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Evidence for a Sex-Dependent MAOAx Childhood Stress Interaction in the Neural Circuitry of Aggression

  • 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-matchingConverging 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.show moreshow less

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Author details:Nathalie Holz, Regina Boecker-Schlier, Arlette F. Buchmann, Dorothea Blomeyer, Sarah Baumeister, Sarah Hohmann, Christine Jennen-Steinmetz, Isabella Wolf, Marcella Rietschel, Stephanie H. Witt, Michael M. Plichta, Andreas Meyer-Lindenberg, Martin H. Schmidt, Günter EsserORCiDGND, Tobias BanaschewskiORCiD, Daniel Brandeis, Manfred LauchtGND
DOI:https://doi.org/10.1093/cercor/bhu249
ISSN:1047-3211
ISSN:1460-2199
Pubmed ID:https://pubmed.ncbi.nlm.nih.gov/25331606
Title of parent work (English):Cerebral cortex
Publisher:Oxford Univ. Press
Place of publishing:Cary
Publication type:Article
Language:English
Year of first publication:2016
Publication year:2016
Release date:2020/03/22
Tag:MAOA; aggression; amygdala; fMRI; life stress
Volume:26
Number of pages:11
First page:904
Last Page:914
Funding institution:German Research Foundation [DFG LA 733/1-2]
Organizational units:Humanwissenschaftliche Fakultät / Strukturbereich Kognitionswissenschaften / Department Psychologie
Peer review:Referiert
Institution name at the time of the publication:Humanwissenschaftliche Fakultät / Institut für Psychologie
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