Post-traumatic stress disorder (PTSD) is characterized by severe distress and associated with cardiometabolic diseases. Studies in military and clinical populations suggest that dysregulated metabolomic processes may be a key mechanism. Prior work identified and validated a metabolite-based distress score (MDS) linked with depression and anxiety and subsequent cardiometabolic diseases. Here, we assessed whether PTSD shares metabolic alterations with depression and anxiety and if additional metabolites are related to PTSD.

We leveraged plasma metabolomics data from three subsamples nested within the Nurses’ Health Study II, including 2835 women with 2950 blood samples collected across three time points (1996–2014) and 339 known metabolites assayed by mass spectrometry-based techniques. Trauma and PTSD exposures were assessed in 2008 and characterized as follows: lifetime trauma without PTSD, lifetime PTSD in remission, and persistent PTSD symptoms. Associations between the exposures and the MDS or individual metabolites were estimated within each subsample adjusting for potential confounders and combined in random-effects meta-analyses.

Persistent PTSD symptoms were associated with higher levels of the previously developed MDS. Out of 339 metabolites, we identified 29 metabolites (primarily elevated glycerophospholipids and glycerolipids) associated with persistent symptoms (false discovery rate < 0.05; adjusting for technical covariates). No metabolite associations were found with the other PTSD-related exposures.

As the first large-scale, population-based metabolomics analysis of PTSD, our study highlighted shared and distinct metabolic differences linked to PTSD versus depression or anxiety. We identified novel metabolite markers associated with PTSD symptom persistence, suggesting further connections with metabolic dysregulation that may have downstream consequences for health.