Lower creatinine levels are associated with an increased risk of depression: evidence from the China Health and Retirement Longitudinal Study

Fajin Liu; Xiaogang Zhong; Cuiting Wang

doi:10.3389/fpsyt.2025.1446897

Lower creatinine levels are associated with an increased risk of depression: evidence from the China Health and Retirement Longitudinal Study

Front Psychiatry. 2025 Feb 25:16:1446897. doi: 10.3389/fpsyt.2025.1446897. eCollection 2025.

Authors

Fajin Liu^{1

2

3}, Xiaogang Zhong⁴, Cuiting Wang^{1

2

3}

Affiliations

¹ Department of Neurological Rehabilitation, The Affiliated Rehabilitation Hospital of Chongqing Medical University, Chongqing, China.
² College of Rehabilitation Medicine, Chongqing Medical University, Chongqing, China.
³ Department of Neurological Rehabilitation, Rehabilitation Hospital of, Chongqing, China.
⁴ NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Abstract

Introduction: Previous studies have found that depressive patients tend to have low levels of creatinine; however, the extent to which creatinine levels are associated with depression has been poorly investigated. Therefore, this study aimed to explore the relationship between creatinine levels and depression.

Methods: The participants and follow-up data from the China Health and Retirement Longitudinal Study (CHARLS), as well as metabolomics data from the Metabolite Network of Depression Database (MENDA), were collected. The 10-item Center for Epidemiologic Studies Depression Scale (CESD-10) was used to assess the severity of depression. Spearman correlation analysis, spline regression, and binary logistic regression models were employed to explore the relationship between creatinine levels and depression.

Results: A total of 7,826 participants and 3,886 follow-up participants were included in the CHARLS 2011 and 2015 surveys. Of these, 37.9% (2,966/7,826) and 34.6% (13,44/3,886) of participants experienced depression in CHARLS 2011 and 2015, respectively. The creatinine level was negatively correlated with the total CESD-10 score and dimensions scores, showing an inverse dose-response relationship between creatinine levels and depression. Compared with participants with high creatinine levels, those with middle creatinine levels were associated with a higher risk of depression (OR = 1.22, 95% CI = 1.08-1.38), while participants with low creatinine levels had the highest risk of depression (OR = 1.30, 95% CI = 1.13-1.49) in the fully adjusted model. Similar results were observed in the follow-up data, and the MENDA metabolomics data validated the negative correlation between creatinine levels and the severity of depression.

Conclusion: Lower levels of creatinine were closely associated with a higher risk of depression, and it could serve as a potential marker for identifying individuals at high risk of depression.

Keywords: CHARLS; Chinese; MENDA; association; creatinine; depression.