Positron emission tomography (PET) will be used to investigate the capacity to alter neurochemical function in response to acute neuroleptic- induced receptor blockade in chronic schizophrenia. A neuroleptic challenge paradigm will be used to test the hypothesis that the capacity to alter neurochemical function in response to acute, neuroleptic-induced receptor blockade is associated with the capacity to produce a therapeutic response to long-term neuroleptic treatment. PET and 18/F-fluoro-2- deoxyglucose (FDG) will be used in a repeated measures design to examine regional changes in glucose metabolism following administration of a single pharmacological challenge dose of the neuroleptic drug haloperidol sufficient to induce receptor blockade. By comparing the metabolic response to this challenge in clinically well-characterized treatment responsive and treatment resistant chronic schizophrenics, we will address our central hypothesis. PET and the muscarinic cholinergic ligand 11/C-benztropine (11/C-BZ) will also be used to measure regional changes in muscarinic activity following administration of the haloperidol challenge in order to characterize the effect of a dopamine-blocking neuroleptic challenge on the separate, but functionally-related muscarinic cholinergic system. By comparing the muscarinic response in treatment responsive and resistant schizophrenics, one aspect of our central hypothesis can be tested: that the capacity to alter neurochemical response to receptor blockade in a separate but functionally related neurotransmitter system is associated with the capacity to produce a therapeutic response to long-term neuroleptic treatment. By accomplishing these aims we will have defined a neurochemical measure that may predict drug treatment response in chronic schizophrenia. Such a measure may provide a neurochemical basis for interpreting treatment response, for clinical sub-typing and for developing new treatment strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH047277-03A2
Application #
2247512
Study Section
Clinical Neuroscience and Biological Psychopathology Review Committee (CNBP)
Project Start
1991-09-30
Project End
1998-04-30
Budget Start
1995-05-01
Budget End
1996-04-30
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
New York University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012
Hutchinson, M; Schiffer, W; Joseffer, S et al. (1999) Task-specific deactivation patterns in functional magnetic resonance imaging. Magn Reson Imaging 17:1427-36
Smith, G S; Schloesser, R; Brodie, J D et al. (1998) Glutamate modulation of dopamine measured in vivo with positron emission tomography (PET) and 11C-raclopride in normal human subjects. Neuropsychopharmacology 18:18-25
Bartlett, E J; Brodie, J D; Simkowitz, P et al. (1998) Effect of a haloperidol challenge on regional brain metabolism in neuroleptic-responsive and nonresponsive schizophrenic patients. Am J Psychiatry 155:337-43
Schlosser, R; Brodie, J D; Dewey, S L et al. (1998) Long-term stability of neurotransmitter activity investigated with 11C-raclopride PET. Synapse 28:66-70
Schlosser, R; Hutchinson, M; Joseffer, S et al. (1998) Functional magnetic resonance imaging of human brain activity in a verbal fluency task. J Neurol Neurosurg Psychiatry 64:492-8
Schloesser, R; Simkowitz, P; Bartlett, E J et al. (1996) The study of neurotransmitter interactions using positron emission tomography and functional coupling. Clin Neuropharmacol 19:371-89
Bartlett, E J; Brodie, J D; Simkowitz, P et al. (1996) Time-dependent effects of a haloperidol challenge on energy metabolism in the normal human brain. Psychiatry Res 60:91-9
Wang, G J; Volkow, N D; Wolf, A P et al. (1994) Intersubject variability of brain glucose metabolic measurements in young normal males. J Nucl Med 35:1457-66
Bartlett, E J; Brodie, J D; Simkowitz, P et al. (1994) Effects of haloperidol challenge on regional cerebral glucose utilization in normal human subjects. Am J Psychiatry 151:681-6