TY - JOUR A1 - Frodl, Thomas A1 - Janowitz, Deborah A1 - Schmaal, Lianne A1 - Tozzi, Leonardo A1 - Dobrowolny, Henrik A1 - Stein, Dan J. A1 - Veltman, Dick J. A1 - Wittfeld, Katharina A1 - van Erp, Theo G. M. A1 - Jahanshad, Neda A1 - Block, Andrea A1 - Hegenscheid, Katrin A1 - Voelzke, Henry A1 - Lagopoulos, Jim A1 - Hatton, Sean N. A1 - Hickie, Ian B. A1 - Frey, Eva Maria A1 - Carballedo, Angela A1 - Brooks, Samantha J. A1 - Vuletic, Daniella A1 - Uhlmann, Anne A1 - Veer, Ilya M. A1 - Walter, Henrik A1 - Schnell, Knut A1 - Grotegerd, Dominik A1 - Arolt, Volker A1 - Kugel, Harald A1 - Schramm, Elisabeth A1 - Konrad, Carsten A1 - Zurowski, Bartosz A1 - Baune, Bernhard T. A1 - van der Wee, Nic J. A. A1 - van Tol, Marie-Jose A1 - Penninx, Brenda W. J. H. A1 - Thompson, Paul M. A1 - Hibar, Derrek P. A1 - Dannlowski, Udo A1 - Grabe, Hans J. T1 - Childhood adversity impacts on brain subcortical structures relevant to depression JF - Journal of psychiatric research N2 - Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of the present study was to investigate whether childhood adversity is associated with subcortical volumes and how it interacts with a diagnosis of MDD and sex. Within the ENIGMA-MDD network, nine university partner sites, which assessed childhood adversity and magnetic resonance imaging in patients with MDD and controls, took part in the current joint mega-analysis. In this largest effort world-wide to identify subcortical brain structure differences related to childhood adversity, 3036 participants were analyzed for subcortical brain volumes using FreeSurfer. A significant interaction was evident between childhood adversity, MDD diagnosis, sex, and region. Increased exposure to childhood adversity was associated with smaller caudate volumes in females independent of MDD. All subcategories of childhood adversity were negatively associated with caudate volumes in females - in particular emotional neglect and physical neglect (independently from age, ICV, imaging site and MDD diagnosis). There was no interaction effect between childhood adversity and MDD diagnosis on subcortical brain volumes. Childhood adversity is one of the contributors to brain structural abnormalities. It is associated with subcortical brain abnormalities that are relevant to psychiatric disorders such as depression. (C) 2016 Published by Elsevier Ltd. KW - Depression KW - Childhood adversity KW - MRI KW - Caudate KW - Hippocampus KW - ENIGMA Y1 - 2016 U6 - https://doi.org/10.1016/j.jpsychires.2016.11.010 SN - 0022-3956 SN - 1879-1379 VL - 86 SP - 58 EP - 65 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Boecker-Schlier, Regina A1 - Holz, Nathalie E. A1 - Buchmann, Arlette F. A1 - Blomeyer, Dorothea A1 - Plichta, Michael M. A1 - Jennen-Steinmetz, Christine A1 - Wolf, Isabella A1 - Baumeister, Sarah A1 - Treutleind, Jens A1 - Rietschel, Marcella A1 - Meyer-Lindenberg, Andreas A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Laucht, Manfred T1 - Interaction between COMT Val(158)Met polymorphism and childhood adversity affects reward processing in adulthood JF - NeuroImage : a journal of brain function N2 - Background: Accumulating evidence suggests that altered dopamine transmission may increase the risk of mental disorders such as ADHD, schizophrenia or depression, possibly mediated by reward system dysfunction. This study aimed to clarify the impact of the COMT Val(158)Met polymorphism in interaction with environmental variation (G x E) on neuronal activity during reward processing. Methods: 168 healthy young adults from a prospective study conducted over 25 years participated in amonetary incentive delay task measured with simultaneous EEG-fMRI. DNA was genotyped for COMT, and childhood family adversity (CFA) up to age 11 was assessed by a standardized parent interview. Results: At reward delivery, a G x E revealed that fMRI activation for win vs. no-win trials in reward-related regions increased with the level of CFA in Met homozygotes as compared to Val/Met heterozygotes and Val homozygotes, who showed no significant effect. During the anticipation of monetary vs. verbal rewards, activation decreased with the level of CFA, which was also observed for EEG, in which the CNV declined with the level of CFA. Conclusions: These results identify convergent genetic and environmental effects on reward processing in a prospective study. Moreover, G x E effects during reward delivery suggest that stress during childhood is associated with higher reward sensitivity and reduced efficiency in processing rewarding stimuli in genetically at-risk individuals. Together with previous evidence, these results begin to define a specific system mediating interacting effects of early environmental and genetic risk factors, which may be targeted by early intervention and prevention. (C) 2016 Elsevier Inc. All rights reserved. KW - Reward processing KW - COMT Val(158)Met polymorphism KW - Childhood adversity KW - Gene-environment interaction KW - Functional magnetic resonance imaging KW - Electroencephalography Y1 - 2016 U6 - https://doi.org/10.1016/j.neuroimage.2016.02.006 