Patterns of cilia gene dysregulations in major psychiatric disorders

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.