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(New page: {{ClinPsy}} ===Perinatal brain development=== It is thought that causal factors can initially come together in early neurodevelopment, including during pregnancy, to increase the risk ...)
 
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{{ClinPsy}}
 
{{ClinPsy}}
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Research indicates that a number of neuroanatomical features differ between groups of people with schizophrenia and groups of matched controls.
  +
 
===Adult brain structure===
 
Differences in the size and structure of certain brain areas have been found in some adults diagnosed with schizophrenia. Early findings came from the discovery of [[ventricular system|ventricular]] enlargement in people diagnosed with schizophrenia with negative symptoms most prominent.<ref name="fn_29">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=62160 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.<br></ref> However, this finding has not proved particularly reliable on the level of the individual person, with considerable variation between patients. The role of antipsychotic medication, which nearly all those studied had taken, in causing such abnormalities is also unclear.<ref>http://ajp.psychiatryonline.org/cgi/content/full/156/11/1843-b</ref>
  +
 
More recent studies have shown a large number of differences in brain structure between people with and without diagnoses of schizophrenia.<ref name="fn_30">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15062627 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.<br></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.
  +
 
===Neuropsychology and brain function===
 
Studies using [[neuropsychological test]]s and [[brain imaging]] technologies such as [[Functional magnetic resonance imaging|fMRI]] and [[Positron emission tomography|PET]] to examine 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<br></ref> These differences are heavily linked to the [[neurocognitive deficit]]s which often occur with schizophrenia, particularly in areas of [[memory]], [[attention]], [[problem solving]], [[executive function]] and [[social cognition]].
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  +
==Schizophrenia and the frontal lobes==
 
[[Image:Schizophrenia_PET_scan.jpg|frame|Data from a [[Positron emission tomography|PET]] study<ref name="fn_25">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11865311 Meyer-Lindenberg A, Miletich RS, Kohn PD, Esposito G, Carson RE, Quarantelli M, Weinberger DR, Berman KF (2002)] Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia. ''Nature Neuroscience'', 5, 267-71.<br></ref> suggests that the less the [[frontal lobe]]s are activated (<font color="red">red</font>) during a [[working memory]] task, the greater the increase in abnormal [[dopamine]] activity in the [[striatum]] (<font color="green">green</font>), thought to be related to the [[neurocognitive deficit]]s in schizophrenia.]]
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{{Main|Schizophrenia - Frontal lobes}}
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{{Main|Schizophrenia - Hippocampus}}
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  +
{{Main|Schizophrenia - Temporal lobes}}
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  +
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==Schizophrenia and neural integration==
 
[[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">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15546988&query_hl=1 Spencer KM, Nestor PG, Perlmutter R, Niznikiewicz MA, Klump MC, Frumin M, Shenton ME, McCarley (2004)] Neural synchrony indexes disordered perception and cognition in schizophrenia. ''Proceedings of the National Academy of Sciences'', 101, 17288-93. ([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])<br></ref> 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 [[interneuron]]s that produced the neurotransmitter [[GABA]].
  +
  +
  +
There are a number of theories about how these structural differences occur:
  +
  +
==Genetic factors in neuroanatomical development==
  +
  +
  +
==Developmental aspects==
 
===Perinatal brain development===
 
===Perinatal brain development===
It is thought that causal factors can initially come together in early [[neurodevelopment]], including during pregnancy, to increase the risk of later developing schizophrenia. One curious finding is that people diagnosed with schizophrenia are more likely to have been born in [[winter]] or [[spring (season)|spring]]<ref name="fn_21">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14609251 Davies G, Welham J, Chant D, Torrey EF, McGrath J. (2003)] A [[systematic review]] and meta-analysis of Northern Hemisphere season of birth studies in schizophrenia. ''Schizophrenia Bulletin'', 29 (3), 587&ndash;93.<br></ref> (at least in the [[northern hemisphere]]). However, the effect is not large. Some researchers postulate that the correlation is due to viral infections during the third trimester (4-6 months) of pregnancy. There is now significant evidence that [[prenatal]] exposure to infections increases the risk for developing schizophrenia later in life, providing additional evidence for a link between in utero developmental pathology and risk of developing the condition.<ref name="fn_73">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16469941&query_hl=1&itool=pubmed_docsum Brown, A.S. (2006)] Prenatal infection as a risk factor for schizophrenia. ''Schizophrenia Bulletin'', 32 (2), 200-2.<br></ref>
+
It is thought that some of the neuroanatmical features associated with early [[neurodevelopment]], including during pregnancy, to increase the risk of later developing schizophrenia. One curious finding is that people diagnosed with schizophrenia are more likely to have been born in winter or spring<ref name="fn_21">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14609251 Davies G, Welham J, Chant D, Torrey EF, McGrath J. (2003)] A [[systematic review]] and meta-analysis of Northern Hemisphere season of birth studies in schizophrenia. ''Schizophrenia Bulletin'', 29 (3),587&ndash;93.<br></ref> (at least in the [[northern hemisphere]]).
  +
  +
{{Main|Schizophrenia - Season of birth}}
  +
  +
However, the effect is not large. Some researchers postulate that the correlation is due to viral infections during the third trimester (4-6 months) of pregnancy. There is now significant evidence that [[prenatal]] exposure to infections increases the risk for developing schizophrenia later in life, providing additional evidence for a link between in utero developmental pathology and risk of developing the condition.<ref name="fn_73">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16469941&query_hl=1&itool=pubmed_docsum Brown, A.S. (2006)] Prenatal infection as a risk factor for schizophrenia. ''Schizophrenia Bulletin'', 32 (2), 200-2.<br></ref>
  +
  +
{{Main|Schizophrenia - Link with early infection}}
   
