Retrospectively reported childhood physical abuse, systemic inflammation, and resting corticolimbic connectivity in midlife adults

Abstract

Childhood abuse confers risk for psychopathology and pathophysiology in midlife through intermediate pathways that remain unclear. Systemic inflammation was tested in the present study as one pathway that may link physical abuse in childhood to the adult functioning of corticolimbic brain circuits broadly implicated in risk for poor mental and physical health. Midlife adults (N = 303; 30-51 years of age; 149 women) without psychiatric, immune, or cardiovascular diagnoses provided retrospective reports of childhood physical abuse. Functional connectivity between corticolimbic brain areas (amygdala, hippocampus, ventromedial prefrontal cortex [vmPFC], anterior cingulate cortex [ACC]) was measured at rest using functional magnetic resonance imaging. Circulating levels of interleukin(IL)-6, a pro-inflammatory cytokine previously linked to childhood abuse and corticolimbic functionality, were measured via blood draw. Consistent with prior studies, retrospectively reported childhood physical abuse was associated positively with circulating IL-6, and negatively with connectivity between the amygdala and vmPFC. IL-6 was also associated negatively with several corticolimbic functional connections, including amygdala-vmPFC connectivity. Moreover, path analyses revealed an indirect effect of IL-6 that partially explained the association between childhood physical abuse and adult amygdala-vmPFC connectivity. Consistent with recent neurobiological models of early life influences on disease risk across the lifespan, associations between childhood physical abuse and adulthood corticolimbic circuit functionality may be partially explained by inflammatory processes.

Keywords: Amygdala; Childhood abuse; Functional connectivity; Inflammation; Interleukin-6; Ventromedial prefrontal cortex.

Figure 1.

(A) Adulthood resting connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC) shown as a function of retrospectively reported childhood physical abuse. (B) Circulating levels of adulthood interleukin-6 (IL-6) shown as a function of childhood physical abuse. (C) Amygdala – vmPFC connectivity shown as a function of IL-6. The scatter plots shown in A-C are unadjusted for covariates for illustration purposes. (D) Path model summarizing the association of childhood physical abuse and amygdala – vmPFC connectivity, as mediated by circulating IL-6. Regions-of-interest corresponding to the amygdala and vmPFC are depicted in red and blue, respectively. The values correspond to each estimate [β(SE)] for the indirect (a, b), direct (c’), and total (c) paths. (E) Distribution of 5000 bootstrap samples of the indirect (a × b) effect for the mediation results shown in D. The gray-shaded area of the distribution encompasses a × b indirect effects falling within a 95% bias corrected and accelerated confidence interval (CI). β, standardized beta; CI, Confidence intervals; CTQ, Childhood Trauma Questionnaire; IL-6, interleukin-6; SE, standard error; vmPFC, ventromedial prefrontal cortex * p < .05. ** p < .01