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Tryptophan and Brain Disorders / Treatment of Major Depression · Journal article
Indian Journal of Psychiatry · August 1, 2026
Early or partial results. Treat as a signal, not a conclusion.
This pilot proteomic study identified 20 differentially expressed proteins in serum of 6 depressed patients versus 6 healthy controls, with fibrinogen, PSG9, and AarF showing AUCs ≥0.861 on ROC analysis. The findings are exploratory and hypothesis-generating; the small, single-site sample precludes clinical recommendation and requires independent validation in larger, prospective cohorts.
Cross-sectional observational pilot study. Individuals with depression from outpatient psychiatry department at AIIMS Rishikesh and age-matched healthy controls; baseline characteristics analyzed using SPSS.. Intervention: Serum proteomic profiling via LC-MS/MS. Compared with: Healthy age-matched controls. n = 12. AIIMS Rishikesh, India.
LC-MS/MS identified 242 total proteins; 9 upregulated and 11 downregulated in depression group versus healthy controls Fibrinogen showed area under the curve (AUC) of 0.944 on ROC analysis PSG9 showed AUC of 0.889; AarF showed AUC of 0.861 on ROC analysis
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These candidate proteomic biomarkers cannot guide clinical practice in their current form due to the pilot nature and minimal sample size. Clinicians should note this as early-stage discovery research that may eventually inform biomarker-based diagnosis or personalized therapy, pending prospective validation in larger independent cohorts.
Pilot proteomic study with very small sample size (n=6 per group) and no external validation, identifying candidate biomarkers that require confirmation in larger cohorts before clinical application.
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These candidate proteomic biomarkers cannot guide clinical practice in their current form due to the pilot nature and minimal sample size. Clinicians should note this as early-stage discovery research that may eventually inform biomarker-based diagnosis or personalized therapy, pending prospective validation in larger independent cohorts.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
ABSTRACT Background: Depression is a major cause of reduced productivity and increased morbidity. Aim: Given its complex and multifactorial pathophysiology, this study investigated serum proteomic profiles in individuals with depression and healthy controls to identify differentially expressed proteins and their functional significance. Methods: This is a cross-sectional observational study. Individuals with depression ( n = 6) were enlisted from the outpatient department of psychiatry at AIIMS Rishikesh, while age-matched healthy controls ( n = 6) were included for comparison. Peripheral whole blood samples were obtained from all participants under fasting conditions. Baseline characteristics were analyzed using Statistical Package for the Social Sciences, (IBM) 21. Continuous and categorical variables were expressed as mean ± SD and number (%), respectively. Proteomic data were analyzed and visualized using MetaboAnalyst 6.0, Cytoscape v3.10.3, Reactome Pathway, and SR plots. Result: In our main finding of the liquid chromatography–tandem mass spectrometry (LC-MS/MS) study of serum samples, a total of 242 proteins were identified, out of that 9 were upregulated and 11 were downregulated in the serum from the depression group and in the healthy control group. Receiver operating characteristic (ROC) analysis of significantly altered proteins showed strong discriminatory ability for fibrinogen, PSG9, and AarF, with area under the curves (AUCs) of 0.944, 0.889, and 0.861, respectively. Conclusion: This study identifies a distinct molecular signature of depression, with PSG9, FGB, ADCK5, C8B, and SORCS1 emerging as key proteins. These markers reflect dysregulation of immune, vascular, mitochondrial, and signaling pathways, highlighting depression as a multisystem disorder, and offering potential targets for biomarker-based diagnosis and personalized therapeutic strategies.
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