Year: 2022
Type: dissertation
Study design: Observational Study
Abstract: It was not until large consortia were established that genome-wide association studies of major depressive disorder (MDD) were able to identify significant variants. However, given the nature of MDD, these studies often have considerable heterogeneity, partly due to various symptom clusters that can be labelled as MDD. Research suggests that focusing on one symptom cluster of MDD may reduce this heterogeneity and allow for smaller sample sizes for genetic studies. Sleep disturbances, mainly insomnia and hypersomnia affect 25-88% of depressed individuals and lead to poorer patient outcomes, including increased suicide risk. Both animal and human studies have shown that sleep is largely controlled by circadian rhythms, which, at the cellular level are regulated by a set of circadian genes. More recently, mitochondria have been suggested to be involved in sleep due to their well-known role in energy metabolism. However, prior to the work in this thesis, there were only a handful of candidate gene studies in sleep and depression, all of which focused on circadian genes. Therefore, the overall goal of this thesis was to extend upon previous work by using state-of-the-art analytical approaches to examine the role of common genetic variants in sleep disturbances among depressed individuals. This thesis is divided into four independent projects. Chapter 3 reviewed mitochondria’s involvement in sleep in the literature. Chapter 4 focused on identifying common variants associated with self-reported problematic sleep in depressed individuals. Chapter 5 examined the genetic overlap between insomnia and hypersomnia in the general population and depressed individuals. Chapter 6 investigated the involvement of common variants from both the autosomal genome and mitochondrial DNA in objectively-derived sleep measures in depressed individuals. Altogether, these studies suggest the involvement of common genetic variants in sleep measures in depressed individuals, thereby suggesting that their sleep disturbances are genetically determined. This work sheds light on novel variants that may be used in the future to improve diagnosis and treatment regimens.
Source: TSpace (University of Toronto)
Author: Melhuish Beaupre, Lindsay
Language: English
Topic: Sleep and related disorders
Subfield: Experimental and Cognitive Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: green
OpenAlex ID: W7133074868