Effect of early adversity and childhood internalizing symptoms on brain structure in young men

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 outcomewas GMvolume 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 GMvolumes 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 GMvolume in the right superior frontal gyrus (β = ..20; P = .002). Early adversity was also associated with higher levels of internalizing symptoms (β = .37; P