Metabolomics in posttraumatic stress disorder: Untargeted metabolomic analysis of plasma samples from Croatian war veterans.

Posttraumatic stress disorder (PTSD) is a severe, multifactorial and debilitating neuropsychiatric disorder, which can develop in a subset of individuals as a result of the exposure to severe stress or trauma. Such traumatic experiences have a major impact on molecular, biochemical and cellular systems, causing psychological and somatic alterations that affect the whole organism. Although the etiology of PTSD is still unclear, it seems to involve complex interaction between various biological genetic and environmental factors. Metabolomics, as one of the rapidly developing "omics" techniques, might be a useful tool for determining altered metabolic pathways and stress-related metabolites as new potential biomarkers of PTSD. The aim of our study was to identify metabolites whose altered levels allow us to differentiate between patients with PTSD and healthy control individuals. The study included two cohorts. The first, exploratory, group included 50 Croatian veterans with PTSD and 50 healthy control subjects, whereas a validation group consisted of 52 veterans with PTSD and 52 control subjects. The metabolomic analysis of plasma samples was conducted using liquid chromatography coupled with mass spectrometry (LC-MS), as well as gas chromatography coupled with mass spectrometry (GC-MS). The LC-MS analysis determined significantly different levels of two glycerophospholipids, PE(18:1/0:0) and PC(18:1/0:0), between control subjects and PTSD patients in both cohorts. The altered metabolites might play a role in multiple cellular processes, including inflammation, mitochondrial dysfunction, membrane breakdown, oxidative stress and neurotoxicity, which could be associated with PTSD pathogenesis.