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Studies suggest that [[genetics]], early [[Environmental Health Perspectives|environmental]], neurobioloic, [[psychological]] and [[Social (pragmatic) communication disorder|socia]]<nowiki/>l processes are important contributory [[Factors 2a|factors]] in the [[development]] of [[schizophrenia]]. Current [[psychiatric]] [[research]] is focused on the role of [[neurobiology]], but a clear [[Organic Chemistry|organic]] [[Cause system|cause]] has not been found.
Studies suggest that [[genetics]], early [[Environmental Health Perspectives|environmental]], neurobioloic, [[psychological]] and [[Social (pragmatic) communication disorder|socia]]<nowiki/>l processes are important contributory [[Factors 2a|factors]] in the [[development]] of [[schizophrenia]]. Current [[psychiatric]] [[research]] is focused on the role of [[neurobiology]], but a clear [[Organic Chemistry|organic]] [[Cause system|cause]] has not been found.


== Pathophysiology ==
==Pathophysiology==
Differences in the size and [[Structure and genome of HIV|structure]] of certain [[brain]] areas have been found in some adults diagnosed with [[schizophrenia]]. Early [[Findings on urinalysis|findings]] came from the discovery of [[ventricular system|ventricular]] enlargement in people diagnosed with [[schizophrenia]] with [[Negative-sense|negative]] [[symptoms]] most prominent.<ref name="fn_29">Johnstone EC, Crow TJ, Frith CD, Husband J, Kreel L. (1976). Cerebral ventricular size and cognitive impairment in chronic schizophrenia. ''Lancet'', 30;2 (7992), 924–6. PMID 62160</ref> However, this [[Findings on urinalysis|finding]] has not proved particularly reliable on the level of the [[Individual analytical psychodrama|individual]] person, with considerable variation between [[patients]].


More recent [[Studies on Hysteria|studies]] have shown a large number of differences in [[brain]] [[Structure and genome of HIV|structure]] between people with and without diagnoses of [[schizophrenia]].<ref name="fn_30">Flashman LA, Green MF (2004). Review of cognition and brain structure in schizophrenia: profiles, longitudinal course, and effects of treatment. ''Psychiatric Clinics of North America'', 27 (1), 1–18, vii. PMID 15062627 </ref> However, as with earlier studies, many of these differences are only reliably detected when comparing groups of people, and are unlikely to predict any differences in [[brain]] structure of an individual person with [[schizophrenia]].
*Differences in the size and [[Structure and genome of HIV|structure]] of certain [[brain]] areas have been found in some adults diagnosed with [[schizophrenia]].
*Early [[Findings on urinalysis|findings]] came from the discovery of [[ventricular system|ventricular]] enlargement in people diagnosed with [[schizophrenia]] with [[Negative-sense|negative]] [[symptoms]] most prominent.<ref name="fn_29">Johnstone EC, Crow TJ, Frith CD, Husband J, Kreel L. (1976). Cerebral ventricular size and cognitive impairment in chronic schizophrenia. ''Lancet'', 30;2 (7992), 924–6. PMID 62160</ref>
*However, this [[Findings on urinalysis|finding]] has not proved particularly reliable on the level of the [[Individual analytical psychodrama|individual]] person, with considerable variation between [[patients]].
 
*More recent [[Studies on Hysteria|studies]] have shown a large number of differences in [[brain]] [[Structure and genome of HIV|structure]] between people with and without diagnoses of [[schizophrenia]].<ref name="fn_30">Flashman LA, Green MF (2004). Review of cognition and brain structure in schizophrenia: profiles, longitudinal course, and effects of treatment. ''Psychiatric Clinics of North America'', 27 (1), 1–18, vii. PMID 15062627 </ref>  
*However, as with earlier studies, many of these differences are only reliably detected when comparing groups of people and are unlikely to predict any differences in [[brain]] structure of an individual person with [[schizophrenia]].