 
A study by Sweden's Karolinska Institute and Bristol University in the UK, looked at the medical records of over 700,000 people and calculated that 15.5% of cases of schizophrenia seen in the group may have been due to the patient having a father who was aged over 30 years at their birth, the researchers argue this is due to build up of mutations in the sperm of elder fathers.<ref name="fn_79"/>
 
A study by Sweden's Karolinska Institute and Bristol University in the UK, looked at the medical records of over 700,000 people and calculated that 15.5% of cases of schizophrenia seen in the group may have been due to the patient having a father who was aged over 30 years at their birth, the researchers argue this is due to build up of mutations in the sperm of elder fathers.<ref name="fn_79"/>
   
  +
{{Main|Schizophrenia - Age of parents}}
Women who were pregnant during the [[Dutch famine of 1944]], where many people were close to starvation, had a higher chance of having a child who would later develop schizophrenia.<ref name="fn_22">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8540774&dopt=Abstract Susser E, Neugebauer R, Hoek HW, Brown AS, Lin S, Labovitz D, Gorman JM (1996)] Schizophrenia after prenatal famine. Further evidence. ''Archives of General Psychiatry'', 53(1), 25&ndash;31.<br></ref> Similarly, studies of [[Finland|Finnish]] mothers who were pregnant when they found out that their husbands had been killed during the [[Winter War]] of 1939&ndash;1940 have shown that their children were much more likely to develop schizophrenia when compared with mothers who found out about their husbands' death after pregnancy,<ref name="fn_23">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=727894&dopt=Abstract Huttunen MO, Niskanen P. (1978)] Prenatal loss of father and psychiatric disorders. ''Archives of General Psychiatry'', 35(4), 429&ndash;31.<br></ref> suggesting that even [[psychological trauma]] in the mother may have an effect.
 
  +
 
Women who were pregnant during the Dutch famine of 1944, where many people were close to starvation, had a higher chance of having a child who would later develop schizophrenia.<ref name="fn_22">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8540774&dopt=Abstract Susser E, Neugebauer R, Hoek HW, Brown AS, Lin S, Labovitz D, Gorman JM (1996)] Schizophrenia after prenatal famine. Further evidence. ''Archives of General Psychiatry'', 53(1), 25&ndash;31.<br></ref> Similarly, studies of [[Finland|Finnish]] mothers who were pregnant when they found out that their husbands had been killed during the Winter War of 1939&ndash;1940 have shown that their children were much more likely to develop schizophrenia when compared with mothers who found out about their husbands' death after pregnancy,<ref name="fn_23">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=727894&dopt=Abstract Huttunen MO, Niskanen P. (1978)] Prenatal loss of father and psychiatric disorders. ''Archives of General Psychiatry'', 35(4), 429&ndash;31.<br></ref> suggesting that even [[psychological trauma]] in the mother may have an effect.
   
 
===Childhood and adolescent development===
 
===Childhood and adolescent development===
Line 13: Line 52:
 
There is on average a somewhat earlier onset for men than women, with the possible protective influence of the female hormone [[Estrogen|oestrogen]] being one hypothesis made and sociocultural influences another.
 
There is on average a somewhat earlier onset for men than women, with the possible protective influence of the female hormone [[Estrogen|oestrogen]] being one hypothesis made and sociocultural influences another.
   
[[Image:Schizophrenia_PET_scan.jpg|frame|Data from a [[Positron emission tomography|PET]] study<ref name="fn_25">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11865311 Meyer-Lindenberg A, Miletich RS, Kohn PD, Esposito G, Carson RE, Quarantelli M, Weinberger DR, Berman KF (2002)] Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia. ''Nature Neuroscience'', 5, 267-71.<br></ref> suggests that the less the [[frontal lobe]]s are activated (<font color="red">red</font>) during a [[working memory]] task, the greater the increase in abnormal [[dopamine]] activity in the [[striatum]] (<font color="green">green</font>), thought to be related to the [[neurocognitive deficit]]s in schizophrenia.]]
 
