Sleep disturbances linked to plasma orexin A levels in patients with bipolar disorder: A preliminary study

Sleep disturbances are a core symptom of bipolar disorder (BD). Other sleep disturbances such as nightmares, sleep apnea and restless legs are also common in BD. Biomarkers related to the sleep-wake cycle, specifically orexins, have attracted research on their role in other psychiatric disorders, but have been less explored in BD. We aimed to analyze the relationship between orexin A levels and sleep characteristics in patients with BD. This is a secondary analysis of a cross-sectional study including 113 outpatients during follow-up. The Oviedo Sleep Questionnaire was used to evaluate sleep characteristics. The Hamilton Depression Rating Scale, the Young Mania Rating Scale, and the Hamilton Anxiety Rating Scale were used to assess clinical status. Orexin A, Interleukin 1 receptor antagonist, and tumor necrosis factor alpha were measured in plasma. Sociodemographic and other clinical variables were collected. Statistical analysis using parametric tests and logistic regression were performed. No differences between sexes (62 % women) were found for any sleep disturbances. Snoring, restless legs, and nightmares, but not insomnia, showed an association with orexin A. In logistic regression models, restless legs were associated with severity of depression (OR: 1.070, p = 0.015), Interleukin 1 receptor antagonist (OR: 1.004, p = 0.037), and orexin A (OR: 0.963, p = 0.022). As for nightmares, only severity of anxiety (OR: 1.113, p < 0.001), and benzodiazepines (OR: 0.166, p = 0.006) showed an association. This is one of the few studies analyzing the relationship of sleep quality and orexin A in BD. Evaluating sleep disturbances other than insomnia in BD is valuable, since they are often associated with worse clinical outcomes.