Psychological Distress and Metabolomic Markers: A Systematic Review

Psychological distress is a multifactorial construct that refers to non-specific symptoms of depression, anxiety, posttraumatic stress disorder (PTSD), or stress more generally. A systematic review of metabolomic markers associated with distress has the potential to reveal underlying molecular mechanisms linking distress to adverse health outcomes. The current systematic review extends prior reviews of clinical depressive disorders by synthesizing 39 existing studies that examined metabolomic markers for PTSD, anxiety disorders, and subclinical psychological distress in biological specimens. Most studies were based on small sets of pre-selected candidate metabolites, with few metabolites overlapping between studies. Vast heterogeneity was observed in study design and inconsistent patterns of association emerged between distress and metabolites. To gain a more robust understanding of distress and its metabolomic signatures, future research should include 1) large, population-based samples and longitudinal assessments, 2) replication and validation in diverse populations, 3) and agnostic metabolomic strategies profiling hundreds of targeted and nontargeted metabolites. Addressing these research priorities will improve the scope and reproducibility of future metabolomic studies of psychological distress. Highlights Literature on metabolomic markers of distress beyond clinical depression is scarce Most existing studies were candidate based and had little overlap of targets Vast heterogeneity exists in methods and patterns of findings from studies reviewed Critical gaps in sample selection, study design, and methods need to be addressed