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The dopamine hypothesis of schizophrenia: version III--the final common pathway
Howes OD, Kapur S.. Schizophrenia bulletin, 2009-03-26
Topic: Brain proteins, microglia and lab models
The dopamine hypothesis of schizophrenia has been one of the most enduring ideas in psychiatry. Initially, the emphasis was on a role of hyperdopaminergia in the etiology of schizophrenia (version I), but it was subsequently reconceptualized to specify subcortical hyperdopaminergia with prefrontal hypodopaminergia (version II). However, these hypotheses focused too narrowly on dopamine itself, conflated psychosis and schizophrenia, and predated advances in the genetics, molecular biology, and imaging research in schizophrenia. Since version II, there have been over 6700 articles about dopamine and schizophrenia. We selectively review these data to provide an overview of the 5 critical streams of new evidence: neurochemical imaging studies, genetic evidence, findings on environmental risk factors, research into the extended phenotype, and animal studies. We synthesize this evidence into a new dopamine hypothesis of schizophrenia-version III: the final common pathway. This hypothesis seeks to be comprehensive in providing a framework that links risk factors, including pregnancy and obstetric complications, stress and trauma, drug use, and genes, to increased presynaptic striatal dopaminergic function. It explains how a complex array of pathological, positron emission tomography, magnetic resonance imaging, and other findings, such as frontotemporal structural and functional abnormalities and cognitive impairments, may converge neurochemically to cause psychosis through aberrant salience and lead to a diagnosis of schizophrenia. The hypothesis has one major implication for treatment approaches. Current treatments are acting downstream of the critical neurotransmitter abnormality. Future drug development and research into etiopathogenesis should focus on identifying and manipulating the upstream factors that converge on the dopaminergic funnel point.
Key findings
- This hypothesis seeks to be comprehensive in providing a framework that links risk factors, including pregnancy and obstetric complications, stress and trauma, drug use, and genes, to increased presynaptic striatal dopaminergic function.
- It explains how a complex array of pathological, positron emission tomography, magnetic resonance imaging, and other findings, such as frontotemporal structural and functional abnormalities and cognitive impairments, may converge neurochemically to cause psychosis through aberrant salience and lead to a diagnosis of schizophrenia.
- The hypothesis has one major implication for treatment approaches.
- Current treatments are acting downstream of the critical neurotransmitter abnormality.
- Future drug development and research into etiopathogenesis should focus on identifying and manipulating the upstream factors that converge on the dopaminergic funnel point.
Why it matters
This review proposes a revised dopamine hypothesis of schizophrenia that links risk factors to increased presynaptic striatal dopaminergic function. It is about schizophrenia, not Alzheimer's disease, and offers no treatment, cure or prevention for Alzheimer's disease.
Study details
- Evidence strengthLow
How this study scored 55/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Schizophrenia bulletin) |
| Journal's citation record | 3 / 4 | Schizophrenia Bulletin: journal h-index 298 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2009 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 7 / 7 | Cited 2,695 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 141.8 citations a year over 19 year(s) since 2009 |
| Impact for its field and year | 6 / 6 | Cited 70.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 4 / 4 | Cited 425 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Shitij Kapur: h-index 115 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Imperial College London: institution h-index 1,744 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 19325164) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Howes, O. D., & Kapur, S. (2009). The dopamine hypothesis of schizophrenia: version III--the final common pathway. Schizophrenia bulletin. https://doi.org/10.1093/schbul/sbp006
Vancouver
Howes OD, Kapur S. The dopamine hypothesis of schizophrenia: version III--the final common pathway. Schizophrenia bulletin. 2009. doi:10.1093/schbul/sbp006. PMID: 19325164.
BibTeX
@article{howes2009-19325164,
author = {Howes, O. D. and Kapur, S.},
title = {{The dopamine hypothesis of schizophrenia: version III--the final common pathway}},
journal = {Schizophrenia bulletin},
year = {2009},
doi = {10.1093/schbul/sbp006},
pmid = {19325164},
url = {https://doi.org/10.1093/schbul/sbp006}
}
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