Psychosis pathophysiology

Jump to navigation Jump to search

Psychosis Microchapters


Patient Information


Historical Perspective




Differentiating Psychosis from other Diseases

Epidemiology and Demographics

Risk Factors


Natural History, Complications and Prognosis


History and Symptoms

Physical Examination

Laboratory Findings


Other Diagnostic Studies


Medical Therapy

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Psychosis pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides


American Roentgen Ray Society Images of Psychosis pathophysiology

All Images
Echo & Ultrasound
CT Images

Ongoing Trials at Clinical

US National Guidelines Clearinghouse

NICE Guidance

FDA on Psychosis pathophysiology

CDC on Psychosis pathophysiology

Psychosis pathophysiology in the news

Blogs on Psychosis pathophysiology

Directions to Hospitals Treating Psychosis

Risk calculators and risk factors for Psychosis pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Vindhya BellamKonda, M.B.B.S [2]


Psychosis has been traditionally linked to the neurotransmitter dopamine. In particular, the dopamine hypothesis of psychosis has been influential and states that psychosis results from an over-activity of dopamine function in the brain, particularly in the mesolimbic pathway. The two major sources of evidence given to support this theory are that dopamine-blocking drugs (i.e. anti psychotics) tend to reduce the intensity of psychotic symptoms, and that drugs which boost dopamine activity (such as amphetamine and cocaine) can trigger psychosis in some people (see amphetamine psychosis).[1] However, increasing evidence in recent times has pointed to a possible dysfunction of the excitory neurotransmitter glutamate, in particular, with the activity of the NMDA receptor. This theory is reinforced by the fact that dissociative NMDA receptor antagonists such as ketamine, PCP and dextromethorphan/dextrorphan (at large overdoses) induce a psychotic state more readily than dopaminergic stimulants, even at "normal" recreational doses. The symptoms of dissociative intoxication are also considered to mirror the symptoms of schizophrenia more closely, including negative psychotic symptoms than amphetamine psychosis. Dissociative induced psychosis happens on a more reliable and predictable basis than amphetamine psychosis, which usually only occurs in cases of overdose, prolonged use or with sleep deprivation, which can independantly produce psychosis. New antipsychotic drugs which act on glutamate and it's receptors are currently undergoing clinical trials. (See glutamate hypothesis of psychosis)

The connection between dopamine and psychosis is generally believed to be complex. While antipsychotic drugs immediately block dopamine receptors, they usually take a week or two to reduce the symptoms of psychosis. Moreover, newer and equally effective antipsychotic drugs actually block slightly less dopamine in the brain than older drugs whilst also affecting serotonin function, suggesting the 'dopamine hypothesis' may be oversimplified.[2] Soyka and colleagues found no evidence of dopaminergic dysfunction in people with alcohol-induced psychosis[3] and Zoldan et al. reported moderately successful use of ondansetron, a 5-HT3 receptor antagonist, in the treatment of levodopa psychosis in Parkinson's disease patients.[4]

Psychiatrist David Healy has criticised pharmaceutical companies for promoting simplified biological theories of mental illness that seem to imply the primacy of pharmaceutical treatments while ignoring social and developmental factors which are known to be important influences in the etiology of psychosis.[5]

Some theories regard many psychotic symptoms to be a problem with the perception of ownership of internally generated thoughts and experiences.[6] For example, the experience of hearing voices may arise from internally generated speech that is mislabeled by the psychotic person as coming from an external source.


  1. Kapur S, Mizrahi R, Li M. (2005) From dopamine to salience to psychosis - linking biology, pharmacology and phenomenology of psychosis. Schizophr Res, 79 (1), 59-68. PMID 16005191
  2. Jones, H. M., & Pilowsky, L. S. (2002) Dopamine and antipsychotic drug action revisited. British Journal of Psychiatry, 181, 271-275. PMID 12356650
  3. Soyka, Michael (2000). "FDG-PET and IBZM-SPECT Suggest Reduced Thalamic Activity but No Dopaminergic Dysfunction in Chronic Alcohol Hallucinosis". Journal of Neuropsychiatry & Clinical Neurosciences. 12 (2): 287–288. PMID 11001615. Retrieved 2006-10-15. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  4. Zoldan, J. (1995). "Psychosis in advanced Parkinson's disease: treatment with ondansetron, a 5-HT3 receptor antagonist". Neurology. 45 (7): 1305–1308. PMID 7617188. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  5. Healy, David (2002). The Creation of Psychopharmacology. Cambridge: Harvard University Press. ISBN 0-674-00619-4. Text "David Healy " ignored (help)
  6. Blakemore, SJ (2000). "The perception of self-produced sensory stimuli in patients with auditory hallucinations and passivity experiences: evidence for a breakdown in self-monitoring". Psychological Medicine. PubMed. 30 (5): 1131–9. PMID 12027049. Retrieved 2006-08-19. Unknown parameter |coauthors= ignored (help)

Template:WH Template:WS