The Metabolomic Signature of Childhood Trauma

Although childhood trauma is an important risk factor for various diseases, the underlying biological mechanisms remain insufficiently understood. To deepen this understanding, we investigated the wide-spectrum metabolomic signature of childhood trauma exposure in a large adult cohort. Baseline and 6-year follow-up data from NESDA (Netherlands Study of Depression and Anxiety) were used (N_participants = 2902, N_observations = 4800). Childhood trauma exposure was retrospectively assessed with the Childhood Trauma Interview. Plasma metabolite levels were measured with the Metabolon mass spectrometry–based untargeted metabolomics platform at both time points. Mixed-effect models were used to evaluate the metabolomic associations of childhood trauma while controlling for sociodemographic, lifestyle, health-related, and technical covariates. We examined the overlap between the metabolomic profiles of childhood trauma and depression. External replication was tested in 308 additional participants. Childhood trauma was associated in a dose-response manner with 18 metabolites. Upregulated metabolites were nominally enriched with compounds involved in fatty acid and branched-chain amino acid metabolism (p = 3.91 × 10⁻², false discovery rate–corrected q [q_FDR] > .05) while downregulated metabolites were nominally enriched with corticosteroids (p = 2.24 × 10⁻³, q_FDR > .05). Six of the 18 metabolites were linked to childhood trauma but not depression. Findings were partially replicated using an alternative measure for childhood trauma (effect size correlation r = 0.94) and an external sample (r = 0.54). Childhood trauma was linked in a dose-response manner to a biological signature encompassing a wide array of metabolites. Dysregulations were observed in amino acid and fatty acid metabolism as well as hypothalamic-pituitary-adrenal axis function. Future studies should corroborate these findings and develop early-intervention strategies that target trauma-related biological mechanisms to prevent cardiometabolic and psychiatric diseases.