Psychological distress and metabolomic markers: A systematic review of posttraumatic stress disorder, anxiety, and subclinical distress

Yiwen Zhu; Shaili C Jha; Katherine H Shutta; Tianyi Huang; Raji Balasubramanian; Clary B Clish; Susan E Hankinson; Laura D Kubzansky

doi:10.1016/j.neubiorev.2022.104954

Psychological distress and metabolomic markers: A systematic review of posttraumatic stress disorder, anxiety, and subclinical distress

Neurosci Biobehav Rev. 2022 Dec:143:104954. doi: 10.1016/j.neubiorev.2022.104954. Epub 2022 Nov 8.

Authors

Yiwen Zhu¹, Shaili C Jha², Katherine H Shutta³, Tianyi Huang⁴, Raji Balasubramanian⁵, Clary B Clish⁶, Susan E Hankinson⁵, Laura D Kubzansky⁷

Affiliations

¹ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: yiwenzhu@mail.harvard.edu.
² Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: sjha@hsph.harvard.edu.
³ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁴ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
⁵ Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, MA, USA.
⁶ Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
⁷ Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Abstract

Psychological distress can be conceptualized as an umbrella term encompassing 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.

Keywords: Anxiety; Depressive symptoms; Metabolomics; Posttraumatic stress disorder (PTSD); Psychological distress; Systematic review.

Publication types

Systematic Review
Review
Research Support, N.I.H., Extramural

MeSH terms

Anxiety
Anxiety Disorders / psychology
Depression
Humans
Psychological Distress*
Reproducibility of Results
Stress Disorders, Post-Traumatic* / psychology
Stress, Psychological / psychology

Grants and funding

R01 AG051600/AG/NIA NIH HHS/United States