Endophenotypes and biomarkers: an approach to molecular genetic studies of mental disorders

Many precise aspects of the etiology and pathophysiology of mental disorders are still unknown. Susceptibility to these disorders depends in part on variability in the genome sequence among individuals. The genotype, a given environment, a specific epigenetic profile and stochastic factors affect the phenotype, which includes body structures, physiological processes, and behavior. Since the access to the Central Nervous System is generally difficult and in most cases there are still no biological tests that necessarily contribute to diagnosis, psychiatric phenotypes are usually limited to clinical symptoms and functioning. Therefore, researchers are currently seeking alternatives to facilitate the identification of genetic risk factors. One strategy is to identify measurable biological, cognitive, and behavioral markers, intermediate phenotypes, or endophenotypes, which in the best case may be simpler than general psychiatric diagnoses, ideally with a precise biological meaning and a more direct relationship with the action of specific genes. Endophenotypes have been very useful in other fields of medicine. Currently, there are several proposed criteria and specifications for endophenotypes. Examples of possible types of endophenotypes or biomarkers, as well as treatment response phenotypes in some psychiatric disorders will be discussed in this review.