Time for a shift in focus in schizophrenia: from narrow phenotypes to broad endophenotypes.

Many manifestations of mental illness, risk factors, course and even response to treatment are shared by several diagnostic groups. For example, cognitive and social impairments are present to some degree in most DSM and ICD diagnostic groups. The idea that diagnostic boundaries of mental illness, including schizophrenia, have to be redefined is reinforced by recent findings indicating that on the one hand multiple genetic factors, each exerting a small effect, come together to manifest as schizophrenia, and on the other hand, depending on interaction with the environment, the same genetic variations can present as diverse clinical phenotypes. Rather than attempting to find a unitary biological explanation for a DSM construct of schizophrenia, it would be reasonable to deconstruct it into the most basic manifestations, some of which are common with other DSM constructs, such as cognitive or social impairment, and then investigate the biological substrate of these manifestations.