This large ongoing study at NIMH investigates the neurobiology of schizophrenia by identifying susceptibility genes, evaluating their impact on brain function to better understand how to treat and prevent this illness.

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, their biological siblings and their parents will be recruited through families of current or former patients at NIMH and physician and community organization referrals, The National Alliance for the Mentally Ill (NAMI), and other sources both locally and nationally.

To be eligible for this research study, patients must be between the ages of 18 and 55 and have a diagnosis of schizophrenia, schizoaffective disorder, psychosis N.O.S., or schizophreniform disorder.

To be eligible for this research study, siblings should be between 18 and 55, and have no major medical problems that may affect their brain including mental retardation or suffering from organic brain damage or neurological disease and have no significant history of alcoholism or substance abuse. Siblings that do not qualify for the 2-day or 1-day study, they may participate in the limited phenotyping arm or be included in as part of a trio (one parent, one sibling, one patient). All parents are eligible for the study.

To be eligible for this research study, healthy volunteers must be between the ages of 18 and 55. They will not be eligible if they have history of major medical problems that may affect their brain or if they have abused illicit drugs or alcohol for a significant amount of time. They may not be eligible for the extended part of the study if they have a first-degree relative with history of schizophrenia spectrum disorders. However, they may be included in the case control analyses and the limited phenotyping arm.

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 2-day or 1-day study