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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Synaptic dopamine is increased in psychosis.
“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 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, paralleling findings in psychotic patients.
“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]
A PET study found higher synaptic DA concentrations in the ventral striatum in schizophrenia.
“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]
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“development of psychosis [7,8] but the underlying molecular cause(s) of this dopamine dysregulation are unknown.”
BackgroundAdversity in childhood linked to elevated striatal dopamine function in adulthood
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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
- 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 › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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