Bipolar disorder (BPD) is a mood disorder caused by the interaction among a large number of genes and the environment. Recently, with the improvement of genome analysis techniques and the introduction of Genome Wide Association Studies (GWAS), the investigation of the genetic causes of BPD has moved several steps forward, allowing the confirmation of previous results and the identification of new genes involved in the pathogenesis of the disorder. Furthermore, in the last few years, several studies focused on the investigation of rare genetic variants, copy number variants (CNV) and epigenetic modifications, leading to a more complete knowledge of the picture. The aim of the present review is to give to the reader a comprehensive view of the current knowledge about the genetics of BPD, focusing on the most investigated genes and their biological function in the context of the more accepted theories about the pathogenesis of the disorder.
Most confirmed liability genes are involved in the serotoninergic, glutamatergic, GABAergic and circadian systems. In particular, a large amount of evidence was found for glutamatergic NMDA and Kainate receptors and some genes of the glutamate cycle, which are thought to be involved in a possible neurotoxic effect on neurotransmission. Other relevant genes are CLOCK, ARNTL and PER3 which may increase the risk of disease by altering circadian rhythms, through the modulation of the serotonin system.
In conclusion, it is still not possible to determine the exact genetic basis of BPD, because several genes are likely to be involved in the pathogenesis of the disorder, as well as environmental factors. Nonetheless, thanks to recent technological advantages, several steps forward have been made, allowing the identification of the main systems involved in the genesis of BPD. Through further technological improvement and the use of specific endophenotypes, more related to genetic and epigenetic variants compared to BPD itself, in the next few years the identification of the exact genetic basis of BPD might be an achievable aim for psychiatric research.
Keywords: bipolar disorder, genetics, epigenetics, endophenotypes