The DOI matches its Crossref record; 88 of the 89 references it cites were found in a registry or an index.
Increased Synaptic Dopamine Function in Associative Regions of the Striatum in Schizophrenia
Abstract
CONTEXT: A long-standing version of the dopamine hypothesis of schizophrenia postulates that hyperactivity of dopaminergic transmission at D(2) receptors in the limbic striatum is associated with the illness and that blockade of mesolimbic D(2) receptors is responsible for the antipsychotic action of D(2) receptor antagonists. OBJECTIVE: To localize dopaminergic hyperactivity within the striatum in schizophrenia. DESIGN: Case-control study. SETTING: Inpatient research unit. PARTICIPANTS: Eighteen untreated patients with schizophrenia and 18 healthy control subjects matched for age, sex, ethnicity, parental socioeconomic status, cigarette smoking, and weight. MAIN OUTCOME MEASURES: Percentage change in dopamine D(2) receptor availability in striatal subregions within each subject measured by positron emission tomography with carbon 11-labeled raclopride before and during pharmacologically induced dopamine depletion. RESULTS: In the associative striatum, acute dopamine depletion resulted in a larger increase in D(2) receptor availability in patients with schizophrenia (mean [SD], 15% [7%]) than in control subjects (10% [7%], P = .045), suggesting higher synaptic dopamine concentration. Within the associative striatum, this effect was most pronounced in the precommissural dorsal caudate (15% [8%] in patients vs 9% [8%] in controls, P = .03). No between-group differences were observed in the limbic and sensorimotor striatum. CONCLUSIONS: These findings suggest that schizophrenia is associated with elevated dopamine function in associative regions of the striatum. Because the precommissural dorsal caudate processes information from the dorsolateral prefrontal cortex, this observation also suggests that elevated subcortical dopamine function might adversely affect performance of the dorsolateral prefrontal cortex in schizophrenia. On the other hand, the absence of a group difference in the limbic striatum brings into question the therapeutic relevance of the mesolimbic selectivity of second-generation antipsychotic drugs.
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In the citing paper
“Synaptic dopamine is also increased in psychosis(50, 51).”
From Aberrant Salience, Information Processing, and Dopaminergic Signaling in People at Clinical High Risk for Psychosis (2020) · cites this paper as [50]
In the citing paper
“In CHR subjects in general, as well as in the subgroup that later become psychotic, the greatest alterations in dopamine synthesis and release capacity have been found in the associative striatum (57-59, 62), paralleling findings in psychotic patients(50, 69).”
From Aberrant Salience, Information Processing, and Dopaminergic Signaling in People at Clinical High Risk for Psychosis (2020) · cites this paper as [50]
In the citing paper
“a PET study found higher synaptic DA concentrations in the ventral striatum in schizophrenia [425].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [425]
Citations
Cites
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Parallel organization of functionally segregated circuits linking basal ganglia and cortex
Alexander, G. E., DeLong, M. R., & Strick, P. L. (1986) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.09.030186.002041 · Cited by 8,527
Four Factor Index of Social Status
Paschou, R. (1975) · Cited by 6,989
Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia
Lieberman, J. A., Stroup, T. S., McEvoy, J. P., Swartz, M. S., Rosenheck, R. A., Perkins, D. O., Keefe, R. S. E., Davis, S. M., Davis, C. E., Lebowitz, B. D., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa051688 · Cited by 5,892
Four Factor Index of Social Status [1975]
Hollingshead, A. B. (1975) · Cited by 5,151
Dopamine Receptor Binding Predicts Clinical and Pharmacological Potencies of Antischizophrenic Drugs
Creese, I., Burt, D. R., & Snyder, S. H. (1976) · Science · doi:10.1126/science.3854 · Cited by 2,220
Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop
Parent, A., & Hazrati, L.-N. (1995) · Brain Research Reviews · doi:10.1016/0165-0173(94)00007-c · Cited by 2,161
Dopamine in schizophrenia: a review and reconceptualization
Davis, K. L., Kahn, R. S., Ko, G., & Davidson, M. (1991) · American Journal of Psychiatry · doi:10.1176/ajp.148.11.1474 · Cited by 2,051
Physiologic Dysfunction of Dorsolateral Prefrontal Cortex in Schizophrenia
Weinberger, D. R. (1986) · Archives of General Psychiatry · doi:10.1001/archpsyc.1986.01800020020004 · Cited by 2,025
Negative v Positive Schizophrenia
Andreasen, N. C. (1982) · Archives of General Psychiatry · doi:10.1001/archpsyc.1982.04290070025006 · Cited by 2,008
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Animal models of neuropsychiatric disorders
Nestler, E. J., & Hyman, S. E. (2010) · Nature Neuroscience · doi:10.1038/nn.2647 · Cited by 2,023
Howes, O. D., Kambeitz, J., Kim, E., Stahl, D., Slifstein, M., Abi-Dargham, A., & Kapur, S. (2012) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2012.169 · Cited by 967
Self-citationSchizophrenia, dopamine and the striatum: From biology to symptoms
McCutcheon, R. A., Abi-Dargham, A., & Howes, O. D. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2018.12.004 · Cited by 763
Self-citationGlutamate and dopamine in schizophrenia: An update for the 21 st century
Howes, O., McCutcheon, R., & Stone, J. (2015) · Journal of Psychopharmacology · doi:10.1177/0269881114563634 · Cited by 702
del Campo, N., Chamberlain, S. R., Sahakian, B. J., & Robbins, T. W. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.02.036 · Cited by 685
Metadata
- Authors
- Kegeles, L. S., Abi-Dargham, A., Frankle, W. G., Gil, R., Cooper, T. B., Slifstein, M., Hwang, D.-R., Huang, Y., Haber, S. N., & Laruelle, M.
- Affiliations
- Columbia University Irving Medical Center (US)
- ORCID
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2010-03-01
- Volume
- 67
- Issue
- 3
- Pages
- 231
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W1999984108
- Cited by
- 565
- References
- 89
- Citations by year
- 2026: 17 · 2025: 26 · 2024: 33 · 2023: 25 · 2022: 42 · 2021: 23 · 2020: 32 · 2019: 42 · 2018: 32 · 2017: 38 · 2016: 45 · 2015: 41 · 2014: 47 · 2013: 32 · 2012: 47
- FWCI
- 25.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (K02MH01603-01, K02MH001603, R01MH054192)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- schizophrenia, synaptic dopamine, associative striatum, dorsal caudate, dopamine depletion, mesolimbic dopamine system, dopamine hypothesis of schizophrenia, atypical antipsychotics, dorsolateral prefrontal cortex, positron emission tomography, raclopride
- MeSH terms
- Adult, Brain Mapping, Carbon Radioisotopes, Caudate Nucleus, Corpus Striatum, Dopamine, Female, Humans, Image Processing, Computer-Assisted, Male, Synaptic Transmission, Putamen, Schizophrenia, Synapses, Case-Control Studies, Prefrontal Cortex, Receptors, Dopamine D2, alpha-Methyltyrosine, Raclopride, Positron-Emission Tomography
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