Reduced hippocampal and medial prefrontal gray matter mediate the association between reported childhood maltreatment and trait anxiety in adulthood and predict sensitivity to future life stress

Abstract

BackgroundThe experience of early life stress is a consistently identified risk factor for the development of mood and anxiety disorders. Preclinical research employing animal models of early life stress has made inroads in understanding this association and suggests that the negative sequelae of early life stress may be mediated by developmental disruption of corticolimbic structures supporting stress responsiveness. Work in humans has corroborated this idea, as childhood adversity has been associated with alterations in gray matter volumes of the hippocampus, amygdala, and medial prefrontal cortex. Yet, missing from this body of research is a full understanding of how these neurobiological vulnerabilities may mechanistically contribute to the reported link between adverse childhood experiences and later affective psychopathology.ResultsAnalyses revealed that self-reported childhood maltreatment was associated with reduced gray matter volumes within the medial prefrontal cortex and left hippocampus. Furthermore, reduced left hippocampal and medial prefrontal gray matter volume mediated the relationship between childhood maltreatment and trait anxiety. Additionally, individual differences in corticolimbic gray matter volume within these same structures predicted the anxious symptoms as a function of life stress 1 year after initial assessment.ConclusionsCollectively, these findings provide novel evidence that reductions in corticolimbic gray matter, particularly within the hippocampus and medial prefrontal cortex, are associated with reported childhood maltreatment and individual differences in adult trait anxiety. Furthermore, our results suggest that these structural alterations contribute to increased affective sensitivity to stress later in life in those that have experienced early adversity. More broadly, the findings contribute to an emerging literature highlighting the critical importance of early stress on the development of corticolimbic structures supporting adaptive functioning later in life.

Brain Regions Related to Impulsivity Mediate the Effects of Early Adversity on Antisocial Behavior

“…A few recent neuroimaging studies, like the current one, have begun to search for specific brain mediators of the negative psychiatric effects produced by adversity. For example, Gorka et al (60) report that frontomedial and hippocampal cortical volumes mediate the relation between childhood mistreatment and trait anxiety, while Rao et al (61) have shown that hippocampal volume mediates the relation between childhood mistreatment and higher risk of depression in adulthood (61). An advantage of the current study was that the brain areas examined were identified by an independent measure of impulsivity rather than by their direct association with adversity.…”

Previous Institutionalization Is Followed by Broader Amygdala–Hippocampal–PFC Network Connectivity during Aversive Learning in Human Development

“…Given evidence that neural adaptations to caregiving adversity can be anxiolytic (Gee et al, 2013), it was hypothesized that altered amygdala-hippocampal-mPFC function during aversive learning would predict reduced anxiety among PI youth.…”

“…Converging cross-species evidence suggests that early adversity alters the structure and function of brain regions involved in aversive learning, including the amygdala, hippocampus, and medial prefrontal cortex (mPFC; Mirescu et Spinelli et al, 2009;Tottenham et al, 2010;Uchida et al, 2010;Jackowski et al, 2011;Tottenham et al, 2011;Gee et al, 2013;Malter Cohen et al, 2013;Pagliaccio et al, 2014;McEwen et al, 2016). Although it is known that early adversity alters the neural bases of aversive learning and predicts anxiety in adults ( …”

Childhood maltreatment and its impact on the mental health

“…Психические травмы ранней жизни оказывают не-благоприятное воздействие на развитие не только гиппо-кампа, но и других отделов нервной системы; в частности, они приводят к поражению кортиколимбических струк-тур, с функциями которых связывают чувствительность к стрессу [31].…”

“…К сказанному выше можно добавить, что проведен-ные на лабораторных животных эксперименты показали, что стрессы раннего возраста могут вызывать и структур-ные изменения серого вещества гиппокампа, миндалины и префронтальной коры большого мозга [31], т.е. структур мозга, которые обеспечивают эмоциональное реагирова-ние, а с двумя последними связано функционирование системы вознаграждения (reward system), механизмов подкрепления (reinforcement) и формирование зависимо-сти от ПАВ.…”