TY - GEN A1 - Fekete, Stefanie A1 - Egberts, K. A1 - Preissler, T. A1 - Wewetzer, C. A1 - Mehler-Wex, C. A1 - Romanos, M. A1 - Gerlach, M. T1 - Correction to: Estimation of a preliminary therapeutic reference range for children and adolescents with tic disorders treated with tiapride T2 - European Journal of Clinical Pharmacology N2 - Correction to: European Journal of Clinical Pharmacology (2021) 77:163–170 https://doi.org/10.1007/s00228-020-03000-0 KW - Erratum Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-329467 VL - 77 IS - 8 ER - TY - JOUR A1 - Kuhn, Manuel A1 - Scharfenort, Robert A1 - Schümann, Dirk A1 - Schiele, Miriam A. A1 - Münsterkötter, Anna L. A1 - Deckert, Jürgen A1 - Domschke, Katharina A1 - Haaker, Jan A1 - Kalisch, Raffael A1 - Pauli, Paul A1 - Reif, Andreas A1 - Romanos, Marcel A1 - Zwanzger, Peter A1 - Lonsdorf, Tina B. T1 - Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament JF - Social Cognitive and Affective Neuroscience N2 - 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. KW - VBM KW - childhood maltreatment KW - adversity KW - stressful life events KW - mismatch KW - allostatic load Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189645 VL - 11 IS - 4 ER - TY - JOUR A1 - Emser, Theresa S. A1 - Johnston, Blair A. A1 - Steele, J. Douglas A1 - Kooij, Sandra A1 - Thorell, Lisa A1 - Christiansen, Hanna T1 - Assessing ADHD symptoms in children and adults: evaluating the role of objective measures JF - Behavioral and Brain Functions N2 - Background: Diagnostic guidelines recommend using a variety of methods to assess and diagnose ADHD. Applying subjective measures always incorporates risks such as informant biases or large differences between ratings obtained from diverse sources. Furthermore, it has been demonstrated that ratings and tests seem to assess somewhat different constructs. The use of objective measures might thus yield valuable information for diagnosing ADHD. This study aims at evaluating the role of objective measures when trying to distinguish between individuals with ADHD and controls. Our sample consisted of children (n = 60) and adults (n = 76) diagnosed with ADHD and matched controls who completed self- and observer ratings as well as objective tasks. Diagnosis was primarily based on clinical interviews. A popular pattern recognition approach, support vector machines, was used to predict the diagnosis. Results: We observed relatively high accuracy of 79% (adults) and 78% (children) applying solely objective measures. Predicting an ADHD diagnosis using both subjective and objective measures exceeded the accuracy of objective measures for both adults (89.5%) and children (86.7%), with the subjective variables proving to be the most relevant. Conclusions: We argue that objective measures are more robust against rater bias and errors inherent in subjective measures and may be more replicable. Considering the high accuracy of objective measures only, we found in our study, we think that they should be incorporated in diagnostic procedures for assessing ADHD. KW - ADHD KW - support vector machines KW - classification KW - objective assessment KW - children/adults Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175717 VL - 14 IS - 11 ER - TY - JOUR A1 - Aster, Hans-Christoph A1 - Romanos, Marcel A1 - Walitza, Susanne A1 - Gerlach, Manfred A1 - Mühlberger, Andreas A1 - Rizzo, Albert A1 - Andreatta, Marta A1 - Hasenauer, Natalie A1 - Hartrampf, Philipp E. A1 - Nerlich, Kai A1 - Reiners, Christoph A1 - Lorenz, Reinhard A1 - Buck, Andreas K. A1 - Deserno, Lorenz T1 - Responsivity of the striatal dopamine system to methylphenidate — A within-subject I-123-β-CIT-SPECT study in male children and adolescents with attention-deficit/hyperactivity disorder JF - Frontiers in Psychiatry N2 - Background: Methylphenidate (MPH) is the first-line pharmacological treatment of attention-deficit/hyperactivity disorder (ADHD). MPH binds to the dopamine (DA) transporter (DAT), which has high density in the striatum. Assessments of the striatal dopamine transporter by single positron emission computed tomography (SPECT) in childhood and adolescent patients are rare but can provide insight on how the effects of MPH affect DAT availability. The aim of our within-subject study was to investigate the effect of MPH on DAT availability and how responsivity to MPH in DAT availability is linked to clinical symptoms and cognitive functioning. Methods Thirteen adolescent male patients (9–16 years) with a diagnosis of ADHD according to the DSM-IV and long-term stimulant medication (for at least 6 months) with MPH were assessed twice within 7 days using SPECT after application of I-123-β-CIT to examine DAT binding potential (DAT BP). SPECT measures took place in an on- and off-MPH status balanced for order across participants. A virtual reality continuous performance test was performed at each time point. Further clinical symptoms were assessed for baseline off-MPH. Results On-MPH status was associated with a highly significant change (−29.9%) of striatal DAT BP as compared to off-MPH (t = −4.12, p = 0.002). A more pronounced change in striatal DAT BP was associated with higher off-MPH attentional and externalizing symptom ratings (Pearson r = 0.68, p = 0.01). Striatal DAT BP off-MPH, but not on-MPH, was associated with higher symptom ratings (Pearson r = 0.56, p = 0.04). Conclusion Our findings corroborate previous reports from mainly adult samples that MPH changes striatal DAT BP availability and suggest higher off-MPH DAT BP, likely reflecting low baseline DA levels, as a marker of symptom severity. KW - methylphenidate KW - attention deficit/hyperactivity disorder (ADHD) KW - striatum KW - single photon emission computed tomography (SPECT) KW - responsivity KW - caudate nucleus KW - dopamine transporter (DAT) Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270862 SN - 1664-0640 VL - 13 ER - TY - JOUR A1 - Susewind, Moritz A1 - Walkowitz, Gari T1 - Symbolic Moral Self-Completion – Social Recognition of Prosocial Behavior Reduces Subsequent Moral Striving JF - Frontiers in Psychology N2 - 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. KW - prosocial behavior KW - social influence KW - social recognition KW - self-regulation KW - moral balancing Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211327 SN - 1664-1078 VL - 11 ER - TY - JOUR A1 - Ziegler, Georg C. A1 - Radtke, Franziska A1 - Vitale, Maria Rosaria A1 - Preuße, André A1 - Klopocki, Eva A1 - Herms, Stefan A1 - Lesch, Klaus-Peter T1 - Generation of multiple human iPSC lines from peripheral blood mononuclear cells of two SLC2A3 deletion and two SLC2A3 duplication carriers JF - Stem Cell Research N2 - 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. KW - congenital heart-deffects KW - transporter gene SLC2A3 KW - copy-number variation Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-264696 VL - 56 ER - TY - JOUR A1 - Grünblatt, Edna A1 - Oneda, Beatrice A1 - Ekici, Arif B. A1 - Ball, Juliane A1 - Geissler, Julia A1 - Uebe, Steffen A1 - Romanos, Marcel A1 - Rauch, Anita A1 - Walitza, Susanne T1 - High resolution chromosomal microarray analysis in paediatric obsessive-compulsive disorder JF - BMC Medical Genomics N2 - 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. KW - Medicine KW - OCD KW - CNV KW - Enrichment analysis KW - De-novo KW - Early-onset Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172791 VL - 10 IS - 68 ER - TY - THES A1 - Daub, Jonas T1 - Der Einfluss von Alter und Ängstlichkeit auf die Furchtgeneralisierung und die Aufmerksamkeitslenkung bei gesunden Kindern und Jugendlichen T1 - The influence of age and anxiety on fear generalization and attentional processes in healthy children and adolescents N2 - Mittels einer klinischen Studie wurden die Furchtgeneralisierung und Aufmerksamkeitslenkung von 44 gesunden Kindern und Jugendlichen im Alter von 9-17 Jahren untersucht. Eine Übergeneralisierung konditionierter Furcht sowie veränderte Aufmerksamkeitsprozesse werden in zahlreichen Arbeiten mit der Entstehung und Aufrechterhaltung von Angsterkrankungen in Verbindung gebracht. Der Hauptteil der Forschung beschränkte sich bislang auf die Untersuchung von erwachsenen Probanden. Da Angsterkrankungen jedoch häufig bereits im Kindes- und Jugendalter entstehen und sich in der Erforschung psychiatrischer Erkrankungen zunehmend eine dimensionale Betrachtungsweise durchsetzt, bestand das Ziel der Studie darin, etwaige Alterseffekte und den Einfluss der Ängstlichkeit auf die genannten Phänomene bei gesunden Probanden zu untersuchen. Darüber hinaus wurde ein potentiell präventiver Ansatz erforscht. Im Ergebnis zeigten sich in den Gruppenvergleichen keine relevanten Differenzen. Interessanterweise deutete sich in der Gruppe der älteren Probanden entgegen der Erwartung eine verstärkte Furchtgeneralisierung an, die womöglich mit einer veränderten Beziehung zu Furcht und Risiko in der Adoleszenz zusammenhängt. Aus den Befunden ergibt sich die Notwendigkeit weiterer, prospektiver Arbeiten, um unser Verständnis der Ätiologie von Angsterkrankungen zu verbessern. Weiterhin ist noch offen, inwiefern es sich bei der Übergeneralisierung und einer veränderten Aufmerksamkeitslenkung um Risikofaktoren für die Entwicklung von Angsterkrankungen oder vielmehr um Epiphänomene handelt, die erst mit Ausbruch der Erkrankung auftreten. Der Einsatz von Methoden der virtuellen Realität erscheint besonders geeignet, diese Prozesse zukünftig noch besser zu erforschen. N2 - In this clinical study fear generalization and attentional processes have been investigated in 44 healthy children and adolescents aged 9-17 years. Overgeneralization of conditioned fear and altered attentional processes have been linked to the development and maintenance of anxiety disorders in numerous studies. The majority of research to date has been limited to the study of adult subjects. However, since anxiety disorders often develop in childhood and adolescence and a dimensional approach has become increasingly important in the study of psychiatric disorders, the aim of the study was to investigate age effects and the influence of anxiety on the aforementioned phenomena in healthy subjects. In addition, a potential preventive approach has been studied. The results showed no relevant differences in the group comparisons. Interestingly and contrary to expectations, there was a trend for increased fear generalization in the group of older subjects, which can possibly be related to a changed relationship to fear and risk in adolescence. The findings suggest the need for further, prospective work to improve our understanding of the aetiology of anxiety disorders. Furthermore, it is still open to what extent overgeneralization and altered attentional processes are risk factors for the development of anxiety disorders or rather epiphenomena