A bioinformatic study revealed serotonergic neurons are involved in the etiology and therapygenetics of anxiety disorders

Abstract

Abstract Genetic factors contribute to the susceptibility of anxiety disorders (ADs) and responses to associated cognitive-behavioral therapy (CBT). However, the type of brain cell affected by the related genes remains unclear. Previous studies have indicated various important brain neurons associated with psychiatric disorders, highlighting the necessity to study the cellular basis of anxiety. We assembled 37 AD-related genes and 23 CBT-related genes from recent large-scale genome-wide association studies, and then investigated their cell-type specificity in single-cell transcriptome data via an expression weighted cell type enrichment method. Additionally, to investigate the cellular differences between ADs and other psychiatric disorders, we excluded the genes associated with major depressive disorder, bipolar disorder, and neuroticism, resulting in 29 AD-specific genes. Remarkably, results indicate that serotonergic neurons are significantly associated with both AD-related and CBT-related genes, despite the two gene sets showing no overlap. These observations provide evidence that serotonergic neurons are involved in the etiology and therapygenetics of ADs. Moreover, results also showed that serotonergic neurons are associated with AD-specific genes, providing a supplementary finding that is in opposition to previous studies that found no evidence for the association between serotonergic neurons and psychiatric disorders via the same strategy. In summary, the current study found that serotonergic neurons are involved in the etiology and therapygenetics of ADs, providing insights into their genetic and cellular basis. Further, this cellular difference study may deepen our understanding of ADs and other psychiatric disorders.