Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence

TLDR

Childhood maltreatment is a major risk factor for internalizing disorders, and altered connectivity of the brain’s fear circuitry is a candidate mechanism that has yet to be directly examined. Resting‑state fMRI revealed that maltreatment reduces prefrontal–hippocampal connectivity in both sexes and prefrontal–amygdala connectivity only in females, and that these connectivity changes mediate internalizing symptoms, highlighting fronto–hippocampal circuitry as a key pathway and suggesting that the additional fronto–amygdala deficit may underlie females’ higher anxiety and depression risk.

Abstract

Significance Childhood maltreatment is a major risk factor for internalizing disorders including depression and anxiety, which cause significant disability. Altered connectivity of the brain’s fear circuitry represents an important candidate mechanism linking maltreatment and these disorders, but this relationship has not been directly explored. Using resting-state functional brain connectivity in adolescents, we show that maltreatment predicts lower prefrontal–hippocampal connectivity in females and males but lower prefrontal–amygdala connectivity only in females. Altered connectivity, in turn, mediated the development of internalizing symptoms. These results highlight the importance of fronto–hippocampal connectivity for both sexes in internalizing symptoms following maltreatment. The additional impact on fronto–amygdala connectivity in females may help explain their higher risk for anxiety and depression.