TY  - THES
A1  - Lüffe, Teresa Magdalena
T1  - Behavioral and pharmacological validation of genetic zebrafish models for ADHD
T1  - Pharmakologische und verhaltensbasierte Validierung genetischer Zebrafischmodelle für ADHS
N2  - 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.
N2  - Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) ist mit einer weltweiten Prävalenz von rund 5 % die am häufigsten vorkommende Neuroentwicklungsstörung. Das Krankheitsbild, das zumeist im Kindesalter auftritt und bis ins Erwachsenenalter bestehen kann, zeigt sich im Wesentlichen durch eine Beeinträchtigung der Aufmerksamkeit, der Aktivität, der Impuls-kontrolle und zum Teil durch emotionale Dysregulation. Darüber hinaus führt das vermehrte Auftreten von psychischen Begleiterkrankungen (so genannte Komorbiditäten) zu einer komplexen Symptomatik vieler Betroffener, die über die klassischen Merkmale von ADHS hinausgeht. Während das Krankheitsbild vielfach beschrieben wurde, ist die Ätiopathogenese trotz intensiver wissenschaftlicher Bemühungen bis heute weitestgehend ungeklärt. Zwillingsstudien weisen darauf hin, dass ADHS zu 70-80 % erblich bedingt ist. Aufgrund mehrerer Genom-Studien wird vermutet, dass es sich dabei um eine polygene Vererbbarkeit handelt und sowohl kleine (SNPs), verhältnismäßig häufig auftretende, als auch große (CNVs) verhältnismäßig seltene Genpolymorphismen beteiligt sind. Die Anzahl der potenziellen Risikogene für ADHS ist in den letzten Jahren kontinuierlich gestiegen, jedoch ist es nach wie vor unklar, inwiefern und durch welche biologischen Prozesse die meisten zur Neuropathologie und Symptomatik von ADHS Patienten beitragen. Diese Prozesse zu identifizieren ist von zentraler Bedeutung für ein besseres Verständnis der Erkrankung, der Identifizierung neuer Angriffsziele und somit, der Entwicklung gezielterer und möglicherweise personalisierter Behandlungsmöglichkeiten. 
Die vorliegende Arbeit befasst sich mit diesen Prozessen am Beispiel der potenziellen Risikogene GRM8, FOXP2 und GAD1. Durch die Etablierung und Validierung entsprechender (geneti-scher) Knockout und Knockdown Zebrafischmodelle und der anschließenden Untersuchung auf Verhaltens-, morphologische und funktionelle Veränderungen liefert die vorliegende Dissertation wichtige Erkenntnisse über die funktionelle Relevanz der einzelnen Kandidaten für die Neuropathologie und die Symptomatik von ADHS. Beispielsweise zeigen die erfassten Aktivitätsdaten von Knockdown und Knockout Larven, dass Grm8a, Grm8b, Foxp2 und Gad1b an der Regulation von Bewegungsaktivität beteiligt sind und dass dies, die korrekte Funktion GABAerger Prozesse bedarf. Des Weiteren liefert die Arbeit Hinweise, dass der Effekt im Subpallium/Striatum verankert ist. Jedoch ist aufgrund vorliegender und bereits publizierter Daten anzunehmen, dass im Falle der einzelnen Kandidaten, zum Teil unterschiedliche Me-chanismen wie die Transmittersynthese, die Transmitterfreisetzung, die Synapsenbildung und die Expression synaptischer Komponenten betroffen sind. Interessanterweise scheinen die durch die Kandidaten betroffenen Signalwege außerdem, laut erhobener Daten, am Wirkmechanismus von Methylphenidat beteiligt zu sein. Kurzum, die vorliegende Dissertation identifiziert die Beeinträchtigung GABAerger Signalübertragung eines, mutmaßlich subpallialen/striatalen aktivitäts-regulierenden neuronalen Netzwerks als neurobiologische Grundlage ADHS-assoziierter Hyperaktivität. Gleichzeitig präsentiert die Arbeit diese Prozesse als funktionelles Bindeglied zwischen der genetischen Veränderung von GRM8, FOXP2 und GAD1 und Hyperaktivität in ADHS. Folglich sind die entwicklungs- und neurobiologischen Mechanismen rund um die GABAerge Übertragung in diesem Netzwerk, und in diesem Zusammenhang die Funktion von Grm8a, (Grm8b), Foxp2 und Gad1b, spannende Ziele für zukünftige Projekte zur Erforschung der Ätiopathogenese und der Entwicklung neuer Therapien von Hyperakti-vität in ADHS. Neben der Rolle in ADHS-assoziierter Hyperaktivität, präsentieren die erhobenen Verhaltensdaten Grm8a, Grm8b und Gad1b außerdem, als interessante Kandidaten für die Erforschung komorbider Angststörung in ADHS. Foxp2 dagegen, wurde mit Hilfe einer Genexpressionsanalyse als Regulator zahlreicher ADHS Risikogene und Entwicklungsstörungs-übergreifenden genetischen und funktionellen Netzwerken, mit möglicher Relevanz für die Polygenie und Komorbidität von ADHS, identifiziert. Im Allgemeinen schafft die vorliegende Dissertation mit der Bestimmung der Genexpressionsmuster und Etablierung und Validierung der (genetischen) Zebrafischmodelle für Grm8a, Grm8b, Foxp2 und Gad1b die Grundlage, diese und weitere Aspekte in zukünftigen Forschungsprojekten zu untersuchen. Beispielsweise die Identifizierung der Netzwerke und Mechanismen, mit dessen Hilfe Grm8a, (Grm8b), Foxp2 und Gad1b in die GABAerge Signalübertragung eingreifen und so letztlich die Aktivität beeinflussen.
KW  - ADHD
KW  - Zebrafish
KW  - FOXP2
KW  - GRM8
KW  - GAD1
KW  - Genetic etiology