[[Image:FMRI.jpg|thumb|[[Functional magnetic resonance imaging]] and other [[brain imaging]] technologies allow for the study of differences in brain activity among people diagnosed with schizophrenia.]]
[[Image:FMRI.jpg|thumb|[[Functional magnetic resonance imaging]] and other [[brain imaging]] technologies allow for the study of differences in brain activity among people diagnosed with schizophrenia.]]
===Brain structure and Imaging===
===Brain structure and Imaging===
Studies using [[neuropsychological test]]s and [[brain imaging]] technologies such as [[Functional magnetic resonance imaging|fMRI]] and [[Positron emission tomography|PET]] to examine [[Functional Analytic Psychotherapy|functional]] differences in [[brain]] activity have shown that differences seem to most commonly occur in the [[frontal lobe]]s, [[hippocampus]], and [[temporal lobe]]s.<ref name="fn_31">Green, M.F. (2001) ''Schizophrenia Revealed: From Neurons to Social Interactions''. New York: W.W. Norton. ISBN 0-393-70334-7</ref> These differences are heavily linked to the [[neurocognitive deficit]] often asssociated with [[schizophrenia]], particularly in areas of [[memory]], [[attention]], [[problem solving]], [[executive function]], and [[social cognition]].
*Studies using [[neuropsychological test]]s and [[brain imaging]] technologies such as [[Functional magnetic resonance imaging|fMRI]] and [[Positron emission tomography|PET]] to examine [[Functional Analytic Psychotherapy|functional]] differences in [[brain]] activity have shown that differences seem to most commonly occur in the [[frontal lobe]]s, [[hippocampus]], and [[temporal lobe]]s.<ref name="fn_31">Green, M.F. (2001) ''Schizophrenia Revealed: From Neurons to Social Interactions''. New York: W.W. Norton. ISBN 0-393-70334-7</ref>  
*These differences are heavily linked to the [[neurocognitive deficit]] often asssociated with [[schizophrenia]], particularly in areas of [[memory]], [[attention]], [[problem solving]], [[executive function]], and [[social cognition]].


A recent study by UCLA researchers [http://www.loni.ucla.edu/~thompson/MEDIA/PNAS/yahoo.html] involved [[MRI]] scanning in recently diagnosed [[schizophrenic]] [[patients]] over a period of 5 years. Researchers found a dramatic destruction of [[gray matter]] in a short period of time in those diagnosed, the destruction spreading from the back of the [[brain]] to the front over time. Interestingly, when the destruction had reached the [[frontal lobe]], the most acute [[symptoms]] arose, and severe [[delusions]] began. Those with the most severe symptoms were shown to have lost the most brain matter per year. This study is important in shedding light on [[schizophrenia]] as a [[Physical culture|physical]] disorder of the [[brain]] and less likely "a [[disease]] invented by society".
*A recent study by UCLA researchers [http://www.loni.ucla.edu/~thompson/MEDIA/PNAS/yahoo.html] involved [[MRI]] scanning in recently diagnosed [[schizophrenic]] [[patients]] over a period of 5 years.  
*Researchers found a dramatic destruction of [[gray matter]] in a short period of time in those diagnosed, the destruction spreading from the back of the [[brain]] to the front over time.  
*Interestingly, when the destruction had reached the [[frontal lobe]], the acutest [[symptoms]] arose, and severe [[delusions]] began.  
*Those with the most severe symptoms were shown to have lost the most brain matter per year.  
*This study is important in shedding light on [[schizophrenia]] as a [[Physical culture|physical]] disorder of the [[brain]] and less likely "a [[disease]] invented by society".


