The Transdiagnostic Association Between Childhood Trauma and Accelerated Brain Aging in Two Independent Datasets

Background and Hypothesis Childhood trauma has been associated with accelerated biological aging, such as early pubertal development and cellular aging. Less is known about the impact of childhood trauma on brain aging, particularly across mental disorders. This cross-sectional study tested the hypothesis that childhood trauma severity is linked to accelerated brain aging using a large discovery MRI dataset. Another independent dataset was included to replicate findings. Study Design The discovery dataset included 495 participants (248 bipolar-I, 126 schizophrenia-spectrum, 121 controls). To replicate findings, we used an independent dataset (n = 163; 80 schizophrenia-spectrum, 83 healthy individuals). Brain age gap estimate (BrainAGE; predicted brain age minus chronological age) was evaluated from T1-weighted MRI scans using pre-trained machine learning models to quantify brain aging, reflecting the difference between brain-predicted and actual age. Linear regressions were performed to assess the relationships between childhood trauma and BrainAGE across samples. Study Results In the discovery dataset, higher childhood trauma severity was associated with increased BrainAGE (β = 0.09, P = .048), independent of diagnosis A categorical approach to trauma confirmed a dose–response pattern, with increased BrainAGE in individuals reporting multiple trauma types and across quartiles of cumulative trauma scores. The replication dataset showed similar results. The dimension of deprivation, but not threat, was associated with increased BrainAGE, in both datasets. Educational attainment moderated the effect of deprivation on BrainAGE in the discovery dataset only. Conclusions This large transdiagnostic study suggests that individuals exposed to childhood trauma, especially deprivation, may undergo a process of accelerated brain aging, independent of psychiatric diagnosis.