Ocular motor abnormalities frequently occur among schizophrenics and their first-degree biological relatives. It also appears that some as yet unidentified aspect of ocular motor dysfunction is specific to schizophrenia among psychiatric patients. furthermore, the results of family studies suggest that ocular motor dysfunction may be a marker variable of genetic liability for this disorder. An important feature of ocular motor functioning as a potential marker variable of liability for schizophrenia is knowledge of its neural circuitry. Particular patterns of ocular motor response are associated with pathology in particular brain regions. Identifying ocular motor abnormalities that are specific to schizophrenics (among psychiatric patients) and their first-degree biological relatives could serve two functions simultaneously: (1) clarification of schizophrenia's neuropathology, and (2) providing a sensitive liability indicator which could be a useful adjunct to clinical diagnoses in subsequent linkage studies. The main purposes of the present project are to (1) identify schizophrenia- specific ocular motor abnormalities using neuro-ophthalmological measurement techniques; (2) clarify the relationship between ocular motor abnormalities and structural brain abnormalities observed among schizophrenics; and (3) identify those specific ocular motor abnormalities which also occur with high frequency among schizophrenics' first-degree biological relatives. Measures of visual fixation, smooth pursuit, and saccadic performance will be obtained from schizophrenic, affective disordered, and non-psychiatric comparison subjects. We will first investigate basic issues concerning which brain areas (vestibulocerebellum, brainstem, cortical and subcortical hemispheric structures) could be involved in schizophrenics' ocular motor dysfunction. The pattern of observed abnormalities will be fully characterized, and we will determine which measures maximally distinguish schizophrenics from other subjects. Those ocular motor abnormalities which are specific to schizophrenia will be correlated with quantified magnetic resonance images to evaluate the relationship between functional and structural measures of neuropathology among such patients. We will also attempt to determine whether these ocular motor abnormalities may be a consequence of having the disease or are associated with a neurobiological predisposition for this illness by studying schizophrenics' first-degree biological relatives. Research projects such as this may be necessary to help clarify the neuropathology and genetics of schizophrenia.
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