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


METHODS
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.


METHODS
Early childhood adversity.


METHODS
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
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.
Department of Psychology, Institute of Psychiatry, Psychology, and Neuroscience, King's College, London, England.
Sarah K G
SK
Jensen
Rotman Research Institute, University of Toronto, Toronto, Ontario, Canada.
Erin W
EW
Dickie
Rotman Research Institute, University of Toronto, Toronto, Ontario, Canada.
Deborah H
DH
Schwartz
School of Psychology, Cardiff University Brain Research Imaging Centre, Cardiff University, Cardiff, Wales.
C John
CJ
Evans
Department of Psychological Sciences, Birkbeck, University of London, London, England.
Iroise
I
Dumontheil
Rotman Research Institute, University of Toronto, Toronto, Ontario, Canada.
Tomáš
T
Paus
Department of Psychology, Institute of Psychiatry, Psychology, and Neuroscience, King's College, London, England.
Edward D
ED
Barker
D000293:Adolescent; D001921:Brain / Q000033:anatomy & histology; D002648:Child; D002675:Child, Preschool; D004739:England; D005260:Female; D066128:Gray Matter / Q000033:anatomy & histology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007389:Internal-External Control; D008279:Magnetic Resonance Imaging; D008297:Male; D011247:Pregnancy; D011446:Prospective Studies; D012307:Risk Factors; D055815:Young Adult