Relationship of Regular Laxative Use, Genetic Susceptibility of Depression, and Risk of Incident Depression in the General Population

Background: The relationship between laxative use and the risk of depression remains uncertain. We aimed to assess the prospective association of regular laxative use with the risk of incident depression and to examine whether genetic risk of depression modifies this association. Methods: Four hundred fifty thousand forty-five participants without depression at baseline and have complete information on laxative use from the UK Biobank were included. The study outcome was incident depression, derived from linkage to primary care records, hospital inpatient data, death register records, or self-reported medical conditions at follow-up visits. Results: During a median follow-up of 12.4 years, 18,651(4.1%) participants have developed depression. Regular laxative use was significantly associated with a higher risk of incident depression (vs. nonregular laxative use; adjusted hazard ratio [HR] = 1.78, 95% confidence interval [CI], 1.68-1.89). Genetic risk of depression did not significantly modify this association. The risk of incident depression increased with increasing types of laxatives used, with a HR of 1.89 (95%CI, 1.73-2.08) for use of single laxative type and 2.32 (95%CI, 1.82-2.96) for combined use of two or more laxative types (P for trend <0.001). The positive association between regular laxative use and incident depression was more pronounced in men (adjusted HR = 2.21, 95%CI, 1.96-2.48) versus women (adjusted HR = 1.67, 95%CI, 1.56-1.79; P interaction <0.001). Compared to those who did not use laxatives regularly and did not have constipation, participants who used laxatives regularly and had constipation had the highest risk of incident depression (adjusted HR = 2.33, 95%CI, 1.94-2.80). Conclusions: Regular laxative use was significantly associated with a higher risk of incident depression, especially in men.