KW  - Animal model
KW  - Thigmotaxis
KW  - Locomotor activity
KW  - Hyperactivity
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257168
ER  - 
TY  - THES
A1  - Posch, Ines Juliane
T1  - Die retrospektive Beurteilung stationärer kinder- und jugendpsychiatrischer Behandlung nach 10 Jahren – Eine Nachbefragung ehemaliger Patienten der Klinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie des Universitätsklinikums Würzburg
T1  - The retrospective assessment of inpatient child and adolescent psychiatric treatment after 10 years - A follow-up survey of former patients of the Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy of Würzburg University Hospital
N2  - Fragestellung:
Pädagogische und medizinische Institutionen betreuen Kinder und Jugendliche, um Aufsicht, Beschulung, Erziehung, Therapie und Schutz sicherzustellen. Gleichwohl sind Kinder in institutioneller Betreuung potentiellen Gefährdungsmomenten bezüglich Misshandlung und Missbrauch ausgesetzt.
Methodik:
Im Rahmen der Etablierung des Schutzkonzeptes der Klinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie am Universitätsklinikum Würzburg wurde eine retrospektive Patientenbefragung durchgeführt. Das Untersuchungskollektiv bildeten alle ehemaligen stationären Patientinnen und Patienten der Jahre 2006 und 2007, die zum Katamnesezeitpunkt volljährig waren. Die Befragung erfolgte postalisch. Der Fragebogen umfasste neben Items zum Kontext von Gewalterfahrungen etablierte Skalen zur Erfassung von Behandlungszufriedenheit und Lebensqualität (FBB-K, WHO-BREF). 
Ergebnisse:
Von 568 ehemaligen Patientinnen und Patienten gaben 87 (15.3 %) eine gültige Rückantwort (59 weiblich, durchschnittliches Alter zum Befragungszeitpunkt: 24.5 Jahre). 35 ehemalige Patientinnen und Patienten (40.2 % der Teilnehmenden) gaben an, Gewalt während der stationären Behandlung erlebt (n=26) oder erlebt und ausgeübt (n=7) oder ausschließlich ausgeübt (n=2) zu haben. Gewalterfahrungen beinhalteten in den meisten Fällen emotionale Gewalt (34.5 %), aber auch körperliche (5.7 %) und sexuelle Gewalt (10.3 %). 
Schlussfolgerung:
Es zeigt sich ein signifikanter Zusammenhang zwischen Gewalterfahrungen einerseits sowie retrospektiver Behandlungszufriedenheit und aktueller Lebensqualität andererseits. Die Ergebnisse der Befragung unterstreichen die Bedeutung der Etablierung von Schutzkonzepten in Kliniken und anderen Institutionen.
N2  - Objective:
Educational and medical institutions care for children and adolescents to provide supervision, schooling, education, therapy and protection. Nevertheless, children in institutional care are exposed to potential danger in terms of maltreatment and abuse. 
Method:
Establishing the protection concept at the University Hospital for Child and Adolescent Psychiatry Würzburg a retrospective patient survey was conducted. The study population consisted of all former in-patient clients from 2006 and 2007, who were of age at the time of the catamnesis. The survey was conducted by mail. In addition to items on experiences of violence, the questionnaire included established scales for the assessment of treatment satisfaction and quality of life (FBB-K, WHO-BREF). 
Results:
Of 568 former patients 87 (15.3 %) gave a valid response (59 female, mean age at the time of the survey: 24.5 years). 35 former patients (40.2 % of participants) reported experiences of violence during their inpatient treatment (26 victims only, 7 experiences as victims and perpetrators, and 2 perpetrators only). Experiences as victims mainly included emotional violence (34.5 %), but also physical (5.7 %) and sexual violence (10.3 %).
Conclusion:
A significant correlation was found between experiences of violence on the one hand and retrospective treatment satisfaction and current quality of life on the other hand. The results of the survey underline the importance of establishing protection concepts in clinics and other institutions.
KW  - Kinder- und Jugendpsychiatrie
KW  - Kinderschutz
KW  - Gewalt
KW  - Missbrauch
KW  - Prävention
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-283135
ER  - 
TY  - JOUR
A1  - Buerger, Arne
A1  - Emser, Theresa
A1  - Seidel, Alexandra
A1  - Scheiner, Christin
A1  - von Schoenfeld, Cornelia
A1  - Ruecker, Viktoria
A1  - Heuschmann, Peter U.
A1  - Romanos, Marcel
T1  - DUDE - a universal prevention program for non-suicidal self-injurious behavior in adolescence based on effective emotion regulation: study protocol of a cluster-randomized controlled trial
JF  - Trials
N2  - Background
Non-suicidal self-injury (NSSI) has become a substantial public health problem. NSSI is a high-risk marker for the development and persistence of mental health problems, shows high rates of morbidity and mortality, and causes substantial health care costs. Thus, there is an urgent need for action to develop universal prevention programs for NSSI before adolescents begin to show this dangerous behavior. Currently, however, universal prevention programs are lacking.

