title: Evidence for a Sex-Dependent MAOA× Childhood Stress Interaction in the Neural Circuitry of Aggression.
abstract: 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 MAOA× CLS interaction for intermediate phenotypes of emotional and inhibitory processing, suggesting a possible mechanism in conferring susceptibility to violence-related disorders.
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Holz
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy.
authors.forename: Regina
authors.initials: R
authors.lastname: Boecker
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy.
authors.forename: Arlette F
authors.initials: AF
authors.lastname: Buchmann
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Blomeyer
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Baumeister
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hohmann
authors.affiliation: Department of Biostatistics.
authors.forename: Christine
authors.initials: C
authors.lastname: Jennen-Steinmetz
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy Department of Neuroimaging.
authors.forename: Isabella
authors.initials: I
authors.lastname: Wolf
authors.affiliation: Department of Genetic Epidemiology in Psychiatry.
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: Department of Genetic Epidemiology in Psychiatry.
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Witt
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Germany.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Plichta
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyer-Lindenberg
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Schmidt
authors.affiliation: Department of Psychology, University of Potsdam, Potsdam, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Esser
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy.
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy Department of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Brandeis
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy Department of Psychology, University of Potsdam, Potsdam, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Laucht
mesh_terms: D000328:Adult; D000374:Aggression / Q000502:physiology*; D001921:Brain / Q000254:growth & development / Q000503:physiopathology*; D001931:Brain Mapping; D002648:Child; D002675:Child, Preschool; D000066499:Facial Recognition / Q000502:physiology; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics*; D009434:Neural Pathways / Q000254:growth & development / Q000503:physiopathology; D009483:Neuropsychological Tests; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human
keywords: MAOA; aggression; amygdala; fMRI; life stress