Objective: The authors investigated the distributions and trajectories of physical illnesses preceding the diagnosis of bipolar disorder with comparison to schizophrenia and general populations. Methods: Using data from the Taiwan National Health Insurance Research Database entered from 1996 to end of 2012, we identified 13,079 patients newly diagnosed as having bipolar disorder between the age of 13 and 40 years (ie, cases). For each case with bipolar disorder, two age- and sex- and diagnosis year- schizophrenia comparisons ( n = 26 , 158 ) (n=26,158) and four age- and sex-matched comparisons representing the general population ( n = 52 , 316 ) (n=52,316) were randomly selected from the cohort. Multivariate conditional logistic regression analyses were conducted to estimate the risk of physical illness before the diagnosis (index date). Variables exhibiting a powerful association (p Results: During the year before diagnosis, patients with newly diagnosed bipolar disorder had a higher risk of numerous physical illnesses across the cardiovascular, respiratory, gastrointestinal, endocrine/metabolic, and musculoskeletal/integument systems compared with those with schizophrenia and the general population. Trends in the risk of specific physical illnesses, mainly hypertension, heart disease, asthma, ulcer disease, hyperlipidemia, and connective tissue disease, were increased across the 3-year prodromal phase of bipolar disorder relative to schizophrenia. Conclusions: Intriguingly, physical illnesses before the diagnosis of bipolar disorder are pervasive with higher risk. Moreover, the trajectories of physical illnesses markedly differ from those of schizophrenia before full manifestation.
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