The effects of antipsychotic treatment on presynaptic dopamine synthesis capacity in first-episode psychosis: a positron emission tomography study
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Background Elevated striatal dopamine synthesis capacity has been implicated in the etiology and antipsychotic response in psychotic illness. The effects of antipsychotic medication on dopamine synthesis capacity are poorly understood, and no prospective studies have examined this question in a solely first-episode psychosis sample. Furthermore, it is unknown whether antipsychotic efficacy is linked to reductions in dopamine synthesis capacity. We conducted a prospective [ 18 F]-dihydroxyphenyl-L - alanine positron emission tomography study in antipsychotic naïve/free people with first-episode psychosis commencing antipsychotic treatment. Methods Dopamine synthesis capacity (indexed as influx rate constant) and clinical symptoms (measured using Positive and Negative Syndrome Scale) were measured before and after at least 5 weeks of antipsychotic treatment in people with first-episode psychosis. Data from a prior study indicated that a sample size of 13 would have >80% power to detect a statistically significant change in dopamine synthesis capacity at alpha = .05 (two tailed). Results A total of 20 people took part in the study, 17 of whom were concordant with antipsychotic medication at therapeutic doses. There was no significant effect of treatment on dopamine synthesis capacity in the whole striatum ( p = .47), thalamus, or midbrain, nor was there any significant relationship between change in dopamine synthesis capacity and change in positive (ρ = .35, p = .13), negative, or total psychotic symptoms. Conclusions Dopamine synthesis capacity is unaltered by antipsychotic treatment, and therapeutic effects are not mediated by changes in this aspect of dopaminergic function.
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Treatment with antipsychotics does not appear to alter DSC.
“a recent study found that treatment with antipsychotics does not appear to alter DSC.55”
From A Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse (2021) · cites this paper as [55]
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Self-citationLin, C., Chen, Y.-M., & Lane, H. (2019) · Current Drug Targets · doi:10.2174/1389450120666191011163539 · Cited by 23 · see citing works
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Potkin, S. G., Kane, J. M., Correll, C. U., Lindenmayer, J., Agid, O., Marder, S. R., Olfson, M., & Howes, O. D. (2020) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.18309 · Cited by 19 · see citing works
Self-citationAn automatic analysis framework for FDOPA PET neuroimaging
Nordio, G., Easmin, R., Giacomel, A., Dipasquale, O., Martins, D., Williams, S., Turkheimer, F., Howes, O. D., Veronese, M., and the FDOPA PET imaging working group:, et al. (2023) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x231168687 · Cited by 18 · see citing works
Self-citationAngelescu, I., Kaar, S. J., Marques, T. R., Borgan, F., Veronesse, M., Sharman, A., Sajjala, A., Deakin, J. F. W., Hutchison, J. B., Large, C. H., et al. (2022) · Journal of Psychopharmacology · doi:10.1177/02698811221122031 · Cited by 17 · see citing works
Self-citationOrhan, F., Goiny, M., Becklén, M., Mathé, L., Piehl, F., Schwieler, L., Fatouros‐Bergman, H., Farde, L., Červenka, S., Sellgren, C. M., et al. (2023) · Schizophrenia Research · doi:10.1016/j.schres.2023.05.012 · Cited by 17 · see citing works
Quantitative Susceptibility Mapping MRI in Deep-Brain Nuclei in First-Episode Psychosis
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The Kraepelian concept of schizophrenia: Dying but not yet dead
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Self-citationD’Ambrosio, E., Pergola, G., Pardiñas, A. F., Dahoun, T., Veronese, M., Sportelli, L., Taurisano, P., Griffiths, K., Jauhar, S., Rogdaki, M., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-16442-6 · Cited by 14 · see citing works
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Self-citationAntipsychotic drugs: from ‘major tranquilizers’ to Neuroscience-based-Nomenclature
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Potassium channel modulators and schizophrenia: an overview of investigational drugs
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Towards a framework to develop neuroimaging biomarkers of relapse in schizophrenia.
