The studies proposed in this application aim (1) to identify specific patterns of regional brain metabolism which may characterize male and female schizophrenic patients; (2) relate measures of psychopathology and regional brain metabolism in schizophrenia; (3) characterize the effect of neuroleptics on brain glucose metabolism. Our work to date and that of other investigators suggest it may well be possible to develop a map of grey matter metabolism which reflects a) psychopathological indices and b) dopamine agonist and antagonist effects in schizophrenia. This could provide a set of psychobiological criteria where none now exist. 1. We propose that a new group of 12 male and 12 female drug-naive schizophrenic patients will demonstrate greater frontal and less parietal glucose metabolism than 12 new control of each sex. The patients are also expected to slow greater left than right temporal lobe activity in the superior temporal gyrus, lower activity in the anterior cingulate gyri and in the hippocampal gyri. They will differ from normals in an inferior portion of the striatum, where they are expected to show greater metabolism than normals. Inter- regional correlations are expected to be significantly lower in schizophrenics than in normals. 2. We will examine the relationship between measures of psychopathology and regional brain metabolism in schizophrenia. The hypothesis, based on our preliminary findings is that certain neuropsychological functions are subserved by different brain regions in schizophrenic patients than in controls. The relation between symptom scores and regional brain metabolism will also be examined For example, we will compare patients drawn from the above sample who do and who do not acknowledge auditory hallucinations in order to add rigor to our study that showed a significant relation between hallucinations and glucose metabolism in temporal cortex and Broca's region. 3. The effect of neuroleptics on specific cortical regions that are correlated with psychopathology will be examined since global effects on cortex at one year are minimal. Long term effects have been observed however. We will determine whether these effects are progressive by examining patients at yearly intervals. In addition, we will examine patients two weeks after drug withdrawal since hypofrontality has been observed at that time. The effect of the dopamine agonist, apomorphine HCl on regional brain metabolism in the above drug naive patients will be examined using a double blind balanced order
