ArticleCNS neuroscience & therapeutics2011
All roads to schizophrenia lead to dopamine supersensitivity and elevated dopamine D2(high) receptors.
Article in CNS neuroscience & therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 3 of them syntheses that pooled it.
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Who cites it
93 citing papers in PubMed, 3 syntheses or guidelines pooled it, 221 citations in OpenAlex.
- Does tobacco use cause psychosis? Systematic review and meta-analysis.The lancet. Psychiatry · 2015Pooled it
- Pooled it
- The nature of dopamine dysfunction in schizophrenia and what this means for treatment.Archives of general psychiatry · 2012Pooled it
- Dopamine D2 receptor occupancy and cognition in schizophrenia: analysis of the CATIE data.Schizophrenia bulletin · 2013Trial
- Cognitive behavioral therapy for subjects at ultrahigh risk for developing psychosis: a randomized controlled clinical trial.Schizophrenia bulletin · 2012Trial
- Robust changes in brain function require high DNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Dopamine supersensitivity psychosis: a critical evaluation of diagnostic validators.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Tryptophan Supplementation Reduces Schizophrenia-Like Symptoms in Apomorphine Treated Rats: Role of D2, GABA, and Glutamate Receptor Expression.International journal of tryptophan research : IJTR · 2026Article
- Resting-State EEG Characteristics of Tardive Dyskinesia: Spectral and Network Connectivity Insights.Neuropsychiatric disease and treatment · 2026Article
- Drawbacks of Olanzapine Therapy: An Emphasis on Its Metabolic Effects and Discontinuation.Journal of clinical medicine · 2025Review
- Telmisartan mitigates behavioral and cytokine level alterations but impairs spatial working memory in a phencyclidine-induced mouse model of schizophrenia.Psychopharmacology · 2025Article
- Molecular Underpinning of Treatment-Resistant Schizophrenia: A Putative Different Neurobiology from Treatment-Responsive Schizophrenia.International journal of molecular sciences · 2025Review
- Underexplored Connections Between Diabetes, Hypomanic States and Insecure Attachment.Psychology research and behavior management · 2025Review
- [Living with psychotropic drugs: A community photovoice study in people with high treatment adherence in Southeastern Spain].Salud colectiva · 2024Article
- Global research trends and hotspots in Parkinson's disease psychosis: a 25-year bibliometric and visual analysis.Frontiers in aging neuroscience · 2024Article
- Dopamine Dynamics and Neurobiology of Non-Response to Antipsychotics, Relevance for Treatment Resistant Schizophrenia: A Systematic Review and Critical Appraisal.Biomedicines · 2023Review
- Should psychiatrists be more cautious about the use of antipsychotics for patients with borderline personality disorder?Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999) · 2022Article
- Using Computational Modeling to Capture Schizophrenia-Specific Reinforcement Learning Differences and Their Implications on Patient Classification.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2022Article
- The effects of social isolation stress and discrimination on mental health.Translational psychiatry · 2022Review
- Dopamine, Psychosis, and Symptom Fluctuation: A Narrative Review.Healthcare (Basel, Switzerland) · 2022Review
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe dopamine D2 receptor is the common target for antipsychotics, and the antipsychotic clinical doses correlate with their affinities for this receptor. Antipsychotics quickly enter the brain to occupy 60-80% of brain D2 receptors in patients (the agonist aripiprazole occupies up to 90%), with most clinical improvement occurring within a few days. The D2 receptor can exist in a state of high-affinity (D2(High) ) or in a state of low-affinity for dopamine (D2Low).
aimThe present aim is to review why individuals with schizophrenia are generally supersensitive to dopamine-like drugs such as amphetamine or methyphenidate, and whether the D2(High) state is a common basis for dopamine supersensitivity in the animal models of schizophrenia.
resultsAll animal models of schizophrenia reveal elevations in D2(High) receptors. These models include brain lesions, sensitization by drugs (amphetamine, phencyclidine, cocaine, corticosterone), birth injury, social isolation, and gene deletions in pathways for NMDA, dopamine, GABA, acetylcholine, and norepinephrine.
conclusionsThese multiple abnormal pathways converge to a final common pathway of dopamine supersensitivity and elevated D2(High) receptors, presumably responsible for psychotic symptoms. Although antipsychotics alleviate psychosis and reverse the elevation of D2(High) receptors, long-term antipsychotics can further enhance dopamine supersensitivity in patients. Therefore, switching from a traditional antipsychotic to an agonist antipsychotic (aripiprazole) can result in psychotic signs and symptoms. Clozapine and quetiapine do not elicit parkinsonism or tardive dyskinesia because they are released from D2 within 12 to 24 h. Traditional antipsychotics remain attached to D2 receptors for days, preventing relapse, but allowing accumulation that can lead to tardive dyskinesia. Future goals include imaging D2(High) receptors and desensitizing them in early-stage psychosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.