Endophenotypes in Psychiatry

The concept of genotype provides information about the DNA structure of an organism. The concept of phenotype, however, is the view of this organism that appears upon the interaction of the genotype and environmental conditions. While a research is made on diseases, their phenotypes are analyzed so that it will be possible to make interpretations on diagnosis, treatment and preventive factors based on genetic factors and environmental conditions.

In a report the published in 1996, John and Lewis used the term “endophenotype” for the very first time, and they defined this term as “microscopic and intrinsic, not visible or extrinsic”. In psychiatry, the interaction of genetic and environmental factors was started to be analyzed in 1965 for the purpose of understanding schizophrenia, and the term “endophenotype in psychiatry” was used in 1973. The symptoms in psychiatry are analyzed over the interaction of the brain parts and neurochemicals with environmental stimulants.

Thanks to endophenotypes, the disorder can be explained by simpler factors, not through intertwined interactions. These factors are the genetic and observable characteristics of the symptoms; they can be neuroanatomic, neurophysiologic, emotional, motivational, cognitive or simple reactions. Endophenotype is a concept that is similar to the biological signs showing the tendency to the disease; its difference can only be spotted through neurogenetic analysis as it is based on evolutionary history.

To say it’s an endophenotype, the symptoms appearing genetically must be peculiar to the disorder, have continuity (not conditional) and have rate of prevalence in the family compared to genetic transmission and other members of the society.

The tendency towards a disorder can be spotted by the number of genes in phenotypes thanks to endophenotypes. In other words, it is possible to carry out a genetic analysis. Endophenotype is explained on a number line, not in the form of “available” or “not available” like the phenotypes. The genetic analysis may become complicated based on the number of genes in phenotype. Low numbers of disease genes present in the phenotype decrease the complexity of the genetic analysis. High numbers of genes present in the phenotype increase the complexity of the genetic analysis.

Studies concerning the characterization of endophenotypes in psychiatric disorders are currently not successful enough. Nevertheless, the studies carried out over the description of endophenotypes in schizophrenia have increased in numbers.

In short, a disorder, in other words, a syndrome like schizophrenia, etc. occurs by the effects of various genes. Revealing the genetic nature of the disorder can become difficult in situations like this. It is aimed to divide the disorder into symptoms and to analyze the genetic infrastructure of each symptom, instead of taking the disorder into consideration as a whole. Thus, the endophenotype of the disorder can be comprehended. For instance, if the increase in frontal alpha occurs on a genetic basis in depression, then this is an endophenotype. If frontal alpha is spotted in close relatives, especially in siblings, the analysis becomes deeper to determine that. When the gene taking a part here is understood, a pattern regarding the endophenotype can be understood.