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 deficits. 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 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.

初级纤毛作为细胞的天线来检测和转导外部刺激，并在细胞信号传导和通信中发挥关键作用。绝大多数与纤毛病有因果关系的纤毛基因也与神经功能缺陷有关，例如认知缺陷。然而，纤毛功能障碍在精神疾病发病机制中的作用尚未得到研究。我们的目标是确定四种主要精神疾病中纤毛基因失调的模式：精神分裂症 (SCZ)、自闭症谱系障碍 (ASD)、双相情感障碍 (BP) 和重度抑郁症 (MDD)。为此，我们从最大和最新的公开数据库中获取了差异表达基因 (DEG)。我们发现 42%、24%、17% 和 15% 的脑纤毛基因在 SCZ 中有显着差异表达，分别为 ASD、BP 和 MDD。几个基因表现出交叉疾病重叠，表明典型纤毛信号通路的功能障碍决定了对不止一种精神疾病的易感性，或者可能部分成为其病理生理学的基础。我们的研究表明，编码几乎所有纤毛下结构和功能区室的蛋白质的基因在四种精神疾病中都存在失调。引人注目的是，75% 的纤毛 GPCR 和 50% 的过渡区蛋白的基因在 SCZ 中差异表达。我们的研究表明，编码几乎所有纤毛下结构和功能区室的蛋白质的基因在四种精神疾病中都存在失调。引人注目的是，75% 的纤毛 GPCR 和 50% 的过渡区蛋白的基因在 SCZ 中差异表达。我们的研究表明，编码几乎所有纤毛下结构和功能区室的蛋白质的基因在四种精神疾病中都存在失调。引人注目的是，75% 的纤毛 GPCR 和 50% 的过渡区蛋白的基因在 SCZ 中差异表达。

本研究首次发现纤毛与主要精神疾病之间的关联，并且是了解纤毛成分在其病理生理过程中所起作用的第一步，这可能会导致这些疾病的新治疗靶点。