Working memory brain activity and capacity link MAOA polymorphism to aggressive behavior during development

M Peyrard-Janvid,J Kere,T Ziermans,T Klingberg,H Matsson,C Roggeman,I Dumontheil

doi:10.1038/tp.2012.7

Abstract

A developmental increase in working memory capacity is an important part of cognitive development, and low working memory (WM) capacity is a risk factor for developing psychopathology. Brain activity represents a promising endophenotype for linking genes to behavior and for improving our understanding of the neurobiology of WM development. We investigated gene–brain–behavior relationships by focusing on 18 single-nucleotide polymorphisms (SNPs) located in six dopaminergic candidate genes (COMT, SLC6A3/DAT1, DBH, DRD4, DRD5, MAOA). Visuospatial WM (VSWM) brain activity, measured with functional magnetic resonance imaging, and VSWM capacity were assessed in a longitudinal study of typically developing children and adolescents. Behavioral problems were evaluated using the Child Behavior Checklist (CBCL). One SNP (rs6609257), located ∼6.6 kb downstream of the monoamine oxidase A gene (MAOA) on human chromosome X, significantly affected brain activity in a network of frontal, parietal and occipital regions. Increased activity in this network, but not in caudate nucleus or anterior prefrontal regions, was correlated with VSWM capacity, which in turn predicted externalizing (aggressive/oppositional) symptoms, with higher WM capacity associated with fewer externalizing symptoms. There were no direct significant correlations between rs6609257 and behavioral symptoms. These results suggest a mediating role of WM brain activity and capacity in linking the MAOA gene to aggressive behavior during development.

Highlights

Working memory (WM) refers to the retention and manipulation of information over a brief period of time.[1]
In order to further reduce the number of comparisons, blood-oxygen level dependent (BOLD) data for each Regions of interest (ROI) was entered into a Principal component analysis (PCA)
The aim of this study was to investigate the role of visuospatial WM (VSWM) development, both in terms of behavior and brain activity, as an intermediate phenotype linking DA-related genes to problem behavior

Summary

Introduction

Working memory (WM) refers to the retention and manipulation of information over a brief period of time.[1] A gradual increase in WM capacity is strongly related to the development of general intellectual ability[2] and academic performance.[3] Impaired WM capacity is a core feature of many psychiatric disorders, including attention-deficit/hyperactivity disorder[4] and schizophrenia.[5] low WM capacity in children is a risk factor for psychopathology later in life, such as psychosis, depression and suicidal ideation.[6,7] WM capacity is an important factor for emotional selfregulation,[8] and restricted self-regulation has been associated with behavioral problems in children, in particular, but not restricted to, externalizing problems (for example, aggression, antisocial behavior).[9] Increasing knowledge of the underlying neurobiological mechanisms of typical WM development is an essential step to understand atypical development and guide initiatives to remediate problem behavior.[10]

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