Metabolite fingerprinting reveals new serum metabolites and associated pathways in posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is associated with an increased risk for adverse physical health outcomes. However, the underlying bio-molecular processes and associated pathways remain poorly elucidated. Using time-of-flight mass spectrometry (TOF-MS), the untargeted and holistic investigation of the metabolome – the total of hydrophilic and amphiphilic metabolites - holds the potential to provide novel insights into PTSD pathophysiology. To address metabolome changes associated with PTSD, serum from 20 individuals with a PTSD diagnosis and 18 healthy controls was analyzed with TOF-MS. Symptom severity of PTSD was assessed using the Clinician-administered PTSD scale (CAPS). Univariate and multivariate approaches, namely Partial Least Square Discriminant Analysis, were applied for statistical analyses. The group comparison revealed 13 metabolites significantly altered in PTSD, including four glycerophospholipids and one metabolite involved in endocannabinoid signaling. Out of the 13, eleven metabolites showed a correlation between the serum level and the CAPS score. In the multivariate approach, a metabolite profile of 19 biomolecules predicted PTSD with an accuracy of 85%. Here, we initially illustrate the potential of metabolite fingerprinting to identify novel pathophysiological underpinnings of PTSD. It further provides the possibility to highlight associated pathways, such as lipid-derived and endocannabinoid signaling. More research will help to gain not only a deeper understanding of the molecular mechanisms and associated pathways in PTSD, but also of the biological processes stimulated by (psycho) therapeutical treatment.