Genetically mediated brain abnormalities in schizophrenia.

Schizophrenia is a highly heritable, neurobehavioral disorder; however, the mode of inheritance is complex, and linkage findings have been difficult to replicate. Some consistent linkage findings have emerged on chromosomes 1, 6, 8, 11, 13, 15, and 22. New methods are being developed for candidate gene identification, including the use of neurobiologic phenotypes observed in relatives of persons with schizophrenia. Neuroimaging studies of relatives implicate abnormal hippocampal structure and inefficient prefrontal network functioning, probably representing mild variants of the abnormalities observed in schizophrenia. These characteristics may represent stable markers of vulnerability to schizophrenia, because they are not confounded by effects of antipsychotic drugs or psychosis. Recent studies provide evidence for a small role of the catechol-O-methyltransferase gene on 22q, and the serotonin receptor transporter gene on 17q11-q12 in the development of schizophrenia. Linking genes and brain regions or networks is an important step in identification of the pathophysiology of schizophrenia.