Methods
The main objective of the present study is to evaluate a newly developed universal prevention program (“DUDE – Du und deine Emotionen / You and your emotions”), based on a skills-based approach in schools, in 3200 young adolescents (age 11–14 years). The effectiveness of DUDE will be investigated in a cluster-randomized controlled trial (RCT) in schools (N = 16). All groups will receive a minimal intervention called “Stress-free through the school day” as a mental health literacy program to prevent burnout in school. The treatment group (N = 1600; 8 schools) will additionally undergo the universal prevention program DUDE and will be divided into treatment group 1 (DUDE conducted by trained clinical psychologists; N = 800; 4 schools) and treatment group 2 (DUDE conducted by trained teachers; N = 800; 4 schools). The active control group (N = 1600; 8 schools) will only receive the mental health literacy prevention. Besides baseline assessment (T0), measurements will occur at the end of the treatment (T1) and at 6- (T2) and 12-month (T3) follow-up evaluations. The main outcome is the occurrence of NSSI within the last 6 months assessed by a short version of the Deliberate Self-Harm Inventory (DSHI-9) at the 1-year follow-up (primary endpoint; T3). Secondary outcomes are emotion regulation, suicidality, health-related quality of life, self-esteem, and comorbid psychopathology and willingness to change.

Discussion
DUDE is tailored to diminish the incidence of NSSI and to prevent its possible long-term consequences (e.g., suicidality) in adolescents. It is easy to access in the school environment. Furthermore, DUDE is a comprehensive approach to improve mental health via improved emotion regulation.
KW  - universal prevention
KW  - NSSI
KW  - self-injury
KW  - emotion regulation
KW  - RCT
KW  - school-based prevention
KW  - adolescence
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265874
VL  - 23
ER  - 
TY  - JOUR
A1  - Briegel, Wolfgang
A1  - Hoyer, Juliane
T1  - Psychiatric disorders and distal 21q deletion — a case report
JF  - International Journal of Environmental Research and Public Health
N2  - Partial deletion of chromosome 21q is a very rare genetic condition with highly variable phenotypic features including heart defects, high or cleft palate, brain malformations (e.g., cerebral atrophy), developmental delay and intellectual disability. So far, there is very limited knowledge about psychiatric disorders and their effective treatment in this special population. To fill this gap, the authors present the case of an initially five-year-old girl with distal deletion (del21q22.2) and comorbid oppositional defiant disorder (main psychiatric diagnosis) covering a period of time of almost four years comprising initial psychological/psychiatric assessment, subsequent treatment with Parent–Child Interaction Therapy (PCIT), and follow-up assessments. Post-intervention results including a 19-month follow-up indicated good overall efficacy of PCIT and high parental satisfaction with the treatment. This case report makes a substantial contribution to enhancing knowledge on psychiatric comorbidity and its effective treatment in patients with terminal 21q deletion. Moreover, it emphasizes the necessity of multidisciplinarity in diagnosis and treatment due to the variety of anomalies associated with 21q deletion. Regular screenings for psychiatric disorders and (if indicated) thorough psychological and psychiatric assessment seem to be reasonable in most affected children, as children with developmental delays are at increased risk of developing psychiatric disorders. As demonstrated with this case report, PCIT seems to be a good choice to effectively reduce disruptive behaviors in young children with partial deletion of chromosome 21q.
