Abstract

Few data are available to inform the associations and timing of the associations between adversity, caregiver support, and brain outcomes. Consideration of timing has important public health implications to inform more precise prevention strategies. To evaluate the timing and regional specificity of the association between adverse childhood experiences (ACEs) and caregiver support to structural development of limbic and striatal brain regions in middle childhood and adolescence. This 15-year developmental, neuroimaging cohort study included 211 children and their caregivers screened from day care centers and preschools in the St Louis, Missouri, metropolitan area during the preschool period, with an additional 4 waves of neuroimaging at school age through adolescence from November 14, 2007, to August 29, 2017. The cohort was oversampled for preschoolers with elevated symptoms of depression using a brief screener. Data analysis was performed from March 19, 2019, to July 26, 2019. Volumes in adolescence and developmental trajectories of volumes of the amygdala, hippocampus, caudate, subgenual cingulate, and insula during 4 waves of scanning; ACEs and observed caregiver support at preschool and school age; and volumes of amygdala, hippocampus, insula, and subgenual cingulate during 4 waves of scanning. A total of 211 children (107 [50.7%] male) completed at least 1 scan. At preschool (mean [SD] age, 5.5 [0.8] years), ACE data were available for 164 children (84 [51.2%] male) and maternal support data for 155 children; at school age (mean [SD], 8.3 [1.2] years), ACE data were available for 172 children and maternal support data for 146 children. Unique patterns of the association between ACEs and support were found, with an association between the interaction of preschool ACEs and school-age support and the development of the hippocampus (t = -2.27; P = .02) and amygdala (t = -2.12; P = .04). A buffering hypothesis was not confirmed because high caregiver support was more strongly associated with the development of these regions only in the context of low ACEs. In contrast, preschool ACEs (t = -2.30; P = .02) and support (t = 2.59; P = .01) had independent associations with the development of the caudate. The findings suggest that there are unique regional associations of support and adversity with key brain structures important for emotional regulation. Results may inform the timing and potential targets of preventive action for the range of poor developmental outcomes.

Highlights

  • Increasing evidence of the associations between early-life experience and human brain development has emerged during the past 2 decades.[1]

  • At preschool, adverse childhood experiences (ACEs) data were available for 164 children (84 [51.2%] male) and maternal support data for 155 children; at school age, ACE data were available for 172 children and maternal support data for 146 children

  • Any variables significant after false discovery rate (FDR) correction in the general linear models (GLMs) described above were included in multilevel models (MLMs) to examine whether ACEs and/or maternal support at preschool and/or school age were significantly associated with the trajectory of brain volumes across scans 1 to 4

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Summary

Introduction

Increasing evidence of the associations between early-life experience and human brain development has emerged during the past 2 decades.[1] Building on animal studies and retrospective data in humans, several prospective neuroimaging studies[2,3,4,5,6] have further elucidated the negative associations of varying forms of adversity and the positive associations of nurturing caregiving in early childhood with the key brain regions critical for adaptive functioning. Data suggest similar associations in the basal ganglia,[12,15,16] with retrospective and some prospective data suggesting associations with the dorsal prefrontal cortex, anterior cingulate, and subgenual cingulate.[9,14,15,17,18,19,20]

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