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Self-citationGiacomel, A., Martins, D., Nordio, G., Easmin, R., Howes, O. D., Selvaggi, P., Williams, S., Turkheimer, F., de Groot, M., Dipasquale, O., et al. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-02938-w · Cited by 10 · see citing works
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Reduced striatal dopamine transmission as a transdiagnostic substrate of psychomotor retardation
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Self-citationStriatal dopamine D2/3 receptors in medication-naïve schizophrenia: an [123I] IBZM SPECT study
Chen, K.-C., Yang, Y.-K., Howes, O., Lee, H. I., Yeh, T.-L., Chiu, N.-T., Chen, P.-S., David, A., & Bramon, E. (2021) · Psychological Medicine · doi:10.1017/s0033291720005413 · Cited by 7 · see citing works
Self-citationOliver, D., Davies, C., Zelaya, F. O., Selvaggi, P., Micheli, A. D., Catalán, A., Baldwin, H., Arribas, M., Modinos, G., Crossley, N. A., et al. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1092213 · Cited by 6 · see citing works
Self-citationGray Matter Iron and Neuromelanin in Psychosis: A Systematic Review and Meta-Analysis of MRI Studies
Vano, L. J., Sedlacik, J., Carr, R. W., Bukala, B. R., Howes, O. D., & McCutcheon, R. (2026) · American Journal of Psychiatry · doi:10.1176/appi.ajp.20251257 · Cited by 3 · see citing works
Self-citationThe downside of downregulation
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Digital data repository and automatic analysis framework for FDOPA PET neuroimagingPreprint
Nordio, G., Easmin, R., Giacomel, A., Dipasquale, O., Martins, D., Williams, S., Turkheimer, F., Howes, O. D., & Veronese, M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.04.14.488129 · Cited by 3 · see citing works
Self-citationGrey Matter Iron and Neuromelanin in Psychosis: A Systematic Review and Meta-Analysis of MRI StudiesPreprint
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Self-citationSeo, S., Sizemore, R. J., Reader, K. L., Smither, R. A., Wicky, H. E., Hughes, S. M., Bilkey, D. K., Parr‐Brownlie, L. C., & Oorschot, D. E. (2021) · The Journal of Comparative Neurology · doi:10.1002/cne.25225 · Cited by 2 · see citing works
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Dopamine and Response to Antipsychotic Medication
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Self-citationHui, C. L. M., Wong, C. C. L., Yang, N. C. L., Choi, E. G., Hui, P. W. M., Lui, E., Tao, J., Ho, E. C., Suen, Y. N., Chen, S., et al. (2026) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-025-02185-8 · Cited by 1 · see citing works
Chang, X., Bryant, L., Mena, S., Howes, O. D., Sedlacik, J., Veronese, M., Schroeter, M. L., Lalousis, P. A., Koutsouleris, N., Vano, L. J., et al. (2026) · Neuropsychopharmacology · doi:10.1038/s41386-026-02426-x · Cited by 1 · see citing works
Self-citationAre neurotransmitters passé? A view from the foothills in response to Rose
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Self-citationCan D2 Receptor–Based Therapies Fix Presynaptic Dopamine?
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Self-citationA Preliminary Study of the Nociceptin Receptor System in Individuals with Psychosis
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The effect of nicotine on schizophrenia
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On the bumpy road of psychotic disorders
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Biological aspects of drug resistance in schizophrenia
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A Case of Constipation During Cobenfy Therapy and a Constipation Prevention Protocol
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Striatal dopamine synthesis in schizophrenia decreases from psychosis to psychotic remission
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- Authors
- Jauhar, S., Veronese, M., Nour, M. M., Rogdaki, M., Hathway, P., Natesan, S., Turkheimer, F., Stone, J., Egerton, A., McGuire, P., Kapur, S., & Howes, O. D.
- Affiliations
- King's College London (GB)
- The University of Melbourne (AU)
- Corresponding author
- Howes, Oliver D.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 85
- Issue
- 1
- Pages
- 79-87
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC6269123
- OpenAlex
- W2869595516
- Cited by
- 75
- References
- 67
- Citations by year
- 2026: 10 · 2025: 3 · 2024: 6 · 2023: 12 · 2022: 9 · 2021: 13 · 2020: 11 · 2019: 10 · 2018: 1
- FWCI
- 6.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biological Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, cc-by)
- Sussex Research Online (University of Sussex) (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sunovion
- Wellcome Trust (094849/Z/10/Z)
- Maudsley Charity
- GW Pharmaceuticals
- NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
- National Institute for Health and Care Research (ACF-2016-17-005)
- King's College London
- Servier
- H. Lundbeck A/S
- Medical Research Council (MC- A656-5QD30, MR/N026063/1)
- 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
- antipsychotic drugs, dopamine synthesis capacity, first-episode psychosis, striatum, antipsychotic efficacy, positive and negative symptoms, thalamus, midbrain, dopaminergic activity
- MeSH terms
- Adult, Corpus Striatum, Dihydroxyphenylalanine, Dopamine, Female, Humans, Male, Prospective Studies, Psychotic Disorders, Antipsychotic Agents, Neostriatum, Positron-Emission Tomography, Young Adult
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