Master Regulator Candidates in Bipolar Disorder: An in silico Transcriptome Analysis in Psychiatry

Abstract

Bipolar disorder (BD) is a chronic and severe psychiatric disorder characterized by episodes of mood disturbance. Literature has already used systems-biology approaches based on transcriptomic analysis to unravel the complexity of this multifactorial disorder. Thus, our study aims to identify the peripheral master regulators (MRs) involved in distinct mood states of BD compared to healthy controls, their pattern of activity, and the biological processes associated with the disorder. Five microarray transcriptomics datasets were obtained from the Gene Expression Omnibus repository. We used master regulator analysis and functional enrichment analysis to find regulators associated with BD and their biological processes. There were 51 MRs candidates identified in BD, and two main MRs (DNMT1 and DMTF1) were present in the three mood states compared to the control. The primary biological process in the three phases of the disorder was related to the inflammatory or immune system. DNMT1 is a mammalian methyltransferase responsible for the catalysis and maintenance of DNA methylation - one of the essential epigenetic changes. The DMTF1 encodes a transcription factor that contains a cyclin D-binding domain - related to the cell cycle. Finally, many biological processes, including RNA metabolism, cellular respiration, and ribosome biogenesis, were found in BD. However, the function most important in BD was the inflammatory or immune system corroborating the role of inflammation as a therapeutic target in the field of Psychiatry. The search for biomarkers with clinical application in psychiatry is hugely relevant, and our study complements the data on the pathophysiology of BD.