Cause-specific mortality and comorbid neurodevelopmental disorder in 167,515 patients with bipolar disorder: An entire population longitudinal study

Abstract

ObjectiveStudies addressing premature mortality in bipolar disorder (BD) patients are limited by small sample sizes. Herein, we used almost 99 % of the population of Taiwan to address this issue, and its association with comorbid neurodevelopmental disorders and severe BD. MethodsBetween 2003 and 2017, we enrolled 167,515 individuals with BD and controls matched 1:4 for sex and birth year from the National Health Insurance Database linked to the Database of National Death Registry in Taiwan. Time-dependent Cox regression models were used to examine cause-specific mortality (all-cause, natural, and unnatural causes [accidents or suicide]). ResultsWith adjustments of sex, age, income, urbanization, and physical conditions, suicide was associated with the highest risk of mortality (reported as hazard ratio with 95 % confidence interval: 9.15; 8.53–9.81) among BD patients, followed by unnatural (4.94; 4.72–5.17), accidental (2.15; 1.99–2.32), and natural causes (1.02; 1.00–1.05). Comorbid attention-deficiency hyperactivity disorder did not contribute to the increased risk of cause-specific mortality; however, comorbid autism spectrum disorder (ASD) increased such risks, particularly for natural (3.00; 1.85–4.88) and accidental causes (7.47; 1.80–31.1). Cause-specific mortality revealed a linear trend with the frequency of psychiatric hospitalization (all, p for trend <0.001), and BD patients hospitalized twice or more each year had 34.63-fold increased risk of suicide mortality (26.03–46.07). ConclusionsBD patients with a higher frequency of psychiatric hospitalization have the highest risk of suicide mortality, and comorbid ASD was associated with an increased risk of natural and accidental causes of mortality.