that only appear with the onset of the disorder. The use of virtual reality methods seems particularly suitable for researching these processes even better in the future. KW - Angst KW - Furcht KW - Anxiety KW - Fear KW - Klinisches Experiment KW - Furchtgeneralisierung KW - Aufmerksamkeitsprozesse KW - Angsterkrankungen KW - Kinder- und Jugendpsychiatrie KW - klinische Studie KW - fear generalization KW - attentional processes KW - anxiety disorders KW - child and adolescent psychiatry KW - clinical study Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300100 ER - TY - JOUR A1 - Hautmann, Christopher A1 - Döpfner, Manfred A1 - Katzmann, Josepha A1 - Schürmann, Stephanie A1 - Wolff Metternich-Kaizman, Tanja A1 - Jaite, Charlotte A1 - Kappel, Viola A1 - Geissler, Julia A1 - Warnke, Andreas A1 - Jacob, Christian A1 - Hennighausen, Klaus A1 - Haack-Dees, Barbara A1 - Schneider-Momm, Katja A1 - Philipsen, Alexandra A1 - Matthies, Swantje A1 - Rösler, Michael A1 - Retz, Wolfgang A1 - Gontard, Alexander von A1 - Sobanski, Esther A1 - Alm, Barbara A1 - Hohmann, Sarah A1 - Häge, Alexander A1 - Poustka, Luise A1 - Colla, Michael A1 - Gentschow, Laura A1 - Freitag, Christine M. A1 - Becker, Katja A1 - Jans, Thomas T1 - Sequential treatment of ADHD in mother and child (AIMAC study): importance of the treatment phases for intervention success in a randomized trial JF - BMC Psychiatry N2 - 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. KW - mothers KW - children KW - adult treatment KW - parent training KW - efficacy Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227930 VL - 18 ER - TY - JOUR A1 - Föcker, Manuel A1 - Timmesfeld, Nina A1 - Bühlmeier, Judith A1 - Zwanziger, Denise A1 - Führer, Dagmar A1 - Grasemann, Corinna A1 - Ehrlich, Stefan A1 - Egberts, Karin A1 - Fleischhaker, Christian A1 - Wewetzer, Christoph A1 - Wessing, Ida A1 - Seitz, Jochen A1 - Herpertz-Dahlmann, Beate A1 - Hebebrand, Johannes A1 - Libuda, Lars T1 - 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 JF - Nutrients N2 - (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. KW - vitamin D KW - supplements KW - anorexia nervosa KW - depressive symptoms KW - adolescents Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242662 SN - 2072-6643 VL - 13 IS - 7 ER - TY - JOUR A1 - Palladino, Viola Stella A1 - Chiocchetti, Andreas G. A1 - Frank, Lukas A1 - Haslinger, Denise A1 - McNeill, Rhiannon A1 - Radtke, Franziska A1 - Till, Andreas A1 - Haupt, Simone A1 - Brüstle, Oliver A1 - Günther, Katharina A1 - Edenhofer, Frank A1 - Hoffmann, Per A1 - Reif, Andreas A1 - Kittel-Schneider, Sarah T1 - Energy metabolism disturbances in cell models of PARK2 CNV carriers with ADHD JF - Journal of Clinical Medicine N2 - 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. KW - ADHD KW - hiPSC KW - PARK2 KW - mitochondria KW - disease modelling Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-220074 SN - 2077-0383 VL - 9 IS - 12 ER - TY - JOUR A1 - Härtel, Christoph A1 - Spiegler, Juliane A1 - Fortmann, Ingmar A1 - Astiz, Mariana A1 - Oster, Henrik A1 - Siller, Bastian A1 - Viemann, Dorothee A1 - Keil, Thomas A1 - Banaschewski, Tobias A1 - Romanos, Marcel A1 - Herting, Egbert A1 - Göpel, Wolfgang T1 - 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 JF - Nutrients N2 - (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. KW - breastfeeding KW - probiotic prophylaxis KW - preterm children KW - strength and difficulties KW - inattention/hyperactivity KW - intelligence Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216319 SN - 2072-6643 VL - 12 IS - 11 ER - TY - JOUR A1 - Plum, Sarah A1 - Eggers, Britta A1 - Helling, Stefan A1 - Stepath, Markus A1 - Theiss, Carsten A1 - Leite, Renata E. P. A1 - Molina, Mariana A1 - Grinberg, Lea T. A1 - Riederer, Peter A1 - Gerlach, Manfred A1 - May, Caroline A1 - Marcus, Katrin T1 - Proteomic characterization of synaptosomes from human substantia nigra indicates altered mitochondrial translation in Parkinson's disease JF - Cells N2 - 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. KW - synaptosomes KW - proteomics KW - Parkinson's disease KW - substantia nigra pars compacta KW - mitochondrial pathology KW - mitochondrial translation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219978 SN - 2073-4409 VL - 9 IS - 12 ER - TY - JOUR A1 - Aster, Hans-Christoph A1 - Evdokimov, Dimitar A1 - Braun, Alexandra A1 - Üçeyler, Nurcan A1 - Kampf, Thomas A1 - Pham, Mirko A1 - Homola, György A. A1 - Sommer, Claudia T1 - CNS imaging characteristics in fibromyalgia patients with and without peripheral nerve involvement JF - Scientific Reports N2 - We tested the hypothesis that reduced skin innervation in fibromyalgia syndrome is associated with specific CNS changes. This prospective case–control study included 43 women diagnosed with fibromyalgia syndrome and 40 healthy controls. We further compared the fibromyalgia subgroups with reduced (n = 21) and normal (n = 22) skin innervation. Brains were analysed for cortical volume, for white matter integrity, and for functional connectivity. Compared to controls, cortical thickness was decreased in regions of the frontal, temporal and parietal cortex in the fibromyalgia group as a whole, and decreased in the bilateral pericalcarine cortices in the fibromyalgia subgroup with reduced skin innervation. Diffusion tensor imaging revealed a significant increase in fractional anisotropy in the corona radiata, the corpus callosum, cingulum and fornix in patients with fibromyalgia compared to healthy controls and decreased FA in parts of the internal capsule and thalamic radiation in the subgroup with reduced skin innervation. Using resting-state fMRI, the fibromyalgia group as a whole showed functional hypoconnectivity between the right midfrontal gyrus and the posterior cerebellum and the right crus cerebellum, respectively. The subgroup with reduced skin innervation showed hyperconnectivity between the inferior frontal gyrus, the angular gyrus and the posterior parietal gyrus. Our results suggest that the subgroup of fibromyalgia patients with pronounced pathology in the peripheral nervous system shows alterations in morphology, structural and functional connectivity also at the level of the encephalon. We propose considering these subgroups when conducting clinical trials. KW - fibromyalgia syndrome KW - CNS imaging KW - peripheral nerve involvement Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300562 VL - 12 IS - 1 ER - TY - JOUR A1 - Hammerle, Florian A1 - Huss, Michael A1 - Ernst, Verena A1 - Bürger, Arne T1 - Thinking dimensional: prevalence of DSM-5 early adolescent full syndrome, partial and subthreshold eating disorders in a cross-sectional survey in German schools JF - BMJ Open N2 - 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." KW - syndrome Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164734 VL - 6 IS - e010843 ER - TY - JOUR A1 - Kuhlmann, S.M. A1 - Huss, M. A1 - Bürger, A. A1 - Hammerle, F. T1 - Coping with stress in medical students: results of a randomized controlled trial using a mindfulness-based stress prevention training (MediMind) in Germany JF - BMC Medical Education N2 - 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. KW - Medical students KW - Distress KW - Stress KW - Stress prevention KW - Mindfulness Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164593 VL - 16 ER - TY - JOUR A1 - Kolar, David R. A1 - Hammerle, Florian A1 - Jenetzky, Ekkehart A1 - Huss, Michael A1 - Bürger, Arne T1 - Aversive tension in female adolescents with Anorexia Nervosa: a controlled ecological momentary assessment using smartphones JF - BMC Psychiatry N2 - 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. KW - Anorexia nervosa KW - Adolescence KW - Aversive tension KW - Ecological momentary assessment KW - Emotion regulation KW - Eating disorder KW - Smartphones Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164720 VL - 16 IS - 97 ER - TY - JOUR A1 - Wulf, Maximilian A1 - Barkovits, Katalin A1 - Schork, Karin A1 - Eisenacher, Martin A1 - Riederer, Peter A1 - Gerlach, Manfred A1 - Eggers, Britta A1 - Marcus, Katrin T1 - The proteome of neuromelanin granules in dementia with Lewy bodies JF - Cells N2 - 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. KW - neuromelanin granules KW - neurodegeneration KW - dementia with Lewy bodies KW - proteomics KW - stress granules KW - substantia nigra pars compacta Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297465 SN - 2073-4409 VL - 11 IS - 22 ER - TY - JOUR A1 - Herzog, Katharina A1 - Andreatta, Marta A1 - Schneider, Kristina A1 - Schiele, Miriam A. A1 - Domschke, Katharina A1 - Romanos, Marcel A1 - Deckert, Jürgen A1 - Pauli, Paul T1 - Reducing Generalization of Conditioned Fear: Beneficial Impact of Fear Relevance and Feedback in Discrimination Training JF - Frontiers in Psychology N2 - 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. KW - fear generalization KW - feedback KW - discrimination training KW - fear-relevant training KW - classical conditioning Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239970 SN - 1664-1078 VL - 12 ER - TY - JOUR A1 - Weselek, Grit A1 - Keiner, Silke A1 - Fauser, Mareike A1 - Wagenführ, Lisa A1 - Müller, Julia A1 - Kaltschmidt, Barbara A1 - Brandt, Moritz D. A1 - Gerlach, Manfred A1 - Redecker, Christoph A1 - Hermann, Andreas A1 - Storch, Alexander T1 - Norepinephrine is a negative regulator of the adult periventricular neural stem cell niche JF - Stem Cells N2 - 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. KW - adult neurogenesis KW - hippocampus KW - noradrenaline KW - norepinephrine KW - olfactory bulb neurogenesis KW - subventricular zone Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218250 VL - 38 IS - 9 SP - 1188 EP - 1201 ER - TY - JOUR A1 - Farmer, Adam D. A1 - Strzelczyk, Adam A1 - Finisguerra, Alessandra A1 - Gourine, Alexander V. A1 - Gharabaghi, Alireza A1 - Hasan, Alkomiet A1 - Burger, Andreas M. A1 - Jaramillo, Andrés M. A1 - Mertens, Ann A1 - Majid, Arshad A1 - Verkuil, Bart A1 - Badran, Bashar W. A1 - Ventura-Bort, Carlos A1 - Gaul, Charly A1 - Beste, Christian A1 - Warren, Christopher M. A1 - Quintana, Daniel S. A1 - Hämmerer, Dorothea A1 - Freri, Elena A1 - Frangos, Eleni A1 - Tobaldini, Eleonora A1 - Kaniusas, Eugenijus A1 - Rosenow, Felix A1 - Capone, Fioravante A1 - Panetsos, Fivos A1 - Ackland, Gareth L. A1 - Kaithwas, Gaurav A1 - O'Leary, Georgia H. A1 - Genheimer, Hannah A1 - Jacobs, Heidi I. L. A1 - Van Diest, Ilse A1 - Schoenen, Jean A1 - Redgrave, Jessica A1 - Fang, Jiliang A1 - Deuchars, Jim A1 - Széles, Jozsef C. A1 - Thayer, Julian F. A1 - More, Kaushik A1 - Vonck, Kristl A1 - Steenbergen, Laura A1 - Vianna, Lauro C. A1 - McTeague, Lisa M. A1 - Ludwig, Mareike A1 - Veldhuizen, Maria G. A1 - De Couck, Marijke A1 - Casazza, Marina A1 - Keute, Marius A1 - Bikson, Marom