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  - 
TY  - JOUR
A1  - Holz, Nathalie
A1  - Boecker-Schlier, Regina
A1  - Buchmann, Arlette F.
A1  - Blomeyer, Dorothea
A1  - Baumeister, Sarah
A1  - Hohmann, Sarah
A1  - Jennen-Steinmetz, Christine
A1  - Wolf, Isabella
A1  - Rietschel, Marcella
A1  - Witt, Stephanie H.
A1  - Plichta, Michael M.
A1  - Meyer-Lindenberg, Andreas
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Banaschewski, Tobias
A1  - Brandeis, Daniel
A1  - Laucht, Manfred
T1  - Evidence for a Sex-Dependent MAOAx Childhood Stress Interaction in the Neural Circuitry of Aggression
JF  - Cerebral cortex
N2  - Converging evidence emphasizes the role of an interaction between monoamine oxidase A (MAOA) genotype, environmental adversity, and sex in the pathophysiology of aggression. The present study aimed to clarify the impact of this interaction on neural activity in aggression-related brain systems. Functional magnetic resonance imaging was performed in 125 healthy adults from a high-risk community sample followed since birth. DNA was genotyped for the MAOA-VNTR (variable number of tandem repeats). Exposure to childhood life stress (CLS) between the ages of 4 and 11 years was assessed using a standardized parent interview, aggression by the Youth/Young Adult Self-Report between the ages of 15 and 25 years, and the VIRA-R (Vragenlijst Instrumentele En Reactieve Agressie) at the age of 15 years. Significant interactions were obtained between MAOA genotype, CLS, and sex relating to amygdala, hippocampus, and anterior cingulate cortex (ACC) response, respectively. Activity in the amygdala and hippocampus during emotional face-matching increased with the level of CLS in male MAOA-L, while decreasing in male MAOA-H, with the reverse pattern present in females. Findings in the opposite direction in the ACC during a flanker NoGo task suggested that increased emotional activity coincided with decreased inhibitory control. Moreover, increasing amygdala activity was associated with higher Y(A)SR aggression in male MAOA-L and female MAOA-H carriers. Likewise, a significant association between amygdala activity and reactive aggression was detected in female MAOA-H carriers. The results point to a moderating role of sex in the MAOAx CLS interaction for intermediate phenotypes of emotional and inhibitory processing, suggesting a possible mechanism in conferring susceptibility to violence-related disorders.
KW  - aggression
KW  - amygdala
KW  - fMRI
KW  - life stress
KW  - MAOA
Y1  - 2016
U6  - https://doi.org/10.1093/cercor/bhu249
SN  - 1047-3211
SN  - 1460-2199
VL  - 26
SP  - 904
EP  - 914
PB  - Oxford Univ. Press
CY  - Cary
ER  -