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Hum Brain Mapp. 2017 Mar;38(3):1622-1635. doi: 10.1002/hbm.23475. Epub 2016 Dec 9.

Cortico-limbic connectivity in MAOA-L carriers is vulnerable to acute tryptophan depletion.

Author information

1
Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany.
2
JARA-Translational Brain Medicine, Aachen, Germany.
3
Department of Human Genetics, Medical School, RWTH Aachen University, Aachen, Germany.
4
Department of Pharmacy, RWTH Aachen University, Aachen, Germany.
5
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.
6
Department of Health in Western Australia, Specialized Child and Adolescent Mental Health Services (CAMHS), Perth, Australia.

Abstract

INTRODUCTION:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

KEYWORDS:

MAOA; aggression; amygdala; resting state fMRI; serotonin

PMID:
27935229
DOI:
10.1002/hbm.23475
[Indexed for MEDLINE]

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