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Original Investigation |

Effect of Early Adversity and Childhood Internalizing Symptoms on Brain Structure in Young Men

Sarah K. G. Jensen, MSc1; Erin W. Dickie, PhD2; Deborah H. Schwartz, MA2; C. John Evans, PhD3; Iroise Dumontheil, PhD4; Tomáš Paus, MD, PhD2; Edward D. Barker, PhD1
[+] Author Affiliations
1Department of Psychology, Institute of Psychiatry, Psychology, and Neuroscience, King’s College, London, England
2Rotman Research Institute, University of Toronto, Toronto, Ontario, Canada
3School of Psychology, Cardiff University Brain Research Imaging Centre, Cardiff University, Cardiff, Wales
4Department of Psychological Sciences, Birkbeck, University of London, London, England
JAMA Pediatr. 2015;169(10):938-946. doi:10.1001/jamapediatrics.2015.1486.
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Importance  Early adversity is an important risk factor that relates to internalizing symptoms and altered brain structure.

Objective  To assess the direct effects of early adversity and child internalizing symptoms (ie, depression, anxiety) on cortical gray matter (GM) volume, as well as the extent to which early adversity associates with variation in cortical GM volume indirectly via increased levels of internalizing symptoms.

Design, Setting, and Participants  A prospective investigation of associations between adversity within the first 6 years of life, internalizing symptoms during childhood and early adolescence, and altered brain structure in late adolescence (age, 18-21 years) was conducted in a community-based birth cohort in England (Avon Longitudinal Study of Parents and Children). Participants from the cohort included 494 mother-son pairs monitored since the mothers were pregnant (estimated date of delivery between April 1, 1991, and December 31, 1992). Data collection for the present study was conducted between April 1, 1991, and November 30, 2010; the neuroimaging data were collected between September 1, 2010, and November 30, 2012, and data analyses for the present study occurred between January 25, 2013, and February 15, 2015. Risk factors were adversity within the first 6 years of the child’s life (including prenatal exposure) and the child’s internalizing symptoms between age 7 and 13 years.

Exposures  Early childhood adversity.

Main Outcomes and Measures  The main outcome was GM volume of cortical regions previously associated with major depression measured through T1-weighted magnetic resonance images collected in late adolescence.

Results  Among 494 young men included in this analysis, early adversity was directly associated with lower GM volumes in the anterior cingulate cortex (β = −.18; P = .01) and higher GM volume in the precuneus (β = .18; P = .009). Childhood internalizing symptoms were associated with lower GM volume in the right superior frontal gyrus (β = −.20; P = .002). Early adversity was also associated with higher levels of internalizing symptoms (β = .37; P < .001), which, in turn, were associated with lower superior frontal gyrus volume (ie, an indirect effect) (β = −.08; 95% CI, −0.14 to −0.01; P = .02).

Conclusions and Relevance  Adversity early in life was associated with higher levels of internalizing symptoms as well as with altered brain structure. Early adversity was related to variation in brain structure both directly and via increased levels of internalizing symptoms. These findings may suggest that some of the structural variation often attributed to depression might be associated with early adversity in addition to the effect of depression.

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Figure 1.
Image Showing the 30 Cortical Regions of Interest (ROIs) on an Inflated Brain After Projection Into FreeSurfer

The 3 significant ROIs are highlighted in red and nonsignificant ROIs are shown in blue. Numbers refer to the ROI numbers presented in Table 1.

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Figure 2.
Diagrams Illustrating the Multivariate Path Models of Direct Effects of Early Adversity and Childhood Internalizing Symptoms

Standardized path coefficients for gray matter volume (A), surface area (B) and cortical thickness (C) analyses. Estimates of significant associations are presented in model A. Models B and C indicate whether findings from model A replicated for surface area (B) and thickness (C). Solid lines indicate paths that were replicated; dashed lines indicate paths that were not replicated (ie, it was not significant).a The gray line in model C indicates that this association was unique to model C (ie, it was not significant in model A).b The diagrams do not show control variables (total brain volume, duration of breastfeeding, and prenatal and adolescent adversity). All correlations between regions of interest were included in the model. R indicates right.

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