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CNS Drugs
Published in: CNS Drugs 5/2020

01-05-2020 | Original Research Article

Predicted Cellular and Molecular Actions of Lithium in the Treatment of Bipolar Disorder: An In Silico Study

Authors: Hadi Najafi, Mehdi Totonchi, Majid Sadeghizadeh

Published in: CNS Drugs | Issue 5/2020

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Abstract

Background

Lithium remains the first-line treatment for bipolar disorder (BD), but patients respond to it variably. 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.

Objective

We aim to present an integrated mechanism for the therapeutic actions of lithium in BD.

Methods

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.

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.

Conclusions

The predicted cellular and molecular events in this study could be considered as mechanisms and also determinants of lithium responsiveness in BD.
Appendix
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Metadata
Title
Predicted Cellular and Molecular Actions of Lithium in the Treatment of Bipolar Disorder: An In Silico Study
Authors
Hadi Najafi
Mehdi Totonchi
Majid Sadeghizadeh
Publication date
01-05-2020
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 5/2020
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.1007/s40263-020-00723-7

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