Richard A.I. Bethlehem

Childhood maltreatment (CM) leads to a lifelong susceptibility to mental ill-health which might be reflected by its 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 effects on adult trauma, BMI, and CRP; (H2) adult trauma, BMI, and CRP are all independently related to adult brain structure; and (H3) childhood maltreatment has indirect effects on adult brain structure mediated in parallel by BMI, CRP, and AT. 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 these two variables mediate CM’s effects on CRP [H1]. Regression analyses on the UKB MRI subsample ( N = 21,738) revealed that greater CRP and BMI were both independently related to a spatially convergent pattern of cortical effects (Spearman’s ρ = 0.87) characterized by fronto-occipital increases and temporo-parietal reductions in thickness. Subcortically, BMI was associated with greater volume, AT with lower volume and CPR with effects in both directions [H2]. Finally, path models indicated that CM has indirect effects in a subset of brain regions mediated through its direct effects on BMI and AT and indirect effects on CRP [H3]. Results provide evidence that childhood maltreatment can influence brain structure decades after exposure by increasing individual risk toward adult trauma, obesity, and inflammation.