Association of Youth Depression With Subsequent Somatic Diseases and Premature Death
Authors: Marica Leone, Ralf Kuja-Halkola, Amy Leval, Brian M. D’Onofrio, Henrik Larsson, Paul Lichtenstein, Sarah E. Bergen
Journal: JAMA Psychiatry (2020)

<h3>Importance</h3> Early-onset depression has been linked to poor health outcomes. However, it is unclear the extent to which this disorder is associated with specific diseases and premature death and whether these associations remain after controlling for psychiatric comorbidity. <h3>Objective</h3> To quantify the association of youth depression with subsequent diagnoses of numerous somatic diseases and mortality. <h3>Design, Setting, and Participants</h3> A population-based cohort study was conducted using Swedish national registers containing data on all individuals born in Sweden between 1982 and 1996. A total of 1 487 964 participants were followed up from age 5 years through 2013 if no censoring occurred. Data analysis was performed from January 15, 2019, to August 10, 2020. <h3>Exposures</h3> Youth depression was defined as having received at least 1 diagnosis of depression from inpatient or outpatient care between ages 5 and 19 years. <h3>Main Outcomes and Measures</h3> This study examined 69 somatic conditions diagnosed after youth depression, as well as all-cause and cause-specific mortalities. Overall and sex-specific hazard ratios (HRs), together with 95% CIs, were estimated using Cox proportional hazards regression with attained age as underlying timescale and time-varying exposure, and adjusted for birth year and sex. All analyses were repeated controlling for psychiatric comorbidities. Absolute risk differences were calculated using standardization with Cox proportional hazards regression. <h3>Results</h3> Of 1 487 964 individuals included in the analysis, 51.2% were male. A total of 37 185 patients (2.5%; 67.4% female) had an inpatient or outpatient contact for depression between ages 5 and 19 years (mean [SD] age at first recorded diagnosis of depression, 16.7 [2.1] years for males and 16.7 [1.8] years for females). Age at the end of follow-up ranged between 17 and 31 years. Individuals with youth depression had higher relative risks for 66 of the 69 somatic diagnoses. Strong associations were observed for certain injuries, especially self-harm in females (HR, 14.4; 95% CI, 13.8-15.1), sleep disorders (HR, 8.1; 95% CI, 7.6-8.7), viral hepatitis (HR, 6.1; 95% CI, 5.4-6.8), all-cause mortality (HR, 5.9; 95% CI, 5.3-6.6), and cause-specific mortalities, especially death by intentional self-harm (HR, 14.6; 95% CI, 12.6-16.9). Most associations were attenuated but persisted after adjusting for psychiatric comorbidity. The absolute risk difference of a specific disease within 12 years from the first diagnosis of depression during youth ranged from −0.2% (95% CI, −1.0% to 0.6%) for arthropathies among males to 23.9% (95% CI, 22.7%-25.0%) for the broader category of injuries among females. <h3>Conclusions and Relevance</h3> In this Swedish population cohort study, patients with depression diagnosed during their youth appeared to have increased risks for many somatic diseases as well as for mortality, even after controlling for other psychiatric disorders. These findings suggest that several medical conditions should be considered when investigating youth depression.