There have also been [[Findings on urinalysis|findings]] of differences in the [[Size consistency|size]] and [[Structure and genome of HIV|structure]] of certain [[brain]] areas in [[schizophrenia]], starting with the discovery of [[ventricular system|ventricular]] enlargement in those for whom [[Negative-sense|negative]] [[symptoms]] were most prominent.<ref name="fn_29">Johnstone EC, Crow TJ, Frith CD, Husband J, Kreel L. (1976). Cerebral ventricular size and cognitive impairment in chronic schizophrenia. ''Lancet'', 30;2 (7992), 924–6. PMID 62160</ref> However, this has not proven particularly reliable on the level of the individual person, with considerable variation between [[patients]]. More recent [[Studies on Hysteria|studies]] have shown various differences in [[brain]] structure between people with and without diagnoses of [[schizophrenia]].<ref name="fn_30">Flashman LA, Green MF (2004). Review of cognition and brain structure in schizophrenia: profiles, longitudinal course, and effects of treatment. ''Psychiatric Clinics of North America'', 27 (1), 1–18, vii. PMID 15062627 </ref> However, as with earlier studies, many of these differences are only reliably detected when comparing groups of people, and are unlikely to predict any differences in [[brain]] structure of an individual person with [[schizophrenia]].
*There have also been [[Findings on urinalysis|findings]] of differences in the [[Size consistency|size]] and [[Structure and genome of HIV|structure]] of certain [[brain]] areas in [[schizophrenia]], starting with the discovery of [[ventricular system|ventricular]] enlargement in those for whom [[Negative-sense|negative]] [[symptoms]] were most prominent.<ref name="fn_29">Johnstone EC, Crow TJ, Frith CD, Husband J, Kreel L. (1976). Cerebral ventricular size and cognitive impairment in chronic schizophrenia. ''Lancet'', 30;2 (7992), 924–6. PMID 62160</ref>  
*However, this has not proven particularly reliable on the level of the individual person, with considerable variation between [[patients]].  
*More recent [[Studies on Hysteria|studies]] have shown various differences in [[brain]] structure between people with and without diagnoses of [[schizophrenia]].<ref name="fn_30">Flashman LA, Green MF (2004). Review of cognition and brain structure in schizophrenia: profiles, longitudinal course, and effects of treatment. ''Psychiatric Clinics of North America'', 27 (1), 1–18, vii. PMID 15062627 </ref>  
*However, as with earlier studies, many of these differences are only reliably detected when comparing groups of people and are unlikely to predict any differences in [[brain]] structure of an individual person with [[schizophrenia]].


===Electroencephalography===
===Electroencephalography===
[[Electroencephalography|Electroencephalograph]] (EEG) recordings of persons with [[schizophrenia]] performing perception oriented tasks showed an absence of [[gamma]] band activity in the brain, indicating weak integration of critical neural networks in the [[brain]].<ref name="fn_32">Spencer KM, Nestor PG, Perlmutter R, ''et al'' (2004). Neural synchrony indexes disordered perception and cognition in schizophrenia. ''Proceedings of the National Academy of Sciences'', 101, 17288-93. PMID 15546988 [http://www.pnas.org/cgi/content/abstract/101/49/17288?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Neural+synchrony+indexes+disordered+perception+and+cognition+in+schizophrenia&searchid=1119032609298_6266&stored_search=&FIRSTINDEX=0&journalcode=pnas Full text], Retrieved [[2007-05-16]].</ref> Those who experienced intense [[hallucinations]], [[delusions]] and disorganized thinking showed the lowest frequency synchronization. None of the [[Drugs (patient information)|drugs]] taken by the persons scanned had moved neural synchrony back into the [[Gamma-One|gamma]] frequency range. Gamma band and working [[memory]] alterations may be related to alterations in [[interneuron]]s that produce the [[neurotransmitter]] [[GABA]].
 
