Reviews and Overviews The Endophenotype Concept in Psychiatry : Etymology and Strategic Intentions

Abstract

Endophenotypes, measurable compo- nents unseen by the unaided eye along the pathway between disease and distal genotype, have emerged as an important concept in the study of complex neuro- psychiatric diseases. An endophenotype may be neurophysiological, biochemical, endocrinological, neuroanatomical, cog- nitive, or neuropsychological (including configured self-report data) in nature. En- dophenotypes represent simpler clues to genetic underpinnings than the disease syndrome itself, promoting the view that psychiatric diagnoses can be decomposed or deconstructed, which can result in more straightforward—and successful— genetic analysis. However, to be most use- ful, endophenotypes for psychiatric dis- orders must meet certain criteria, includ- ing association with a candidate gene or gene region, heritability that is inferred from relative risk for the disorder in rela- tives, and disease association parameters. In addition to furthering genetic analysis, endophenotypes can clarify classification and diagnosis and foster the develop- ment of animal models. The authors dis- cuss the etymology and strategy behind the use of endophenotypes in neuropsy- chiatric research and, more generally, in research on other diseases with complex genetics