Application of Endophenotype Approach in Psychiatric Research

The identification of genes that contribute to a susceptibility to psychiatric disorders has been elusive using conventional genetic approaches. One problem to gene finding is that we cannot identify carriers of genes in the absence of manifest symptoms. Also, psychiatric diagnoses are likely to be heterogeneous in that not all people with the same diagnosis carry the same susceptibility genes. A new direction that appears encouraging is the identification of neurobiological or neurobehavioral characteristics associated with schizophrenia, or endophenotypes, that may be more closely linked to gene expression. Endophenotypes are internal phenotypes discovered by a biochemical test or microscopic examination, they are not the obvious and external but the microscopic and internal, endophenotypes are more approach the biological basis than the external manifestations, less affected by other factors, so it has obvious advantages in studying the genetics of psychiatric disease. And the present diagnostic and classification systems are based on clinical manifestations and behavioral descriptions, lack of biological basis, the endophenotype approach is of great importance in establishing the neurobiological basis of diagnostic and classification systems. Endophenotypes can be neurophysiologic, biochemical, neuroanatomical, cognitive, and neuropsychological measures. To be an endophenotype, it must fulfill some criteria: associate with the disease, heritable, stable or state-independent, cosegragate in the family, endophenotypes should have a higher rate in nonpsychotic relatives than in general population. The paper introduced the concept of endophenotype, illustrated its rational, advantages and usefulness, and the criteria that must be fulfilled, then take three common psychiatric diseases as examples to demonstrate the research development of endophenotypes, e.g., response inhibition and working memory as endophenotypes of attention deficit/hyperactivity disorder, attention, verbal memory and working memory as endophenotypes of schizophrenia and depression. At last, it points out the future directions of endophenotype research.