SN - 1053-8119 SN - 1095-9572 VL - 132 SP - 556 EP - 570 PB - Elsevier CY - San Diego ER - TY - JOUR A1 - Buchmann, Arlette F. A1 - Holz, Nathalie A1 - Boecker-Schlier, Regina A1 - Blomeyer, Dorothea A1 - Rietschel, Marcella A1 - Witt, Stephanie H. A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Zimmermann, Ulrich S. A1 - Laucht, Manfred T1 - Moderating role of FKBP5 genotype in the impact of childhood adversity on cortisol stress response during adulthood JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology N2 - Recent research suggests an important role of FKBP5, a glucocorticoid receptor regulating co-chaperone, in the development of stress-related diseases such as depression and anxiety disorders. The present study aimed to replicate and extend previous evidence indicating that FKBP5 polymorphisms moderate hypothalamus-pituitary-adrenal (HPA) function by examining whether FKBP5 rs1360780 genotype and different measures of childhood adversity interact to predict stress-induced cortisol secretion. At age 19 years, 195 young adults (90 males, 105 females) participating in an epidemiological cohort study completed the Trier Social Stress Test (TSST) to assess cortisol stress responsiveness and were genotyped for the FKBP5 rs1360780. Childhood adversity was assessed using the Childhood Trauma Questionnaire (CTQ) and by a standardized parent interview yielding an index of family adversity. A significant interaction between genotype and childhood adversity on cortisol response to stress was demonstrated for exposure to childhood maltreatment as assessed by retrospective self-report (CTQ), but not for prospectively ascertained objective family adversity. Severity of childhood maltreatment was significantly associated with attenuated cortisol levels among carriers of the rs1360780 CC genotype, while no such effect emerged in carriers of the T allele. These findings point towards the functional involvement of FKBP5 in long-term alterations of neuroendocrine stress regulation related to childhood maltreatment, which have been suggested to represent a premorbid risk or resilience factor in the context of stress-related disorders. (C) 2013 Elsevier B.V. and ECNR This is an open access article under the CC BY-NC-ND license. KW - FKBP5 KW - Stress KW - HPA KW - Cortisol KW - Childhood adversity Y1 - 2014 U6 - https://doi.org/10.1016/j.euroneuro.2013.12.001 SN - 0924-977X SN - 1873-7862 VL - 24 IS - 6 SP - 837 EP - 845 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Holz, Nathalie E. A1 - Buchmann, Arlette F. A1 - Boecker-Schlier, Regina A1 - Blomeyer, Dorothea A1 - Baumeister, Sarah A1 - Wolf, Isabella A1 - Rietschel, Marcella A1 - Witt, Stephanie H. A1 - Plichta, Michael M. A1 - Meyer-Lindenberg, Andreas A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Laucht, Manfred T1 - Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume JF - Brain structure & function N2 - Accumulating evidence suggests a role of FKBP5, a co-chaperone regulating the glucocorticoid receptor sensitivity, in the etiology of depression and anxiety disorders. Based on recent findings of altered amygdala activity following childhood adversity, the present study aimed at clarifying the impact of genetic variation in FKBP5 on threat-related neural activity and coupling as well as morphometric alterations in stress-sensitive brain systems. Functional magnetic resonance imaging during an emotional face-matching task was performed in 153 healthy young adults (66 males) from a high-risk community sample followed since birth. Voxel-based morphometry was applied to study structural alterations and DNA was genotyped for FKBP5 rs1360780. Childhood adversity was measured using retrospective self-report (Childhood Trauma Questionnaire) and by a standardized parent interview assessing childhood family adversity. Depression was assessed by the Beck Depression Inventory. There was a main effect of FKBP5 on the left amygdala, with T homozygotes showing the highest activity, largest volume and increased coupling with the left hippocampus and the orbitofrontal cortex (OFC). Moreover, amygdala-OFC coupling proved to be associated with depression in this genotype. In addition, our results support previous evidence of a gene-environment interaction on right amygdala activity with respect to retrospective assessment of childhood adversity, but clarify that this does not generalize to the prospective assessment. These findings indicated that activity in T homozygotes increased with the level of adversity, whereas the opposite pattern emerged in C homozygotes, with CT individuals being intermediate. The present results point to a functional involvement of FKBP5 in intermediate phenotypes associated with emotional processing, suggesting a possible mechanism for this gene in conferring susceptibility to stress-related disorders. KW - FKBP5 KW - Childhood adversity KW - Amygdala KW - fMRI KW - Connectivity KW - Voxel-based morphometry Y1 - 2015 U6 - https://doi.org/10.1007/s00429-014-0729-5 SN - 1863-2653 SN - 1863-2661 VL - 220 IS - 3 SP - 1355 EP - 1368 PB - Springer CY - Heidelberg ER -