A1 - Andreatta, Marta A1 - D'Agostini, Martina A1 - Weymar, Mathias A1 - Betts, Matthew A1 - Prigge, Matthias A1 - Kaess, Michael A1 - Roden, Michael A1 - Thai, Michelle A1 - Schuster, Nathaniel M. A1 - Montano, Nicola A1 - Hansen, Niels A1 - Kroemer, Nils B. A1 - Rong, Peijing A1 - Fischer, Rico A1 - Howland, Robert H. A1 - Sclocco, Roberta A1 - Sellaro, Roberta A1 - Garcia, Ronald G. A1 - Bauer, Sebastian A1 - Gancheva, Sofiya A1 - Stavrakis, Stavros A1 - Kampusch, Stefan A1 - Deuchars, Susan A. A1 - Wehner, Sven A1 - Laborde, Sylvain A1 - Usichenko, Taras A1 - Polak, Thomas A1 - Zaehle, Tino A1 - Borges, Uirassu A1 - Teckentrup, Vanessa A1 - Jandackova, Vera K. A1 - Napadow, Vitaly A1 - Koenig, Julian T1 - International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020) JF - Frontiers in Human Neuroscience N2 - Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice. KW - transcutaneous vagus nerve stimulation KW - minimum reporting standards KW - guidelines & recommendations KW - transcutaneous auricular vagus nerve stimulation KW - transcutaneous cervical vagus nerve stimulation Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234346 SN - 1662-5161 VL - 14 ER - TY - JOUR A1 - Briegel, Wolfgang A1 - Greuel, Jan A1 - Stroth, Sanna A1 - Heinrichs, Nina T1 - Parents' perception of their 2−10-year-old children's contribution to the dyadic parent-child relationship in terms of positive and negative behaviors JF - International Journal of Environmental Research and Public Health N2 - Parent-child relationship is developed and changed through reciprocal interactions between a child and his/her parent, and these interactions can strongly influence the child's development across domains (e.g., emotional, physical, and intellectual). However, little is known about the parental perception of the child's contribution to the dyadic parent-child relationship in terms of positive and negative behaviors. We therefore aimed to develop and validate an economical parent-report instrument to assess these important aspects. The validation study included 1642 mothers (M\(_{age}\) = 37.1) and 1068 fathers (M\(_{age}\) = 40.4) of 1712 children aged 2–10 years (M\(_{age}\) = 6.6) who completed the new instrument, the Child Relationship Behavior Inventory (CRBI). Statistical results indicated that the CRBI is a reliable and valid measure. Mothers reported more positive child behaviors towards them, whereas fathers perceived fewer problems with problematic relationship behavior than mothers. In their parents' perception, girls showed more positive and less problematic relationship behaviors than boys. The frequency of problematic child relationship behavior significantly decreased with increasing child age while positive relationship behavior did not show any correlation with the child's age. To assess both positive and negative child relationship behaviors could be helpful to better understand the relevance of these different aspects for the development of the parent-child relationship. KW - parent-child relationship KW - child behavior KW - parental perception KW - inventory Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197411 SN - 1660-4601 VL - 16 IS - 7 ER - TY - JOUR A1 - Fauser, Mareike A1 - Weselek, Grit A1 - Hauptmann, Christine A1 - Markert, Franz A1 - Gerlach, Manfred A1 - Hermann, Andreas A1 - Storch, Alexander T1 - Catecholaminergic Innervation of Periventricular Neurogenic Regions of the Developing Mouse Brain JF - Frontiers in Neuroanatomy N2 - The major catecholamines—dopamine (DA) and norepinephrine (NE)—are not only involved in synaptic communication but also act as important trophic factors and might ultimately be involved in mammalian brain development. The catecholaminergic innervation of neurogenic regions of the developing brain and its putative relationship to neurogenesis is thus of pivotal interest. We here determined DA and NE innervation around the ventricular/subventricular zone (VZ/SVZ) bordering the whole ventricular system of the developing mouse brain from embryonic day 14.5 (E14.5), E16.5, and E19.5 until postnatal day zero (P0) by histological evaluation and HPLC with electrochemical detection. We correlated these data with the proliferation capacity of the respective regions by quantification of MCM\(^{2+}\) cells. During development, VZ/SVZ catecholamine levels dramatically increased between E16.5 and P0 with DA levels increasing in forebrain VZ/SVZ bordering the lateral ventricles and NE levels raising in midbrain/hindbrain VZ/SVZ bordering the third ventricle, the aqueduct, and the fourth ventricle. Conversely, proliferating MCM\(^{2+}\) cell counts dropped between E16.5 and E19.5 with a special focus on all VZ/SVZs outside the lateral ventricles. We detected an inverse strong negative correlation of the proliferation capacity in the periventricular neurogenic regions (log-transformed MCM\(^{2+}\) cell counts) with their NE levels (r = −0.932; p < 0.001), but not their DA levels (r = 0.440; p = 0.051) suggesting putative inhibitory effects of NE on cell proliferation within the periventricular regions during mouse brain development. Our data provide the first framework for further demandable studies on the functional importance of catecholamines, particularly NE, in regulating neural stem/progenitor cell proliferation and differentiation during mammalian brain development. KW - brain development KW - ventricular zone KW - catecholamines KW - norepinephrine KW - dopamine KW - neurogenesis Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212485 VL - 14 ER - TY - THES A1 - Reefschläger, Lennart Gunnar T1 - Expressionsanalysen monoaminerger Kandidatengene bei der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung und Autismusspektrumsstörung T1 - Expression analysis of monoaminergic candidate genes in ADHD and ASS N2 - 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. N2 - Die Genese der neuropsychiatrischen Entwicklungsstörung ADHS ist multifaktoriell, die Pathophysiologie jedoch noch nicht vollständig geklärt. Eine zentrale Rolle scheint eine Dysregulation des Monoaminmetabolismus zu spielen. Dies geht aus zahlreichen tierexperimentellen, bildgebenden und molekulargenetischen Studien hervor. In diesem Kontext werden verschiedene Kandidatengene genannt, die für eine Dysregulation des zentralen Monoaminstoffwechsels mitverantwortlich gemacht werden. In molekulargenetischen Studien wurden dabei mehrfach Polymorphismen von DRD4 und DRD5 sowie TPH1 in Assoziation mit ADHS-Symptomatik identifiziert. Gegenstand der vorliegenden Arbeit war es, die mRNA-Expression dieser Kandidatengene in Vollblut bei Patienten mit ADHS sowie Patienten mit ASS als weiterer, häufig komorbider neuropsychiatrischer Entwicklungsstörung im Vergleich zu gesunden Probanden zu analysieren. Zudem sollte ein möglicher Einfluss durch bestehende Medikation respektive durch die Kovariaten Alter, Geschlecht und Intelligenz ermittelt werden. Weiterhin war es Ziel dieser Arbeit zu prüfen, ob die erhobenen mRNA-Expressionsbefunde die untersuchten monoaminergen Gene als mögliche Kandidaten für „periphere Marker“ der ADHS stützen. Es zeigte sich eine signifikant geringere mRNA-Expression von DRD4 in der Gruppe der Kinder und Jugendlichen mit ADHS und ASS im Vergleich zur gesunden Kontrollgruppe. Die DRD5-mRNA-Expression war bei der Gruppe autistischer Patienten im Vergleich zu den anderen Gruppen signifikant verringert. Bezüglich der Expression von TPH1 ließen sich keine Expressionsunterschiede feststellen. Ebenso ließen sich keine modulierenden Effekte durch Medikation, Alter, Geschlecht und Intelligenzniveau nachweisen. Die Kriterien für den Einsatz allein der genannten Expressionsbefunde als mögliche Krankheitsmarker der ADHS wurden nicht erfüllt. In dieser Arbeit wurde jedoch erstmalig eine veränderte mRNA-Expression dopaminerger Kandidatengene bei Patienten mit ADHS sowie autistischen Patienten in peripherem Gewebe nachgewiesen. Dieses Ergebnis untermauert die bisher vermutete Hypothese einer zentralen Dysregulation des Monoaminstoffwechsels bei den neuropsychiatrischen Entwicklungsstörungen ADHS und ASS. Weitere Studien mit einer größeren Probandenanzahl unter Einbezug phänotypisch ähnlicher psychiatrischer Störungsbilder sind für eine Ergänzung und Verifizierung der Ergebnisse notwendig. KW - mRNA expression KW - attention deficit hyperactivity disorder (ADHD) KW - autism spectrum disorder (ASD) KW - dopamine receptor D4 KW - D5 (DRD4, DRD5) Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162371 ER - TY - JOUR A1 - Lechermeier, Carina G. A1 - Zimmer, Frederic A1 - Lüffe, Teresa M. A1 - Lesch, Klaus-Peter A1 - Romanos, Marcel A1 - Lillesaar, Christina A1 - Drepper, Carsten T1 - 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 JF - Frontiers in Molecular Neuroscience N2 - 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. KW - glucose transporter KW - nervous system KW - brain disorders KW - psychiatric disorders KW - brain development KW - GABA KW - GAD1 Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201797 VL - 12 IS - 199 ER - TY - JOUR A1 - Ziegler, Georg C. A1 - Ehlis, Ann-Christine A1 - Weber, Heike A1 - Vitale, Maria Rosaria A1 - Zöller, Johanna E. M. A1 - Ku, Hsing-Ping A1 - Schiele, Miriam A. A1 - Kürbitz, Laura I. A1 - Romanos, Marcel A1 - Pauli, Paul A1 - Kalisch, Raffael A1 - Zwanzger, Peter A1 - Domschke, Katharina A1 - Fallgatter, Andreas J. A1 - Reif, Andreas A1 - Lesch, Klaus-Peter T1 - A Common CDH13 Variant is Associated with Low Agreeableness and Neural Responses to Working Memory Tasks in ADHD JF - Genes N2 - 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. KW - ADHD KW - CDH13 KW - neurodevelopment KW - executive functions KW - working memory KW - Big Five KW - agreeableness Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245220 SN - 2073-4425 VL - 12 IS - 9 ER - TY - JOUR A1 - Briegel, Wolfgang A1 - Andritschky, Christoph T1 - Psychological adjustment of children and adolescents with 22q11.2 deletion syndrome and their mothers' stress and coping — a longitudinal study JF - International Journal of Environmental Research and Public Health N2 - At present, there is a lack of longitudinal studies on the psychological adjustment of both children and adolescents with 22q11.2 deletion syndrome (22q11.2DS) and their primary caregivers. To fill this gap, we performed a four-year follow-up study. Mothers filled out the Child Behavior Checklist 4–18, the Social Orientation of Parents with Handicapped Children questionnaire to assess maternal stress and coping strategies, and the Freiburger Personality Inventory-Revised — subscales strain and life satisfaction. Fifty-five subjects with 22q11.2DS (26 males and 29 females; age: M = 10.79 years, SD = 3.56 years) and their biological mothers (age: M = 40.84 years, SD = 4.68 years) were included in this