Childhood maltreatment influences adult brain structure through its effects on immune, metabolic and psychosocial factors

Abstract

AbstractChildhood maltreatment (CM) leads to a lifelong susceptibility to mental ill-health which might be reflected by it’s effects on adult brain structure, perhaps indirectly mediated by its effects on adult metabolic, immune, and psychosocial systems. Indexing these systemic factors via body mass index (BMI), C-reactive protein (CRP) and rates of adult trauma (AT), respectively, we tested three hypotheses: (H1) CM has direct or indirect causal effects on adult trauma, BMI and CRP; (H2) adult trauma, BMI and CRP are all independently related to adult brain structure; and (H3) effects of CM on adult brain structure are mediated by its effects on adult trauma, BMI and CRP. Using path analysis and data from N=116,887 participants in UK Biobank we find that CM is related to greater BMI and AT levels, and that only these two variables mediate CM’s effects on CRP [H1]. Regression analyses on the UKB MRI sub-sample (N=21,738) revealed that greater CRP and BMI were both related to a spatially convergent pattern of cortical effects (Spearman’sρ=0.87) characterised by fronto-occipital increases and temporo-parietal reductions in thickness, and that AT is related to lower subcortical volumes [H2]. Finally, path models indicated that CM has indirect effects in a subset of brain regions through its influence on BMI, CRP and AT [H3]. Results provide evidence that childhood maltreatment can influence brain structure decades after exposure by increasing individual risk towards adult trauma, obesity or inflammation.