Association Between Cerebrospinal Fluid Ghrelin Levels and Depressive Symptoms is Moderated by Smoking: A Case‐Control Study

ABSTRACT Objective Smoking has been linked to both peripheral ghrelin levels and depressive symptoms. However, the association between cerebrospinal fluid (CSF) ghrelin levels and depressive symptoms, and the moderating role of smoking, remains unclear. This study aims to investigate the specific relationship among the three categories. Methods In this case‐control study, we examined the association between smoking, depressive symptoms, and CSF ghrelin levels in 173 adult male volunteers (94 non‐smokers and 79 active smokers). Demographic data, clinical parameters, and Beck Depression Inventory (BDI‐SF) scores were assessed, and CSF ghrelin levels were measured. Statistical analyses, including the Mann‐Whitney rank‐sum test, Spearman correlation, and linear regression, were used to explore the relationships among these variables. Results Active smokers had significantly higher BDI scores (3.57 ± 4.74 vs. 1.44 ± 2.33, p < 0.001) and lower CSF ghrelin levels (1201.99 ± 145.97 vs. 1563.61 ± 153.3, p < 0.001) compared with non‐smokers. Correlation analysis revealed a significant negative association between CSF ghrelin levels and BDI scores ( r = −0.197, p < 0.01). Smoking was positively correlated with BDI scores ( r = 0.332, p < 0.001) and negatively correlated with CSF ghrelin levels ( r = −0.780, p < 0.001). Moderation analysis further indicated that smoking significantly moderated the association between CSF ghrelin levels and depressive symptoms (Smoking × CSF ghrelin: p = 0.047). Conclusion CSF ghrelin levels are associated with depressive symptoms. A significant negative correlation exists between CSF ghrelin levels and smoking, and smoking appears to moderate the association between CSF ghrelin and depressive symptoms. These findings provide potential insights into the pre‐clinical mechanisms of depression and early prevention strategies.