study. Significantly higher levels of behavior problems than in the general population and an increase in these problems, especially internalizing ones, over time could be found. In contrast, maternal stress did not change significantly over time, but mothers demonstrated increased levels of strain and reduced life satisfaction at T2. Thus, careful monitoring as well as early and adequate interventions, if indicated, should be offered to families with a child with 22q11.2DS, not only for somatic complaints but also for problems with psychological adjustment. KW - 22q11.2 deletion syndrome KW - behavior problems KW - coping strategies KW - longitudinal study KW - maternal stress KW - satisfaction with life Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234101 SN - 1660-4601 VL - 18 IS - 5 ER - TY - JOUR A1 - Kaiser, Anna A1 - Aggensteiner, Pascal-M. A1 - Holtmann, Martin A1 - Fallgatter, Andreas A1 - Romanos, Marcel A1 - Abenova, Karina A1 - Alm, Barbara A1 - Becker, Katja A1 - Döpfner, Manfred A1 - Ethofer, Thomas A1 - Freitag, Christine M. A1 - Geissler, Julia A1 - Hebebrand, Johannes A1 - Huss, Michael A1 - Jans, Thomas A1 - Jendreizik, Lea Teresa A1 - Ketter, Johanna A1 - Legenbauer, Tanja A1 - Philipsen, Alexandra A1 - Poustka, Luise A1 - Renner, Tobias A1 - Retz, Wolfgang A1 - Rösler, Michael A1 - Thome, Johannes A1 - Uebel-von Sandersleben, Henrik A1 - von Wirth, Elena A1 - Zinnow, Toivo A1 - Hohmann, Sarah A1 - Millenet, Sabina A1 - Holz, Nathalie E. A1 - Banaschewski, Tobias A1 - Brandeis, Daniel T1 - EEG data quality: determinants and impact in a multicenter study of children, adolescents, and adults with attention-deficit/hyperactivity disorder (ADHD) JF - Brain Sciences N2 - 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. KW - electroencephalography (EEG) KW - data quality KW - attention-deficit/hyperactivity disorder (ADHD) KW - artifacts KW - multicenter study Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228788 SN - 2076-3425 VL - 11 IS - 2 ER - TY - JOUR A1 - Geissler, Julia A1 - Jans, Thomas A1 - Banaschewski, Tobias A1 - Becker, Katja A1 - Renner, Tobias A1 - Brandeis, Daniel A1 - Döpfner, Manfred A1 - Dose, Christina A1 - Hautmann, Christopher A1 - Holtmann, Martin A1 - Jenkner, Carolin A1 - Millenet, Sabina A1 - Romanos, Marcel T1 - 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 JF - Trials N2 - 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. KW - ADHD KW - adolescents KW - attention-deficit/hyperactivity disorder KW - behaviour therapy KW - RCT KW - individualised modular treatment programme KW - telephone-assisted self-help Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176061 VL - 19 IS - 254 ER - TY - JOUR A1 - Lüffe, Teresa M. A1 - D'Orazio, Andrea A1 - Bauer, Moritz A1 - Gioga, Zoi A1 - Schoeffler, Victoria A1 - Lesch, Klaus-Peter A1 - Romanos, Marcel A1 - Drepper, Carsten A1 - Lillesaar, Christina T1 - Increased locomotor activity via regulation of GABAergic signalling in foxp2 mutant zebrafish – implications for neurodevelopmental disorders JF - Translational Psychiatry N2 - 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. KW - comparative genomics KW - molecular neuroscience Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-264713 VL - 11 ER - TY - THES A1 - Kneer, Katharina Johanna T1 - The association of three anxiety dimensions in children and adolescents: their influence on the brain and malleability by a prevention program T1 - Der Zusammenhang dreier Angstdimensionen bei Kindern und Jugendlichen: ihr Einfluss auf das Gehirn und ihre Veränderbarkeit durch ein Präventionsprogramm N2 - 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. N2 - Angststörungen sind die am häufigsten auftretende Gruppe neuropsychiatrischer Erkrankungen und führen in vielen Fällen zu großem Leid. Sie beginnen häufig in der Kindheit und Spontanremissionen sind selten, im Gegenteil - die Erkrankungen verschlimmern sich häufig und führen zu weiteren psychischen Erkrankungen. Dabei stellt die Kindheit eine Lebensphase mit besonderer Vulnerabilität für die Entwicklung von Angsterkrankungen dar. Trotzdem werden die meisten Studien zu Angststörungen weiterhin mit Erwachsenen durchgeführt. Vor diesem Hintergrund scheint es von größter Bedeutung, prädiktive Faktoren für Angststörungen bei Kindern und Jugendlichen zu identifizieren. Temperament- oder Persönlichkeitsmerkmale werden als Risikomarker für Angststörungen gesehen. Dabei ist das genaue Zusammenspiel dieser Risikomarker im Kindes- und Jugendalter nicht klar. Diese Dissertation leistet dabei einen Beitrag zum Verständnis des Zusammenspiels der Risikomarker Trait-Angst, Angstsensitivität und Trennungsangst. Während Trait-Angst als eine eher allgemeinere Tendenz angesehen wird, ängstlich auf bedrohliche Situationen oder Reize zu reagieren (Unnewehr et al., 1992), ist Angstsensitivität die Tendenz, mit Angst auf die eigenen potentiell angst-assoziierten Empfindungen zu reagieren (Allan et al., 2014; S. Reiss et al., 1986). Trennungsangst bezieht sich auf das Ausmaß, in dem das Kind bestimmt Situationen vermeidet, weil es befürchtet von Primärbezugspersonen getrennt zu werden (In-Albon & Schneider, 2011). Darüber hinaus befasst sich diese Dissertation damit, wie diese drei Angstmaße mit negativen Lebensereignissen und Gehirnaktivierung zusammenhängen und evaluiert deren Veränderbarkeit durch ein indiziertes Präventionsprogram. Zu diesem Zweck wurden drei Studien durchgeführt. In Studie 1 war das Ziel, das Wissen, um die Wechselbeziehungen dieser Angstmaße und negativer Lebensereignisse zu erweitern. Die Ergebnisse zeigten enge Zusammenhänge zwischen den drei Angstmaßen und ebenso mit der Anzahl negativer Lebensereignissen. Darüber hinaus fungierten negative Lebensereignisse als Mediator zwischen Angstsensitivität und Trait-Angst, was darauf hinweist, dass ein Teil des Zusammenhangs dieser beiden Angstmaße durch negative Lebensereignisse erklärt wird. In Studie 2 erweiterten wir die Ergebnisse aus Studie 1 um ein neurobiologisches Maß und untersuchten den Einfluss der Angstmaße auf Hirnaktivierung während emotionaler Verarbeitung mittels der Durchführung des „emotional face matching task“. Die Analyse zeigte eine Aktivierung während der Aufgabe in bilateralen präfrontalen Regionen sowie beiden Hippocampi und der rechten Amygdala. Angstspezifische Aktivierungen zeigten eine Trait-Angst-spezifische Hyperaktivierung im linken gyrus frontalis inferior (IFG) und eine Trennungsangst-spezifische Hypoaktivierung in beiden IFG und dem rechten gyrus frontalis medius. Darüber hinaus wurde der Zusammenhang zwischen Trennungsangst und Angstsensitivität durch bi-hemisphärische Trennungsangst-spezifische IFG Aktivierung moderiert. Wir konnten also Hirnregionen identifizieren, die spezifisch mit den Angstmaßen assoziiert waren (Trait-Angst und Trennungsangst) und auch deren Verbindung moderierten (Trennungsangst und Angstsensitivität). Ziel der Studie 3 war es, die Veränderbarkeit der Angstmaße anhand eines Präventionsprogramms in einer Risikopopulation zu untersuchen. Wir konnten eine Verringerung aller drei Angstmaße durch die Prävention feststellen und dieser Effekt war für Angstsensitivität und Trait-Angst statistisch signifikant. Darüber hinaus konnten wir zeigen, dass die Trennungsangst vor der Prävention signifikant mit der Angstsensitivität nach der Prävention korrelierte. Zusätzlich sagte das Ausmaß der Angstmaße vor der Prävention die durch die Intervention induzierten Veränderung innerhalb eines Maßes signifikant voraus (Je höher die Werte vor der Intervention, desto höher die präventionsinduzierte Änderung), zudem vermochte Angstsensitivität vor der Intervention Änderung der Trennungsangstwerte zu prognostizierten. Alle gefunden Zusammenhänge schienen darüber hinaus direkt zu sein, da Mediations- / Moderationsanalysen mit negativen Lebensereignissen keinen signifikanten Effekt zeigten. Diese Ergebnisse sind sehr vielversprechend, da es nur wenig Forschung zur Angstprävention bei Kindern und Jugendlichen gibt und unsere Ergebnisse darauf hinweisen das Präventionsprogramme, welche auf Kognitiv-verhaltenstherapeutischen Elementen beruhen in einer indizierten Population gute Effekte erzielen können, selbst wenn es sich, wie in unserem Fall, um eine kleine Stichprobengröße handelt. Zusammenfassend deuten die vorliegenden Ergebnisse auf unterschiedliche Mechanismen hin, die den drei verschiedenen Angstmaßen auf phänomenologischer und neurobiologischer Ebene zugrunde liegen. Darüber hinaus wurden enge Assoziationen zwischen Angstsensitivität und Trait-Angst sowie Trennungsangst und Angstsensitivität gefunden. Insbesondere konnten wir eine neuronale Manifestation des Zusammenhangs zwischen Trennungsangst und Angstsensitivität (Trennungangstspezifische IFG-Aktivierung) und ein Vorhersagepotential für den Einfluss der Prävention finden. Die Resultate der beschriebenen Studien tragen zu einem besseren Verständnis der Ätiologie von Angststörungen und dem Zusammenspiel verschiedener angstspezifischer Temperamentmerkmale bei, und können zu weiteren wertvollen Erkenntnissen über Interventions- sowie Präventionsstrategien führen. KW - Prävention KW - Angst KW - Kind KW - Jugend KW - Angsterkrankungen KW - Kindheit und Jugend KW - Angst als Eigenschaft Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257468 ER - TY - THES A1 - Nachtigall, Lea T1 - Vergleichende Untersuchung der Beeinträchtigung der Gesundheit und Arbeitsfähigkeit von Eltern mit Kindern, welche an ADHS leiden, gegenüber einer Stichprobe von Eltern mit unauffälligen Kindern T1 - Comparative study of the impairment of health and work ability of parents with children with ADHD compared to a sample of parents with children without ADHD N2 - 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 zunächst der Fragestellung nachgegangen, in wieweit das von ADHS betroffene Kind in der Familie selbst zu einer erhöhten Belastung der Eltern am Arbeitsplatz und somit zu einer gesteigerten gesundheitlichen Einschränkung führt. Zudem untersuchten wir die Auswirkungen einer möglichen eigenen ADHS-Symptomatik in der Kindheit laut WURS auf die gesundheitliche Verfassung und die Leistungsfähigkeit 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) durchgeführt. Um die verschiedenen Einflussfaktoren verifizierbar zu machen, wurden verschiedene Untersuchungsinstrumente in Form von Fragebögen sowohl an die klinische Stichprobe als auch an die Vergleichsstichprobe (Familien, deren Kinder als gesund beschrieben wurden) verteilt. Zur allgemeinen Einschätzung von Verhaltensauffälligkeiten der Kinder in den jeweiligen Familien wurde die Child-Behavior-Checklist von den Eltern ausgefüllt. Zudem schätzten die Eltern über den Fremdbeurteilungsbogen für hyperkinetische Störungen die ADHS-Symptomatik ihrer Kinder ein. Darüber hinaus beurteilten die Eltern eine mögliche eigene