THE GENETICS OF ENDOPHENOTYPES AND SCHIZOPHRENIA

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this research is to learn more about the genetic transmission of schizophrenia by attempting to identify how specific sub-clinical phenomena associated with the disorder, commonly referred to as the endophenotype, may run in families of a schizophrenic proband. A number of different studies have shown various neurophysiological and neurocognitive deficits to be associated with schizophrenia. Neurophysiological deficits include abnormal event related potentials, inhibited startle response and eye movements. Neurocognitive deficits include poor performance on both verbal and working memory. These same deficits are in seen in unaffected relatives of schizophrenics, which indicated that they might reflect part of the heritable risk for the illness. This conclusion is reinforced by findings of the deficits in non-psychotic, unmedicated schizophrenics and schizotypals. This study will recruit families with at least one member who has schizophrenia. Trained raters will then conduct a family history interview using the Family Interview for Genetic Studies (FIGS). We will also interview each family member individually using the Diagnostic Interview for Genetic Studies (DIGS) to assess for the presence or absence of psychiatric disorders. Once a diagnosis of schizophrenia is confirmed for at least one member of the family, we then conduct the following noninvasive, minimal risk protocol on all members of the family. There are three neurophysiological and three neurocognitive assessments included in this battery. The neurophysiological assessments measure deficits in response to various auditory and visual stimuli. The three neurocognitive assessments measure deficits in eye tracking, verbal memory and working memory. We will also collect blood samples from each participating family member, which will be used for DNA extraction and genetic analysis. Our collaborative team is composed of investigators at seven sites. Within a time period of five years, the combined sites will recruit 1680 subjects affected with DSM-IV schizophrenia and 525 normal subjects. All sites will recruit the subjects from large regional health care systems and/or large metropolitan hospitals. Findings of heritable deficits in specific measures will be used to guide further studies of schizophrenia genetics.