KW  - chromosome 21
KW  - distal deletion
KW  - 21q22.2-q22.3
KW  - oppositional defiant disorder
KW  - attention deficit/hyperactivity disorder
KW  - Parent–Child Interaction Therapy (PCIT)
KW  - case report
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203769
SN  - 1660-4601
VL  - 17
IS  - 9
ER  - 
TY  - THES
A1  - Peters, Katharina
T1  - Biological Substrates of Waiting Impulsivity in Children and Adolescents with and without ADHD
T1  - Biologische Substrate der Warte-Impulsivität bei Kindern und Jugendlichen mit und ohne ADHS
N2  - 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.
N2  - Im Mittelpunkt der vorliegenden Arbeit steht das Konzept der Warte-Impulsivität (WI), definiert als die Fähigkeit der Antwort-Inhibition, während eine Belohnung erwartet wird, welche mittels des 4-choice serial reaction time task (4-CSRTT) erfasst werden kann. Es sollte untersucht werden ob und auf welche Weise WI und der 4-CSRTT genutzt werden können, um die neurobiologischen Grundlagen der Aufmerksamkeits-Defizit/Hyperaktivitäts-Störung (ADHS) besser zu verstehen. 
Es wurden zwei Studien durchgeführt: In einer ersten Studie wurde der Zusammenhang zwischen 4-CSRTT Verhaltensmaßen, ihren neuronalen Korrelaten und den ADHS Kern-Symptomen, Unaufmerksamkeit (IA) und Hyperaktivität/Impulsivität (H/I), überprüft. Es wurden 90 Kinder und Jugendliche mit (n=44) und ohne (n=46) ADHS-Diagnose unter-sucht. Erwartungsgemäß war IA, auf funktioneller und struktureller Ebene, mit dorsolate-ralen präfrontalen Hirnregionen assoziiert, die für Exekutivfunktionen und die Aufmerk-samkeitskontrolle zuständig sind. Stärkere Ausprägungen von IA und H/I gingen mit ver-ringerter Aktivität im rechten ventrolateralen präfrontalen Cortex (PFC), einer zentralen Struktur für die Inhibition von Antworten, einher. Moderationsanalysen ergaben, dass diese H/I-assoziierte geringere Aktivität nicht direkt mit Einschränkungen auf Verhaltens-ebene zusammenhing: Die Hirnaktivierung war nur in Abwesenheit von H/I Symptomen ein signifikanter Prädiktor der Sorgfaltsleistung, was bei stärkerer ADHS-Symptomatik nicht der Fall war. Darüber hinaus wiesen die Ergebnisse auf einen Zusammenhang zwi-schen H/I und dysfunktionaler Belohnungsverarbeitung hin. Beide Symptombereiche korrelierten während der Belohnungserwartung positiv mit Aktivität im Hippocampus (HC). Zusätzlich zeigte sich, dass bei stark ausgeprägten H/I-Symptomen eine höhere HC-Aktivierung mit höherer Motivation auf Verhaltensebene einher ging. Dies deutet da-rauf hin, dass Lernprozesse und ein Bewusstsein für Kontingenz bei der Verarbeitung von Belohnungen bei ADHS eine Rolle spielen könnten. 
