks in ADHD}, series = {Genes}, volume = {12}, journal = {Genes}, number = {9}, issn = {2073-4425}, doi = {10.3390/genes12091356}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245220}, year = {2021}, abstract = {The cell—cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on personality traits, behavior, and executive functions. However, evidence for functional effects of common gene variation in the CDH13 gene in humans is sparse. Therefore, we tested for association of a functional intronic CDH13 SNP rs2199430 with ADHD in a sample of 998 adult patients and 884 healthy controls. The Big Five personality traits were assessed by the NEO-PI-R questionnaire. Assuming that altered neural correlates of working memory and cognitive response inhibition show genotype-dependent alterations, task performance and electroencephalographic event-related potentials were measured by n-back and continuous performance (Go/NoGo) tasks. The rs2199430 genotype was not associated with adult ADHD on the categorical diagnosis level. However, rs2199430 was significantly associated with agreeableness, with minor G allele homozygotes scoring lower than A allele carriers. Whereas task performance was not affected by genotype, a significant heterosis effect limited to the ADHD group was identified for the n-back task. Heterozygotes (AG) exhibited significantly higher N200 amplitudes during both the 1-back and 2-back condition in the central electrode position Cz. Consequently, the common genetic variation of CDH13 is associated with personality traits and impacts neural processing during working memory tasks. Thus, CDH13 might contribute to symptomatic core dysfunctions of social and cognitive impairment in ADHD.}, language = {en} } @article{ZieglerRadtkeVitaleetal.2021, author = {Ziegler, Georg C. and Radtke, Franziska and Vitale, Maria Rosaria and Preuße, Andr{\´e} and Klopocki, Eva and Herms, Stefan and Lesch, Klaus-Peter}, title = {Generation of multiple human iPSC lines from peripheral blood mononuclear cells of two SLC2A3 deletion and two SLC2A3 duplication carriers}, series = {Stem Cell Research}, volume = {56}, journal = {Stem Cell Research}, doi = {10.1016/j.scr.2021.102526}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264696}, year = {2021}, abstract = {Copy number variants of SLC2A3, which encodes the glucose transporter GLUT3, are associated with several neuropsychiatric and cardiac diseases. Here, we report the successful reprogramming of peripheral blood mononuclear cells from two SLC2A3 duplication and two SLC2A3 deletion carriers and subsequent generation of two transgene-free iPSC clones per donor by Sendai viral transduction. All eight clones represent bona fide hiPSCs with high expression of pluripotency genes, ability to differentiate into cells of all three germ layers and normal karyotype. The generated cell lines will be helpful to enlighten the role of glucometabolic alterations in pathophysiological processes shared across organ boundaries.}, language = {en} } @article{ZieglerKaiserIgeletal.2021, author = {Ziegler, Mirjam and Kaiser, Anna and Igel, Christine and Geissler, Julia and Mechler, Konstantin and Holz, Nathalie E. and Becker, Katja and D{\"o}pfner, Manfred and Romanos, Marcel and Brandeis, Daniel and Hohmann, Sarah and Millenet, Sabina and Banaschewski, Tobias}, title = {Actigraphy-derived sleep profiles of children with and without attention-deficit/hyperactivity disorder (ADHD) over two weeks — comparison, precursor symptoms, and the chronotype}, series = {Brain Sciences}, volume = {11}, journal = {Brain Sciences}, number = {12}, issn = {2076-3425}, doi = {10.3390/brainsci11121564}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250084}, year = {2021}, abstract = {Although sleep problems are common in children with ADHD, their extent, preceding risk factors, and the association between neurocognitive performance and neurobiological processes in sleep and ADHD, are still largely unknown. We examined sleep variables in school-aged children with ADHD, addressing their intra-individual variability (IIV) and considering potential precursor symptoms as well as the chronotype. Additionally, in a subgroup of our sample, we investigated associations with neurobehavioral functioning (n = 44). A total of 57 children (6-12 years) with (n = 24) and without ADHD (n = 33) were recruited in one center of the large ESCAlife study to wear actigraphs for two weeks. Actigraphy-derived dependent variables, including IIV, were analyzed using linear mixed models in order to find differences between the groups. A stepwise regression model was used to investigate neuropsychological function. Overall, children with ADHD showed longer sleep onset latency (SOL), higher IIV in SOL, more movements during sleep, lower sleep efficiency, and a slightly larger sleep deficit on school days compared with free days. No group differences were observed for chronotype or sleep onset time. Sleep problems in infancy predicted later SOL and the total number of movements during sleep in children with and without ADHD. No additional effect of sleep problems, beyond ADHD symptom severity, on neuropsychological functioning was found. This study highlights the importance of screening children with ADHD for current and early childhood sleep disturbances in order to prevent long-term sleep problems and offer individualized treatments. Future studies with larger sample sizes should examine possible biological markers to improve our understanding of the underlying mechanisms.}, language = {en} }