Schizophrenia is a complex genetic disorder which likely involves many genes each producing a slight increase in risk. Finding weak acting genes in complex gentic disorders has been challenging and will likely require a number of approaches and large clinical samples. Several strategies have emerged recently that appear to markedly improve the power of genetic studies for detecting such genes. These include using association (rather than linkage) and using intermediate phenotypes in addition to DMS-IV diagnosis. We propose to take advantage of these techniques by studying quantitative traits related to schizophrenia in patients, siblings, and controls. We will employ an association design, rather than linkage. Traits will include quantifiable neurobiological variables that have been implicated previously as possible phenotypes related to schizophrenia. These include tests of attention and cognition, eye tracking, evoked potentials and a variety of parameters using brain imaging. We will use several statistical methods to show that specific genetic polymorphisms affect these phenotypes, including case control and family based association studies.

• INCLUSION CRITERIA

Patients with schizophrenia and their siblings will be recruited through families of current or former patients at NIMH, physician referrals, The National Alliance for the Mentally Ill (NAMI), Chestnut Lodge Hospital, St. Elizabeth's Hospital, and other sources both locally and nationally.

Subjects will range in age from 18-65 years.

The affected siblings must have evidence of a diagnosis of schizophrenia, schizo-affective disorder, psychosis N.O.S., or schizophreniform disorder as determined by a preliminary screen of records and treating therapists' reports.

EXCLUSION CRITERIA

Persons who are mentally retarded, who suffer from organic brain damage, neurological disease, or have a significant history of alcoholism or substance abuse will not be included in the extensive phenotyping arm.