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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH046614-03
Application #
3386427
Study Section
Psychopathology and Clinical Biology Research Review Committee (PCB)
Project Start
1990-04-01
Project End
1995-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Diwadkar, Vaibhav A; DeBellis, Michael D; Sweeney, John A et al. (2004) Abnormalities in MRI-measured signal intensity in the corpus callosum in schizophrenia. Schizophr Res 67:277-82
Keshavan, M S; Stanley, J A; Montrose, D M et al. (2003) Prefrontal membrane phospholipid metabolism of child and adolescent offspring at risk for schizophrenia or schizoaffective disorder: an in vivo 31P MRS study. Mol Psychiatry 8:316-23, 251
Keshavan, Matcheri S; Diwadkar, Vaibhav A; DeBellis, Michael et al. (2002) Development of the corpus callosum in childhood, adolescence and early adulthood. Life Sci 70:1909-22
Keshavan, M S; Diwadkar, V A; Harenski, K et al. (2002) Abnormalities of the corpus callosum in first episode, treatment naive schizophrenia. J Neurol Neurosurg Psychiatry 72:757-60
Yao, Jeffrey k; Stanley, Jeffrey A; Reddy, Ravinder D et al. (2002) Correlations between peripheral polyunsaturated fatty acid content and in vivo membrane phospholipid metabolites. Biol Psychiatry 52:823-30
Keshavan, M S; Haas, G L; Kahn, C E et al. (1998) Superior temporal gyrus and the course of early schizophrenia: progressive, static, or reversible? J Psychiatr Res 32:161-7
Keshavan, M S; Pettegrew, J W; Reynolds 3rd, C F et al. (1995) Biological correlates of slow wave sleep deficits in functional psychoses: 31P-magnetic resonance spectroscopy. Psychiatry Res 57:91-100
Keshavan, M S; Miewald, J; Haas, G et al. (1995) Slow-wave sleep and symptomatology in schizophrenia and related psychotic disorders. J Psychiatr Res 29:303-14
Minshew, N J; Goldstein, G; Dombrowski, S M et al. (1993) A preliminary 31P MRS study of autism: evidence for undersynthesis and increased degradation of brain membranes. Biol Psychiatry 33:762-73