Discriminative performance of serum homocysteine in drug-naïve depression: a case-control study with ROC and regression analysis
4 affiliations
- 1Department of Pharmacology, Sri Ramachandra Institute of Higher Education and Research (SRIHER)
- 2Department of Psychiatry, Sri Ramachandra Institute of Higher Education and Research (SRIHER)
- 3Department of Human Genetics, Sri Ramachandra Institute of Higher Education and Research (SRIHER)
- 4Research and Education, Dr RK Diabetic Foot and Podiatry Institute & Rakesh Jhunjhunwala Amputation Prevention Centre
Abstract
Depression is a multifactorial disorder involving neurochemical, metabolic, and inflammatory dysregulation. Elevated homocysteine, a marker of impaired one-carbon metabolism, has been implicated in neurotoxicity and oxidative stress pathways associated with depressive pathology. This study evaluated serum homocysteine levels and their association with body mass index (BMI) in patients with incident drug naiive depression compared to healthy controls. This case-control study enrolled 200 participants: 100 patients with newly diagnosed depressive disorder (DSM-5 criteria) and 100 age- and sex-matched healthy controls recruited from a tertiary psychiatry centre in South India. Serum homocysteine was measured using standard enzymatic assay and BMI was calculated from standardised anthropometric measurements. Independent samples t-test, Pearson’s correlation, ROC analysis and Binomial logistic regression analyses were performed. Serum homocysteine was significantly higher in depressed patients than controls (35.8 ± 7.04 µmol/L vs. 13.6 ± 2.48 µmol/L; p < 0.001, Cohen’s d = 4.193; 95% CI for difference: 20.66–23.58 µmol/L). BMI was also significantly elevated in the depression group (25.67 ± 4.97 kg/m2 vs. 21.92 ± 2.96 kg/m2. p < 0.001, Cohen’s d = 0.912). A positive homocysteine—BMI correlation was observed in depression(r = 0.42, p < 0.001) but not in controls (r = 0.04, p = 0.71). ROC analysis yielded an AUC of 1.000 (optimal cutoff: 20.065 µmol/L, sensitivity: 100%, specificity: 100%), reflecting complete distributional separation in this clinical sample. Binary logistic regression analysis showed homocysteine to be a significant predictor of depression(omnibus χ2 = 277.26, df = 1, p < 0.001; 100% classification accuracy; Nagelkerke R2 = 1.00), though standard odds ratio estimation was precluded by complete separation. Elevated homocysteine and a group-specific BMI—homocysteine correlation were identified in depressed patients. The AUC of 1.000 reflects complete distributional separation in a tightly controlled institutional sample and requires external validation before clinical application. As folate, vitamin B12, and lifestyle confounders were unmeasured, findings are hypothesis-generating and warrant prospective multicentre validation.
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BibTeX
@article{bhaskaran2026discriminative,
title = {{Discriminative performance of serum homocysteine in drug-naïve depression: a case-control study with ROC and regression analysis}},
author = {Remya Bhaskaran S. and Ramya S and Suvarna Jyothi Kantipudi and C. D. Mohana Priya and C. Sheela Sasikumar},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-63312-6},
url = {https://doi.org/10.1038/s41598-026-63312-6},
note = {CC BY},
}
RIS
TY - JOUR
TI - Discriminative performance of serum homocysteine in drug-naïve depression: a case-control study with ROC and regression analysis
AU - Remya Bhaskaran S.
AU - Ramya S
AU - Suvarna Jyothi Kantipudi
AU - C. D. Mohana Priya
AU - C. Sheela Sasikumar
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-63312-6
UR - https://doi.org/10.1038/s41598-026-63312-6
AB - Depression is a multifactorial disorder involving neurochemical, metabolic, and inflammatory dysregulation. Elevated homocysteine, a marker of impaired one-carbon metabolism, has been implicated in neurotoxicity and oxidative stress pathways associated with depressive pathology. This study evaluated serum homocysteine levels and their association with body mass index (BMI) in patients with incident drug naiive depression compared to healthy controls. This case-control study enrolled 200 participants: 100 patients with newly diagnosed depressive disorder (DSM-5 criteria) and 100 age- and sex-matched healthy controls recruited from a tertiary psychiatry centre in South India. Serum homocysteine was measured using standard enzymatic assay and BMI was calculated from standardised anthropometric measurements. Independent samples t-test, Pearson’s correlation, ROC analysis and Binomial logistic regression analyses were performed. Serum homocysteine was significantly higher in depressed patients than controls (35.8 ± 7.04 µmol/L vs. 13.6 ± 2.48 µmol/L; p < 0.001, Cohen’s d = 4.193; 95% CI for difference: 20.66–23.58 µmol/L). BMI was also significantly elevated in the depression group (25.67 ± 4.97 kg/m2 vs. 21.92 ± 2.96 kg/m2. p < 0.001, Cohen’s d = 0.912). A positive homocysteine—BMI correlation was observed in depression(r = 0.42, p < 0.001) but not in controls (r = 0.04, p = 0.71). ROC analysis yielded an AUC of 1.000 (optimal cutoff: 20.065 µmol/L, sensitivity: 100%, specificity: 100%), reflecting complete distributional separation in this clinical sample. Binary logistic regression analysis showed homocysteine to be a significant predictor of depression(omnibus χ2 = 277.26, df = 1, p < 0.001; 100% classification accuracy; Nagelkerke R2 = 1.00), though standard odds ratio estimation was precluded by complete separation. Elevated homocysteine and a group-specific BMI—homocysteine correlation were identified in depressed patients. The AUC of 1.000 reflects complete distributional separation in a tightly controlled institutional sample and requires external validation before clinical application. As folate, vitamin B12, and lifestyle confounders were unmeasured, findings are hypothesis-generating and warrant prospective multicentre validation.
SN - 2045-2322
ER -