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  - 
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  -