Bipolar Disorder and Ubiquitin Proteasome System Dysfunction: Peripheral Blood Levels of Molecules Playing a Role in Ubiquitination and Their Relationship to Sleep Quality.

Abstract

Background: Bipolar disorder (BD) is a serious mood disorder, notable for its morbidity and prevalence. It ranks among the top 10 diseases globally in terms of functional impairment among affected individuals. Studies investigating neurobiological processes in the development of BD also aim to identify biological markers. Ubiquitin is a protein that is abundant in all eukaryotic cells and regulates many processes through the ubiquitin-proteasome system. It has been reported to be associated with circadian rhythm and sleep disorders. Circadian rhythm plays a key role in maintaining mood stability in individuals with BD. In this study, we investigated the peripheral levels of molecules involved in the ubiquitination process and their relationship to sleep quality in individuals with BD.

Methods: Forty-nine patients with BD and 50 healthy volunteers without any psychiatric disorders were included. The Pittsburgh Sleep Quality Index, the Young Mania Rating Scale, and the Hamilton Depression Rating Scale were administered to the participants. Peripheral blood levels of proteins and enzymes that play a role in ubiquitination processes were determined by the immunosorbent assay method.

Results: TAR DNA-binding protein-43 (TDP-43) (p < 0.001), ubiquitin C-terminal hydrolase-L1 enzyme (UCH-L1) (p = 0.037), ubiquitin C-terminal hydrolase-L3 enzyme (UCH-L3) (p = 0.007), histone deacetylase I (Histone Dea-1) (p = 0.006), histone deacetylase II (Histone Dea-2) (p = 0.047), and ligase cullin-3 (p = 0.031) levels were found to be significantly lower in the BD group than in the control group, but these parameters were not associated with sleep quality scores in the BD group.

Conclusions: Our results support the data in the literature but show that the ubiquitination process can be affected in BD patients without being associated with sleep quality.