Iranian Researchers Investigate Lithium Action in Bipolar Disorder Treatment

Saturday, July 25, 2020 - 10:14
Bipolar Disorder

A group of Iranian researchers from Tarbiat Modares University and Royan Institute for Stem Cell Biology and Technology, have investigated the cellular and molecular actions of lithium in the treatment of bipolar disorder.

According to an ISCA report, bipolar disorder (formerly called manic-depressive illness or manic depression) is a mental disorder that causes unusual shifts in mood, energy, activity levels, concentration and the ability to carry out day-to-day tasks. Lithium remains the first-line treatment for bipolar disorder (BD), but patients respond to it variably.

Based on the research, which its results is available in CNS Drugs, while a myriad of studies have attributed many genes and signaling pathways to lithium responsiveness, a comprehensive study with an integrated conclusion is still lacking.

In this research, researchers aimed to present an integrated mechanism for the therapeutic actions of lithium in BD. First, a list of lithium responsiveness-associated genes (LRAGs) was collected by searching in the literature. Thereafter, gene set enrichment analysis together with gene-gene interaction network analysis was performed, in order to find the cellular and molecular events related to the LRAGs.

According to the results, gene set enrichment analyses showed that the chromosomal regions 3p26, 4p21, 5q34 and 7p13 could be novel associated loci for lithium responsiveness in BD. Also, expression pattern analysis of the LRAGs showed their enrichment in adulthood stages and different cell lineages of brain, blood and immune system.

Most of the LRAGs exhibited enriched expression in central parts of human brain, suggesting major contribution of these parts in lithium responsiveness. Beside the prediction of several biological processes and signaling pathways related to lithium responsiveness, an interaction network between these processes was constructed that was found to be regulated by a set of microRNAs.

Proteins of the network were mainly classified as transcription factors and kinases, which also highlighted the crucial role of glycogen synthase kinase 3β (GSK3β) in lithium responsiveness. The predicted cellular and molecular events in this study could be considered as mechanisms and also determinants of lithium responsiveness in BD.

Hadi Najafi and Majid Sadeghizadeh from Faculty of Biological Sciences, Tarbiat Modares University, and Mehdi Totonchi, from Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology cooperated in this research.


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