Psychiatric comorbidity and risk of premature mortality and suicide among those with chronic respiratory diseases, cardiovascular diseases, and diabetes in Sweden: A nationwide matched cohort study of over 1 million patients and their unaffected siblings
Authors: Sariaslan Amir , Sharpe Michael , Larsson Henrik , Wolf Achim , Lichtenstein Paul , Fazel Seena 
Published: January 2022

Background
Persons with noncommunicable diseases have elevated rates of premature mortality. The contribution of psychiatric comorbidity to this is uncertain. We aimed to determine the risks of premature mortality and suicide in people with common noncommunicable diseases, with and without psychiatric disorder comorbidity.

Methods and findings
We used nationwide registries to study all individuals born in Sweden between 1932 and 1995 with inpatient and outpatient diagnoses of chronic respiratory diseases (n = 249,825), cardiovascular diseases (n = 568,818), and diabetes (n = 255,579) for risks of premature mortality (≤age 65 years) and suicide until 31 December 2013. Patients diagnosed with either chronic respiratory diseases, cardiovascular diseases, or diabetes were compared with age and sex-matched population controls (n = 10,345,758) and unaffected biological full siblings (n = 1,119,543). Comorbidity with any psychiatric disorder, and by major psychiatric categories, was examined using diagnoses from patient registers. Associations were quantified using stratified Cox regression models that accounted for time at risk, measured sociodemographic factors, and unmeasured familial confounders via sibling comparisons. Within 5 years of diagnosis, at least 7% (range 7.4% to 10.8%; P < 0.001) of patients with respiratory diseases, cardiovascular diseases, or diabetes (median age at diagnosis: 48 to 54 years) had died from any cause, and 0.3% (0.3% to 0.3%; P < 0.001) had died from suicide, 25% to 32% of people with these medical conditions had co-occurring lifetime diagnoses of any psychiatric disorder, most of which antedated the medical diagnosis. Comorbid psychiatric disorders were associated with higher all-cause mortality (15.4% to 21.1%) when compared to those without such conditions (5.5% to 9.1%). Suicide mortality was also elevated (1.2% to 1.6% in comorbid patients versus 0.1% to 0.1% without comorbidity). When we compared relative risks with siblings without noncommunicable diseases and psychiatric disorders, the comorbidity with any psychiatric disorder was associated with substantially increased mortality rates (adjusted HR range: aHRCR = 7.2 [95% CI: 6.8 to 7.7; P < 0.001] to aHRCV = 8.9 [95% CI: 8.5 to 9.4; P < 0.001]). Notably, comorbid substance use disorders were associated with a higher mortality rate (aHR range: aHRCR = 8.3 [95% CI: 7.6 to 9.1; P < 0.001] to aHRCV = 9.9 [95% CI: 9.3 to 10.6; P < 0.001]) than depression (aHR range: aHRCR = 5.3 [95% CI: 4.7 to 5.9; P < 0.001] to aHRCV = 7.4 [95% CI: 7.0 to 7.9; P < 0.001]), but risks of suicide were similar for these 2 psychiatric comorbidities.
One limitation is that we relied on secondary care data to assess psychiatric comorbidities, which may have led to missing some patients with less severe comorbidities. Residual genetic confounding is another limitation, given that biological full siblings share an average of half of their cosegregating genes. However, the reported associations remained large even after adjustment for shared and unmeasured familial confounders.

Conclusions
In this longitudinal study of over 1 million patients with chronic health diseases, we observed increased risks of all-cause and suicide mortality in individuals with psychiatric comorbidities. Improving assessment, treatment, and follow-up of people with comorbid psychiatric disorders may reduce the risk of mortality in people with chronic noncommunicable diseases.