EPILEPSY AS A NEUROLOGICAL MODEL OF SCHIZOPHRENIA

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Neuroanatomical abnormalities reported in idiopathic schizophrenia (ISZ) include evidence for focal as well as global nonspecific neuropathology. These abnormalities are often subtle and it is uncertain which are specific to pathogenesis and clinical symptoms. Comparison of patients with epilepsy who share analogous symptoms with ISZ enables identification of converging brain abnormalities which may be specific to the schizophrenic syndrome. Though seizures are not a feature of ISZ, the two conditions have commonalities: schizophrenia-like states occur in ictal, post-ictal, or interictal phases of epilepsy and medial temporal, neurodevelopmental, and eletrophysiological abnormalities are implicated in each. While ictal and post-ictal psychosis are related to discrete eletrophysiological events, interictal schizophrenia-like illness may represent additional brain disease, i.e., structural pathology, not related to seizure generation. In particular, the associated neuropathology should be over and above that seen in epilepsy without ISZ-like symptoms. Using clinical assessments and quantitative MRI and EEG methods, the broad research objectives of this project are to identify converging clinical, neuroanatomical, and electrophysiological features, and clinicopathological relationships in ISZ as compared to epilepsy with interictal schizophrenia-like symptoms(ESZ) and localization-related epilepsy of unilateral temporal lobe origin (TLE) withour interictal psychosis. Healthy controls will provide normative MRI data. Such knowledge will help establish the location, specificity, and pathophysiological significance of abnormalities in ISZ and further direct studies of regional neuropathology and brain dysfunction in ISZ to focus on areas of etiologic significance. The specific aims are to test whether (1) ISZ and ESZ share a common profile of positive symptoms (hallucinations, delusions, and thought disorder) and negative symptoms (e.g., flat affect and amotivation); (2) ISZ and ESZ share a profile of predominant frontal and temporal lobe neocortical structural abnormalities, whereas TLE shows hippocampas and neocortical deficits predominantly in the epileptogenic temporal lobe; (3) ISZ and ESZ show more background EEG slowing, especially in frontal and temporal regions, relative to TLE in which focal slowing is concordant with the seizure focus. Epileptiform discharges (ED) are most abundant and multifocal in ESZ, less frequent and concordant with the seizure focus in TLE, and rare in ISZ; and, (4) Positive and negative symptoms are related to MRI and EEG abnormalities in neocortical temporal and frontal lobes, respectively. EEG slowing and ED are associated with tissue abnormalities in corresponding electrical fields.