   
  +
==Methods of neuroanatomical study in schizophrenia==
===Adult brain structure===
 
  +
With advances in [[neuroimaging]] techniques there has been an enormous growth of activity in the area over recent years.
Differences in the size and structure of certain brain areas have been found in some adults diagnosed with schizophrenia. Early findings came from the discovery of [[ventricular system|ventricular]] enlargement in people diagnosed with schizophrenia with negative symptoms most prominent.<ref name="fn_29">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=62160 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.<br></ref> However, this finding has not proved particularly reliable on the level of the individual person, with considerable variation between patients. The role of antipsychotic medication, which nearly all those studied had taken, in causing such abnormalities is also unclear.<ref>http://ajp.psychiatryonline.org/cgi/content/full/156/11/1843-b</ref>
 
 
More recent studies have shown a large number of differences in brain structure between people with and without diagnoses of schizophrenia.<ref name="fn_30">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15062627 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.<br></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.
 
 
===Neuropsychology and brain function===
 
Studies using [[neuropsychological test]]s and [[brain imaging]] technologies such as [[Functional magnetic resonance imaging|fMRI]] and [[Positron emission tomography|PET]] to examine 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<br></ref> These differences are heavily linked to the [[neurocognitive deficit]]s which often occur with schizophrenia, particularly in areas of [[memory]], [[attention]], [[problem solving]], [[executive function]] and [[social cognition]].
 
 
[[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">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15546988&query_hl=1 Spencer KM, Nestor PG, Perlmutter R, Niznikiewicz MA, Klump MC, Frumin M, Shenton ME, McCarley (2004)] Neural synchrony indexes disordered perception and cognition in schizophrenia. ''Proceedings of the National Academy of Sciences'', 101, 17288-93. ([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])<br></ref> 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 [[interneuron]]s that produced the neurotransmitter [[GABA]].
 
   
  +
{{Main|Schizophrenia - PET studies}}
  +
{{Main|Schizophrenia - EEG studies}}
 
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Revision as of 20:28, 23 March 2007

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Research indicates that a number of neuroanatomical features differ between groups of people with schizophrenia and groups of matched controls.

Adult brain structure

Differences in the size and structure of certain brain areas have been found in some adults diagnosed with schizophrenia. Early findings came from the discovery of ventricular enlargement in people diagnosed with schizophrenia with negative symptoms most prominent.[1] However, this finding has not proved particularly reliable on the level of the individual person, with considerable variation between patients. The role of antipsychotic medication, which nearly all those studied had taken, in causing such abnormalities is also unclear.[2]

More recent studies have shown a large number of differences in brain structure between people with and without diagnoses of schizophrenia.[3] 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.

Neuropsychology and brain function

Studies using neuropsychological tests and brain imaging technologies such as fMRI and PET to examine functional differences in brain activity have shown that differences seem to most commonly occur in the frontal lobes, hippocampus, and temporal lobes.[4] These differences are heavily linked to the neurocognitive deficits which often occur with schizophrenia, particularly in areas of memory, attention, problem solving, executive function and social cognition.

Schizophrenia and the frontal lobes

Schizophrenia PET scan

Data from a PET study[5] suggests that the less the frontal lobes are activated (red) during a working memory task, the greater the increase in abnormal dopamine activity in the striatum (green), thought to be related to the neurocognitive deficits in schizophrenia.

Main article: Schizophrenia - Frontal lobes
Main article: Schizophrenia - Hippocampus
Main article: Schizophrenia - Temporal lobes


Schizophrenia and neural integration

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.[6] 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 produced the neurotransmitter GABA.


There are a number of theories about how these structural differences occur:

Genetic factors in neuroanatomical development

Developmental aspects

Perinatal brain development

It is thought that some of the neuroanatmical features associated with early neurodevelopment, including during pregnancy, to increase the risk of later developing schizophrenia. One curious finding is that people diagnosed with schizophrenia are more likely to have been born in winter or spring[7] (at least in the northern hemisphere).

