Association of Timing of Adverse Childhood Experiences and Caregiver Support With Regionally Specific Brain Development in Adolescents.

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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.