*[[Electroencephalography|Electroencephalograph]] (EEG) recordings of persons with [[schizophrenia]] performing perception oriented tasks showed an absence of [[gamma]] band activity in the brain, indicating weak integration of critical neural networks in the [[brain]].<ref name="fn_32">Spencer KM, Nestor PG, Perlmutter R, ''et al'' (2004). Neural synchrony indexes disordered perception and cognition in schizophrenia. ''Proceedings of the National Academy of Sciences'', 101, 17288-93. PMID 15546988 [http://www.pnas.org/cgi/content/abstract/101/49/17288?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Neural+synchrony+indexes+disordered+perception+and+cognition+in+schizophrenia&searchid=1119032609298_6266&stored_search=&FIRSTINDEX=0&journalcode=pnas Full text], Retrieved [[2007-05-16]].</ref>  
*Those who experienced intense [[hallucinations]], [[delusions]] and disorganized thinking showed the lowest frequency synchronization.  
*None of the [[Drugs (patient information)|drugs]] taken by the persons scanned had moved neural synchrony back into the [[Gamma-One|gamma]] frequency range.  
*Gamma band and working [[memory]] alterations may be related to alterations in [[interneuron]]s that produce the [[neurotransmitter]] [[GABA]].
 
===Dopamine===
===Dopamine===
Particular focus has been placed upon the function of [[dopamine]] in the [[mesolimbic pathway]] of the [[brain]]. This focus largely resulted from the accidental [[Findings on urinalysis|finding]] that a [[drug]] group which blocks [[dopamine]] function, known as the [[phenothiazines]], could reduce [[psychotic]] [[symptoms]]. An influential [[theory]], known as the "dopamine hypothesis of [[schizophrenia]]", proposed that a malfunction involving [[dopamine]] pathways was therefore the [[Cause system|cause]] of (the positive symptoms of) [[schizophrenia]]. This theory is now thought to be overly simplistic as a complete explanation, partly because newer [[antipsychotic]] [[medication]] (called [[atypical antipsychotic]] medication) can be equally effective as older medication (called [[typical antipsychotic]] medication) while also affecting [[serotonin]] function and having somewhat less of a [[dopamine]] blocking effect. In addition, [[dopamine]] pathway [[dysfunction]] has not been reliably shown to correlate with [[symptom]] onset or severity.
 
*Particular focus has been placed upon the function of [[dopamine]] in the [[mesolimbic pathway]] of the [[brain]].  
*This focus largely resulted from the accidental [[Findings on urinalysis|finding]] that a [[drug]] group which blocks [[dopamine]] function, known as the [[phenothiazines]], could reduce [[psychotic]] [[symptoms]].  
*An influential [[theory]], known as the "dopamine hypothesis of [[schizophrenia]]", proposed that a malfunction involving [[dopamine]] pathways was therefore the [[Cause system|cause]] of (the positive symptoms of) [[schizophrenia]].  
*This theory is now thought to be overly simplistic as a complete explanation, partly because newer [[antipsychotic]] [[medication]] (called [[atypical antipsychotic]] medication) can be equally effective as older medication (called [[typical antipsychotic]] medication) while also affecting [[serotonin]] function and having somewhat less of a [[dopamine]] blocking effect.  
**In addition, [[dopamine]] pathway [[dysfunction]] has not been reliably shown to correlate with [[symptom]] onset or severity.
 
