Transcriptome profiling as a biological marker for bipolar disorder sub-phenotypes

Joanna Pawlak; Aleksandra Szczepankiewicz; Maria Skibińska; Beata Narożna; Paweł Kapelski; Przemysław Zakowicz; Karolina Gattner; Dominik Spałek; Łukasz Mech; Monika Dmitrzak-Węglarz

doi:10.1016/j.advms.2024.02.002

Transcriptome profiling as a biological marker for bipolar disorder sub-phenotypes

Adv Med Sci. 2024 Feb 17;69(1):61-69. doi: 10.1016/j.advms.2024.02.002. Online ahead of print.

Affiliations

¹ Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznań, Poland.
² Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznań, Poland; Molecular and Cell Biology Unit, Poznan University of Medical Sciences, Poznań, Poland.
³ Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznań, Poland; Center for Child and Adolescent Treatment in Zabór, Zielona Góra, Poland.
⁴ Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznań, Poland; HCP Medical Center, Poznań, Poland.
⁵ Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznań, Poland; Regional Hospital for Psychiatric and Neurological Patients, Gniezno, Poland.
⁶ Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznań, Poland. Electronic address: mweglarz@ump.edu.pl.

PMID: 38368745
DOI: 10.1016/j.advms.2024.02.002

Abstract

Purpose: Bipolar affective disorder (BP) causes major functional impairment and reduced quality of life not only for patients, but also for many close relatives. We aimed to investigate mRNA levels in BP patients to find differentially expressed genes linked to specific clinical course variants; assuming that several gene expression alterations might indicate vulnerability pathways for specific course and severity of the disease.

Materials: We searched for up- and down-regulated genes comparing patients with diagnosis of BP type I (BPI) vs type II (BPII), history of suicide attempts, psychotic symptoms, predominance of manic/hypomanic episodes, and history of numerous episodes and comorbidity of substance use disorders or anxiety disorders. RNA was extracted from peripheral blood mononuclear cells and analyzed with use of microarray slides.

Results: Differentially expressed genes (DEGs) were found in all disease characteristics compared. The lowest number of DEGs were revealed when comparing BPI and BPII patients (18 genes), and the highest number when comparing patients with and without psychotic symptoms (3223 genes). Down-regulated genes identified here with the use of the DAVID database were among others linked to cell migration, defense response, and inflammatory response.

Conclusions: The most specific transcriptome profile was revealed in BP with psychotic symptoms. Differentially expressed genes in this variant include, among others, genes involved in inflammatory and immune processes. It might suggest the overlap of biological background between BP with a history of psychotic features and schizophrenia.

Keywords: Bipolar affective disorder; Clinical sub-phenotype; Transcriptome profile.