Patterns of Cilia Gene Dysregulations in Major Psychiatric Disorders

Authors

Wedad Alhassen, University of California, Irvine
Siwei Chen, University of California, Irvine
Marquis Vawter, University of California, Irvine
Brianna Kay Robbins, University of California, Irvine
Henry Nguyen, University of California, Irvine
Thant Nyi Myint, University of California, Irvine
Yumiko Saito, Hiroshima University
Anton Schulmann, Howard Hughes Medical Institute
Surya M. Nauli, Chapman UniversityFollow
Olivier Civelli, University of California, Irvine
Pierre Baldi, University of California, Irvine
Amal Alachkar, University of California, Irvine

Document Type

Article

Publication Date

1-27-2021

Abstract

Primary cilia function as cells' antennas to detect and transduce external stimuli and play crucial roles in cell signaling and communication. The vast majority of cilia genes that are causally linked with ciliopathies are also associated with neurological deficits, such as cognitive impairments. Yet, the roles of cilia dysfunctions in the pathogenesis of psychiatric disorders have not been studied. Our aim is to identify patterns of cilia gene dysregulation in the four major psychiatric disorders: schizophrenia (SCZ), autism spectrum disorder (ASD), bipolar disorder (BP), and major depressive disorder (MDD). For this purpose, we acquired differentially expressed genes (DEGs) from the largest and most recent publicly available databases. We found that 42%, 24%, 17%, and 15% of brain-expressed cilia genes were significantly differentially expressed in SCZ, ASD, BP, and MDD, respectively. Several genes exhibited cross-disorder overlap, suggesting that typical cilia signaling pathways' dysfunctions determine susceptibility to more than one psychiatric disorder or may partially underlie their pathophysiology. Our study revealed that genes encoding proteins of almost all sub-cilia structural and functional compartments were dysregulated in the four psychiatric disorders. Strikingly, the genes of 75% of cilia GPCRs and 50% of the transition zone proteins were differentially expressed in SCZ.

The present study is the first to draw associations between cilia and major psychiatric disorders, and is the first step toward understanding the role that cilia components play in their pathophysiological processes, which may lead to novel therapeutic targets for these disorders.

Comments

NOTICE: this is the author’s version of a work that was accepted for publication in Progress in Neuro-Psychopharmacology and Biological Psychiatry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Progress in Neuro-Psychopharmacology and Biological Psychiatry, volume 109, in 2021. https://doi.org/10.1016/j.pnpbp.2021.110255

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Recommended Citation

Alhassen W, Chen S, Vawter M, et al. Patterns of cilia gene dysregulations in major psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2021;109:110255. https://doi.org/10.1016/j.pnpbp.2021.110255

Copyright

Elsevier

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.