|
| | |
|
Am J Psychiatry 1996; 153:41-49
Copyright © 1996 by American Psychiatric Association
Functional sites of neuroleptic drug action in the human brain: PET/FDG studies with and without haloperidol
HH Holcomb, NG Cascella, GK Thaker, DR Medoff, RF Dannals and CA Tamminga
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, USA.
OBJECTIVE: The functional pathways through which antipsychotic drugs act in
the brain to decrease psychosis remain unknown, despite our knowledge that
their site of initial action is through blockade of dopamine D2 receptors.
The authors sought to define the brain regions that are functionally
altered by neuroleptic drugs. METHODS: Regional cerebral glucose metabolism
was studied in 12 subjects with schizophrenia while they were receiving a
fixed dose of haloperidol, again 5 days after withdrawal of the drug, and a
third time 30 days after withdrawal. Positron emission tomography with an
[18F]fluorodeoxyglucose tracer was used in a within-subject design.
RESULTS: The analysis demonstrated a decrease in glucose metabolism in the
caudate and putamen 30 days after withdrawal, indicating that haloperidol
treatment enhanced glucose utilization in these areas. The thalamus,
bilaterally but only in anterior areas, showed the same response to
haloperidol. Only in the frontal cortex and in the anterior cingulate had
metabolism increased 30 days after withdrawal, indicating that in those two
cortical areas haloperidol depressed glucose metabolism. In the 5-day drug
free scans, no regions differed significantly from those in the haloperidol
condition, despite numerical changes. CONCLUSIONS: It appears that 5 days
of neuroleptic withdrawal are inadequate to escape the effects of
neuroleptic drugs on regional cerebral glucose metabolism. The pattern and
localization of changes in metabolic activity between the haloperidol
condition and the 30-day drug-free condition suggest that haloperidol
exerts its primary antidopaminergic action in the basal ganglia. It is
proposed that the additional changes in the thalamus and cortex are
secondary to this primary site of drug action, mediated through classically
described striato-thalamo-cortical pathways.
This article has been cited by other articles:
|
|
|
|
 
C. A. Tamminga and J. M. Davis
The Neuropharmacology of Psychosis
Schizophr Bull,
July 1, 2007;
33(4):
937 - 946.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. H.Y. Fu, J. Suckling, S. C.R. Williams, C. M. Andrew, G. N. Vythelingum, and P. K. McGuire
Effects of Psychotic State and Task Demand on Prefrontal Function in Schizophrenia: An fMRI Study of Overt Verbal Fluency
Am J Psychiatry,
March 1, 2005;
162(3):
485 - 494.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Chang, N. E. Adleman, K. Dienes, D. I. Simeonova, V. Menon, and A. Reiss
Anomalous Prefrontal-Subcortical Activation in Familial Pediatric Bipolar Disorder: A Functional Magnetic Resonance Imaging Investigation
Arch Gen Psychiatry,
August 1, 2004;
61(8):
781 - 792.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Yasuno, T. Suhara, Y. Okubo, Y. Sudo, M. Inoue, T. Ichimiya, A. Takano, K. Nakayama, C. Halldin, and L. Farde
Low Dopamine D2 Receptor Binding in Subregions of the Thalamus in Schizophrenia
Am J Psychiatry,
June 1, 2004;
161(6):
1016 - 1022.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. K. Stark, H. B.M. Uylings, E. Sanz-Arigita, and B. Pakkenberg
Glial Cell Loss in the Anterior Cingulate Cortex, a Subregion of the Prefrontal Cortex, in Subjects With Schizophrenia
Am J Psychiatry,
May 1, 2004;
161(5):
882 - 888.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Clinton, V. Haroutunian, K. L. Davis, and J. H. Meador-Woodruff
Altered Transcript Expression of NMDA Receptor-Associated Postsynaptic Proteins in the Thalamus of Subjects With Schizophrenia
Am J Psychiatry,
June 1, 2003;
160(6):
1100 - 1109.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Levitt, R. W. McCarley, C. C. Dickey, M. M. Voglmaier, M. A. Niznikiewicz, L. J. Seidman, Y. Hirayasu, A. A. Ciszewski, R. Kikinis, F. A. Jolesz, et al.
MRI Study of Caudate Nucleus Volume and Its Cognitive Correlates in Neuroleptic-Naive Patients With Schizotypal Personality Disorder
Am J Psychiatry,
July 1, 2002;
159(7):
1190 - 1197.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G D Honey, P C Fletcher, and E T Bullmore
Functional brain mapping of psychopathology
J. Neurol. Neurosurg. Psychiatry,
April 1, 2002;
72(4):
432 - 439.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E T C Ngan, C J Lane, T J Ruth, and P F Liddle
Immediate and delayed effects of risperidone on cerebral metabolism in neuroleptic naive schizophrenic patients: correlations with symptom change
J. Neurol. Neurosurg. Psychiatry,
January 1, 2002;
72(1):
106 - 110.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Suhara, Y. Okubo, F. Yasuno, Y. Sudo, M. Inoue, T. Ichimiya, Y. Nakashima, K. Nakayama, S. Tanada, K. Suzuki, et al.
