Exercise Intensity and 5-Yr Trajectories in Peak Oxygen Uptake in Older Adults: Analysis from the Generation 100 Study.

Mental health disorders have been a growing global health challenge, with incidence rising more than 15% from 1990 to 2021. () Among them, depressive disorders contribute the greatest share of this burden, leading all mental illnesses in disability-adjusted life years in 2021. () Depression has been associated with the development and prognosis of stroke (), coronary heart disease (), and diabetes mellitus (). Increasing evidence indicates a potential role of depression and chronic psychological stress in cancer initiation (–). Plausible mechanisms include overactivation of the hypothalamic-pituitary-adrenal axis and downstream immunological dysfunction which may promote neoplasia (, ). Animal studies have shown a link between elevated levels of stress-related hormones (epinephrine, norepinephrine, and cortisol) and cancer induction, impacting 7 out of 10 hallmarks of cancer (, ). Additionally, chronic stress and its effector cortisol centrally and peripherally regulate food intake and energy homeostasis. () Elevated cortisol promotes appetite, obesity (), insulin resistance and low-grade inflammation, all of which are implicated in colorectal carcinogenesis (, ). Despite biologic plausibility and observational data linking psychological distress and colorectal cancer (CRC) development, epidemiological findings remain inconsistent. Some studies reported higher CRC risk among individuals with depressive symptoms. For example, a prospective cohort in women found that those with the highest level of depressive symptoms had 43% higher CRC risk than those with the lowest (HR 1.43, 95% CI: 0.97–2.11; p-trend = 0.04) (). Similarly, a Danish registry-based study observed a modestly increased risk of colon cancer (SIR = 1.16, 95% CI: 1.03–1.30) among patients hospitalized with reactive depression or dysthymia, primarily during the first year after admission (). In contrast, other large cohorts, including the HUNT study () and the Women’s Health Initiative (), did not find significant relationships between depression and CRC risk. Furthermore, a comprehensive meta-analysis using individual participant data found no robust evidence for depression or anxiety as a cancer risk factor. () Regarding colorectal adenomatous polyps, the precursor lesions to CRC, direct evidence linking depressive symptoms to their occurrence or development is sparse. The only pertinent findings come from the Nurses’ Health Study I analysis in 2005, which focused solely on distal adenomas and found no significant association with depression. ()