Depression and bipolar disorder subtypes differ in their genetic correlations with biological rhythms

Abstract

Major Depression and Bipolar Disorder Type I (BIP-I) and Type II (BIP-II), are characterized by depressed, manic, and hypomanic episodes in which specific changes of physical activity, circadian rhythm, and sleep are observed. It is known that genetic factors contribute to variation in mood disorders and biological rhythms, but unclear to what extent there is an overlap between their underlying genetics. In the present study, data from genome-wide association studies were used to examine the genetic relationship between mood disorders and biological rhythms. We tested the genetic correlation of depression, BIP-I, and BIP-II with physical activity (overall physical activity, moderate activity, sedentary behaviour), circadian rhythm (relative amplitude), and sleep features (sleep duration, daytime sleepiness). Genetic correlations of depression, BIP-I, and BIP-II with biological rhythms were compared to discover commonalities and differences. A gene-based analysis tested for associations of single genes and common circadian genes with mood disorders. Depression was negatively correlated with overall physical activity and positively with sedentary behaviour, while BIP-I showed associations in the opposite direction. Depression and BIP-II had negative correlations with relative amplitude. All mood disorders were positively correlated with daytime sleepiness. Overall, we observed both genetic commonalities and differences across mood disorders in their relationships with biological rhythms: depression and BIP-I differed the most, while BIP-II was in an intermediate position. Gene-based analysis suggested potential targets for further investigation. The present results suggest shared genetic underpinnings for the clinically observed associations between mood disorders and biological rhythms. Research considering possible joint mechanisms may offer avenues for improving disease detection and treatment.

Bipolar Chronobiology in Men and Mice: A Narrative Review

“…Self-report measures of sleep duration had a significant genetic correlation with BD but not MDD [58], and there was no significant genetic correlation with either MDD or BD when considering objectively measured sleep duration. All analyzed affective disorders significantly positively correlated with daytime sleepiness [34]. In concordance with the clinical picture, all affective disorders resembled each other regarding daytime sleepiness.…”

“…Mood disorders and biological rhythms might have overlapping underlying genetics, but it remains unclear whether the observed phase shifts during affective episodes are the cause or consequence of the given mood episode. [34]. CRD might be a common underlying factor that bridges mental health disorders and mediates similar clinical phenotypes [35].…”

Circadian rhythm biomarker from wearable device data is related to concurrent antidepressant treatment response

“…Such a model can be expanded to include other demographics and measures of actigraphy time series data (e.g., energy expenditure, sleep duration, etc.) and activity related circadian genes 56 as well as clinical notes, lab values, and medical imaging 46 , 57 for a comprehensive clinical decision support tool. Continuous actigraphy data can be used to identify changes in circadian motor activity over time, by quantifying patterns in sequential time series data, which is also useful for forecasting 58 .…”