Early Adversity, Internalizing & Brain Structure

Presented here to further illustrate the nature + nurture hypothesis with respect to how sz develops. Because while meds can only do so much to change nature, psychotherapy can do a lot to change the effects of nurture.

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

Sarah K. G. Jensen, MSc1; Erin W. Dickie, PhD; Deborah H. Schwartz, MA; C. John Evans, PhD; Iroise Dumontheil, PhD; Tomáš Paus, MD, PhD; Edward D. Barker, PhD

JAMA Pediatrics.
Published online August 17, 2015. doi: 10.1001/jamapediatrics.2015[1].1486


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.

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).

[Each of these brain regions is associated with the capacity to observe and override misperception of and behavioral reaction to threat by the insular-amygdalar-hypothalamic-pituitary-adrenal axis in the mid-brain below the three regions listed in the paragraph above.]

Conclusions and Relevance: Adversity early in life was associated with higher levels of internalizing symptoms [the typical mental actions seen in paranoid sz, sza, szt and psychotic bipolar] as well as with altered brain structure [likewise in such disorders]. 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.