ADHS-Symptomatik in der Kindheit über die retrospektiv ausgelegte Wender Utah Rating Scale. Der individuelle Gesundheitszustand der Väter und Mütter wurde über den „EQ-5D“ erfragt, während die Belastung am Arbeitsplatz mittels der Work Limitation Questionnaire ermittelt wurde. Schließlich füllten alle teilnehmenden Eltern einen sozioökonomischen Fragebogen aus, in dem Alter, Geschlecht, Familienstand, Schulabschluss und das Haushaltsnettoeinkommen berücksichtigt wurden. In zahlreichen, im Diskussionsteil bereits erwähnten Studien wurde eine Mehrbelastung der Eltern festgestellt. In der vorliegenden Arbeit wurden darüber hinaus die konkreten Auswirkungen dieser bereits festgestellten Mehrbelastung auf den Gesundheitszustand und das berufliche Umfeld untersucht. Die Untersuchung dieser Auswirkungen auf das alltägliche Leben der betroffenen Eltern geriet bislang kaum in den Fokus wissenschaftlicher Arbeiten. Um zukünftig betroffene Familien gezielter in unterschiedlichen Lebensbereichen unterstützen zu können ist es jedoch von eminenter Bedeutung, diese Auswirkungen zu kennen und besser zu verstehen. In den Ergebnissen konnte konkret gezeigt werden, dass bezüglich 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 mögliche eigene ADHS-Symptomatik in der Kindheit sich auf unterschiedliche Dimensionen im beruflichen Umfeld auswirkt, jedoch nicht signifikant auf den individuellen Gesundheitszustand. Väter und Mütter, die selbst in ihrer Kindheit ADHS-Symptome angaben, geben eine signifikante Beeinträchtigung bezüglich der mentalen Fähigkeiten, des Zeitmanagements und der allgemeinen Arbeitsproduktivität laut Selbsteinschätzung im WLQ an. Eine physische Einschränkung am Arbeitsplatz laut WLQ war bei den Vätern signifikant feststellbar, nicht jedoch bei den Müttern. Die Ergebnisse der Hypothese III ergaben, dass bezüglich der Arbeitsfähigkeit bereits bei einem oder mehr Kindern mit ADHS die kognitiven Fähigkeiten der Eltern am Arbeitsplatz laut WLQ beeinträchtigt sind. Gleichermaßen wird die Arbeitsproduktivität bereits bei einem oder mehr von ADHS betroffenen Kindern signifikant beeinflusst. Auf die physische Konstitution der Eltern laut Selbsteinschätzung 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 beeinträchtigt, 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 lässt 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 Beeinträchtigung am Arbeitsplatz führt. Diese Erkenntnis zeigt, dass die eigene ADHS-Symptomatik der Eltern in der Kindheit neben der Anwesenheit eines ADHS - Kindes nicht unerhebliche Auswirkungen auf die alltäglichen Aufgaben der Betroffenen hat. Die Erkenntnis dieser neuen Zusammenhänge sollte in zukünftigen Forschungsvorhaben berücksichtigt werden. N2 - In this present study, different hypotheses were examined with regard to the work-related and health-related burden on parents with children suffering from ADHD. First, we examined the question to what extent the child affected by ADHD in the family itself, leads to an increased burden on the parents at work and therefore to an increased health impairement. Apart from this we investigated the effects of a possible own ADHD symptomatology in childhood by using the Wender Utah Rating Scale (WURS) on the state of health and working power. Finally, the third hypothesis investigated the question to what extent an effect of the number of affected children with ADHD within a family is ascertainable. Correspondingly, a comparative study was conducted with a clinical sample (n=91) and a healthy comparison sample (n=198). In order to make the various influencing factors comprehensible, several research instruments in the form of questionnaires were distributed to both the clinical sample and the comparison sample.For the general assessment of behavioral disorders of the children in the families, the Child Behavior Checklist (CBCL) was completed by the parents. Furthermore, the parents assessed their children's ADHD symptomatology via external evaluation form for hyperkinetic disorders (FBB-HKS). In addition, parents assessed possible own ADHD symptomatology in childhood via the retrospectively designed Wender Utah Rating Scale (WURS). The individual health status of the fathers and mothers was collected via the "EQ-5D", while the individual workload was determined via the Work Limitation Questionnaire (WLQ). Finally, all parents completed a socioeconomic questionnaire that included age, gender, marital status, school degrees, and net household income. Several studies found an additional burden on parents. In addition, in this study, the specific effects of this already identified extra burden on health status and working environment were examined. The investigation of these effects on the daily life of the affected parents was little subject of scientific studies. However, in order to be able to support affected families in different areas of life in a more focused manner in the future, it is important to know these effects. In the results it could be shown that regarding hypothesis 1 the presence of an ADHD child within a family significantly influences the health status of the parents according to EQ-5D. Relating to personal workload, it was found that an ADHD child significantly affects the physical constitution according to the answers of WLQ of the parents. The examination of hypothesis II showed that a possible own ADHD symptomatology in childhood affects different dimensions in the working environment, but not significantly on the individual health status. Fathers and mothers who reported ADHD symptoms in childhood report significant disadvantages in terms of mental abilities, time management, and overall work productivity (according to self-assessment in the WLQ). Physical limitation at work according to the WLQ was significantly determinable in fathers but not in mothers. The results of hypothesis III suggested that concerning work productivity, already one or more children with ADHD have impaired cognitive abilities at work according to the WLQ. Similarly, work productivity is already significantly affected in one or more children with ADHD. However, one or more children affected by ADHD have no significant influence on the physical constitution of the parents according to the self-assessment in the WLQ. Consequently, the parents' time organization at work according to the WLQ is not yet significantly affected if one child is affected with ADHD, but it is, if more than one child is affected. Also the health status of the parents according to EQ-5D is only influenced by this circumstance when there are two children with ADHD in a family. In summary, the presence of a child with ADHD in a family is more likely to impaired the parents' health status, whereas the parents' own ADHD symptomatology in childhood is much more likely to lead to multidimensional disadvantage at work. The results show that parents' own ADHD symptomatology in childhood, in addition to the presence of an ADHD child, has a significant impact on the daily excercises of those affected. The finding of these new correlations should be taken into account in future research projects. KW - Aufmerksamkeitsdefizit-Syndrom KW - Arbeitsbelastung KW - ADHS KW - ADHD KW - Belastung Eltern KW - Gesundheitsbeeinträchtigung KW - berufliche Einschränkungen KW - Eltern ADHS KW - individual workload KW - health status KW - parents Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259495 ER - TY - THES A1 - Frey, Lillien Mara T1 - Furchtgeneralisierung und Attentional Bias bei Kindern und Jugendlichen mit einer Störung des Sozialverhaltens T1 - Fear Generalization And Attentional Bias in Children And Adolescents With Conduct Disorder N2 - Bereits vorangegangene Studien haben zeigen können, dass eine verstärke Generali- sierung von Furcht sowohl bei Erwachsenen, bei denen beispielsweise eine Angststörung 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 Störung des Sozialverhaltens aufwiesen, auf die Konditionierbarkeit von Furcht und eine mögliche 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. Zusätzlich führten 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 für beide Gruppen erreichen. Im Vergleich mit der gesunden Kontrollgruppe zeigte die externalisierende Probandengruppe eine verstärke Furchtgeneralisierung. Hinsichtlich der subjektiven Valenz- und Kontingenzratings wurden die Unterschiede besonders deutlich. Eine verstärkte Generalisierungsneigung bei erhöhter 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 verstärkte Aufmerksamkeitslenkung hin zu glücklichen Gesichtern festzustellen. Für die gesunde Kontrollgruppe konnten wir keine Besonderheiten bezüglich der Aufmerksamkeitsrichtung finden. Weiterführende Studien sollten mit größ- eren Probandengruppen und nach Geschlecht und Alter gepaarten Probanden durch- geführt werden. Mit externalisierenden Probanden sollte ein Furchtgeneralisierungs- paradigma mit neutralen Stimuli (z.B. Ringe) gewählt werden, um eine subjektive Wertung emotionaler Gesichter bei den Ratings als Störfaktor auszuschließen. Für externalisierende Probanden sollte außerdem die Ausprägung von CU-Traits erfasst und die Dauer der Testung verkürzt oder auf zwei Termine aufgeteilt werden, um eine ausreichende Konzentrationsfähigkeit zu ermöglichen. N2 - Previous studies have already been able to show that increased generalization of fear plays a role both in adults diagnosed with anxiety disorder or PTSD, but also in healthy children. In our study we examined a group of children and adolescents (n = 31, m = 25, f = 6; age = 13.35 ± 2.03) with conduct disorder for possible fear conditioning and overgeneralization of fear. We compared this group with a healthy control group (n = 29, m = 11, f = 18; age = 14.28 ± 2.43). As generalization stimuli we used a fear generalization paradigm with two female faces that were matched in four steps. In addition both groups performed a dot-probe task to objectify attentional processes in terms of attentional bias or attentional avoidance with emotional faces. We were able to achieve successful fear conditioning for both groups. Compared with the healthy control group the externalizing subject group showed increased fear generalization. Regarding the subjective valence and contingency ratings the differences were particularly evident. We could not find an increased generalization tendency for subjects with increased trait anxiety. The externalizing group showed an attentional bias towards emotional faces compared to neutral faces. Most clearly there was an increased attentional bias towards happy faces. For the healthy control group we could not find any particularities regarding attentional bias or avoidance. Further studies should be conducted with larger subject groups and subjects paired by gender and age. With externalizing subjects a fear-generalization paradigm with neutral