Putative structural neuroimaging endophenotypes in schizophrenia: a comprehensive review of the current evidence

Abstract

The genetic contribution to schizophrenia etiopathogenesis is underscored by the fact that the best predictor of developing schizophrenia is having an affected first-degree relative, which increases lifetime risk by tenfold, as well as the observation that when both parents are affected, the risk of schizophrenia increases to approximately 50%, compared with 1% in the general population. The search to elucidate the complex genetic architecture of schizophrenia has employed various approaches, including twin and family studies to examine co-aggregation of brain abnormalities, studies on genetic linkage and studies using genome-wide association to identify genetic variations associated with schizophrenia. ‘Endophenotypes’, or ‘intermediate phenotypes’, are potentially narrower constructs of genetic risk. Hypothetically, they are intermediate in the pathway between genetic variation and clinical phenotypes and can supposedly be implemented to assist in the identification of genetic diathesis for schizophrenia and, possibly, in redefining clinical phenomenology.