Investigators Link Sleeping Habits with Bipolar Disorder Subtype

The connection between sleeping long durations or suffering from insomnia differs between the different bipolar disorder (BD) subtypes.

A team led by Katie J. S. Lewis, PhD, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, conducted a case-control study in the UK and Sweden involving 4672 patients with bipolar disorder, as well as 5714 control participants to test whether genetic liability to insomnia, hypersomnia, and chronotype differentiate subtypes of bipolar disorder.

The investigators found that patients with bipolar disorder I had significantly greater genetic liability to sleep longer durations, while patients with bipolar disorder II had significantly greater genetic liability to insomnia.

The team then replicated the results in an independent sample and found that individuals with bipolar subtypes did not differ in genetic liability to morning or evening chronotype.

Patients with bipolar disorder commonly suffer from insomnia and hypersomnia and have an evening chronotype. However, it is unknown whether this reflects shared genetic liability.

In the study, the investigators used multinomial regression to assess whether polygenetic risk scores for insomnia, daytime sleepiness, sleep duration, and chronotype is associated with specific bipolar disorder subtypes compared with control participants.

Among the study participants, 3132 patients were female with a median age of 46 years old. A total of 3404 participants met criteria for BD-I, and 1268 met criteria for BD-II.

Standardized polygenetic risk scores were derived using alleles from genome-wide association studies of insomnia, sleep duration, day-time sleepiness, and chronotype, which were adjusted for the first 10 population principal components, genotyping platforms, and sex.

“Insomnia PRS was associated with increased risk of BD-II (RR, 1.14 [95% CI, 1.07-1.21]; P  = 8.26 × 10⁻⁵) but not BD-I (RR, .98 [95% CI, .94-1.03]; P = .409) relative to control participants,” the authors wrote. “Sleep-duration PRS was associated with BD-I (RR, 1.10 [95% CI, 1.06-1.15]; P = 1.13 × 10⁻⁵) but not BD-II (RR, .99 [95% CI, .93-1.06]; P = .818).”

The association between insomnia polygenetic risk scores and bipolar disorder II and sleep duration polygenetic risk scores and bipolar disorder I were replicated in the Swedish sample of 4366 patients with bipolar disorder and 6091 control participants.

They also found that chronotype and daytime-sleepiness polygenic risk scores were not linked to bipolar disorder subtypes.

“Per this analysis, BD subtypes differ in genetic liability to insomnia and hypersomnia, providing further evidence that the distinction between BD-I and BD-II has genetic validity,” the authors wrote. “This distinction will be crucial in selecting participants for future research on the role of sleep disturbance in BD.”

The stronger association between insomnia polygenetic risk score and bipolar disorder II may explain non-significant genetic correlations between bipolar disorder and insomnia in previous research, because individuals with bipolar disorder II are generally underrepresented in genome-wide association studies.

The investigators suggest future studies should look at possible reasons for this association.

The connection between hypersomnia in bipolar disorder populations has remained relatively under researched.

“To our knowledge, this is the first study to explore whether genetic liability for sleep traits is associated with clinical strata of individuals with BD,” the authors wrote. “Future work should explore potential mechanisms underlying differences between the BD subtypes in genetic liability for sleep traits.”