stimuli (e.g., rings) should be chosen to exclude subjective scoring of emotional faces in the ratings as a confounding factor. For externalizing subjects, the expression of CU traits should also be recorded and the duration of testing should be shortened or divided into two sessions to enable sufficient concentration. KW - Psychische Störung KW - Kind KW - Furchtgeneralisierung KW - Attentional Bias KW - Attentional Avoidance KW - Störung des Sozialverhaltens KW - Verhaltensstörung KW - Jugend KW - Sekundärkrankheit KW - Angststörung Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259746 ER - TY - THES A1 - Buchner, Kim T1 - Untersuchungen zur Assoziation von Schlafbruxismus und psychischer Belastung bei Kindern T1 - Studies on the association of sleep bruxism and psychological distress in children N2 - Bruxismus bezeichnet eine sich wiederholende Kaumuskelaktivität mit Knirschen oder Aufeinanderpressen der Zähne. Während bei Erwachsenen die Ursachen und die Pathophysiologie schon weitreichend erforscht wurden, gab es bei Kindern bislang keine systematische Untersuchung hinsichtlich des Zusammenhangs mit psychopathologischen Faktoren. Deshalb wurde unsere Studie nun erstmals mit Bruxismusmessung nach Goldstandard sowie mit normierten und validierten Fragebögen zu verschiedenen psychosozialen Dimensionen als Querschnittsuntersuchung bei 53 acht- bis zwölfjährigen Kindern durchgeführt. Besonderes Augenmerk wurde dabei auf den hypothetisierten Zusammenhang zwischen Schlafbruxismus und Angstsensitivität sowie Angstintensität gelegt. Außerdem wurde der Einfluss weiterer psychosozialer Faktoren (wie Lebensqualität, Anzahl negativer Lebensereignisse, Verhaltensauffälligkeiten, ADHS-Symptomatik, depressive Symptomatik, Zwangssymptomatik, Ticsymptomatik, Alter und Geschlecht) auf die o.g. Prädiktoren per multipler Regressionsanalyse geprüft. Auf Basis der durchgeführten Untersuchung ergaben sich keine Hinweise auf eine Assoziation von Bruxismus zu psychosozialen Dimensionen. Die vorbeschriebenen Zusammenhänge erwiesen sich als statistisch nicht signifikant. Dies mag zum einen der Stichprobenauswahl von gesunden Kindern geschuldet sein, die weder von Bruxismus noch von anderen Faktoren vorbekannt klinisch beeinträchtigt waren. Andererseits können aber auch fehlerhafte Ausgangsüberlegungen durch nicht dem Goldstandard entsprechenden Messungen der Vorstudien zu diesem Ergebnis geführt haben. Darüber hinaus verläuft die Kindesentwicklung interindividuell sehr variabel und temporäre myofunktionelle Beeinträchtigungen können ohne Bezug zu psychischer Belastung auftreten. N2 - Bruxism is defined as repetitive masticatory muscle activity with grinding or clenching of the teeth. While the causes and pathophysiology of bruxism have been extensively studied in adults, there has been no systematic investigation of its association with psychopathological factors in children. Therefore, our study was conducted for the first time with bruxism measurement according to the gold standard as well as with standardized and validated questionnaires on different psychosocial dimensions as a cross-sectional study in 53 eight- to twelve-year-old children. Special attention was paid to the hypothesized relationship between sleep bruxism and anxiety sensitivity as well as anxiety intensity. In addition, the influence of other psychosocial factors (such as quality of life, number of negative life events, behavioral problems, ADHD symptomatology, depressive symptomatology, obsessive-compulsive symptomatology, tic symptomatology, age and gender) on the above predictors was tested by multiple regression analysis. On the basis of the investigation conducted, no evidence of an association of bruxism with psychosocial dimensions was found. The aforementioned associations proved not to be statistically significant. On the one hand, this may be due to the sample selection of healthy children who were not clinically impaired by bruxism or by any other factors known beforehand. On the other hand, faulty initial considerations due to non-gold standard measurements of the preliminary studies may have led to this result. Furthermore, child development is highly variable between individuals and temporary myofunctional impairments may occur without relation to psychological distress. KW - Bruxismus KW - Schlafbruxismus KW - psychische Belastung KW - kindliche Zahnentwicklung KW - Angstsensitivität KW - Angstintensität KW - sleep bruxism KW - psychological distress KW - dental development in children KW - anxiety sensitivity KW - anxiety intensity Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225639 ER - TY - JOUR A1 - Geissler, Julia M. A1 - Werner, Elisabeth A1 - Dworschak, Wolfgang A1 - Romanos, Marcel A1 - Ratz, Christoph T1 - 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 JF - Frontiers in Psychiatry N2 - 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. KW - intellectual disabilities KW - developmental disabilities KW - challenging behaviours KW - employee stress KW - coercive measures KW - residential institutions Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-249030 SN - 1664-0640 VL - 12 ER - TY - JOUR A1 - Oezkur, Mehmet A1 - Magyar, Atilla A1 - Thomas, Phillip A1 - Reif, Andreas A1 - Störk, Stefan A1 - Heuschmann, Peter U. A1 - Leyh, Rainer G. A1 - Wagner, Martin T1 - The COMT-polymorphism is not associated with the incidence of acute kidney injury after cardiac surgery - a prospective cohort study JF - BMC Nephrology N2 - 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. KW - AKI KW - COMT KW - cardiac surgery KW - KDIGO Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175529 VL - 19 IS - 34 ER - TY - JOUR A1 - Schiele, Miriam A. A1 - Reinhard, Julia A1 - Reif, Andreas A1 - Domschke, Katharina A1 - Romanos, Marcel A1 - Deckert, Jürgen A1 - Pauli, Paul T1 - Developmental aspects of fear: Comparing the acquisition and generalization of conditioned fear in children and adults JF - Developmental Psychobiology N2 - 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. KW - fear conditioning KW - fear generalization KW - development KW - skin conductance KW - maturation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189488 VL - 58 IS - 4 ER - TY - JOUR A1 - Geissler, Julia A1 - Werner, Elisabeth A1 - Dworschak, Wolfgang A1 - Romanos, Marcel A1 - Ratz, Christoph T1 - Freiheitsentziehende Maßnahmen in bayerischen Heimeinrichtungen für Kinder, Jugendliche und junge Volljährige mit Intelligenzminderung JF - Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie N2 - Fragestellung: In Bayern leben etwa 10 % aller jungen Menschen mit Intelligenzminderung in Heimeinrichtungen. 2016 wurde in Presseberichten der Vorwurf unzulässiger freiheitsentziehender Maßnahmen formuliert. Im Rahmen des Projekts REDUGIA wurde in bayerischen Heimeinrichtungen eine repräsentative Erhebung zu freiheitsentziehenden Maßnahmen (FeM), herausforderndem Verhalten (hfV) und der Mitarbeiterbelastung (MaB) durchgeführt. Methodik: 65 Einrichtungen für 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 durchgeführt. Ergebnisse: Es wurden Daten zu 1839 Personen in 61 Einrichtungen erhoben. 84.3 % der Einrichtungen berichteten geringe Raten an hfV und FeM, während 15.7 % ein gehäuftes Vorkommen von hfV und FeM angaben. Auf n = 1809 Vollzeitäquivalente kam es innerhalb von 14 Tagen zu 639 körperlichen Angriffen durch Bewohner_innen. In 12 Monaten wurden problemverhaltensassoziiert 85 Krankmeldungen sowie 33 Versetzungsanträge/Kündigungen 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 flächendeckendes Phänomen darstellen, sondern sich auf wenige spezialisierte Einrichtungen fokussieren. Mögliche Maßnahmen zur Prävention von Problemverhalten und Freiheitsentzug werden diskutiert. N2 - Objective: In Bavaria, around 10 % of youths with an intellectual disability (ID) live in residential facilities. In 2015, media raised accusations of inadmissible use of coercive measures. The REDUGIA project carried out a representative survey in Bavarian facilities regarding coercive measures (FeM), challenging behavior (hfV), and employee stress (MaB). Method: We sent a questionnaire concerning structural conditions, MaB, hfV and FeM to 65 Bavarian facilities for young people with ID. In addition to preparing descriptive evaluations, we performed correlative and regression analyses concerning the relationship between hfV, FeM, and MaB. Results: We retrieved data from 1,839 subjects in 61 facilities. 84.3 % of facilities reported low rates of hfV and FeM, while 15.7 % reported an increased incidence of hfV and FeM. For n = 1809 full-time position equivalents there were 639 physical attacks by residents over the course of 14 days. We observed 85 instances of sick leave and 33 transfer apllications/resignation associated with hfV. The frequency of hfV predicted the frequency of FeM (R² = 0.307, F = 21.719, p < .001). MaB correlated positively with hfV (r = 0.507, p < .001). Conclusions: The descriptive data indicate that hfV and FeM are not general phenomena but occur mainly in a circumscript number of highly specialized facilities. This emphasizes the need for prevention of hfV and FeM. T2 - Freedom-restricting measures in Bavarian residential facilities for children, adolescents, and young adults with intellectual disabilities KW - Geistige Behinderung KW - herausforderndes Verhalten KW - freiheitsentziehende Maßnahmen KW - Heimeinrichtungen KW - Mitarbeiterbelastung KW - intellectual disability KW - challenging behavior KW - coercive measures KW - residential institutions KW - employee stress Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244859 SN - 1422-4917 SN - 1664-2880 VL - 49 IS - 4 ER - TY - JOUR A1 - Gottschalk, Michael G. A1 - Richter, Jan A1 - Ziegler, Christiane A1 - Schiele, Miriam A. A1 - Mann, Julia A1 - Geiger, Maximilian J. A1 - Schartner, Christoph A1 - Homola, György A. A1 - Alpers, Georg W. A1 - Büchel, Christian A1 - Fehm, Lydia A1 - Fydrich, Thomas A1 - Gerlach, Alexander L. A1 - Gloster, Andrew T. A1 - Helbig-Lang, Sylvia A1 - Kalisch, Raffael A1 - Kircher, Tilo A1 - Lang, Thomas A1 - Lonsdorf, Tina B. A1 - Pané-Farré, Christiane A. A1 - Ströhle, Andreas A1 - Weber, Heike A1 - Zwanzger, Peter A1 - Arolt, Volker A1 - Romanos, Marcel A1 - Wittchen, Hans-Ulrich A1 - Hamm, Alfons A1 - Pauli, Paul A1 - Reif, Andreas A1 - Deckert, Jürgen A1 - Neufang, Susanne A1 - Höfler, Michael A1 - Domschke, Katharina T1 - Orexin in the anxiety spectrum: association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes JF - Translational Psychiatry N2 - 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. KW - human behaviour KW - molecular neuroscience KW - personalized medicine KW - predictive markers KW - psychiatric disorders Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227479 VL - 9 ER - TY - JOUR A1 - Hommers, L. G. A1 - Richter, J. A1 - Yang, Y. A1 - Raab, A. A1 - Baumann, C. A1 - Lang, K. A1 - Schiele, M. A. A1 - Weber, H. A1 - Wittmann, A. A1 - Wolf, C. A1 - Alpers, G. W. A1 - Arolt, V. A1 - Domschke, K. A1 - Fehm, L. A1 - Fydrich, T. A1 - Gerlach, A. A1 - Gloster, A. T. A1 - Hamm, A. O. A1 - Helbig-Lang, S. A1 - Kircher, T. A1 - Lang, T. A1 - Pané-Farré, C. A. A1 - Pauli, P. A1 - Pfleiderer, B. A1 - Reif, A. A1 - Romanos, M. A1 - Straube, B. A1 - Ströhle, A. A1 - Wittchen, H.