Serum folate and homocysteine as biomarkers for suicide risk in major depressive disorder: insights in males and younger patients

Abstract Background Major depressive disorder (MDD) is a leading contributor to the global disease burden, with suicide constituting a critical complication. Current clinical assessment tools are limited by subjectivity and diagnostic delays, highlighting the urgent need for objective biomarkers to...

Full description

Saved in:
Bibliographic Details
Main Authors: Anqi Zhang, Yuncong Qin, Han Wang, Nan Lyu, Qian Zhao, Ling Zhang, Juan Huang
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Psychiatry
Subjects:
Online Access:https://doi.org/10.1186/s12888-025-07183-7
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849332358932594688
author Anqi Zhang
Yuncong Qin
Han Wang
Nan Lyu
Qian Zhao
Ling Zhang
Juan Huang
author_facet Anqi Zhang
Yuncong Qin
Han Wang
Nan Lyu
Qian Zhao
Ling Zhang
Juan Huang
author_sort Anqi Zhang
collection DOAJ
description Abstract Background Major depressive disorder (MDD) is a leading contributor to the global disease burden, with suicide constituting a critical complication. Current clinical assessment tools are limited by subjectivity and diagnostic delays, highlighting the urgent need for objective biomarkers to enable early detection of suicide risk. Methods We conducted a retrospective observational study by extracting electronic health records (EHRs) from the Hospital Information System of Beijing Anding Hospital. A total of 1,115 patients diagnosed with MDD between January 1, 2013, and December 31, 2020, were identified. Using propensity score matching (PSM), 483 patients exhibiting suicidal ideation or behavior (MDS) were matched to 483 non-suicidal controls (MDNS). Binary logistic regression analyses were performed to assess the associations between suicide risk and serum levels of folate, homocysteine (HCY), C-reactive protein (CRP), adrenocorticotropic hormone (ACTH), and testosterone. Results After PSM, higher serum folate levels (> 6 ng/mL) were significantly associated with a reduced risk of suicidal ideation or behavior (OR = 0.648; 95% CI: 0.496–0.847; p = 0.001). This association was particularly pronounced among male patients (OR = 0.569; 95% CI: 0.338–0.959; p = 0.034) and individuals aged ≤ 45 years (OR = 0.561; 95% CI: 0.394–0.799; p = 0.001). Furthermore, lower HCY levels (≤ 11.1 µmol/L) were positively associated with suicide risk among individuals aged ≤ 45 years (OR = 0.617; 95% CI: 0.409–0.931; p = 0.022). No significant associations were found between CRP, ACTH, or testosterone levels and suicide risk. Conclusion Serum folate and HCY levels may serve as potential biomarkers for assessing suicide risk in patients with MDD, particularly in specific demographic subgroups. Further longitudinal studies are needed to validate these findings and explore the underlying mechanisms.
format Article
id doaj-art-332efe6b4dae4739a5ce74792f1edac6
institution Kabale University
issn 1471-244X
language English
publishDate 2025-07-01
publisher BMC
record_format Article
series BMC Psychiatry
spelling doaj-art-332efe6b4dae4739a5ce74792f1edac62025-08-20T03:46:13ZengBMCBMC Psychiatry1471-244X2025-07-0125111010.1186/s12888-025-07183-7Serum folate and homocysteine as biomarkers for suicide risk in major depressive disorder: insights in males and younger patientsAnqi Zhang0Yuncong Qin1Han Wang2Nan Lyu3Qian Zhao4Ling Zhang5Juan Huang6Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical UniversityBeijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical UniversityBeijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical UniversityBeijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical UniversityBeijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical UniversityBeijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical UniversityBeijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical UniversityAbstract Background Major depressive disorder (MDD) is a leading contributor to the global disease