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Early Life Adversity and Brain Structure in Children and Adolescents: A Systematic Review and Meta-Analysis

Wed, April 7, 4:20 to 5:50pm EDT (4:20 to 5:50pm EDT), Virtual

Abstract

Background
Early life adversity (ELA; e.g., child maltreatment, institutionalization, trauma, poverty) profoundly affects the developing brain. Although many existing qualitative reviews examine effects of ELA on structural neurodevelopment (e.g., Bick & Nelson 2016), particularly in adults, no meta-analyses have ever been published on this subject. Therefore, this preregistered study will review and quantitatively summarize existing empirical research that examines associations between ELA and children’s structural neurodevelopment, to provide a more accurate depiction of the literature than presently available, and to elucidate moderating influences of exposure timing and experience type.

Methods
This meta-analysis adheres to PRISMA statement guidelines (Moher, 2007). A search term algorithm (e.g., “child” AND “abuse” AND “MRI”) searched four bibliographic databases: Pubmed, Medline, PsycInfo, and Proquest (Figure 1). Backward searches, forward searches, and cited-by searches of discovered articles ensured saturation.

After identifying duplicates, trained research assistants screened abstracts for inclusion (Figure 2). Eligibility requirements included: 1) human subjects aged birth to 18 years; 2) at least one childhood psychosocial adversity (excluding accidental injury, neurodevelopmental disorders, and prenatal adversity); 3) a measure of brain structure, typically ROI volumes or whole-brain voxel-based morphometry; and 4) sufficient data to calculate at least one effect size. Full study texts were then screened for all requirements listed above in addition to: available data, and no duplicate samples and/or review articles. Study data extraction is underway, and on track to be completed mid-October.

Analysis Plan
Analyses will compare differences between adversity and non-adversity exposed groups across studies. We will assess brain structure using two common metrics: ROI (more precise, but more reporting bias) and voxel-based morphometry (less biased, less precise) (Radua & Mataix-Coles, 2012). ROI analysis will assess group differences in mean/variability of brain structure volumes. We will examine sample age, adversity type, and onset age as moderators (Hedges & Olkin, 1985). Voxel-based analysis will use the ALE method via GingerAle. For both analyses, leave-one-out procedures will measure reliability and robustness of significant results. We will organize results into functionally-distinct canonical brain networks for interpretation.

Anticipated Results
We expect negative associations between ELA and hippocampal, cerebellar, and PFC regional structural volumes, and cortical thickness, such that ELA-exposed children and adolescents will have smaller regional volumes than non-exposed samples (Bick & Nelson, 2016; McLaughlin, et al., 2019). For the amygdala, consistent with the stress-acceleration hypothesis, we predict an interaction between adversity exposure and sample age, such that younger ELA-exposed children will have larger regional volumes than non-exposed samples (Callaghan & Tottenham, 2016). As our age and adversity type analyses are exploratory, we do not have specific hypotheses.

Conclusion
Our review will provide a meaningful synthesis of existing work to direct future empirical research on ELA and brain structure. By examining brain structure from infancy to adolescence, we may also illuminate effects of adversity type and timing on specific brain regions across development. As ELA has been heavily associated with psychopathology, perhaps due to stress-induced changes in the brain (VanTieghem & Tottenham, 2018), this work could inform preventative interventions for affected children.

Authors