Connection between seasonality in hospitalizations and sleeping traits in bipolar disorder

Abstract

Background: Bipolar disorder (=BD) is a relatively common mood disorder which is characterized by episodes of depression and mania/hypomania. These episodes are not evenly distributed along the year but show a seasonal trend: there are more manic episodes during spring and summer and more depressive episodes during autumn and winter. This phenomenon is called seasonality. Leading theory explaining this phenomenon is so called light hypothesis; amount of sunlight through the year affect mood of BD patients and therefore acts a episode provoking factor. Additionally genetic predisposition to BD is considered high (73-93%) but exact genes and mechanism is widely unknown. It has been previously pointed out that sleep traits differ between normal population and those with BD. For example ”night owl” -chronotype, hypersomnia and insomnia are more common with those with BD. Whether this has to do with lifestyle or has a connection to genetic factors is unknown. It has been hypothesized that society living on 8-16 schedule is harmful to the ”night owl” chronotype and therefore could be BD provoking factor, on the other hand there is a speculation that same genes that determinate chronotype and other sleeping traits also play a role with predisposition to BD. Additionally previous studies have pointed out that one mechanism for developing BD is malfunction of clock genes that control our circadian rhythm, both on daily- and seasonal level. Most important of these genes are PER- and CRY- gene families. Furthermore, one of the most potent drug against BD is lithium that affects expression of the exact same clock genes. This leads to hypothesis that there could be same genetic factors that contribute to both seasonality and sleeping traits. Aims: Purpose of this master thesis work is to further clarify the role of chronotype and other sleeping traits in BD. More specific our aim was to study connection between genetic predisposition to following sleeping traits: chronotype, daytime sleepiness, sleep duration and insomnia and their connection to seasonality in BD. Furthermore this thesis focuses on trying to understand genetic predisposition to BD itself and it most distinguish subtypes BD-I and BD-II. Methods: Genetic patient data for this study has been provided by Swedish Bipolar Collection (SWEBIC 2009-2013). SWEBIC consists of data of over 6000 Swedish BD patients. Data includes both information of patient’s hospitalization history and genetic information in form of GWAS (genome wide association study). We used statistical programming software R to generate phenotype using clinical data from NPR (National Patient Register) to represent seasonality in hospitalizations among BD patients. As a result we got a specific value that describes seasonality for every individual in our database that fulfills inclusion criteria of our study. Our geneticist created PRS’s (polygenic risk score) for every individual in our database that describes individual’s genetic predisposition to sleeping traits we are examining: chronotype, sleep duration, daytime sleepiness and insomnia. Lastly, we calculated OR (Odds Ratio) comparing correlation between our phenotype and all of our genotypes separately using linear regression analysis. Results: Our preliminary findings suggest that there is slight, yet statistic significant connection between seasonality in hospitalizations and both daytime sleepiness and sleep duration genotypes. On the other hand, we could not find statistic relevant connection between seasonality of hospitalizations and two other genotypes, chronotype and insomnia. Conclusions: Our results suggest that among BD patients chronotype and other sleeping traits do play a role in the disease and its role should be further investigated.