Neuroanatomical abnormalities reported in schizophrenia include evidence for focal dysmorphology 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 neurological disorders who share symptoms with schizophrenia enables identification of converging brain abnormalities which may be specific to the schizophrenic syndrome, rather than epiphenomena. Epilepsy is a candidate disorder for such a study. Though seizures are not a feature of schizophrenia, the two conditions have commonalities: schizophrenia-like syndromes can occur in ictal, post-ictal, and interictal phases of epilepsy, and medial temporal lobe and neurodevelopmental pathology are implicated in each. While ictal and post-ictal psychosis are related to recurrent electrophysiological events, occurrence of interictal schizophrenia-like illness may represent additional brain disease, i.e., structural pathology, not related to seizure generation. In particular, the associated brain dysmorphology should be over and above that seen in epilepsy without schizophrenic symptoms. Establishment of the location, specificity, and pathophysiological significance of abnormalities in schizophrenic syndromes will further direct studies of regional neuropathology and brain dysfunction in schizophrenia to focus on areas of etiologic significance. This proposal attempts to identify, with clinical assessments and MRI, converging clinical and neuroanatomical features, and clinicopathological relationships in idiopathic schizophrenia (ISZ) as compared to two subgroups of epilepsy patients: 1) ESZ, and 2) Localization-related epilepsy of unilateral temporal lobe origin (TLE) without interictal psychosis. Healthy controls will provide normative MRI data. The following hypotheses will be tested: Hypothesis 1: ESZ and ISZ will demonstrate similar profiles of positive symptoms (hallucinations, delusions, and thought disorder) and negative symptoms (e.g., motivation and flat affect), but positive symptom severity will be greater in ESZ due to their relatively increased temporolimbic dysfunction because of epilepsy. Hypothesis 2: ISZ and ESZ share a profile of widespread neocortical gray matter deficits, particularly in the temporal and frontal lobes, but ESZ has more extreme cortical dysmorphology as well as medial temporal abnormalities. TLE is characterized by hippocampal volume deficits ipsilateral to the origin of the seizure focus and by widespread neocortical gray matter deficits which are most pronounced in the epileptogenic temporal lobe. Hypothesis 3: Positive symptoms in ISZ and ESZ are related to neocortical temporal lobe MRI abnormalities; negative symptoms in ISZ and ESZ are correlated with frontal lobe abnormalities.
