The Metabolomic Signature of Childhood Trauma

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: Adult survivors of child abuse; Adverse childhood experiences; Child abuse; Metabolome; Metabolomics.