N-acetylaspartate (NAA) is a neuronal and axonal marker detectable by in-vivo proton magnetic resonance spectroscopy (1H MRS). NAA alterations appear to be sensitive to both neuronal dysfunction as well as neuronal loss. Previous 1H MRS studies have noted decreased NAA in the frontal and temporal lobes in schizophrenia. However, due to prior constraints in MRS methodology, these studies have been unable to provide NAA measures that are specific to regional gray matter. Such information is crucial for proper interpretation of alterations in NAA because: 1) the NAA composition of gray matter, white matter, and CSF is different; 2) spectroscopic voxels contain varying mixtures of gray matter, white matter, and CSF; and 3) disease processes can alter NAA concentrations in each tissue type differently. The primary objective of this proposal is to determine whether there is an association between regional gray matter NAA measures and specific symptom dimensions in schizophrenia. Fifty schizophrenic patients and 50 control subjects will undergo high resolution magnetic resonance imaging (MRI) combined with multi-slice proton magnetic resonance spectroscopic imaging (1H MRSI) to generate NAA concentrations that are specific to gray matter in the frontal cortex, temporal cortex, hippocampus, and thalamus. These regional gray matter NAA measures along with MRI measures of regional gray matter volumes and clinical rating scales will be used to test whether: 1) gray matter NAA is decreased in frontal cortex, temporal cortex, hippocampi, and thalamus of schizophrenics that demonstrate evidence of gray matter tissue loss; 2) hippocampal neuronal dysfunction or loss as measured by NAA is associated with or independent of the severity of the psychoticism and/or disorganization dimension of positive symptoms as assessed by the Scale for the Assessment of Positive Symptoms (SAPS); 3) prefrontal cortex or temporal cortex neuronal dysfunction/loss as measured by gray matter NAA is associated with or independent of the severity of negative symptoms as assessed by the Scale for the Assessment of Negative Symptoms (SANS); and 4) thalamic neuronal dysfunction/loss as measured by NAA is associated with or independent of the severity of negative symptoms as assessed by the SANS.
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