GATA1: a novel target for gene therapy in major depressive disorder

Abstract

Major depressive disorder is the most common psychiatric disorder in the world, affecting 350 million people worldwide. According to the World Health Organization (WHO), it is expected to become the second greatest cause of illness by 2020. For individuals in the age group of 15-44 years, major depression is already considered as the first cause of disease in the 2012 WHO survey. Thus, as the social burden continues to increase worldwide, the need to study the causes and treatment of major depression has been rapidly growing. Due to the limited efficacy of chemical-based antidepressants, which have been used for the treatment of major depression, new antidepressants and gene targeting therapies are garnering more attention in treatment of major depressive disorder. To identify the genes responsible for major depressive disorder, many gene-profiling studies have been performed on various regions of postmortem human brains with major depression and compared to control brains. In this review, it is examined gene expression changes in the prefrontal cortex of patients with major depression compared to that in the normal population using high throughput analysis and bioinformatics. It is also discussed how this altered gene expression can contribute to structural and functional losses in the brain of patients with major depression. In the concluding part, it is considered the possibility that GATA1 - a newly identified transcriptional repressor for synapse-related genes under stressed condition, which induced depressive behavior by high copy expression in the dorsolateral prefrontal cortex of rodents - can be developed as a new therapeutic target for major depressive disorder.