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Background: Sarcopenia is reported to be associated with depression. Recently, serum creatinine to cystatin C ratio (CCR) has been recommended as a promising biomarker for detecting sarcopenia. The purpose of this study was to explore the relationship between CCR and depressive symptoms among middle-aged and older adults using the baseline data of the China Health and Retirement Longitudinal Study (CHARLS).Methods: This study included 7083 participants aged 45 and older. A score of 10-item Center for Epidemiological Studies Depression Scale (CESD-10) ≥ 12 was used as the cut-off of having depressive symptoms. CCR was calculated by serum creatinine (mg/dL)/cystatin C (mg/L). The t-test and Chi-squared test were applied to compare the differences between the depressive symptoms group and no depressive symptoms group in both sexes. Unadjusted and adjust logistic regression models were used to further investigate the relationship between CCR and depressive symptoms.Results: In the fully adjusted logistic regression models, higher CCR was significantly correlated with a lower incidence of depressive symptoms in males (OR = 0.486, P = 0.001, 95 % CI = 0.314-0.752), but not in females (OR = 0.775 P = 0.184, 95 % CI = 0.532-1.129).Limitations: 1. Self-reported method was used to define depressive symptoms by CESD-10; 2. History of chronic diseases were all self-reported; 3. Residual bias was still possible after controlling for many confounding factors.Conclusions: Lower CCR was significantly correlated with increased depressive symptoms in males, but not in females. More studies are needed to further confirm this conclusion. [ABSTRACT FROM AUTHOR]