Proteomic Biomarkers in Major Depressive Disorders

Major depressive disorder (MDD) imposes a substantial global health burden, and its complex aetiology spans genetic, neurochemical and environmental factors. Proteomic approaches seek to profile large panels of proteins in blood, cerebrospinal fluid or tissue to uncover molecular signatures that distinguish affected individuals, predict disease onset or guide treatment selection. High-throughput methods, notably liquid chromatography–tandem mass spectrometry and multiplex immunoassays, have mapped alterations in immune, metabolic and neurotrophic pathways in MDD. Key findings include dysregulation of cytokines, growth factors and proteins involved in synaptic plasticity, myelination and coagulation. Such biomarkers offer objective measures to complement symptom-based diagnosis, stratify clinical subtypes and monitor therapeutic response. Ongoing efforts focus on integrating proteomic data with imaging, genomics and clinical parameters to establish robust panels for early detection, personalised intervention and refinement of the precision psychiatry paradigm.

Research from Nature Portfolio

Recent studies have applied plasma proteomics in young people and cerebrospinal fluid profiling in adults to illuminate MDD risk and heterogeneity. In an adolescent cohort, 58 plasma proteins correlated with self-reported mental health scores, implicating immune response, blood coagulation and neurogenesis pathways. This work highlights candidate susceptibility biomarkers for early identification of at-risk individuals. In adults, elevated cerebrospinal fluid fibrinogen defined a subgroup of MDD patients who also exhibited white matter tract abnormalities on diffusion imaging. This subgroup was not distinguished by plasma fibrinogen, emphasising the value of central fluid markers in resolving pathophysiological subtypes and tailoring interventions.

Proteomic Biomarkers in Major Depressive Disorders publication trend

The graph below shows the total number of articles in proteomic biomarkers in major depressive disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Proteomics: The large-scale study of all proteins produced in a biological sample, including their quantities, structures and functions.

Biomarker: A measurable indicator, often molecular, of a biological state or condition, used for diagnosis, prognosis or monitoring.

Liquid chromatography–tandem mass spectrometry (LC-MS/MS): An analytical technique that separates peptides by liquid chromatography and identifies them by mass spectrometry, enabling quantitative proteome profiling.

Cerebrospinal fluid (CSF): The fluid surrounding the brain and spinal cord, analysed to detect central nervous system biomarkers distinct from those in blood.

Multiplex immunoassay: A method that simultaneously measures multiple proteins in a single sample using antibody-based detection, increasing throughput and efficiency.

References

1. Plasma proteomics identifies proteins and pathways associated with incident depression in 46,165 adults. Science Bulletin (2024).
2. Proteomic insights into mental health status: plasma markers in young adults. Translational Psychiatry (2024).
3. Plasma proteomics discovery of mental health risk biomarkers in adolescents. Nature Mental Health (2023).
4. The new field of ‘precision psychiatry’. BMC Medicine (2017).
5. Plasma Protein Biomarkers for Depression and Schizophrenia by Multi Analyte Profiling of Case-Control Collections. PLOS ONE (2010).
6. Increased cerebrospinal fluid fibrinogen in major depressive disorder. Scientific Reports (2015).