title: A critique of the dopamine hypothesis of schizophrenia and psychosis.
abstract: The dopamine hypothesis of schizophrenia and psychosis originated from observations of the dopamine-blocking actions of early neuroleptic drugs. These results support the dopamine hypothesis, however, only on the assumption that the drugs act by reversing an underlying disease mechanism (or part of it). An alternative explanation is that the drugs work by inducing a state of neurological suppression that reduces the intensity of symptoms. Although stimulant drugs are known to induce episodes of psychosis, the mechanism for stimulant-induced psychosis has not been clarified, and stimulants are known to affect many neurotransmitters other than dopamine. Recent imaging studies suggest that there may be increased dopamine release in response to amphetamine administration compared to controls. Some studies indicate increased uptake of L-dopa in parts of the striatum, but some do not. The potential confounding effects of factors associated with dopamine release--such as movement, arousal, attention, stress, and smoking--have rarely been examined, and prior medication use may also have influenced results in some studies. Comparable research on other psychiatric conditions associated with increased arousal, stress, and physical activity is sparse. Research on dopamine concentrations in postmortem brain tissue, on homovanillic acid concentrations, and on dopamine receptors has been negative or inconclusive. Therefore, the idea that the symptoms of psychosis or schizophrenia are caused by the overactivity of dopamine is not supported by current evidence.
authors.affiliation: Department of Mental Health Sciences, University College London, North East London Mental Health Trust, London, UK. j.moncrieff@ucl.ac.uk
authors.forename: Joanna
authors.initials: J
authors.lastname: Moncrieff
mesh_terms: D014150:Antipsychotic Agents / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D006801:Humans; D007980:Levodopa / Q000378:metabolism; D008959:Models, Neurological; D011618:Psychotic Disorders / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D007980:Levodopa; D004298:Dopamine