-U. A1 - Frantz, S. A1 - Ertl, G. A1 - Lohse, M. J. A1 - Lueken, U. A1 - Deckert, J. T1 - A functional genetic variation of SLC6A2 repressor hsa-miR-579-3p upregulates sympathetic noradrenergic processes of fear and anxiety JF - Translational Psychiatry N2 - 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. KW - clinical genetics KW - psychiatric disorders Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-322497 VL - 8 ER - TY - THES A1 - Pollerhoff, Lena Katharina T1 - Age differences in prosociality across the adult lifespan: Insights from self-reports, experimental paradigms, and meta-analyses T1 - Altersunterschiede in Prosozialität über die erwachsene Lebensspanne hinweg: Erkenntnisse aus Selbstberichten, experimentellen Paradigmen und Meta-Analysen N2 - 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. N2 - Menschliche Prosozialität beinhaltet Verhaltensweisen wie Großzügigkeit, Kooperation und freiwilliges Engagement und spielt eine entscheidende Rolle in unserem täglichen Leben. In den letzten Jahrzehnten hat die Frage, ob sich Prosozialität über die erwachsene Lebensspanne hinweg verändert, zunehmende Bedeutung in der Forschung erfahren. Frühere Studien zeigten eine erhöhte Prosozialität bei älteren im Vergleich zu jüngeren Erwachsenen. Meta-Analysen zeigten jedoch, dass dieser Alterseffekt heterogen und geringfügig sein könnte. Zusätzlich sind die Faktoren und Mechanismen, die zu diesen altersbedingten Veränderungen beitragen, noch wenig verstanden. Um die altersbedingten Unterschiede in Prosozialität besser zu charakterisieren, wurde in der ersten Studie dieser Dissertation ein meta-analytischer Ansatz verfolgt, um vorhandene Forschungsergebnisse systematisch zusammenzufassen und Einblicke in die zugrundeliegende Heterogenität zu erhalten. Hierfür wurden lineare und quadratische Alterseffekte auf selbstberichtete und verhaltensbezogene Prosozialität untersucht. Zusätzlich untersuchten zwei empirische Studien, ob diese altersbedingten Unterschiede in prosozialem Verhalten auch im realen Leben durch „ecological momentary assessment“ (wiederholte Selbstberichte im Alltag; Studie 2) und in einer kontrollierten Laboruntersuchung mittels eines modifizierten Diktator-Spiels (Studie 3) beobachtbar sind. Im Rahmen dieser drei Studien wurden zudem potenzielle zugrundeliegende Verhaltens- und komputationale Mechanismen untersucht. Die Ergebnisse der Meta-Analyse (Studie 1) zeigten einen geringfügigen linearen Anstieg von Prosozialität über das erwachsene Alter hinweg und signifikante Unterschiede zwischen jüngeren und älteren Erwachsenen, wobei ältere Erwachsene prosozialer waren. Zusätzlich zeigte eine explorative Analyse einen quadratischen Effekt von Alter auf prosoziales Verhalten, mit den höchsten Werten im mittleren Erwachsenenalter. Darüber hinaus verhielten sich mittelalte Erwachsene prosozialer im Vergleich zu jüngeren Erwachsenen, während keine signifikanten Unterschiede zwischen mittelalten und älteren Erwachsenen gefunden wurden. Situative und kontextuelle Merkmale, wie beispielsweise das Setting der Studie und bestimmte Merkmale des Paradigmas, moderierten den Zusammenhang zwischen Alter und Prosozialität und heben damit die Bedeutung des (sozialen) Kontextes bei der Untersuchung von Prosozialität hervor. Studie 2 konnte keinen signifikanten Zusammenhang zwischen Alter und prosozialem Verhalten im realen Leben finden. Es zeigte sich jedoch ein signifikanter linearer und quadratischer Alterseffekt auf das Erleben von Empathie im realen Leben, mit den höchsten Werten im mittelern Erwachsenenalter. Zudem zeigte sich, dass der Zusammenhang zwischen der Möglichkeit, in einer Situation Empathie zu empfinden, und dem Alter das Ausmaß an prosozialem Verhalten im realen Leben vorhersagte. Dieser Effekt, d.h. ein höheres Maß an prosozialem Verhalten in Situationen, die Empathie auslösen, war am stärksten im mittleren Erwachsenenalter ausgeprägt. In Studie 3 hingegen wurden Altersunterschiede in der Art und Weise beobachtet, wie ältere und jüngere Erwachsene die Werte potenzieller Gewinne für sich selbst versus für eine andere Person berücksichtigen, um eine mögliche prosoziale Entscheidung zu treffen. Jüngere Erwachsene kombinierten beide Werte auf multiplikative Weise, was zu einer erhöhten Entscheidungseffizienz führte. Ältere Erwachsene zeigten hingegen einen additiven Effekt der Werte für sich selbst und die andere Person auf ihre Entscheidungen und waren effizienter in ihrer Entscheidungsfindung, wenn sie die Werte separat betrachteten. Eine stärkere inhibitorische Kontrolle ermöglichte es älteren Erwachsenen, Informationen beider Werte in ihre Entscheidungsprozesse einzubeziehen. Die Ergebnisse dieser Dissertation liefern wertvolle Erkenntnisse zur vielschichtigen Natur der Prosozialität über die erwachsene Lebensspanne hinweg sowie zu den Mechanismen, die diese altersbedingten Unterschiede erklären können. Obwohl die Ergebnisse eine Zunahme an Prosozialität mit dem Alter stützen, hinterfragen sie auch die Annahme, dass ältere Erwachsene grundsätzlich prosozialer sind. Die einzelnen Studien setzen die Lebensmitte als möglichen Höhepunkt der sozialen Entwicklung in den Fokus, betonen aber auch die Bedeutung des (sozialen) Kontexts sowie die Tatsache, dass unterschiedliche Operationalisierungen möglicherweise unterschiedliche Facetten der Prosozialität erfassen. Dies hebt die Notwendigkeit einer umfassenden Übersichtsarbeit hervor, um Alterseffekte von Prosozialität besser verstehen und mögliche Interventionen erarbeiten zu können. KW - Altersunterschied KW - prosocial behavior KW - adult development KW - prosociality KW - older adults KW - Lebenslauf KW - Metaanalyse KW - prosocial Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359445 ER - TY - THES A1 - Waltmann, Maria T1 - Neurocognitive mechanisms of loss of control in Binge Eating Disorder T1 - Neurokognitive Mechanismen des Kontrollverlusts im Rahmen der Binge- Eating-Störung N2 - 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. N2 - Binge-Eating-Störung (BES) ist eine weit verbreitete psychische Erkrankung, die häufig im Jugend- oder jungen Erwachsenenalter beginnt und von Episoden unkontrollierten Überessens gefolgt von negativen Emotionen wie Schuld und Scham gekennzeichnet ist. Ein verbessertes Verständnis der neurokognitiven Mechanismen, die der BES zugrunde liegen, ist zentral für die Entwicklung zielgerichteterer und effektiverer Therapieansätze. Die vorliegende Dissertation umfasst eine systematische Übersichtsarbeit und drei empirische Studien, die zu diesem Vorhaben beitragen. BES kann als eine Störung der kognitiven oder Verhaltenskontrolle betrachtet werden. Selbsteinschätzungsdaten aus Fragebogenstudien deuten klar auf erhöhte Impulsivität und Zwanghaftigkeit hin. Retrospektive Selbsteinschätzungsdaten können jedoch wenig Aufschluss über die Mechanismen geben, die impulsiven und zwanghaften Kontrollverlusten zugrunde liegen. Als Ausgangspunkt dieser Arbeit haben wir daher eine systematische Übersicht der experimentellen Literatur zu Impulsivität und Zwanghaftigkeit bei BES erstellt, die in dieser Hinsicht mehr Einblick verspricht. Die Studienlage war sehr heterogen, aber es gab vorläufige Hinweise auf veränderte zielgerichtete Kontrolle und Verhaltensflexibilität bei BES. Wir zeigen auf, dass unzureichende Reliabilität experimenteller Paradigmen und mangelnde Berücksichtigung wichtiger Störvariablen wie Körpergewicht mögliche Gründe für die großen Inkonsistenzen zwischen Studien sein könnten. Weiterhin vermuten wir, dass Impulsivität und/oder Zwanghaftigkeit im Rahmen der BES selektiv erhöht sein könnten, wenn Patient*innen sich in negativen Gemütszuständen befinden, und daher in Laborstudien nicht konsistent nachgewiesen werden können. Die empirischen Studien untersuchten die Rolle von Verhaltensflexibilität bei BES anhand experimenteller und bildgebender Verfahren sowie mathematischer Modellierung. In der ersten empirischen Studie untersuchten wir die Reliabilität der Probabilistic Reversal Learning Task (PRLT), eines gängigen Maßes der Verhaltensflexibilität. Wir konnten zeigen, dass die Verhaltensmaße und Metriken der mathematischen Modelle der PRLT adäquate Reliabilität aufweisen – allerdings nur, wenn sie anhand von hierarchischen Modellen errechnet werden. Letzteres reduziert die Fehlervarianz und verbessert die Reliabilität damit erheblich. Die Ergebnisse stützen die Verwendung der PRLT in unseren Studien zu Verhaltensflexibilität in der Entwicklung und bei BES. Da BES seine Erstmanifestation oft im Jugend- oder frühen Erwachsenenalter hat, liegt die Vermutung nahe, dass sie sich als Folge einer gestörten oder defizitären Reifung der Verhaltensflexibilität entwickeln könnte. Da jedoch wenig über die typische Entwicklung in diesem Bereich bekannt ist, haben wir in der zweiten empirischen Studie zunächst die normative Entwicklung von Reversal- Learning vom Jugend- zum Erwachsenenalter untersucht. Gesunde Jugendliche zeigten weniger adaptives, erratischeres und explorativeres Verhalten als Erwachsene. Unser mathematisches Modell des Verstärkungslernens erklärt dieses Muster durch eine verringerte Empfindlichkeit gegenüber positivem Feedback. Zudem konnten wir zeigen, dass dieses Verhalten teilweise durch reduzierte Aktivierung des medialen prefrontalen Kortex vermittelt war, einer Region, die im Jugendalter eine substanzielle Reifung durchmacht. In der dritten empirischen Studie haben wir schließlich Reversal-Learning bei BES untersucht und dabei spezielles Augenmerk auf potenzielle Verzerrungen im Lernen zum Erlangen von Belohnungen im Gegensatz zum Lernen zur Verlustvermeidung gelegt. Um Effekte von BES und Adipositas zu unterscheiden, haben wir Daten von adipösen Personen mit und ohne BES, sowie gesunden Normalgewichtigen erhoben. Wie erwartet gab es subtile neurokognitive Unterschiede zwischen adipösen Proband*innen mit und ohne BES im Hinblick auf Lernen zum Erlangen von Belohnungen und Vermeiden von Verlusten. So war Adipositas durch relativ beeinträchtigtes Lernen zum Erlangen von Belohnungen gekennzeichnet, während BES durch relativ beeinträchtigtes Lernen zur Vermeidung von Verlusten gekennzeichnet war. Dieser Unterschied spiegelte sich in der neuronalen Kodierung von Lernsignalen wieder und korrelierte mit der Symptomschwere der BES. Zusammenfassend zeigt diese Dissertation, dass die Literatur zu Impulsivität und Zwanghaftigkeit