Risk of Anxiety and Depression after Diagnosis of Young-Onset Colorectal Cancer: A Population-Based Cohort Study

Abstract

Given the increasing incidence of young-onset colorectal cancer (yCRC; <50 years), we aimed to evaluate the risk of depression and anxiety in individuals with yCRC in comparison to average-age-onset CRC (aCRC; ≥50 years) and to cancer-free controls, with stratification by sex. Our cohort study identified individuals (≥18 years) with CRC and cancer-free controls (10:1) matched on age and sex using population-based linked administrative health databases in British Columbia, Canada. We assessed depression and anxiety using validated algorithms. We evaluated the risk of depression and anxiety using multivariable Cox proportional hazard models. The cohort included 54,634 individuals with CRC (46.5% female, mean age 67.9 years) and 546,340 controls (46.5% female, mean age 67.9 years). Those with yCRC as compared to aCRC had an increased risk for depression (adjusted hazard ratio [aHR] 1.41; 95% confidence interval [CI] 1.25 to 1.60), and when stratified by sex, the risk was only significant among males (aHR 1.76; 95% CI 1.48 to 2.10). When comparing individuals with yCRC to cancer-free controls, the overall risk of depression (aHR 1.00; 95% CI 0.92 to 1.10) and anxiety (aHR 1.10; 95% CI 0.95 to 1.27) was non-significant; however, males had a significantly higher risk for mental health disorders, specifically depression (aHR 1.17; 95% CI 1.03 to 1.33). Altogether, our findings that individuals with yCRC experience higher risk of depression compared to those with aCRC as well as cancer-free controls, particularly among males, suggest effects of age and sex on mental health outcomes.

Colorectal Cancer and Onset of Anxiety and Depression: A Systematic Review and Meta-Analysis

“…Out of the included studies, six studies [ 6 , 8 , 17 , 18 , 19 , 20 ] assessed both anxiety and depression, and two studies [ 7 , 21 ] assessed depression only. Included studies were predominantly conducted in developed countries: United States ( n = 3) [ 6 , 17 , 21 ], Taiwan ( n = 2) [ 18 , 20 ], Netherlands ( n = 1) [ 19 ], Denmark ( n = 1) [ 7 ], and Canada ( n = 1) [ 8 ]. All studies used administrative health data from their respective countries as their main data source.…”

“…However, we note that, although studies were assessed to be reporting sex, as generally administrative health data do not capture gender, sex and gender terminology were conflated in half of the studies ( n = 2) [ 17 , 21 ], where the terms ‘men’ and ‘women’ (which refer to sex) were used interchangeably with ‘males’ and ‘females’ (which refer to gender), respectively. In regard to age, the majority of studies ( n = 7) [ 6 , 8 , 17 , 18 , 19 , 20 , 21 ] reported the age at the time of CRC diagnosis and one study [ 7 ] reported age at the time of the study. However, all studies varied in their reporting of age, as we observed either the reporting of mean and standard deviation or proportion according to varying age categories.…”

“…The pooled age at CRC diagnosis was 68.2 years (95% CI 65.54 to 70.85). Regarding cancer stage at diagnosis, two studies [ 18 , 20 ] did not report cancer stage, three studies [ 6 , 7 , 19 ] included CRC patients with stage 1 to IV disease, two studies [ 8 , 17 ] included CRC patients with stage 0 to IV disease, and one study [ 21 ] included CRC patients with stage 1 to III disease. Lastly, the quality assessment scores of included studies resulted in a “Fair” ranking for two studies [ 17 , 19 ], with scores ranging from 3 to 5, and a “Good” ranking for six studies [ 6 , 7 , 8 , 18 , 20 , 21 ], with scores ranging from 6 to 8.…”

“…Among included studies, six [ 6 , 8 , 17 , 18 , 19 , 20 ] assessed both anxiety and depression and two assessed depression only [ 7 , 21 ]. The majority of studies ( n = 7) [ 6 , 7 , 8 , 17 , 18 , 20 , 21 ] assessed anxiety and depression using ICD-9 (International Classification of Diseases, Ninth Revision) codes, whereas only one study, Mols et al [ 19 ], used validated questionnaires (Hospital Anxiety and Depression Scale (HADS)). Out of the studies that used ICD-9 codes, Zhang et al [ 17 ] assessed diagnostic rates of anxiety and depression versus other studies that evaluated anxiety and depression as outcomes.…”

“…In addition, a 2021 cohort study in Denmark found that, compared to the cancer-free population, patients with CRC also had a significantly higher risk of depression, even 5 years after enrollment into the study (aHR 2.65; 95% CI 1.61 to 4.36) [ 7 ]. Recently, a Canadian cohort study in 2022 using administrative health databases evaluated risks of mental health disorders among patients with CRC stratified by sex and found that the risk of depression among males (aHR 1.11; 95% CI 1.06 to 1.16) and the risk of anxiety among both males (aHR 1.15; 95% CI 1.06 to 1.25) and females (aHR 1.09; 95% CI 1.02 to 1.16) were higher for those with CRC compared to the cancer-free group [ 8 ].…”