Clinical and Biological Characterization of Bipolar Disorder Patients With Chronic Insomnia Reveals Cortisol Reductions, Elevated TNF ‐α, and Increased Genetic Risk for Accelerated Aging

BACKGROUND: Among patients with bipolar disorder, chronic insomnia is a common comorbidity that adversely affects mood instability, quality of life, disability, accelerated aging, and increased suicide risk. METHODS: This matched case-control study characterized the clinical features of insomnia in a bipolar disorder clinic population and identified biological and genetic correlates affecting diurnal patterns of cortisol, inflammation, and aging. Cross-sectional data were collected from 22 patients with bipolar disorder and chronic insomnia (BD + INS), and 22 age- and sex-matched bipolar disorder patients without insomnia (BD-INS). RESULTS: BD + INS patients reported sleep problems independent of current mood state with a mean insomnia duration of 22.5 years. Compared to BD-INS participants, BD + INS patients reported more disturbed sleep, more use of daytime anxiolytics, and reduced use of antidepressants, but reported no differences in overall functioning, quality of life, or severity of mood episodes. Compared to matched participants, BD + INS patients also had reduced waking cortisol, increased levels of the inflammatory cytokine tumor necrosis factor α (TNF-α), and were more likely to be homozygous for a genetic variant in TERT previously linked with short telomere length and premature aging. CONCLUSIONS: These findings suggest that chronic insomnia in BD can persistently alter sleep independent of mood symptoms and may be associated with distinct biological features, including cortisol and inflammatory systems.