Cited by 565Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorParkinson's Disease Mechanisms and Treatments

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Increased Synaptic Dopamine Function in Associative Regions of the Striatum in Schizophrenia

Kegeles, Lawrence S., Abi-Dargham, Anissa, Frankle, W. Gordon, Gil, Roberto, Cooper, Thomas B., Slifstein, Mark, Hwang, Dah-Ren, Huang, Yiyun, Haber, Suzanne N., Laruelle, Marc·2010·Archives of General Psychiatry

DOI 10.1001/archgenpsychiatry.2010.10

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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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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: Kegeles, Lawrence S.
Frankle, W. Gordon
Cooper, Thomas B.
Slifstein, Mark
Huang, Yiyun
Haber, Suzanne N.
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)
DOI: 10.1001/archgenpsychiatry.2010.10
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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Increased Synaptic Dopamine Function in Associative Regions of the Striatum in Schizophrenia

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