Cholecystectomy Linked to Higher Incidence of Major Depressive Disorder

Researchers investigated the incidence of major depressive disorder in adult patients who underwent cholecystectomy.

Patients who undergo cholecystectomy have an increased incidence of major depressive disorder (MDD) compared with control participants, researchers reported in Clinical and Translational Gastroenterology.

The retrospective cohort study was based on data from the Korean National Health Insurance Corporation (NHIC) database and included patients who underwent cholecystectomy at ages ≥40 years from January 2010 through December 2015. The patients with cholecystectomy were matched 1:2 with control participants who did not undergo cholecystectomy. The primary endpoint was newly diagnosed depression.

A total of 111,934 patients undergoing cholecystectomy and 223,868 age- and sex-matched control participants were included in the final analysis. In both cohorts, the mean age was 55.3±10.68 years and 61.14% were men.

The overall mean follow-up after a 1-year lag was 3.67±1.79 years (3.59±1.81 years for the cholecystectomy group and 3.71±1.78 years for the control group), and the maximum follow-up after cholecystectomy was 7 years. For the cholecystectomy group, the incidence of MDD was 27.3 per 1000 person-years, compared with 20.3 per 1000 person-years in the control group.

Participants who had a cholecystectomy had a higher relative risk of MDD than those who did not have a cholecystectomy (adjusted hazard ratio [aHR], 1.34; 95% CI, 1.31-1.37; P <.001), after adjustment for age, sex, income, place of residence, diabetes mellitus, hypertension, and dyslipidemia.

For the cholecystectomy group, multivariable analysis-estimated aHRs for MDD were 1.51 (95% CI, 1.44-1.58) in those aged 40 to 49 years, 1.22 (95% CI, 1.18-1.26) in those aged 50 to 59 years, 1.30 (95% CI, 1.24-1.35) in those aged 60 to 69 years, 1.17 (95% CI, 1.11-1.24) in those aged 70 to 79 years, and 1.00 (95% CI, 0.87-1.14) in those aged ≥80 years.

The overall incidence of MDD increased with comorbid diabetes mellitus. The aHR of MDD after cholecystectomy was higher in participants without diabetes mellitus (aHR, 1.36; 95% CI, 1.33-1.39) than in those with diabetes mellitus (aHR, 1.17; 95% CI, 1.11-1.23). Participants without hypertension and dyslipidemia (aHR, 1.38 and 1.35, respectively) had a higher relative risk of MDD after cholecystectomy compared against those with hypertension and dyslipidemia (aHR, 1.24 and 1.24, respectively).

The estimated aHR for depression after cholecystectomy was 1.39 (95% CI, 1.34-1.45) for 2 years (13-24 months) relative to the control group. The aHR values were 1.34 at 3 years, 1.27 at 4 years, and 1.30 at 5+ years.

Study limitations included use of health insurance claims data and the number of medical visits for depression based on ICD codes, allowing for the possibility of misdiagnosis. Additionally, confounding factors such as postoperative pain, infection, marital status, education, occupational status, body mass index, smoking habits, and alcohol intake were not included in the analysis. Finally, the study authors could not exclude participants who already had symptoms of depression but were not diagnosed with MDD before the index date.

“[P]hysicians should implement an enhanced program of MDD screening for at least several years after cholecystectomy,” the researchers advised.


Jin EH, Han K, Lee DH. Increased risk of major depressive disorder after cholecystectomy: a nationwide population-based cohort study in Korea. Clin Transl Gastroenterol. 2021;12(4):e00339. doi: 10.14309/ctg.0000000000000339