Study identifies 19 genes that could increase the risk of depression

A Spanish study has identified 19 genes that could increase the risk of depression, anxiety, and traits such as irritability and neuroticism. The research was conducted by the University of Barcelona (UB) and published in the journal Progress in Neuro-Psychopharmacology and Biological Psychiatry. According to the university's statement released this Friday, these genes are regulated by the gene RBFOX1, which acts as a "conductor of an orchestra" within a genetic network, coordinating when and how different brain-related genes are activated or processed. The findings are particularly significant for complex psychiatric disorders because conditions like depression, anxiety, and neuroticism typically do not depend on a single gene but rather on small cumulative effects of hundreds or thousands of genes. Researchers Bru Cormand and Noèlia Fernández, who coordinated the study, explained that if a central regulator like RBFOX1 is altered, it could have a cascading effect on multiple processes simultaneously, such as neuronal development, communication between neurons, and neurotransmission regulation. This might explain why these disorders often occur together. In addition to researchers from the University of Barcelona, the study included scientists from the Goethe University of Frankfurt in Germany. During their investigation, they identified 19 genes regulated by RBFOX1 that appear especially relevant to depression and other traits commonly found in patients. Among these, the researchers highlighted RBFOX1 as a central node, along with three other genes, SP4, TCF4, and PAX6—that regulate the expression of other genes, as well as CADM2. These genes have been linked to various disorders beyond depression. For instance, RBFOX1 is associated with several psychiatric disorders, while CADM2 is connected to addictions and other mental health issues. TCF4 has been linked to schizophrenia and insomnia, and both SP4 and PAX6 have been found altered in mouse models subjected to stress. The results enhance understanding of the biological mechanisms involved in depression and related disorders. In the future, they could help identify risk biomarkers, improve patient stratification, and develop new treatments targeting specific molecular pathways. Researchers suggest that intervening in shared mechanisms could benefit multiple disorders that frequently co-occur in patients. Despite the importance of these findings, the researchers emphasized the need to validate them in other samples and explore differences between men and women, given the higher prevalence of depression among women, according to previous studies. They noted that further research is necessary to confirm the implications of these genetic associations and to understand how they might vary across populations. The study contributes to ongoing efforts to uncover the genetic underpinnings of mental health conditions, offering potential avenues for more personalized approaches to diagnosis and treatment. It underscores the complexity of psychiatric disorders and highlights the role of genetic regulators in shaping susceptibility to these conditions. Researchers plan to continue investigating the functional roles of these genes and their interactions in larger and more diverse cohorts.