In a series of studies, we and others have found that patients with schizophrenia have relatively reduced metabolic rates in their frontal cortex when assessed with positron emission tomography imaging with 18-F 2-deoxyglucose (FDG). We proposed to extend these results with four studies to assess the effects of neuroleptic medication, to examine never-medicated patients, to explore frontal lobe function in additional patients with affective disorder, and to characterize the attentional deficit of patients showing relative hypofrontality. In Experiment 1, 24 patients with schizophrenia will participate in a 12-week trial of a standard neuroleptic; the design will be a double-blind, random assignment crossover with PET scans after each 6-week period. In experiment 2, 24 never-medicated patients will be scanned for comparison with off-medication patients already tested to examine potential medication artifacts. In experiment 3, 24 patients with major affective disorder, 12 bipolar and 12 unipolar, will be scanned. In experiment 4, PET scans on a memory-load but non-degraded stimulus CPT will be compared in normals and schizophrenics to further assess right lateralization seen in the current series. Patients will be evaluated clinically with an expanded lifetime version of the Present State exam structured interview, diagnosed by DSM-III criteria, and screened for medical illness. Non- prescription drug use will be assessed by urine testing. Subjects will perform the Continuous Performance Test during FDG uptake. Following uptake of FDG and labeling of brain structures in the psychophysical laboratory, the NeuroEcat scanner (7.6 mm in plane and 11.6 mm axial resolution) will obtain slice images to assess the metabolic rate of glucose. PET images will be converted to units of micromoles glucose/100g/minute and analyzed quantitatively. All subjects will receive MRI scans using the same individually fitted, thermoplastic head holder to allow specific structures to be identified by reference to the anatomic image. Multivariate analyses of frontal cortex and basal ganglia metabolic rates will evaluate drug effects and group differences to test specific hypotheses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH040071-03
Application #
3377984
Study Section
(SRCM)
Project Start
1986-03-01
Project End
1991-02-28
Budget Start
1988-04-01
Budget End
1989-02-28
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Hazlett, Erin A; Byne, William; Brickman, Adam M et al. (2010) Effects of sex and normal aging on regional brain activation during verbal memory performance. Neurobiol Aging 31:826-38
Hazlett, Erin A; Buchsbaum, Monte S; Haznedar, M Mehmet et al. (2008) Cortical gray and white matter volume in unmedicated schizotypal and schizophrenia patients. Schizophr Res 101:111-23
Buchsbaum, Monte S; Buchsbaum, Bradley R; Hazlett, Erin A et al. (2007) Relative glucose metabolic rate higher in white matter in patients with schizophrenia. Am J Psychiatry 164:1072-81
Mitelman, Serge A; Byne, William; Kemether, Eileen M et al. (2006) Correlations between volumes of the pulvinar, centromedian, and mediodorsal nuclei and cortical Brodmann's areas in schizophrenia. Neurosci Lett 392:16-21
Brickman, Adam M; Buchsbaum, Monte S; Ivanov, Zlatin et al. (2006) Internal capsule size in good-outcome and poor-outcome schizophrenia. J Neuropsychiatry Clin Neurosci 18:364-76
Mitelman, Serge A; Byne, William; Kemether, Eileen M et al. (2006) Metabolic thalamocortical correlations during a verbal learning task and their comparison with correlations among regional volumes. Brain Res 1114:125-37
Haznedar, M Mehmet; Buchsbaum, Monte S; Hazlett, Erin A et al. (2006) Volumetric analysis and three-dimensional glucose metabolic mapping of the striatum and thalamus in patients with autism spectrum disorders. Am J Psychiatry 163:1252-63
Mitelman, Serge A; Shihabuddin, Lina; Brickman, Adam M et al. (2005) Cortical intercorrelations of temporal area volumes in schizophrenia. Schizophr Res 76:207-29
Mitelman, Serge A; Byne, William; Kemether, Eileen M et al. (2005) Metabolic disconnection between the mediodorsal nucleus of the thalamus and cortical Brodmann's areas of the left hemisphere in schizophrenia. Am J Psychiatry 162:1733-5
Hazlett, Erin A; New, Antonia S; Newmark, Randall et al. (2005) Reduced anterior and posterior cingulate gray matter in borderline personality disorder. Biol Psychiatry 58:614-23

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