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The Impact of 5-HTTLPR Polymorphism on Depression and Lymphocyte Changes in Colorectal Cancer Patients Undergoing FOLFOX Chemotherapy

Year: 2026

Type: article

Abstract: OBJECTIVE: Depression could be related to immune function among cancer patients. The serotonin transporter gene has been reported for its associations with both depression and immune regulation. This study investigates the interaction between depression, immunity, and 5-HT transporter gene-linked polymorphism (5-HTTLPR) among colorectal cancer (CRC) patients undergoing chemotherapy. METHODS: This prospective longitudinal study collected information on depression and lymphocyte percentages at two time points: the first cycle and the final cycles of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. Clinical depression was assessed using the Hospital Anxiety and Depression Scale-depression subscale (HADS-D) score. Genotyping identified 5-HTTLPR alleles. The dependent variables were changes in the percentages of CD4+, CD8+, CD19+, and CD16/56+ lymphocytes between the two time points. Moderated regression analysis was used to find interactions. RESULTS: Among 104 patients, no significant direct associations were observed between changes in lymphocyte percentages and HADS-D scores. However, with the interaction of 5-HTTLPR polymorphism, the moderated regression analysis revealed two significant associations between HADS-D scores and changes in the percentages of CD4+ and CD16/56+ lymphocytes. Specifically, the percentage of CD4+ cells decreased, and the percentage of CD16/56+ cells increased, in relation to the s allele as depression worsened. These findings were consistent in a sensitivity analysis. CONCLUSION: Changes in the percentage of CD4+ cells and CD16/56+ cells under depression were moderated by 5-HTTLPR alleles among CRC patients undergoing FOLFOX chemotherapy, suggesting a gene-environment interaction. Further research on the role of 5-HTTLPR in the immune system under depression among CRC patients is warranted.

Source: Psychiatry Investigation

DOI: 10.30773/pi.2025.0267