In einer zweiten Studie wurde eine mögliche serotonerge Modulation von WI und dem WI-ADHS Zusammenhang betrachtet. Eine Teilstichprobe von 86 Probanden aus Studie I wurde untersucht. Eine funktionelle Genvariante des Enzyms, welches den entschei-denden Schritt in der Serotonin-Synthese im Gehirn katalysiert, wurde bezüglich seiner Effekte auf WI-Verhalten sowie Struktur und Funktion des WI-Netzwerks getestet. Mode-rationsanalysen zeigten, dass auf Verhaltensebene eine negative Korrelation zwischen IA und der Sorgfaltsleistung bei GG-Homozygoten, aber kein signifikanter Zusammenhang für Träger des T-Allels bestand. Unterschiedliche Effekte von serotonerger Modulation auf die Aufmerksamkeitsleistung in Abhängigkeit von ADHS-Symptomatik wurden be-reits in der Literatur berichtet. Ein Trend-Effekt für die Interaktion zwischen Genotyp und IA und dem Volumen des rechten Gyrus frontalis medius wurde als Hinweis auf eine Be-teiligung des PFC in diesem Zusammenhang interpretiert. Auf Grund möglicher Entwick-lungseffekte, ist aber ein komplexeres Zusammenspiel der verschiedenen Faktoren an-zunehmen. Interaktionseffekte von Genotyp und IA für Aktivität der Amygdala (AMY) und dem HC sowie für H/I und Genotyp bezüglich des Volumens der rechten AMY könn-ten auf eine serotonerge Modulation der emotionalen Bewertung von Belohnung hindeu-ten, die je nach ADHS-Symptomatik unterschiedlich ausfällt. 
Zusammenfassend zeigte sich, dass mittels des 4-CSRTT ADHS-relevante Aspekte von Impulsivität untersucht werden können: Schwierigkeiten der Antwortinhibition im Kontext von Belohnungserwartung. Sowohl IA als auch H/I hatten unterschiedlichen Einfluss auf WI. Sie sollten in der ADHS-Forschung differenziert betrachtet werden. Die Ergebnisse der zweiten Studie verdeutlichen, dass die serotonerge Transmission bei ADHS beson-ders bei Aufmerksamkeitsprozessen und emotionaler Verarbeitung eine Rolle spielt. Die vorliegenden Befunde sollten in homogeneren Alterskohorten überprüft werden. Sie ma-chen jedoch Hoffnung, dass mittels des 4-CSRTT und dimensionaler Forschungsansätze psychiatrische Störungen der Impulskontrolle besser verstanden werden können.
KW  - Aufmerksamkeitsdefizit-Syndrom
KW  - Impulsivität
KW  - ADHD
KW  - Waiting Impulsivity
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246368
ER  - 
TY  - JOUR
A1  - Waltmann, Maria
A1  - Schlagenhauf, Florian
A1  - Deserno, Lorenz
T1  - Sufficient reliability of the behavioral and computational readouts of a probabilistic reversal learning task
JF  - Behavior Research Methods
N2  - 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.
KW  - probabilistic reversal learning
KW  - reliability
KW  - reinforcement learning
KW  - computational modeling
KW  - hierarchical modeling
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324246
SN  - 1554-3528
VL  - 54
IS  - 6
ER  - 
TY  - JOUR
A1  - Taurines, R.
A1  - Fekete, S.
A1  - Preuss-Wiedenhoff, A.
A1  - Warnke, A.
A1  - Wewetzer, C.
A1  - Plener, P.
A1  - Burger, R.
A1  - Gerlach, M.
A1  - Romanos, M.
A1  - Egberts, K. M.
T1  - Therapeutic drug monitoring in children and adolescents with schizophrenia and other psychotic disorders using risperidone
JF  - Journal of Neural Transmission
N2  - 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.
KW  - risperidone
KW  - children
KW  - serum concentration
KW  - schizophrenia
KW  - therapeutic drug monitoring
KW  - pharmacovigilance
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324833
VL  - 129
IS  - 5-6
ER  - 
TY  - THES
A1  - López de Miguel, Pilar
T1  - Patientenzufriedenheit mit dem Aufklärungsgespräch
T1  - Patient satisfaction with informed consent
N2  - Ziele: Das Ziel der vorliegenden Arbeit ist eine standardisierte Analyse der Patientenzufriedenheit mit dem Aufklärungsgespräch und die mögliche Einflussfaktoren, die hier eine Rolle spielen können, zu bieten.