in BES inkonsistent ist und legt Gründe für diese Inkonsistenzen nahe. Sie hebt die kritische Rolle der Reliabilität von Instrumenten in der Forschung in differentieller und klinischer Psychologie sowie Psychiatrie hervor und zeigt Möglichkeiten auf, diese zu verbessern. Weiterhin zeichnet sie ein Bild der Entwicklung von Reversal Learning vom Jugend- zum Erwachsenenalter und unterstreicht die Relevanz von Explorationsverhalten im Kontext von Lernen und Entscheiden im Jugendalter. Schließlich zeigt sie qualitative Unterschiede zwischen BES und Adipositas auf und legt weitere Forschung in Hinblick auf eine möglicherweise zentrale Rolle negativer Emotionen für Kontrollverlust bei BES nahe. KW - Binge-eating Disorder KW - Kognitive Entwicklung KW - Reliabilität KW - Impulsivität KW - Computational Psychiatry KW - fMRI / Neuroimaging KW - Binge-Eating-Störung Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-364300 ER - TY - THES A1 - Banaschewski, Nora Malaika Marcia Cathérine T1 - Erleichterungslernen bei Jugendlichen mit nicht-suizidalem selbstverletzendem Verhalten T1 - Pain relief learning in adolescents with non-suicidal self-injury N2 - Die Erleichterung von einem körperlichen Schmerzreiz besitzt appetitiven Charakter (Leknes et al., 2008; 2011; Seymour et al., 2005), aktiviert belohnungsassoziierte Hirnstrukturen (Leknes et al., 2011; Leknes & Brock, 2014; Leknes & Tracey, 2008; Navratilova & Porreca, 2014) und fördert durch ihre Konditionierbarkeit als Erleichterungslernen bezeichnete appetitive Lern- und Konditionierungsprozesse (Andreatta et al., 2010, 2012; 2013; 2017; Gerber et al., 2014; Tanimoto et al., 2004; Yarali et al., 2008). Die vorliegende Arbeit bestätigt das angewandte Versuchsparadigma als valides Modell für Erleichterungslernen im Menschen und zeigt erstmals, dass der appetitive Charakter von Schmerzerleichterung auch in Jugendlichen konditionierbar ist. Erfolgreiches Erleichterungslernen zeigte sich dabei in der untersuchten Stichprobe lediglich auf impliziter, nicht aber auf expliziter, kognitiver Ebene. Dies stützt Thesen und vorherige Forschungsbefunde einer Dualität assoziativen Lernens in ein implizites Lernen, welches vornehmlich subkortikale Strukturen erfordert und ein explizites Lernen, das vorrangig kortikale Strukturen wie den präfrontalen Cortex involviert (Andreatta et al., 2010; Strack & Deutsch, 2004; Williams et al., 2001). Die Beobachtungen einer differenten Furcht- versus Erleichterungs-Extinktion bestärken die Thesen eines diversen neuronalen Hintergrunds dieser beiden Lernformen (Diegelmann et al., 2013; Gerber et al., 2014; Yarali et al., 2009; Yarali & Gerber, 2010). Gleichzeitig werfen die Studienergebnisse die Frage auf, ob und inwiefern im Erleichterungslernen von Jugendlichen Unterschiede zu jenem in Erwachsenen bestehen. Die Hypothese einer verstärkten Akquisition von Erleichterungslernen bei Jugendlichen mit NSSV im Vergleich zu gesunden Jugendlichen ließ sich in der vorliegenden Studie nicht bestätigen. Somit liefern die Ergebnisse keinen direkten Hinweis darauf, dass ein verstärktes Lernen durch Schmerzerleichterung an der Ätiopathogenese von NSSV beteiligt sein könnte. Die vorliegende Arbeit zeigte vielmehr die Tendenz eines abgeschwächten impliziten Erleichterungslernens bei den Jugendlichen mit NSSV. Die tendenziellen Gruppenunterschiede ließen sich nicht hinreichend durch eine differente aktuelle Stimmungslage oder durch eine unterschiedlich starke Ausprägung aversiver emotionaler Anspannungen oder momentaner Angstaffekte erklären. Innerhalb der Gruppe Jugendlicher mit NSSV zeigte sich auch kein Hinweis darauf, dass der Erfolg von Erleichterungslernen vom Schweregrad des NSSV oder von der aktuellen Einnahme von Antidepressiva abhängig sein könnte. Explorative Analysen ergaben, dass Gruppeneffekte in der vorliegenden Studie womöglich aufgrund einer statistischen Unterschätzung, bedingt durch einen zu geringen Stichprobenumfang, nicht das Signifikanzniveau erreichten und dass Unterschiede im Erleichterungslernen von Jugendlichen mit und ohne NSSV tatsächlich sogar noch stärker ausgeprägt sein könnten. Somit sollte die vorliegende Arbeit als Pilotstudie für zukünftige größer angelegte Studien zu Erleichterungslernen bei NSSV betrachtet werden. Zukünftige Studien erscheinen insbesondere sinnvoll mit Blick auf die hohe klinische sowie gesellschaftliche Relevanz von NSSV für welches, trotz der hohen Prävalenzen und des deutlich erhöhten Morbiditäts- und Mortalitätsrisikos, zum aktuellen Zeitpunkt noch keine hinreichenden Erklärungsmodelle bestehen. Die Studie bestätigte das Vorliegen eines erhöhten Grades aversiver emotionaler Anspannung in Jugendlichen mit NSSV, welcher zuvor nur an Erwachsenen mit einer BPD untersucht und festgestellt worden war (Niedtfeld et al., 2010; Stiglmayr et al., 2005). Die Abnahme negativer Affekte bei den Jugendlichen mit NSSV im Studienverlauf repliziert die Ergebnisse vorheriger Studien, in denen eine Reduktion selbst-berichteter negativer Affekte durch die Beendigung eines Schmerzreizes beobachtet wurde (Bresin et al., 2010; Bresin & Gordon, 2013). Damit bestärken die Studienergebnisse bestehende Erklärungsmodelle für NSSV, welche eine entscheidende Beteiligung der körperlichen Schmerzen und der Schmerzerleichterung bei der Selbstverletzung an der Affektregulation vermuten. Weiterhin wirft die vorliegende Arbeit die Frage auf, welche Rolle eine veränderte Wahrnehmung von Schmerz und Schmerzerleichterung in der Ätiopathogenese von NSSV einnimmt und wie diese sich auf Lernprozesse auswirkt. Insgesamt erbrächten weitere Erkenntnisse über den potenziellen Zusammenhang von NSSV und abweichendem Erleichterungslernen ein besseres Verständnis für Mechanismen der Entstehung und Aufrechterhaltung von NSSV und böten zudem möglicherweise Ansätze für neue Therapiemöglichkeiten des Störungsbildes. N2 - Relief from a physical pain stimulus has an appetitive character (Leknes et al., 2008; 2011; Seymour et al., 2005), activates reward-associated brain structures (Leknes et al., 2011; Leknes & Brock, 2014; Leknes & Tracey, 2008; Navratilova & Porreca, 2014) and, due to its conditionability, promotes learning and conditioning processes called relief learning (Andreatta et al., 2010, 2012; 2013; 2017; Gerber et al., 2014; Tanimoto et al., 2004; Yarali et al., 2008). The present work confirms the applied experimental paradigm as a valid model for relief learning in humans and shows for the first time that the appetitive nature of pain relief is also conditionable in adolescents. Successful relief learning was shown in the investigated sample only on an implicit, but not on an explicit, cognitive level. This supports theses and prior research findings of a duality of associative learning into implicit learning, which primarily requires subcortical structures, and explicit learning, which primarily involves cortical structures such as the prefrontal cortex (Andreatta et al., 2010; Strack & Deutsch, 2004; Williams et al., 2001). The observations of differential fear versus relief extinction reinforce the hypotheses of a diverse neural background of these two forms of learning (Diegelmann et al., 2013; Gerber et al., 2014; Yarali et al., 2009; Yarali & Gerber, 2010). At the same time, the study results raise the question of whether and to what extent differences exist in the relief learning of adolescents compared to that in adults. The hypothesis of increased acquisition of relief learning in adolescents with non-suicidal self-injury (NSSI) compared with healthy adolescents could not be confirmed in the present study. Thus, the results do not provide direct evidence that enhanced relief learning may be involved in the etiopathogenesis of NSSI. Rather, the present work demonstrated a tendency for attenuated implicit relief learning among adolescents with NSSI. The tendential group differences could not be adequately explained by a differential current mood state or by different degrees of aversive emotional tension or momentary anxiety effects. Within the group of adolescents with NSSI, there was also no evidence that the success of relief learning might depend on the severity of NSSI or on the current use of antidepressants. Exploratory analyses revealed that group effects in the present study did not reach the significance level possibly because of statistical underestimation due to an insufficient sample size and that differences in relief learning between adolescents with and without NSSI might actually be even bigger. Thus, the present work should be considered as a pilot study for future larger-scale studies on relief learning in NSSI. Future studies seem particularly useful in view of the high clinical as well as societal relevance of NSSI for which, despite the high prevalences and the significantly increased risk of morbidity and mortality, no adequate explanatory models exist at the present time. The study confirmed the presence of increased levels of aversive emotional tension in adolescents with NSSI, which had previously been studied and found only in adults with a borderline personality disorder (Niedtfeld et al., 2010; Stiglmayr et al., 2005). The decrease in negative affect in adolescents with NSSI over the course of the study replicates the findings of previous studies in which a reduction in self-reported negative affect was observed as a result of the cessation of a pain stimulus (Bresin et al., 2010; Bresin & Gordon, 2013). Thus, the study results reinforce existing explanatory models for NSSI that suggest a crucial involvement of physical pain and pain relief during self-injury in affect regulation. Furthermore, the present work raises the question of the role of altered perception of pain and pain relief in the etiopathogenesis of NSSI and how this affects learning processes. Overall, further insights into the potential link between NSSI and deviant relief learning would provide a better understanding of mechanisms involved in the development and maintenance of NSSI, and, on top of that, might offer approaches for new treatment options for the disorder. KW - Selbstbeschädigung KW - Erleichterungslernen KW - Nicht-suizidales selbstverletzendes Verhalten KW - NSSV Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-323673 ER - TY - JOUR A1 - Franke, Maximilian A1 - Conzelmann, Annette A1 - Grünblatt, Edna A1 - Werling, Anna M. A1 - Spieles, Helen A1 - Wewetzer, Christoph A1 - Warnke, Andreas A1 - Romanos, Marcel A1 - Walitza, Susanne A1 - Renner, Tobias J. T1 - No Association of Variants of the NPY-System With Obsessive-Compulsive Disorder in Children and Adolescents JF - Frontiers in Molecular Neuroscience N2 - 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. KW - NPY KW - obsessive-compulsive KW - children KW - anxiety KW - neuropeptide Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229051 VL - 12 ER -