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Articles   |    
Gray Matter Abnormalities in Childhood Maltreatment: A Voxel-Wise Meta-Analysis
Lena Lim; Joaquim Radua, M.D.; Katya Rubia, Ph.D.
Am J Psychiatry 2014;171:854-863. doi:10.1176/appi.ajp.2014.13101427
View Author and Article Information

Dr. Rubia has received a grant from Lilly and speakers honoraria from Shire, Lilly, and Novartis. The other authors report no financial relationships with commercial interests.

Ms. Lim was supported by the National Medical Research Council (Singapore); the Kids Company, London; and the Rita Lila Weston Foundation, London.

From the Department of Child and Adolescent Psychiatry, Institute of Psychiatry, King’s College London; the Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; and FIDMAG Germanes Hospitalaries, CIBERSAM, Barcelona, Spain.

Address correspondence to Ms. Lim (lena.lim@kcl.ac.uk).

Copyright © 2014 by the American Psychiatric Association

Received October 29, 2013; Revised February 27, 2014; Accepted March 13, 2014.

Abstract

Objective  Childhood maltreatment acts as a severe stressor that produces a cascade of physiological and neurobiological changes that lead to enduring alterations in brain structure. However, structural neuroimaging findings have been inconsistent. The authors conducted a meta-analysis of published whole-brain voxel-based morphometry studies in childhood maltreatment to elucidate the most robust volumetric gray matter abnormalities relative to comparison subjects to date.

Method  Twelve data sets were included, comprising 331 individuals (56 children/adolescents and 275 adults) with a history of childhood maltreatment and 362 comparison subjects (56 children/adolescents and 306 adults). Anisotropic effect size-signed differential mapping, a voxel-based meta-analytic method, was used to examine regions of smaller and larger gray matter volumes in maltreated individuals relative to comparison subjects.

Results  Relative to comparison subjects, individuals exposed to childhood maltreatment exhibited significantly smaller gray matter volumes in the right orbitofrontal/superior temporal gyrus extending to the amygdala, insula, and parahippocampal and middle temporal gyri and in the left inferior frontal and postcentral gyri. They had larger gray matter volumes in the right superior frontal and left middle occipital gyri. Deficits in the right orbitofrontal-temporal-limbic and left inferior frontal regions remained in a subgroup analysis of unmedicated participants. Abnormalities in the left postcentral and middle occipital gyri were found only in older maltreated individuals relative to age-matched comparison subjects.

Conclusions  The findings demonstrate that the most consistent gray matter abnormalities in individuals exposed to childhood maltreatment are in relatively late-developing ventrolateral prefrontal-limbic-temporal regions that are known to mediate late-developing functions of affect and cognitive control, which are typically compromised in this population.

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FIGURE 1. Regions of Gray Matter Volume Differences in Participants Exposed To Childhood Maltreatment Relative to Unexposed Comparison Subjectsa

a Slices are shown in axial view and marked with the z coordinate as distance in millimeters from the anterior-posterior commissure. The right side of the image corresponds to the right side of the brain. Smaller volumes are indicated in red and larger volumes in blue.

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TABLE 1.Demographic and Clinical Characteristics of the 12 Voxel-Based Morphometry Studies Included in the Meta-Analysisa
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a ADHD=attention deficit hyperactivity disorder; NR=not reported; OCD=obsessive-compulsive disorder; PTSD=posttraumatic stress disorder; SSRIs=selective serotonin reuptake inhibitors.

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b Types of maltreatment: EA=emotional abuse; EN=emotional neglect; HCP=harsh corporal punishment; N=neglect; PA=physical abuse; PN=physical neglect; PVA=parental verbal abuse; SA=sexual abuse; WDV=witnessed domestic violence; WV=witnessed violence.

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c Participants in the De Brito et al. study (24) all reported no psychiatric diagnoses and are matched on anxiety, depression, and PTSD symptoms.

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TABLE 2.Gray Matter Volume Differences in Participants Exposed To Childhood Maltreatment Relative to Unexposed Comparison Subjectsa
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a BA=Brodmann’s area; MNI=Montreal Neurological Institute; SDM=Signed Differential Mapping.

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b Uncorrected p.

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