In a series of studies, we and others have found that patients with schizophrenia have relatively reduced metabolic rates in their frontal cortex, temporal lobe and basal ganglia when assessed with positron emi- ssion tomography with 18-F 2-deoxyglucose (FDG). We propose to identify and validate subtypes of schizophrenia based on functional neuroanatomy of these three regions. We will refine our image analysis routines using our MRI template method, assess the accuracy with our new anatomically accurate brain phantom method, replicate findings of a relationship between basal ganglia metabolic rate and neuroleptic response, trace longitudinal change and evaluate familial effects. In Experiment 1, 40 patients with schizophrenia will participate in a 10-week trial of a standard neuroleptic; the design will be a double-- blind, random assignment crossover with PET scans after each five-week period. We will enlarge our current sample of 30 never-medicated patients, and enter as many as possible into the drug trial. In Experiment 2, we will rescan subjects at a five-year followup and evaluate developmental effects with a study of psychotic adolescents and an age-matched depression control group. In Experiment 3, we will scan the siblings of 24 patients with schizophrenia to evaluate familial effects. Patients in all experiments will be evaluated clinically with an expanded life-time version of the Present State Exam structured interview, diagnosed by DSM-III-R criteria, and screened for medical illness. Urine testing will verify drug status. Subjects will perform the degraded Continuous Performance Test during FDG uptake. Following uptake of FDG, the scanner (7.6 mm in plane and 11.6 mm axial resolution) will obtain slice images in micromoles glucose/l00g/ minute. All subjects will receive MRI scans at 5 mm intervals, using the same individually fitted, thermoplastic head holder to allow specific structures to be identified by reference to the anatomic image. Computer algorithms for tracing the caudate, putamen, and other regions will be employed to yield PET templates as well as size and shape assessments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH040071-07
Application #
3377990
Study Section
Clinical Neuroscience Review Committee (CNR)
Project Start
1992-09-30
Project End
1995-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
7
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029
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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