‘Milder’ Form of Bipolar Linked to Higher Risk of Early Death

Bipolar II disorder was associated with an increased risk of premature mortality, including from both natural and unnatural causes, according to a population-based retrospective cohort study from Taiwan.

Comparing over 11,000 patients with bipolar II disorder with over 45,000 matched controls, 1,089 patients and 1,879 controls died (aHR 1.62, 95% CI 1.47-1.78), reported Yang-Chieh Brian Chen, MD, of the University of Texas Health Science Center at Houston, and co-authors in JAMA Network Open.

Compared with people without bipolar disorder, those with bipolar II had increased mortality from natural causes, including mental and behavioral disorders, as well as circulatory, respiratory, digestive, and skin or subcutaneous diseases (adjusted HR 1.37, 95% CI 1.23-1.52), and mortality from unnatural causes, including unintentional injuries, suicide, and assault or homicide (aHR 4.46, 95% CI 3.53-5.64).

In analyses comparing those with bipolar II with unaffected biological siblings, bipolar II remained associated with higher all-cause mortality (aHR 1.31, 95% CI 1.00-1.72) and unnatural-cause mortality (aHR 2.05, 95% CI 1.43-2.95), but not natural-cause mortality.

Meanwhile, in an analysis comparing those with bipolar II and bipolar I disorder, bipolar II was linked to higher all-cause mortality (aHR 1.24, 95% CI 1.01-1.53) and natural-cause mortality (aHR 1.45, 95% CI 1.14-1.86), but not unnatural-cause mortality.

Bipolar II is often viewed as the “milder” of the bipolar disorders, because patients tend to experience less intense manic symptoms than patients with bipolar I disorder. However, patients with bipolar II typically have more frequent and longer depressive episodes, resulting in significant functional impairment, Chen told MedPage Today.

The increased risk of natural deaths among patients with bipolar II suggests they may struggle more to manage their personal healthcare, even compared to those with bipolar I, Chen added.

The authors noted that bipolar II should not be regarded as simply a milder form of the disorder, and that the higher risk of natural death may reflect “more frequent delays in recognition and treatment” of bipolar II, which “could reduce engagement with physical healthcare and allow greater accumulation of medical risk.”

They explained that bipolar disorder has been tied to accelerated biological aging, with studies showing shortened telomere length compared with people without the disorder.

“Additionally, atypical depressive symptoms common in [bipolar II], including hyperphagia, marked fatigue, and resultant low physical activity, may increase the risk of obesity and consequences, such as metabolic dysfunction-associated fatty liver disease, cardiovascular disease, and diabetes,” they wrote.

Previous studies including a meta-analysis suggested that all-cause mortality is roughly doubled in those with bipolar disorder overall, while the relative risk for suicide is increased 12-fold, and the risk for deaths from other unnatural causes is increased sevenfold. However, most studies have not distinguished bipolar II from bipolar I.

“Taken together, our findings align with contemporary models that conceptualize [bipolar disorder] as a somatoprogressive illness,” in which physical comorbidities occur in parallel with worsening neuropsychiatric disorders, “and reinforce the need for integrated psychiatric and medical care,” the authors wrote.

Chen said that “future studies should investigate the association of specific factors leading to the increased risks of death in bipolar II disorder, including, but not limited to, lifestyle habits such as smoking, diet, and occupational exposure.”

The study is among the first to examine mortality risk with bipolar II disorder alone, Chen said. The authors relied on data from Taiwan’s National Health Insurance Research Database from January 2000 through December 2022 for patients ages 12 and older with two or more bipolar II diagnoses confirmed by psychiatrists. Patients were matched to four controls without bipolar II disorder by sex and birthdate.

Altogether, the study included 11,427 patients with bipolar II and 45,708 matched controls. Mean age was 39.6, and 61.9% were women. Mean follow-up was 7.3 years.

In their analyses, the authors controlled for age, sex, income, urbanization, healthcare use, and comorbidity.