In the proposed Schizophrenia Premorbid Endophenotype study we plan to investigate the suitability of premorbid general intellectual ability ('g') and social functioning measures to serve as endophenotypes for genetic studies in schizophrenia. For the purpose of the proposed study we will link data from the Israeli Draft Board Sibling Registry and the National Psychiatric Registly, identifying all sib-pairs discordant for schizophrenia, who had abnormal premorbid 'g' and/or social functioning. We will recruit nuclear families with an affected proband who exhibit either abnormal 'g' or abnormal social functioning (at least 2 SD below population mean). We will also enroll a random sample of healthy individuals. We will obtain Draft Board cognitive and behavioral data and conduct face-to-face diagnostic interviews and neuropsychological assessment in probands, their family members and in controls to verify the diagnosis and collect additional data. Blood samples will also be collected, and DNA extracts will be stored, and added to the NIMH genetic initiative. The strengths of the study include its size and complete ascertainment, as well as the use of a well-defined phenotype with high heritability, and known association to schizophrenia ('g' and social functioning). In addition, using premorbid data to define the phenotype will protect against bias induced by the active manifestations of the illness or circumstances related to the illness such as treatment, stigma or the awareness of having an ill first-degree relative. Finally, the phenotype can be expended and refined since the Draft Board database includes additional measures shown to be associated with risk for schizophrenia (e.g., language abnormalities, measures of physical activity and individual autonomy).
The aims are to assess the heritability and mode of inheritance of 'g' and social functioning. The blood samples collected will lay groundwork for further genetic analysis.
