Depression Promotes the Development of Colorectal Precancerous Lesions and Colorectal Cancer: BLNK as a Mediator

Aims Our objective is to elucidate whether depression represents an independent risk factor for colorectal polyp, adenoma (CRA/P) and cancer, and to explore its potential underlying mechanism.

Methods A cohort study was conducted from September 22, 2022, to June 15, 2023, in Renmin Hospital of Wuhan University to explore the relationship between depression and the risk of CRA/P detection rate. Patients undergoing screening coloscopy were recruited to complete questionnaires of Patient Health Questionaire-9 (PHQ-9) with some baseline information. Subsequently, we corroborated our clinical findings using data from NHANES (National Health and Nutrition Examination Survey), a comprehensive and nationally representative collection of health data in the United State. To delve deeper into causality, we employed mendelian randomization (MR) analysis to elucidate the potential reciprocal causal relationship between depression and CRA/P and CRC. And lastly, we explored the potential mediation role of plasma protein between depression and CRA/P, as well as CRC [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15].

Results In the prospective clinical study, 2913 patients were included for analysis. Finally, 2524, 218, 86 and 29 patients were assigned into non-depression, minimal depression, minor depression and major depression groups, respectively. Patients who came for colonoscopy with higher level of depression disorder were associated with a higher detection rate of CRA/P [OR(95%CI)=1.17 (1.00-1.35); p=0.044]. In NHANES dataset, 26076 participants were included for analysis. Depression level was categorized as non-depression, minimal depression, minor depression and major depression. As shown in Table 1, depression level was an independent factor associated with higher risk of CRC [ OR (95%CI), 1.27 (1.06 -1.53); p=0.011] after adjusting sex, BMI, ethnicity, education, PIR, alcohol, smoking, and diabetes. In the MR analysis, depress has causal effect on CRA/P and CRC. In two step MR, depress has causal effect on BLNK and BLNK has causal effect on CRC and CRA/P. Enzyme-Linked Immunosorbent Assay showed that patients who were diagnosed with depression or CRC were associated with higher plasma protein of BLNK.

Conclusions Individuals affected by depression are more likely to be affected by CRA/P and CRC. BLNK plays an important role of depression in the progression of CRC in both precancerous stage and advanced stage.

Publikationsverlauf

Artikel online veröffentlicht:
27. März 2025

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