Denmark: Study on CSF Biomarkers in Unipolar Depression

Cerebrospinal fluid marker concentrations in individuals with unipolar depression may differ from healthy control subjects, says an article published in the Journal of American Medical Association-Psychiatry.

Depression affects approximately 10-20% of the world's population over the course of a lifetime and is one of the top causes of disability-adjusted life-years globally. Depression is a complex disorder with an increasing number of hypotheses aiming to unravel its pathophysiology. Cerebrospinal fluid is an excellent option for biomarker study since it is near to the brain and can reflect ongoing metabolic changes. Previous cross-sectional studies indicate that CSF concentrations of various biomarkers differ between patients suffering from depression and non-depressed, healthy controls. As a result, Ina Viktoria Mousten and colleagues undertook this study to compare quantified CSF biomarkers in patients with unipolar depression with healthy control people.

Methodology

From the launch of the database through August 25, 2021, EMBASE, PubMed, PsycINFO, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched for qualifying studies. All studies that looked at CSF biomarkers in people over the age of 18 with unipolar depression and healthy controls were included.

One author reviewed the titles and abstracts, while two independent reviewers looked at the full-text reports. Excluded were studies that did not contain healthy controls or included controls who had recent hospital visits or hospitalizations that might impact CSF biomarker concentrations.

Data extraction and quality evaluation were carried out by two reviewers in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting standards.

Key Findings

• There were 167 studies that satisfied the qualifying criteria, and 97 of them had accessible data and were included in the meta-analysis.
• There were 165 biomarkers measured in these 97 investigations, 42 of which were measured in two or more studies. Interleukin 6, total protein, and cortisol levels in CSF were greater in unipolar depression patients compared to healthy controls, but homovanillic acid, -aminobutyric acid, somatostatin, brain-derived neurotrophic factor, amyloid- 40, and transthyretin levels were reduced.
• The results for the remaining 33 biomarkers were insignificant.

In conclusion, these findings appear to link many neurocircuits to the etiology of depression. Many studies used tiny cohorts and only measured a few biomarkers. Future high-quality CSF biomarker investigation in large cohorts of depressed individuals is required.

"The study found numerous biomarkers in the CSF were altered in individuals with unipolar depression, indicating a multifactorial pathogenesis implicating several neurocircuits; however, there is a need for high-quality studies investigating multiple CSF markers," wrote the authors.

Reference

Mousten, I. V., Sørensen, N. V., Christensen, R. H. B., & Benros, M. E. (2022). Cerebrospinal Fluid Biomarkers in Patients With Unipolar Depression Compared With Healthy Control Individuals. In JAMA Psychiatry. American Medical Association (AMA). https://doi.org/10.1001/jamapsychiatry.2022.0645