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

Abstract

Maltreatment during childhood is a major risk factor for anxiety and depression, which are major public health problems. However, the underlying brain mechanism linking maltreatment and internalizing disorders remains poorly understood. Maltreatment may alter the activation of fear circuitry, but little is known about its impact on the connectivity of this circuitry in adolescence and whether such brain changes actually lead to internalizing symptoms. We examined the associations between experiences of maltreatment during childhood, resting-state functional brain connectivity (rs-FC) of the amygdala and hippocampus, and internalizing symptoms in 64 adolescents participating in a longitudinal community study. Childhood experiences of maltreatment were associated with lower hippocampus-subgenual cingulate rs-FC in both adolescent females and males and lower amygdala-subgenual cingulate rs-FC in females only. Furthermore, rs-FC mediated the association of maltreatment during childhood with adolescent internalizing symptoms. Thus, maltreatment in childhood, even at the lower severity levels found in a community sample, may alter the regulatory capacity of the brain's fear circuit, leading to increased internalizing symptoms by late adolescence. These findings highlight the importance of fronto-hippocampal connectivity for both sexes in internalizing symptoms following maltreatment in childhood. Furthermore, the impact of maltreatment during childhood on both fronto-amygdala and -hippocampal connectivity in females may help explain their higher risk for internalizing disorders such as anxiety and depression.

Keywords: child maltreatment; sex differences; ventromedial prefrontal cortex.

Fig. 1.

Childhood experiences of maltreatment predict lower rs-FC of the amygdala and hippocampus (n = 64; 30 female). (A) CTQ scores negatively correlated with rs-FC between the right amygdala and sgACC across all participants. This association was specific to females (scatterplots, Right). (B) CTQ scores negatively correlated with rs-FC between the left hippocampus and sgACC in all participants. This association was present in both females and males (scatterplots, Right). Seed regions are displayed in the left panels. Connectivity results are displayed at P < 0.05, family-wise error corrected at the whole brain level.

Fig. 2.

In girls, experiences of maltreatment during childhood remain negatively correlated with amygdala–sgACC connectivity when cortisol values at age 4.5 y are included in the model (A). In addition, experiences of maltreatment and cortisol values at age 4.5 y are associated with amygdala connectivity to different regions of the vmPFC (B).

Fig. 3.

SEM examining the effect of rs-FC in mediating between childhood experiences of maltreatment (measured by CTQ scores) and internalizing symptoms at age 18 y, as moderated by sex. Connectivity variables included total connectivity of the amygdala and hippocampus to sgACC and differential connectivity (the difference between the amygdala– and hippocampus–sgACC scores) to examine overall and relative effects of each region. Models are shown by sex in Fig. 4.

Fig. 4.

SEM examining the effect of functional connectivity in mediating between childhood experiences of maltreatment (measured by CTQ scores) and adolescent internalizing symptoms in girls (A) and boys (B). Connectivity variables included both total connectivity of the amygdala and hippocampus to sgACC and differential connectivity (the difference between the amygdala– and hippocampus–sgACC scores) to examine overall and relative effects of each region. (A) In girls, lower total functional connectivity of the amygdala and hippocampus to sgACC mediated the association between CTQ scores and internalizing symptoms. Lower amygdala–sgACC connectivity (i.e., a lower differential score) contributed more substantially to the association between CTQ scores and internalizing symptoms. (B) In boys, findings were similar except that lower hippocampus–sgACC connectivity (i.e., a higher differential score) contributed more substantially to this effect. The full model with moderation by sex is shown in Fig. 3.