Elevated Striatal Dopamine Function Linked to Prodromal Signs of Schizophrenia
Abstract
CONTEXT: A major limitation on the development of biomarkers and novel interventions for schizophrenia is that its pathogenesis is unknown. Although elevated striatal dopamine activity is thought to be fundamental to schizophrenia, it is unclear when this neurochemical abnormality develops in relation to the onset of illness and how this relates to the symptoms and neurocognitive impairment seen in individuals with prodromal symptoms of schizophrenia. OBJECTIVES: To determine whether striatal dopamine function is elevated in individuals with prodromal symptoms of schizophrenia before the onset of psychosis and to assess how this relates to the symptoms and neurocognitive impairment. DESIGN: Case-control study of in vivo striatal dopaminergic function. SETTING: Academic research. Patients Patients were recruited from a community mental health service. Twenty-four patients having prodromal symptoms of schizophrenia were compared with 7 patients having schizophrenia and with 12 matched healthy control subjects from the same community. Main Outcome Measure Striatal 6-fluoro-l-dopa F 18-dopa uptake measured using positron emission tomographic (18)F-dopa imaging. RESULTS: Striatal (18)F-dopa uptake was elevated in patients with prodromal symptoms of schizophrenia (effect size, 0.75) to an intermediate degree compared with that in patients with schizophrenia (effect size, 1.25). The elevation was localized in the associative striatum in both groups. Moreover, striatal (18)F-dopa uptake in patients with prodromal symptoms of schizophrenia was correlated with the severity of prodromal psychopathologic and neuropsychological impairment but not with the severity of anxiety or depressive symptoms. CONCLUSIONS: These findings indicate that dopamine overactivity predates the onset of schizophrenia in individuals with prodromal psychotic symptoms, is predominantly localized in the associative striatum, and is correlated with the severity of symptoms and neurocognitive dysfunction.
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PET studies indicate dopamine overactivity in the associative and sensorimotor striatum in both patients with a schizophrenia diagnosis and patients with attenuated psychotic symptoms considered to be at ultra-high risk.
“PET studies indicate dopamine over activity in the associative and sensorimotor striatum in both patients with a schizophrenia diagnosis and patients with attenuated psychotic symptoms considered to be at ultra-high risk [130,131] .”
From The traumagenic neurodevelopmental model of psychosis revisited (2014) · cites this paper as [130]
In the ultra high-risk group, striatal 18F-dopa uptake, a measure of dopamine activity, is associated with severity of psychotic symptoms and neurocognitive dysfunction.
“In the ultra highrisk group, striatal 18 F-dopa uptake, a measure of dopamine activity, has been associated with severity of psychotic symptoms and neurocognitive dysfunction [130] .”
From The traumagenic neurodevelopmental model of psychosis revisited (2014) · cites this paper as [130]
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 [57]
CHR subjects show increased dopamine synthesis capacity relative to healthy controls with effect sizes of about 0.8 in the striatum, and in its associative and sensorimotor but not limbic sub-divisions.
“In contrast, CHR subjects show increased dopamine synthesis capacity relative to HC with effect sizes of about 0.8 in the striatum (57-59), and its associative (57-59, 62) and sensorimotor (58, 59), but not limbic sub-divisions.”
From Aberrant Salience, Information Processing, and Dopaminergic Signaling in People at Clinical High Risk for Psychosis (2020) · cites this paper as [57]
Howes et al. (57) found increased dopamine synthesis capacity in the associative striatum in clinical high risk individuals compared to healthy controls, with an effect size of 0.83.
“| (57) 1 | 12 HC | | capacity | AS | CHR | 0.83 |”
From Aberrant Salience, Information Processing, and Dopaminergic Signaling in People at Clinical High Risk for Psychosis (2020) · cites this paper as [57]
Howes et al. (57) found increased dopamine synthesis capacity in the striatum in clinical high risk individuals compared to healthy controls, with an effect size of 0.75.
“Howes et al. | 24 CHR | [ 18 F]-DOPA | dopamine synthesis | Striatum | CHR | 0.75 |”
From Aberrant Salience, Information Processing, and Dopaminergic Signaling in People at Clinical High Risk for Psychosis (2020) · cites this paper as [57]
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References 51 · Cited by 744
- Authors
- Howes, O. D., Montgomery, A. J., Asselin, M.-C., Murray, R. M., Valli, I., Tabraham, P., Bramon-Bosch, E., Valmaggia, L., Johns, L., Broome, M., McGuire, P. K., & Grasby, P. M.
- Affiliations
- King's College London (GB)
- Hammersmith Hospital (GB)
- ORCID
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2009-01-01
- Volume
- 66
- Issue
- 1
- Pages
- 13
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2012007142
- Cited by
- 744
- References
- 51
- Citations by year
- 2026: 20 · 2025: 21 · 2024: 28 · 2023: 31 · 2022: 41 · 2021: 30 · 2020: 45 · 2019: 45 · 2018: 51 · 2017: 44 · 2016: 55 · 2015: 45 · 2014: 52 · 2013: 57 · 2012: 67
- FWCI
- 35.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Keywords
- schizophrenia, prodromal symptoms, striatal dopamine, 18F-DOPA PET, associative striatum, neurocognitive impairment, transition to psychosis
- MeSH terms
- Adult, Brain Mapping, Cognition Disorders, Corpus Striatum, Dominance, Cerebral, Dihydroxyphenylalanine, Dopamine, Female, Humans, Image Processing, Computer-Assisted, Male, Neuropsychological Tests, Psychiatric Status Rating Scales, Reference Values, Risk Factors, Schizophrenia, Schizotypal Personality Disorder, Diagnostic and Statistical Manual of Mental Disorders, Positron-Emission Tomography, Young Adult
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