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 amygdalasubgenual 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.child maltreatment | sex differences | ventromedial prefrontal cortex I n both clinical and community samples, maltreatment during childhood represents one of the strongest risk factors for developing depression and anxiety (1-3). Childhood maltreatment and other adversities account for up to a third of the risk for mood and anxiety disorders (4). Further, depression and anxiety disorders are major public health problems, affecting 15 and 32% of youth, respectively, by the age of 18 y (5). The burden of these disorders is significant, representing the second and fifth leading causes, respectively, of years lived with disability in the United States (6). Some evidence suggests that maltreatment may impart greater risk for the development of internalizing symptoms in females than in males (e.g., refs. 7-9). This differential risk could account, in part, for the higher incidence of internalizing problems in females than in males (10, 11). However, the neurobiological pathways from maltreatment during childhood to the expression of internalizing problems, including potential differences for females and males, remain poorly understood. Such information is crucial for improving the treatment of depression and anxiety disorders and for mitigating the effects of maltreatment during childhood.Both maltreatment during childhood (12) and internalizing disorders (13, 14) have been associated with altered activity in specific b...

Amygdala–Hippocampal Connectivity Changes During Acute Psychosocial Stress: Joint Effect of Early Life Stress and Oxytocin

“…At a first glance, this seems inconsistent with previous findings that ELS is associated with decreased amygdala-prefrontal FC during resting state (Burghy et al, 2012;Fan et al, 2014;Herringa et al, 2013). However, it is important to emphasize that task-evoked FC changes reflect transient changes in brain network coupling in response to specific task demands.…”

“…Task-evoked FC changes between amygdala and other limbic-prefrontal regions have been demonstrated during transient acute stress (Hermans et al, 2011;Vaisvaser et al, 2013;Veer et al, 2011). It has also been shown that ELS impacts structural connectivity and trait-like rs-FC within the limbic-prefrontal circuit (Burghy et al, 2012;Fan et al, 2014;Hart and Rubia, 2012;Herringa et al, 2013). Here we hypothesize that ELS influences stress-induced FC changes from amygdala to mPFC and hippocampus.…”

“…resting state (Burghy et al, 2012;Fan et al, 2014;Herringa et al, 2013), suggesting ELS-associated aberration in the traitlike functional integrity of the limbic-prefrontal circuit. Adding to this evidence, our finding highlights the association between EA and transient task-evoked changes in amygdala-hippocampal FC in response to acute psychosocial stress.…”

“…ELS-associated deficits in structural connectivity among these regions are also evident, supporting network abnormalities in the limbic-prefrontal circuit (Hart and Rubia, 2012). Recent studies have found ELS-associated decreases in resting-state FC (rs-FC) within the limbicprefrontal circuit (Burghy et al, 2012;Fan et al, 2014;Herringa et al, 2013). Although rs-FC is postulated to reflect trait-like individual differences in circuitry integrity, taskevoked FC changes (eg, measured by psychophysiological interactions (PPIs)) are supposed to reflect transient changes in brain network coupling in response to specific task demands.…”

Future Directions in Emotion Dysregulation and Youth Psychopathology

“…Other research indicates that (a) behavioral inhibition in infancy predicts structural abnormalities in the ventromedial PFC in young adulthood (Schwartz et al, 2010); (b) early life stress mediates-via increased cortisol levels-decreased functional connectivity between the amygdala and the vmPFC 14 years later (Burghy et al, 2012); and (c) childhood maltreatment portends compromised functional connectivity between the subgenual cingulate cortex and both the amygdala and the hippocampus in adolescence (Herringa et al, 2013). Thus, environmental experience appears to play an important role in the development of neural vulnerability to emotion dysregulation among those with internalizing as well as externalizing disorders.…”