IN VIVO 31-P NMR STUDIES IN SCHIZOPHRENICS

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Clinical studies supported by animal research have implicated the dorsal prefrontal cortex in the cognitive deficits observed in schizophrenia. Physiological studies to date have demonstrated decreased frontal lobe cerebral blood flow (xenon 133) and 2-deoxyglucose uptake (positron emission tomography, PET) in some patients with schizophrenia. In contrast PET studies in autism have reported increased uptake of 2-deoxyglucose in the frontal lobes of adult autistic men. 31P NMR spectroscopy provides in vivo assessment of both high-energy phosphate and membrane metabolism directly and non-invasively facilitating longitudinal studies. Preliminary 31P NMR studies from this laboratory reveal alterations in membrane phospholipid metabolism in 8 first episode, never medicated schizophrenics that are strikingly similar to those observed with normal aging. In addition the levels of PCr have a positive correlation with the severity of positive symptoms. Similar phospholipid but different high energy phosphate findings have been observed in 5 normal IQ adult autistics. Based on these preliminary findings, this study proposes to study 30 first episode, never medicated schizophrenics at entry and at 4 weeks, 6 and 12 months and 2 years after entry into the study. Results in the 30 schizophrenics will be compared with results in controls (30 normal controls and 30 autistics) obtained at entry and at 1 and 2 years after entry. The normal IQ adult autistics are chosen as a comparison group as these autistics share many of the negative symptoms with schizophrenia, are sometimes misdiagnosed as schizophrenia but have a different age of onset and a different clinical course.