Effects of Age, Sex, and Independent Life Events on Amygdala and Nucleus Accumbens Volumes in Child Bipolar I Disorder

Abstract

Relationships between environment and cortical-limbic-striatal pathways are not well-researched in child bipolar I disorder (BP-I). This was a controlled, blindly rated magnetic resonance imaging study of children with DSM-IV BP-I, manic or mixed type, compared with matched typically developing children (TC). There were 47 subjects (21 BP-I, 26 TC) aged 14.0+/-3.1 (BP-I onset age 8.8+/-4.2). Total intracranial volume was greater in male subjects (n=28) versus female subjects (n=19) [F(1,44)=24.3, p< .001], controlling for age. Volumes were not significantly different in BP-I and TC groups, after accounting for multiple comparisons, in the medial orbital frontal cortex, rostral anterior cingulate cortex, hippocampus, amygdala (AMG), or nucleus accumbens (NAcc). Across subjects (n=47), a greater number of independent life events (ILE) was associated with smaller AMG [F(1,36)=7.8, p= .009] and NAcc [F(1,36) = 9.4, p= .004] volumes, controlling for total intracranial volume (TICV), group, age, sex, and family psychopathology. Use of stimulant medication at the time of the scan was associated with larger AMG volume [F(1,41)=9.0, p= .005], controlling for TICV, group, age, and sex. In male subjects, the age x group interaction was a significant predictor in general linear models of AMG (p= .028) and NAcc (p= .030) volumes. Effects of low maternal warmth were not significant. Findings suggest that ILE affect AMG and NAcc volume, but further research is needed to examine specificity to child BP-I. Furthermore, differential age x group (child BP-I vs. TC) effects only in male subjects are consistent with differential brain development by sex.