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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
7R29MH053485-03
Application #
2675286
Study Section
Clinical Neuroscience and Biological Psychopathology Review Committee (CNBP)
Project Start
1996-09-30
Project End
2001-03-31
Budget Start
1998-04-20
Budget End
1999-03-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Marsh, Laura; Rao, Vani (2002) Psychiatric complications in patients with epilepsy: a review. Epilepsy Res 49:11-33
Ford, J M; Mathalon, D H; Kalba, S et al. (2001) N1 and P300 abnormalities in patients with schizophrenia, epilepsy, and epilepsy with schizophrenialike features. Biol Psychiatry 49:848-60
Marsh, L; Sullivan, E V; Morrell, M et al. (2001) Structural brain abnormalities in patients with schizophrenia, epilepsy, and epilepsy with chronic interictal psychosis. Psychiatry Res 108:1-15
Schwartz, J M; Marsh, L (2000) The psychiatric perspectives of epilepsy. Psychosomatics 41:31-8
Ford, J M; Mathalon, D H; Marsh, L et al. (1999) P300 amplitude is related to clinical state in severely and moderately ill patients with schizophrenia. Biol Psychiatry 46:94-101
Marsh, L; Lim, K O; Hoff, A L et al. (1999) Severity of schizophrenia and magnetic resonance imaging abnormalities: a comparison of state and veterans hospital patients. Biol Psychiatry 45:49-61
Faull, K F; Rafie, R; Pascoe, N et al. (1999) N-acetylaspartic acid (NAA) and N-acetylaspartylglutamic acid (NAAG) in human ventricular, subarachnoid, and lumbar cerebrospinal fluid. Neurochem Res 24:1249-61
Pearlson, G D; Marsh, L (1999) Structural brain imaging in schizophrenia: a selective review. Biol Psychiatry 46:627-49
Marsh, L; Morrell, M J; Shear, P K et al. (1997) Cortical and hippocampal volume deficits in temporal lobe epilepsy. Epilepsia 38:576-87