Eye tracking abnormalities seem to be the most robust and sensitive (55-85%) psychobiological marker for schizophrenia. Although they are being used widely in high risk and genetic studies, their basic methodological underpinnings and validity as a marker for schizophrenia are not well established. The purposes of this study are to: 1) identify specific components of oculomotor functioning that are deviant; 2) establish diagnostic specificity; 3) assess stability over time; 4) evaluate effects of neuroleptics; and 5) determine clinical and neuroanatomic correlates of tracking deficits. To develop the eye tracking methodology and establish its validity, we will undertake studies with the following aims: 1) to precisely characterize the parameters of oculomotor deficits in schizophrenia we will use computer analysis of infrared eye movement recordings to replicate and extend previous findings of abnormalities in pursuit gain and the saccadic eye movement system; 2) to assess diagnostic specificity we will compare the performance characteristics of the test with schizophrenics, bipolars, psychotic unipolars, nonpsychotic unipolars, and normal controls; 3) to evaluate stability over time, we will test patients at admission, at weeks 2 & 4 of hospitalization, and at 6 month followup; 4) to assess neuroleptic effects, we will test unmedicated patients at hospitalization, and compare outpatient schizophrenics after 2 years of randomly assigned high, low or intermittent dose fluphenazine with known blood levels. An unmedicated subset of stabilized outpatients will be followed longitudinally; 5) to characterize patients with tracking deficits, we will assess relationships between tracking performance and premorbid adjustment, ventricular enlargement, thought disorder (TDI), positive and negative symptoms, and cognitive deficits. This investigation will be the first systematic assessment of eye tracking impairment in schizophrenia. It will allow us to learn about its sensitivity, stability and diagnostic specificity, and thereby develop the methodology and ascertain the degree to which tracking impairment has certain necessary characteristics of a valid psychobiologic/genetic marker.
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