===Glutamate===
===Glutamate===
Interest has also focused on the [[neurotransmitter]] [[glutamate]] and the reduced function of the [[NMDA receptor|NMDA glutamate receptor]] in [[schizophrenia]]. This has largely been suggested by abnormally low levels of [[glutamate]] [[receptors]] found in [[postmortem]] [[Brainstem|brains]] of people previously diagnosed with [[schizophrenia]]<ref name="fn_27">Konradi C, Heckers S. (2003). Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment. ''Pharmacology and Therapeutics'', 97(2), 153–79. PMID 12559388</ref> and the discovery that the [[glutamate]] blocking [[drugs]] such as [[phencyclidine]] and [[ketamine]] can mimic the [[symptoms]] and [[cognitive]] [[Problems with coordination|problems]] associated with the [[condition]].<ref name="fn_59">Lahti AC, Weiler MA, Tamara Michaelidis BA, Parwani A, Tamminga CA. (2001). Effects of ketamine in normal and schizophrenic volunteers. ''Neuropsychopharmacology'', 25(4), 455–67. PMID 11557159</ref> The fact that reduced glutamate [[Function (biology)|function]] is linked to poor performance on tests requiring [[frontal lobe]] and [[hippocampus|hippocampal]] function and that [[glutamate]] can affect [[dopamine]] function, all of which have been implicated in [[schizophrenia]], have suggested an important mediating (and possibly causal) role of [[glutamate]] pathways in [[Schizophrenia, genetic types|schizophrenia]].<ref name="fn_28">Coyle JT, Tsai G, Goff D. (2003). Converging evidence of NMDA receptor hypofunction in the pathophysiology of schizophrenia. ''Annals of the New York Academy of Sciences'', 1003, 318–27. PMID 14684455</ref> Further support of this theory has come from preliminary trials suggesting the efficacy of coagonists at the [[NMDA receptor]] complex in reducing some of the [[Positive-sense RNA|positive]] [[symptoms]] of [[schizophrenia]].<ref name="fn_60">Tuominen HJ, Tiihonen J, Wahlbeck K. (2005). Glutamatergic drugs for schizophrenia: a systematic review and meta-analysis. ''Schizophr Res'', 72:225–34. PMID 15560967</ref>
 
*Interest has also focused on the [[neurotransmitter]] [[glutamate]] and the reduced function of the [[NMDA receptor|NMDA glutamate receptor]] in [[schizophrenia]]. *This has largely been suggested by abnormally low levels of [[glutamate]] [[receptors]] found in [[postmortem]] [[Brainstem|brains]] of people previously diagnosed with [[schizophrenia]] and the discovery that the [[glutamate]] blocking [[drugs]] such as [[phencyclidine]] and [[ketamine]] can mimic the [[symptoms]] and [[cognitive]] [[Problems with coordination|problems]] associated with the [[condition]].<ref name="fn_27">Konradi C, Heckers S. (2003). Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment. ''Pharmacology and Therapeutics'', 97(2), 153–79. PMID 12559388</ref><ref name="fn_59">Lahti AC, Weiler MA, Tamara Michaelidis BA, Parwani A, Tamminga CA. (2001). Effects of ketamine in normal and schizophrenic volunteers. ''Neuropsychopharmacology'', 25(4), 455–67. PMID 11557159</ref>
*The fact that reduced glutamate [[Function (biology)|function]] is linked to poor performance on tests requiring [[frontal lobe]] and [[hippocampus|hippocampal]] function and that [[glutamate]] can affect [[dopamine]] function, all of which have been implicated in [[schizophrenia]], have suggested an important mediating (and possibly causal) role of [[glutamate]] pathways in [[Schizophrenia, genetic types|schizophrenia]].<ref name="fn_28">Coyle JT, Tsai G, Goff D. (2003). Converging evidence of NMDA receptor hypofunction in the pathophysiology of schizophrenia. ''Annals of the New York Academy of Sciences'', 1003, 318–27. PMID 14684455</ref> *Further support of this theory has come from preliminary trials suggesting the efficacy of coagonists at the [[NMDA receptor]] complex in reducing some of the [[Positive-sense RNA|positive]] [[symptoms]] of [[schizophrenia]].<ref name="fn_60">Tuominen HJ, Tiihonen J, Wahlbeck K. (2005). Glutamatergic drugs for schizophrenia: a systematic review and meta-analysis. ''Schizophr Res'', 72:225–34. PMID 15560967</ref>


==References==
==References==

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

Overview

Studies suggest that genetics, early environmental, neurobioloic, psychological and social processes are important contributory factors in the development of schizophrenia. Current psychiatric research is focused on the role of neurobiology, but a clear organic cause has not been found.

