Analysis of the Genome Sequence for the Purpose of Understanding the Causes and Treatments of Bipolar Disorder and Related Disorders

Abstract

In cases of bipolar disorder (BD), genetic factors have only been shown to contribute to a minor portion of the condition's heritability. Because of this, people have been looking into sub-phenotypes of BD, such as treatment response, in an effort to narrow the heterogeneity of BD. Using a variety of methods, the researchers in this study conducted a series of experiments with the goal of identifying molecular signatures that are related to bipolar disorder (BD), the response to lithium medication, and other subclinical traits in a cohort of individuals who have BD. First, we investigated the connection between lithium response and essential candidate genes already known to influence lithium response in other populations. In the second step of the process, a global and CpG island DNA methylation profiling was carried out with the goal of locating genomic loci that had distinct methylation patterns in lithium responders as opposed to non-responders. Third, a genome-wide copy number variation (CNV) study was done to find and describe CNVs that are linked to BD symptoms and how well lithium works. Finally, the results of an untargeted plasma metabolomic profiling showed that patients with bipolar disorder, both those who responded to lithium treatment and those who did not, had different amounts of a number of different metabolite species. The study's results support the idea that BD is most likely caused by the dynamic dysregulation of a large number of gene regulatory networks, proteins, and metabolic pathways, which is a sign of complex problems in the system.