CIRCULATING REELIN AND PSYCHOSIS VULNERABILITY

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DESCRIPTION: (Adapted from applicant's abstract) Reelin is a large secreted glycoprotein which plays a critical role in development of laminated structures within the brain, and which is expressed in adult brain as well. Reelin expression is decreased about50 percent in multiple regions of post-mortem brains of patients with schizophrenia and bipolar illness. Reeler heterozygous mutant mice, which express reelin within the brain at 50 percent of wild-type levels, exhibit discrete neuroanatomical and behavioral abnormalities including loss of prepulse inhibition of startle, a trait characteristic of psychosis. These findings suggest that reelin deficits similar in magnitude to those seen in psychosis can affect normal brain function, and that reelin abnormalities in psychotics may precede their illness and render their brains more vulnerable to pathogenetic factors that cause psychosis. The investigators have recently discovered that reelin is expressed in the serum and plasma in mice, rats and humans, which raises the exciting possibility that reelin abnormalities may be detectable in living humans even prior to the onset of symptoms, allowing one to follow the early course of psychosis and to begin early interventions. In order to assess the value of measuring circulating reelin levels as an indicator of schizophrenic vulnerability, the investigators propose to: 1. Establish a quantitative competitive RIA for measuring reelin in plasma. And 2. Raise monoclonal antibodies that recognize the mid- and C-terminal domains of reelin. These studies will not only set the stage for studies of human populations with (or at risk of) schizophrenia, but will have broader implications for investigating the potential utility of measuring CSF and circulating reelin in other neurological and psychiatric diseases, as well as for base issues regarding the physiologic role(s) of reelin in the periphery.