Psychosis pathophysiology
|
Psychosis Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Psychosis pathophysiology On the Web |
|
American Roentgen Ray Society Images of Psychosis pathophysiology |
|
Risk calculators and risk factors for Psychosis pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Pathophysiology
Brain imaging studies of psychosis, investigating both changes in brain structure and changes in brain function of people undergoing psychotic episodes, have shown mixed results.
The first brain image of an individual with psychosis was completed as far back as 1935 using a technique called pneumoencephalography[1] (a painful and now obsolete procedure where cerebrospinal fluid is drained from around the brain and replaced with air to allow the structure of the brain to show up more clearly on an X-ray picture).
More recently, a 2003 study investigating structural changes in the brains of people with psychosis showed there was significant grey matter reduction in the cortex of people before and after they became psychotic.[2] Findings such as these have led to debate about whether psychosis is itself neurotoxic and whether potentially damaging changes to the brain are related to the length of psychotic episode. Recent research has suggested that this is not the case[3] although further investigation is still ongoing.
Functional brain scans have revealed that the areas of the brain that react to sensory perceptions are active during psychosis. For example, a PET or fMRI scan of a person who claims to be hearing voices may show activation in the auditory cortex, or parts of the brain involved in the perception and understanding of speech.[4]
On the other hand, there is not a clear enough psychological definition of belief to make a comparison between different people particularly valid. Brain imaging studies on delusions have typically relied on correlations of brain activation patterns with the presence of delusional beliefs.[5]
One clear finding is that persons with a tendency to have psychotic experiences seem to show increased activation in the right hemisphere of the brain.[6] This increased level of right hemisphere activation has also been found in healthy people who have high levels of paranormal beliefs[7] and in people who report mystical experiences.[8] It also seems to be the case that people who are more creative are also more likely to show a similar pattern of brain activation.[9] Some researchers have been quick to point out that this in no way suggests that paranormal, mystical or creative experiences are in any way by themselves a symptom of mental illness, as it is still not clear what makes some such experiences beneficial whilst others lead to the impairment or distress of diagnosable mental pathology. However, people who have profoundly different experiences of reality or hold unusual views or opinions have traditionally held a complex role in society, with some being viewed as kooks, whilst others are lauded as prophets or visionaries.
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 overactivity 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. antipsychotics) 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).[10] 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 dopinergic 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.[11] Soyka and colleagues found no evidence of dopaminergic dysfunction in people with alcohol-induced psychosis[12] 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.[13]
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 aetiology of psychosis.[14]
Some theories regard many psychotic symptoms to be a problem with the perception of ownership of internally generated thoughts and experiences.[15] 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
- ↑ Moore, M T (1935). "Encephalographic studies in mental disease". American Journal of Psychiatry. 92 (1): 43–67. Unknown parameter
|coauthors=ignored (help) - ↑ Pantelis, C (2003). "Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison". Lancet. PubMed. 25 (361 (9354)): 281–8. PMID 12559861. Retrieved 2006-08-19. Unknown parameter
|coauthors=ignored (help) - ↑ Ho, BC (2003). "Untreated initial psychosis: relation to cognitive deficits and brain morphology in first-episode schizophrenia". American Journal of Psychiatry. PubMed. 160 (1): 142–148. PMID 12505813. Retrieved 2006-08-19. Unknown parameter
|coauthors=ignored (help) - ↑ Copolov DL, Seal ML, Maruff P, Ulusoy R, Wong MT, Tochon-Danguy HJ, Egan GF. (2003) Cortical activation associated with the experience of auditory hallucinations and perception of human speech in schizophrenia: a PET correlation study. Psychiatry Res, 122 (3), 139-52. PMID 12694889.
- ↑ Bell, V., Halligan, P.W. & Ellis, H.D. (2006) A Cognitive Neuroscience of Belief. In P.W. Halligan & M. Aylward (eds) The Power of Belief. Oxford: Oxford University Press.
- ↑ Lohr, JB (1997). "Lateralized hemispheric dysfunction in the major psychotic disorders: historical perspectives and findings from a study of motor asymmetry in older patients". Schizophrophrenia Research. PubMed. 30 (27 (2-3)): 191–8. PMID 9416648. Retrieved 2006-08-19. Unknown parameter
|coauthors=ignored (help) - ↑ Pizaagalli, D (2000). "Brain electric correlates of strong belief in paranormal phenomena: intracerebral EEG source and regional Omega complexity analyses". Psychiatry Research. PubMed. 100 (3): 139–154. PMID 11120441. Retrieved 2006-08-19. Unknown parameter
|coauthors=ignored (help) - ↑ Makarec, K (1985). "Temporal lobe signs: electroencephalographic validity and enhanced scores in special populations". Perceptual and Motor Skills. PubMed. 60 (3): 831–842. PMID 3927256. Retrieved 2006-08-19. Unknown parameter
|coauthors=ignored (help) - ↑ Weinstein, S (2002). "Are creativity and schizotypy products of a right hemisphere bias?". Brain and Cognition. PubMed. 49 (1): 138–151. PMID 12027399. Retrieved 2006-08-19. Unknown parameter
|coauthors=ignored (help) - ↑ 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
- ↑ Jones, H. M., & Pilowsky, L. S. (2002) Dopamine and antipsychotic drug action revisited. British Journal of Psychiatry, 181, 271-275. PMID 12356650
- ↑ 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) - ↑ 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) - ↑ Healy, David (2002). The Creation of Psychopharmacology. Cambridge: Harvard University Press. ISBN 0-674-00619-4. Text "David Healy " ignored (help)
- ↑ 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)