Blunted change in cerebral glucose utilization after haloperidol treatment in schizophrenic patients with prominent negative symptoms.

OBJECTIVE The purpose of this report was to determine 1) the effects of chronic haloperidol treatment on cerebral metabolism in schizophrenic patients, 2) the relation between negative symptoms and haloperidol-induced regional changes in cerebral glucose utilization, and 3) the relation between metabolic change and clinical antipsychotic effect. METHOD Cerebral glucose utilization, as determined by position emission tomography (PET), was studied in 18 male schizophrenic subjects before and after chronic treatment with haloperidol at a standardized plasma level. RESULTS Overall, haloperidol caused a widespread decrease in absolute cerebral glucose metabolism. The cerebral metabolic response to haloperidol was blunted in patients with high pretreatment negative symptom scores. CONCLUSIONS Taken together with the results from a previously reported PET study of the effects of an acute amphetamine challenge (in which 14 of the current subjects participated), these data suggest that the negative symptom complex is associated with diminished cerebral response to change in dopaminergic activity. This deficit cannot be solely accounted for by structural differences.

[1]  M S Buchsbaum,et al.  Striatal metabolic rate and clinical response to neuroleptics in schizophrenia. , 1992, Archives of general psychiatry.

[2]  M S Buchsbaum,et al.  The frontal lobes, basal ganglia, and temporal lobes as sites for schizophrenia. , 1990, Schizophrenia bulletin.

[3]  C. D. Arnett,et al.  Glucose Metabolic Rate Kinetic Model Parameter Determination in Humans: The Lumped Constants and Rate Constants for [18F]Fluorodeoxyglucose and [11C]Deoxyglucose , 1985, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[4]  M S Buchsbaum,et al.  Effects of clozapine and thiothixene on glucose metabolic rate in schizophrenia. , 1992, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[5]  Jonathan D. Brodie,et al.  Importance of pharmacologic control in PET studies: Effects of thiothixene and haloperidol on cerebral glucose utilization in chronic schizophrenia , 1991, Psychiatry Research: Neuroimaging.

[6]  K. Hamacher,et al.  Efficient stereospecific synthesis of no-carrier-added 2-[18F]-fluoro-2-deoxy-D-glucose using aminopolyether supported nucleophilic substitution. , 1986, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[7]  G. Brown,et al.  17. Neuroleptic effects on regional brain metabolism in first episode schizophrenics , 1991, Schizophrenia Research.

[8]  L. DeLisi,et al.  Positron emission tomography studies of basal ganglia and somatosensory cortex neuroleptic drug effects: Differences between normal controls and schizophrenic patients , 1987, Biological Psychiatry.

[9]  J S Fowler,et al.  Effects of haloperidol challenge on regional cerebral glucose utilization in normal human subjects. , 1994, The American journal of psychiatry.

[10]  T. Cooper,et al.  Acute d-amphetamine challenge in schizophrenia: Effects on cerebral glucose utilization and clinical symptomatology , 1994, Biological Psychiatry.

[11]  J. Brodie,et al.  Negative symptoms and hypofrontality in chronic schizophrenia. , 1992, Archives of general psychiatry.

[12]  H. Nelson.  A Modified Card Sorting Test Sensitive to Frontal Lobe Defects , 1976, Cortex.

[13]  S. Holm.  A Simple Sequentially Rejective Multiple Test Procedure , 1979 .

[14]  P. Liddle,et al.  Three Syndromes in Chronic Schizophrenia , 1989, British Journal of Psychiatry.

[15]  J. Fuster.  Prefrontal Cortex , 2018 .

[16]  A Carlsson,et al.  The current status of the dopamine hypothesis of schizophrenia. , 1988, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[17]  G. Bianchetti,et al.  Rapid and sensitive method for determination of haloperidol in human samples using nitrogen-phosphorus selective detection. , 1978, Journal of chromatography.

[18]  L. DeLisi,et al.  Positron Emission Tomography in Schizophrenic Patients with and without Neuroleptic Medication , 1985, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[19]  T. Cooper,et al.  Dopamine receptor occupancy and plasma haloperidol levels. , 1989, Archives of general psychiatry.

[20]  P. McKenna,et al.  Schizophrenia – a Brain Disease? a Critical Review of Structural and Functional Cerebral Abnormality in the Disorder , 1995, British Journal of Psychiatry.

[21]  W. Carpenter,et al.  Deficit and nondeficit forms of schizophrenia: the concept. , 1988, The American journal of psychiatry.

[22]  J. Brodie,et al.  Low frontal glucose utilization in chronic schizophrenia: a replication study. , 1988, The American journal of psychiatry.

[23]  Jonathan D. Brodie,et al.  Effects of amphetamine on local cerebral metabolism in normal and schizophrenic subjects as determined by positron emission tomography , 2004, Psychopharmacology.

[24]  Crow Tj.  A current view of the type II syndrome: age of onset, intellectual impairment, and the meaning of structural changes in the brain. , 1989 .

[25]  J D Brodie,et al.  Persistence of cerebral metabolic abnormalities in chronic schizophrenia as determined by positron emission tomography. , 1985, The American journal of psychiatry.

[26]  N. Andreasen,et al.  Positive and negative symptoms in schizophrenia. A critical reappraisal. , 1990, Archives of general psychiatry.

[27]  N C Andreasen,et al.  Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia. Assessment with xenon 133 single-photon emission computed tomography and the Tower of London. , 1992, Archives of general psychiatry.

[28]  N. Andreasen.  Neural Mechanisms of Negative Symptoms , 1989, British Journal of Psychiatry.

[29]  G. E. Alexander,et al.  Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, "prefrontal" and "limbic" functions. , 1990, Progress in brain research.

[30]  R. Buchanan,et al.  The deficit syndrome: functional and structural characteristics , 1991, Schizophrenia Research.

[31]  M. Taylor,et al.  A rating scale for emotional blunting. , 1978, The American journal of psychiatry.

[32]  D. Weinberger,et al.  Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia. IV. Further evidence for regional and behavioral specificity. , 1988, Archives of general psychiatry.

[33]  G. E. Alexander,et al.  Parallel organization of functionally segregated circuits linking basal ganglia and cortex. , 1986, Annual review of neuroscience.

[34]  Jonathan D. Brodie,et al.  Stability of resting deoxyglucose metabolic values in PET studies of schizophrenia , 1991, Psychiatry Research: Neuroimaging.

[35]  P. Liddle.  Schizophrenic syndromes, cognitive performance and neurological dysfunction , 1987, Psychological Medicine.

[36]  D. Weinberger,et al.  Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. I. Regional cerebral blood flow evidence. , 1986, Archives of general psychiatry.

[37]  Karl J. Friston,et al.  Patterns of Cerebral Blood Flow in Schizophrenia , 1992, British Journal of Psychiatry.

[38]  F. Quitkin,et al.  Akinesia: A Poorly Recognized Drug-Induced Extrapyramidal Behavioral Disorder , 1975 .

[39]  T. Barnes,et al.  Is the Concept of Frontal–Subcortical Dementia Relevant to Schizophrenia? , 1992, British Journal of Psychiatry.

[40]  T. White,et al.  The association among negative symptoms, movement disorders, and frontal lobe psychological deficits in schizophrenic patients , 1991, Biological Psychiatry.

[41]  W T Carpenter,et al.  Limbic system abnormalities identified in schizophrenia using positron emission tomography with fluorodeoxyglucose and neocortical alterations with deficit syndrome. , 1992, Archives of general psychiatry.