Methodik: Es wurden 189 Fragebögen bzw. Aufklärungsgespräche in den Kliniken für Anästhesie 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-Selektivität. Die Kriteriumsvalidität konnte bestätigt werden jedoch nicht die diskriminante Validität. Die Patienten waren zufriedener mit Ärzten, die Deutsch als Muttersprache angaben, mit längeren Aufklärungsgesprächen und mit Fachärzten im Vergleich zu Assistenzärzten. Eine höhere allgemeine Lebenszufriedenheit war mit höherer Patientenzufriedenheit mit dem Aufklärungsgespräch assoziiert. Der moralistische Bias kann einen Störfaktor der Validität der Messungen darstellen. 

Zusammenfassung: Eine angemessene Gesprächdauer, die deutsche Muttersprache und der Facharztstatus des aufklärenden Arztes haben einen positiven Einfluss auf die Patientenzufriedenheit mit dem Aufklärungsgespräch. Um sicher zu stellen, welche von diesen drei Faktoren besondere Wichtigkeit besitzt, werden weitere Untersuchungen benötigt.
N2  - Objective: The aim of the present study is to provide a standardized analysis of patient 
satisfaction with informed consent process and the possible influencing factors that can play a role here.

Methoden:  189 questionnaires/informed consent were examined in the clinics for anesthesia and internal medicine in St. Josef Hospital and surgery and child and adolescent psychiatry in Leopoldina Hospital in Schweinfurt.

Results: The questionnaire used was reliable. There was poor item selectivity. The criterion validity was confirmed but not the discriminant validity. Patients were more satisfied with doctors who spoke German as their native language, with longer duration oft the informed consent process and with specialists compared to assistant doctors. Higher general life satisfaction was associated with higher patient satisfaction. The moralistic bias can represent a confounding factor in the validity of the measurements.