Decreased Dopamine D2 Receptor Binding in the Anterior Cingulate Cortex in Schizophrenia
Arch Gen Psychiatry,
January 1, 2002;
59(1):
25 - 30.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Rubinsztein, P. C. Fletcher, R. D. Rogers, L. W. Ho, F. I. Aigbirhio, E. S. Paykel, T. W. Robbins, and B. J. Sahakian
Decision-making in mania: a PET study
Brain,
December 1, 2001;
124(12):
2550 - 2563.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Lahti, H. H. Holcomb, D. R. Medoff, M. A. Weiler, C. A. Tamminga, and W. T. Carpenter Jr.
Abnormal Patterns of Regional Cerebral Blood Flow in Schizophrenia With Primary Negative Symptoms During an Effortful Auditory Recognition Task
Am J Psychiatry,
November 1, 2001;
158(11):
1797 - 1808.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Gilbert, D. R. Rosenberg, K. Harenski, S. Spencer, J. A. Sweeney, and M. S. Keshavan
Thalamic Volumes in Patients With First-Episode Schizophrenia
Am J Psychiatry,
April 1, 2001;
158(4):
618 - 624.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
D. J. Lang, L. C. Kopala, R. A. Vandorpe, Q. Rui, G. N. Smith, V. M. Goghari, and W. G. Honer
An MRI Study of Basal Ganglia Volumes in First-Episode Schizophrenia Patients Treated With Risperidone
Am J Psychiatry,
April 1, 2001;
158(4):
625 - 631.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
H. M. Ibrahim, A. J. Hogg Jr., D. J. Healy, V. Haroutunian, K. L. Davis, and J. H. Meador-Woodruff
Ionotropic Glutamate Receptor Binding and Subunit mRNA Expression in Thalamic Nuclei in Schizophrenia
Am J Psychiatry,
November 1, 2000;
157(11):
1811 - 1823.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
H. H. Holcomb, A. C. Lahti, D. R. Medoff, M. Weiler, R. F. Dannals, and C. A. Tamminga
Brain Activation Patterns in Schizophrenic and Comparison Volunteers During a Matched-Performance Auditory Recognition Task
Am J Psychiatry,
October 1, 2000;
157(10):
1634 - 1645.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
G. D. Honey, E. T. Bullmore, W. Soni, M. Varatheesan, S. C. R. Williams, and T. Sharma
Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia
PNAS,
November 9, 1999;
96(23):
13432 - 13437.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. C. Andreasen
A Unitary Model of Schizophrenia: Bleuler's "Fragmented Phrene" as Schizencephaly
Arch Gen Psychiatry,
September 1, 1999;
56(9):
781 - 787.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Millan, A. Gobert, A. Newman-Tancredi, V. Audinot, F. Lejeune, J.-M. Rivet, D. Cussac, J.-P. Nicolas, O. Muller, and G. Lavielle
S 16924 ((R)-2-{1-[2-(2,3-Dihydro-Benzo[1,4] Dioxin-5-Yloxy)-Ethyl]-Pyrrolidin-3yl}-1-(4-Fluoro-Phenyl)-Ethanone), a Novel, Potential Antipsychotic with Marked Serotonin (5-HT)1A Agonist Properties: I. Receptorial and Neurochemical Profile in Comparison with Clozapine and Haloperidol
J. Pharmacol. Exp. Ther.,
September 1, 1998;
286(3):
1341 - 1355.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
E. J. Bartlett, J. D. Brodie, P. Simkowitz, S. L. Dewey, J.-P. Lindenmayer, H. Rusinek, A. Wolkin, R. Cancro, and W. Schiffer
Effect of a Haloperidol Challenge on Regional Brain Metabolism in Neuroleptic-Responsive and Nonresponsive Schizophrenic Patients
Am J Psychiatry,
March 1, 1998;
155(3):
337 - 343.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
L. Shihabuddin, M. S. Buchsbaum, E. A. Hazlett, M. M. Haznedar, P. D. Harvey, A. Newman, D. B. Schnur, J. Spiegel-Cohen, T. Wei, J. Machac, et al.
Dorsal Striatal Size, Shape, and Metabolic Rate in Never-Medicated and Previously Medicated Schizophrenics Performing a Verbal Learning Task
Arch Gen Psychiatry,
March 1, 1998;
55(3):
235 - 243.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. S. Carter, M. Mintun, T. Nichols, and J. D. Cohen
Anterior Cingulate Gyrus Dysfunction and Selective Attention Deficits in Schizophrenia: [15O]H2O PET Study During Single-Trial Stroop Task Performance
Am J Psychiatry,
December 1, 1997;
154(12):
1670 - 1675.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K. J. Black, M. H. Gado, and J. S. Perlmutter
PET Measurement of Dopamine D2 Receptor-Mediated Changes in Striatopallidal Function
J. Neurosci.,
May 1, 1997;
17(9):
3168 - 3177.
[Abstract]
[Full Text]
[PDF]
|
|
|
Get information about faster international access.
Privacy Policy
Copyright © 1996
American Psychiatric Association.
All rights reserved.
Home
| Search
| Current Issue
| Past Issues
| Subscribe
| All APPI Journals
| Help
| Contact Us
|
