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]

Pathophysiology[edit | edit source]

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.

References[edit | edit source]

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