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. Smooth pursuit eye movement abnormality (SPEM) is observed in about 40% of schizophrenic patients and a proportion of their non-ill, first-degree biological relatives. The latter suggests that the SPEM deficit marks schizophrenia liability. The goal of the current application is to identify the specific neurocognitive mechanisms underlying the SPEM phenotype in schizophrenia. A specific physiological deficit is likely to be more proximal to the effects of genes, and therefore more accurate in identifying a homogenous subgroup of individuals with schizophrenia liability. This work has significance for use of the refined phenotype in molecular genetic and pathophysiologic studies of schizophrenia. We will test patients with schizophrenia, their 1st degree relatives who show other evidence of schizophrenia liability (i.e., schizophrenia spectrum personality (SSP) symptoms, SSP), and community subjects with no family history of psychotic illness. The study will be carried in out in two phases. In the initial phase we will test groups of 5-10 subjects from each diagnostic category in order to insure that newly designed tasks and equipment are working properly. Once the pilot testing is completed, we will recruit 30 subjects with schizophrenia, 30 1st degree relatives with SSP, 60 healthy, community subjects with no family history of schizophrenia (30 of whom exhibit SSP symptoms in the absence of a family history of psychotic illness). A battery of cognitive, motion perception and eye movement tasks will be administered in these subjects. Some of the testing will be carried out in Dr. Turano's laboratory at Johns Hopkins. Standard non-invasive methods are used for all testing.
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