Main article: Schizophrenia - Season of birth

However, the effect is not large. Some researchers postulate that the correlation is due to viral infections during the third trimester (4-6 months) of pregnancy. There is now significant evidence that prenatal exposure to infections increases the risk for developing schizophrenia later in life, providing additional evidence for a link between in utero developmental pathology and risk of developing the condition.[8]

Main article: Schizophrenia - Link with early infection

A study by Sweden's Karolinska Institute and Bristol University in the UK, looked at the medical records of over 700,000 people and calculated that 15.5% of cases of schizophrenia seen in the group may have been due to the patient having a father who was aged over 30 years at their birth, the researchers argue this is due to build up of mutations in the sperm of elder fathers.[9]

Main article: Schizophrenia - Age of parents

Women who were pregnant during the Dutch famine of 1944, where many people were close to starvation, had a higher chance of having a child who would later develop schizophrenia.[10] Similarly, studies of Finnish mothers who were pregnant when they found out that their husbands had been killed during the Winter War of 1939–1940 have shown that their children were much more likely to develop schizophrenia when compared with mothers who found out about their husbands' death after pregnancy,[11] suggesting that even psychological trauma in the mother may have an effect.

Childhood and adolescent development

Schizophrenia is most commonly first diagnosed during late adolescence or early adulthood suggesting it is often the end process of childhood and adolescent development. Studies have indicated that genetic dispositions can interact with early environment to increase the risk of developing schizophrenia, including through global neurobehavioral deficits,[12] a poorer family environment and disruptive school behaviour,[13] poor peer engagement, immaturity or unpopularity[14] or poorer social competence and increasing schizophrenic symptomology emerging during adolescence[15] These developmental problems have also been linked to socioeconomic disadvantage or early experiences of traumatic events.[16]

There is on average a somewhat earlier onset for men than women, with the possible protective influence of the female hormone oestrogen being one hypothesis made and sociocultural influences another.


Methods of neuroanatomical study in schizophrenia

With advances in neuroimaging techniques there has been an enormous growth of activity in the area over recent years.

Main article: Schizophrenia - PET studies
Main article: Schizophrenia - EEG studies

See also

References & Bibliography

  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.
  2. http://ajp.psychiatryonline.org/cgi/content/full/156/11/1843-b
  3. 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.
  4. Green, M.F. (2001) Schizophrenia Revealed: From Neurons to Social Interactions. New York: W.W. Norton. ISBN 0-393-70334-7
  5. Meyer-Lindenberg A, Miletich RS, Kohn PD, Esposito G, Carson RE, Quarantelli M, Weinberger DR, Berman KF (2002) Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia. Nature Neuroscience, 5, 267-71.
  6. Spencer KM, Nestor PG, Perlmutter R, Niznikiewicz MA, Klump MC, Frumin M, Shenton ME, McCarley (2004) Neural synchrony indexes disordered perception and cognition in schizophrenia. Proceedings of the National Academy of Sciences, 101, 17288-93. (full text)
  7. Davies G, Welham J, Chant D, Torrey EF, McGrath J. (2003) A systematic review and meta-analysis of Northern Hemisphere season of birth studies in schizophrenia. Schizophrenia Bulletin, 29 (3),587–93.
  8. Brown, A.S. (2006) Prenatal infection as a risk factor for schizophrenia. Schizophrenia Bulletin, 32 (2), 200-2.
  9. Cite error: Invalid <ref> tag; no text was provided for refs named fn_79
  10. Susser E, Neugebauer R, Hoek HW, Brown AS, Lin S, Labovitz D, Gorman JM (1996) Schizophrenia after prenatal famine. Further evidence. Archives of General Psychiatry, 53(1), 25–31.
  11. Huttunen MO, Niskanen P. (1978) Prenatal loss of father and psychiatric disorders. Archives of General Psychiatry, 35(4), 429–31.
  12. Hans SL, Marcus J, Nuechterlein KH, Asarnow RF, Styr B, Auerbach JG. (1999) Neurobehavioral deficits at adolescence in children at risk for schizophrenia: The Jerusalem Infant Development Study. Arch Gen Psychiatry. 56(8):741-8.
  13. Carter JW, Schulsinger F, Parnas J, Cannon T, Mednick SA. (2002) A multivariate prediction model of schizophrenia. Schizophrenia Bulletin 28(4):649-82.
  14. Hans SL, Auerbach JG, Asarnow JR, Styr B, Marcus J. (2000) Social adjustment of adolescents at risk for schizophrenia: the Jerusalem Infant Development Study. J Am Acad Child Adolesc Psychiatry. 39(11):1406-14.
  15. Dworkin RH, Bernstein G, Kaplansky LM, Lipsitz JD, Rinaldi A, Slater SL, Cornblatt BA, Erlenmeyer-Kimling L. (1991) Social competence and positive and negative symptoms: a longitudinal study of children and adolescents at risk for schizophrenia and affective disorder. Am J Psychiatry. Sep;148(9):1182-8.
  16. Read J, Perry BD, Moskowitz A, Connolly J (2001) The contribution of early traumatic events to schizophrenia in some patients: a traumagenic neurodevelopmental model. Psychiatry, 64, 319-45. (full text)

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