Conclusion: An appropriate duration of the conversation, the German native language and the doctor's specialist status have a positive influence on patient satisfaction with informed consent process. Further research is needed to determine which of these three factors is particularly important.
KW  - Zufriedenheit
KW  - Patientenzufriedenheit
KW  - Informed consent
KW  - Aufklärung
KW  - Aufklärungsgespräch
KW  - Satisfaction
Y1  - 2024
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-347201
ER  - 
TY  - JOUR
A1  - Fekete, Stefanie
A1  - Kulpok, Christine
A1  - Taurines, Regina
A1  - Egberts, Karin
A1  - Geissler, Julia
A1  - Gerlach, Manfred
A1  - Malonga Makosi, Dorothée
A1  - König, Jochem
A1  - Urschitz, Michael S.
A1  - Toni, Irmgard
A1  - Neubert, Antje
A1  - Romanos, Marcel
T1  - Value of a web-based pediatric drug information system to prevent serious adverse drug reactions in child and adolescent psychiatry
JF  - Journal of Neural Transmission
N2  - 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.
KW  - adverse effects
KW  - pharmacovigilance
KW  - drug safety
KW  - psychotropic drugs
KW  - mental health
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324817
VL  - 130
IS  - 1
ER  - 
TY  - JOUR
A1  - Buerger, Arne
A1  - Vloet, Timo D.
A1  - Haber, Lisa
A1  - Geissler, Julia M.
T1  - Third-wave interventions for eating disorders in adolescence - systematic review with meta-analysis
JF  - Borderline Personality Disorder and Emotion Dysregulation
N2  - Context: Third-wave therapies have demonstrated efficacy as a treatment option for EDs in adulthood. Data on the suitability for EDs in adolescence are lacking.

Objective: To estimate the efficacy of third-wave interventions to reduce ED symptoms in adolescents in randomized controlled trials (RCTs) and uncontrolled studies.

Data sources: We systematically reviewed the databases PubMed (1976-January 2021), PsycINFO (1943-January 2021), and the Cochrane database (1995-January 2021) for English-language articles on third-wave therapies. References were screened for further publications of interest.

Study selection: RCTs and pre-post studies without control group, comprising patients aged 11-21 years (mean age = 15.6 years) with an ED diagnosis (anorexia nervosa, bulimia nervosa, binge eating disorder, eating disorder not otherwise specified) investigating the efficacy of third-wave psychological interventions were included. Efficacy had to be evaluated according to the Eating Disorder Examination or Eating Disorder Examination-Questionnaire, the Eating Disorder Inventory-2, the Eating Disorder Inventory-3, or the Structured Interview for Anorexic and Bulimic Disorders for DSM-IV and ICD-10. The outcome assessed in the meta-analysis was the EDE total score.

Data extraction: Independent extraction of data by two authors according to a pre-specified data extraction sheet and quality indicators.

Data synthesis: We identified 1000 studies after removal of duplicates, assessed the full texts of 48 articles for eligibility, and included 12 studies with a total of 487 participants (female 97.3%/male 2.6%) in the qualitative synthesis and seven studies in the meta-analysis. Articles predominantly reported uncontrolled pre-post trials of low quality, with only two published RCTs. Treatments focused strongly on dialectical behaviour therapy (n = 11). We found moderate effects of third-wave therapies on EDE total score interview/questionnaire for all EDs (d = - 0.67; z = - 5.53; CI95% = - 0.83 to - 0.59). Descriptively, the effects appeared to be stronger in patients with BN and BED.

Conclusion: At this stage, it is not feasible to draw conclusions regarding the efficacy of third-wave interventions for the treatment of EDs in adolescence due to the low quality of the empirical evidence. Since almost all of the identified studies used DBT, it is unfortunately not possible to assess other third-wave treatments' efficacy.
KW  - DBT
KW  - adolescence
KW  - eating disorders
KW  - third-wave psychotherapy
KW  - meta-analysis
KW  - review
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260545
VL  - 8
ER  -