Pathophysiology

  • More recent studies have shown a large number of differences in brain structure between people with and without diagnoses of schizophrenia.[2]
  • However, as with earlier studies, many of these differences are only reliably detected when comparing groups of people and are unlikely to predict any differences in brain structure of an individual person with schizophrenia.
Functional magnetic resonance imaging and other brain imaging technologies allow for the study of differences in brain activity among people diagnosed with schizophrenia.

Brain structure and Imaging

  • A recent study by UCLA researchers [3] involved MRI scanning in recently diagnosed schizophrenic patients over a period of 5 years.
  • Researchers found a dramatic destruction of gray matter in a short period of time in those diagnosed, the destruction spreading from the back of the brain to the front over time.
  • Interestingly, when the destruction had reached the frontal lobe, the acutest symptoms arose, and severe delusions began.
  • Those with the most severe symptoms were shown to have lost the most brain matter per year.
  • This study is important in shedding light on schizophrenia as a physical disorder of the brain and less likely "a disease invented by society".
  • There have also been findings of differences in the size and structure of certain brain areas in schizophrenia, starting with the discovery of ventricular enlargement in those for whom negative symptoms were most prominent.[1]
  • However, this has not proven particularly reliable on the level of the individual person, with considerable variation between patients.
  • More recent studies have shown various differences in brain structure between people with and without diagnoses of schizophrenia.[2]
  • However, as with earlier studies, many of these differences are only reliably detected when comparing groups of people and are unlikely to predict any differences in brain structure of an individual person with schizophrenia.

Electroencephalography

  • Electroencephalograph (EEG) recordings of persons with schizophrenia performing perception oriented tasks showed an absence of gamma band activity in the brain, indicating weak integration of critical neural networks in the brain.[4]
  • Those who experienced intense hallucinations, delusions and disorganized thinking showed the lowest frequency synchronization.
  • None of the drugs taken by the persons scanned had moved neural synchrony back into the gamma frequency range.
  • Gamma band and working memory alterations may be related to alterations in interneurons that produce the neurotransmitter GABA.

Dopamine

Glutamate

References

  1. ↑ 1.0 1.1 Johnstone EC, Crow TJ, Frith CD, Husband J, Kreel L. (1976). Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet, 30;2 (7992), 924–6. PMID 62160
  2. ↑ 2.0 2.1 Flashman LA, Green MF (2004). Review of cognition and brain structure in schizophrenia: profiles, longitudinal course, and effects of treatment. Psychiatric Clinics of North America, 27 (1), 1–18, vii. PMID 15062627
  3. ↑ Green, M.F. (2001) Schizophrenia Revealed: From Neurons to Social Interactions. New York: W.W. Norton. ISBN 0-393-70334-7
  4. ↑ Spencer KM, Nestor PG, Perlmutter R, et al (2004). Neural synchrony indexes disordered perception and cognition in schizophrenia. Proceedings of the National Academy of Sciences, 101, 17288-93. PMID 15546988 Full text, Retrieved 2007-05-16.
  5. ↑ Konradi C, Heckers S. (2003). Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment. Pharmacology and Therapeutics, 97(2), 153–79. PMID 12559388
  6. ↑ Lahti AC, Weiler MA, Tamara Michaelidis BA, Parwani A, Tamminga CA. (2001). Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology, 25(4), 455–67. PMID 11557159
  7. ↑ Coyle JT, Tsai G, Goff D. (2003). Converging evidence of NMDA receptor hypofunction in the pathophysiology of schizophrenia. Annals of the New York Academy of Sciences, 1003, 318–27. PMID 14684455
  8. ↑ Tuominen HJ, Tiihonen J, Wahlbeck K. (2005). Glutamatergic drugs for schizophrenia: a systematic review and meta-analysis. Schizophr Res, 72:225–34. PMID 15560967

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