burden, with suicide constituting a critical complication. Current clinical assessment tools are limited by subjectivity and diagnostic delays, highlighting the urgent need for objective biomarkers to enable early detection of suicide risk. Methods We conducted a retrospective observational study by extracting electronic health records (EHRs) from the Hospital Information System of Beijing Anding Hospital. A total of 1,115 patients diagnosed with MDD between January 1, 2013, and December 31, 2020, were identified. Using propensity score matching (PSM), 483 patients exhibiting suicidal ideation or behavior (MDS) were matched to 483 non-suicidal controls (MDNS). Binary logistic regression analyses were performed to assess the associations between suicide risk and serum levels of folate, homocysteine (HCY), C-reactive protein (CRP), adrenocorticotropic hormone (ACTH), and testosterone. Results After PSM, higher serum folate levels (> 6 ng/mL) were significantly associated with a reduced risk of suicidal ideation or behavior (OR = 0.648; 95% CI: 0.496–0.847; p = 0.001). This association was particularly pronounced among male patients (OR = 0.569; 95% CI: 0.338–0.959; p = 0.034) and individuals aged ≤ 45 years (OR = 0.561; 95% CI: 0.394–0.799; p = 0.001). Furthermore, lower HCY levels (≤ 11.1 µmol/L) were positively associated with suicide risk among individuals aged ≤ 45 years (OR = 0.617; 95% CI: 0.409–0.931; p = 0.022). No significant associations were found between CRP, ACTH, or testosterone levels and suicide risk. Conclusion Serum folate and HCY levels may serve as potential biomarkers for assessing suicide risk in patients with MDD, particularly in specific demographic subgroups. Further longitudinal studies are needed to validate these findings and explore the underlying mechanisms.https://doi.org/10.1186/s12888-025-07183-7FolateHomocysteineSuicideMajor depressive disorderBiomarker
spellingShingle Anqi Zhang
Yuncong Qin
Han Wang
Nan Lyu
Qian Zhao
Ling Zhang
Juan Huang
Serum folate and homocysteine as biomarkers for suicide risk in major depressive disorder: insights in males and younger patients
BMC Psychiatry
Folate
Homocysteine
Suicide
Major depressive disorder
Biomarker
title Serum folate and homocysteine as biomarkers for suicide risk in major depressive disorder: insights in males and younger patients
title_full Serum folate and homocysteine as biomarkers for suicide risk in major depressive disorder: insights in males and younger patients
title_fullStr Serum folate and homocysteine as biomarkers for suicide risk in major depressive disorder: insights in males and younger patients
title_full_unstemmed Serum folate and homocysteine as biomarkers for suicide risk in major depressive disorder: insights in males and younger patients
title_short Serum folate and homocysteine as biomarkers for suicide risk in major depressive disorder: insights in males and younger patients
title_sort serum folate and homocysteine as biomarkers for suicide risk in major depressive disorder insights in males and younger patients
topic Folate
Homocysteine
Suicide
Major depressive disorder
Biomarker
url https://doi.org/10.1186/s12888-025-07183-7
work_keys_str_mv AT anqizhang serumfolateandhomocysteineasbiomarkersforsuicideriskinmajordepressivedisorderinsightsinmalesandyoungerpatients
AT yuncongqin serumfolateandhomocysteineasbiomarkersforsuicideriskinmajordepressivedisorderinsightsinmalesandyoungerpatients
AT hanwang serumfolateandhomocysteineasbiomarkersforsuicideriskinmajordepressivedisorderinsightsinmalesandyoungerpatients
AT nanlyu serumfolateandhomocysteineasbiomarkersforsuicideriskinmajordepressivedisorderinsightsinmalesandyoungerpatients
AT qianzhao serumfolateandhomocysteineasbiomarkersforsuicideriskinmajordepressivedisorderinsightsinmalesandyoungerpatients
AT lingzhang serumfolateandhomocysteineasbiomarkersforsuicideriskinmajordepressivedisorderinsightsinmalesandyoungerpatients
AT juanhuang serumfolateandhomocysteineasbiomarkersforsuicideriskinmajordepressivedisorderinsightsinmalesandyoungerpatients