The use of intermediate phenotypes to reveal disease mechanism depends on the assumption that a complex phenotype, such as schizophrenia, addiction or depression, can be broken down into a series of simpler component units. These intermediate phenotypes are thought to be more biologically coherent than the primary disease phenotype; that is, disease classification is derived from clinical needs, primarily reproducibility, whereas intermediate phenotypes arise from neuroscience research. In this sense, the use of intermediate phenotypes reduces to the challenge to understand the biology of brain mechanisms as it relates to disease. There are two ways in which the biological coherence of an intermediate phenotype is critical for its use.
