title: Cortico-limbic connectivity in MAOA-L carriers is vulnerable to acute tryptophan depletion.
abstract: A gene-environment interaction between expression genotypes of the monoamine oxidase A (MAOA) and adverse childhood experience increases the risk of antisocial behavior. However, the neural underpinnings of this interaction remain uninvestigated. A cortico-limbic circuit involving the prefrontal cortex (PFC) and the amygdala is central to the suppression of aggressive impulses and is modulated by serotonin (5-HT). MAOA genotypes may modulate the vulnerability of this circuit and increase the risk for emotion regulation deficits after specific life events. Acute tryptophan depletion (ATD) challenges 5-HT regulation and may identify vulnerable neuronal circuits, contributing to the gene-environment interaction.
  
  
  
  Functional magnetic resonance imaging measured the resting-state state activity in 64 healthy males in a double-blind, placebo-controlled study. Cortical maps of amygdala correlation identified the impact of ATD and its interaction with low- (MAOA-L) and high-expression variants (MAOA-H) of MAOA on cortico-limbic connectivity.
  
  
  
  Across all Regions of Interest (ROIs) exhibiting an ATD effect on cortico-limbic connectivity, MAOA-L carriers were more susceptible to ATD than MAOA-H carriers. In particular, the MAOA-L group exhibited a larger reduction of amygdala connectivity with the right prefrontal cortex and a larger increase of amygdala connectivity with the insula and dorsal PCC.
  
  
  
  MAOA-L carriers were more susceptable to a central 5-HT challenge in cortico-limbic networks. Such vulnerability of the cortical serotonergic system may contribute to the emergence of antisocial behavior after systemic challenges, observed as gene-environment interaction. Hum Brain Mapp 38:1622-1635, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany.|JARA-Translational Brain Medicine, Aachen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Eisner
authors.affiliation: Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany.|JARA-Translational Brain Medicine, Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Klasen
authors.affiliation: Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany.|JARA-Translational Brain Medicine, Aachen, Germany.
authors.forename: Dhana
authors.initials: D
authors.lastname: Wolf
authors.affiliation: Department of Human Genetics, Medical School, RWTH Aachen University, Aachen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Zerres
authors.affiliation: Department of Human Genetics, Medical School, RWTH Aachen University, Aachen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Eggermann
authors.affiliation: Department of Pharmacy, RWTH Aachen University, Aachen, Germany.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Eisert
authors.affiliation: Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany.|JARA-Translational Brain Medicine, Aachen, Germany.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Zvyagintsev
authors.affiliation: Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany.|JARA-Translational Brain Medicine, Aachen, Germany.
authors.forename: Pegah
authors.initials: P
authors.lastname: Sarkheil
authors.affiliation: Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany.|JARA-Translational Brain Medicine, Aachen, Germany.
authors.forename: Krystyna A
authors.initials: KA
authors.lastname: Mathiak
authors.affiliation: Department of Child and Adolescent Psychiatry, School of Psychiatry and Clinical Neurosciences and School of Pediatrics and Child Health; Faculty of Medicine, Dentistry and Health Sciences; The University of Western Australia (M561), Perth, Australia.|Department of Health in Western Australia, Specialized Child and Adolescent Mental Health Services (CAMHS), Perth, Australia.
authors.forename: Florian
authors.initials: F
authors.lastname: Zepf
authors.affiliation: Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany.|JARA-Translational Brain Medicine, Aachen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Mathiak
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D007839:Functional Laterality / Q000235:genetics; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008032:Limbic System / Q000000981:diagnostic imaging / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics*; D019964:Mood Disorders / Q000209:etiology / Q000235:genetics / Q000473:pathology; D009434:Neural Pathways; D010100:Oxygen / Q000097:blood; D014364:Tryptophan / Q000172:deficiency*; D055815:Young Adult
chemical_list: D014364:Tryptophan; D008995:Monoamine Oxidase; D010100:Oxygen
keywords: MAOA; aggression; amygdala; resting state fMRI; serotonin