Cited by 2,346Schizophrenia research and treatmentMental Health and PsychiatryHallucinations in medical conditions

A review of MRI findings in schizophrenia

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Shenton, Martha E., Dickey, Chandlee C., Frumin, Melissa, McCarley, Robert W.·2001·Schizophrenia Research

Abstract

After more than 100 years of research, the neuropathology of schizophrenia remains unknown and this is despite the fact that both Kraepelin (1919/1971: Kraepelin, E., 1919/1971. Dementia praecox. Churchill Livingston Inc., New York) and Bleuler (1911/1950: Bleuler, E., 1911/1950. Dementia praecox or the group of schizophrenias. International Universities Press, New York), who first described 'dementia praecox' and the 'schizophrenias', were convinced that schizophrenia would ultimately be linked to an organic brain disorder. Alzheimer (1897: Alzheimer, A., 1897. Beitrage zur pathologischen anatomie der hirnrinde und zur anatomischen grundlage einiger psychosen. Monatsschrift fur Psychiarie und Neurologie. 2, 82-120) was the first to investigate the neuropathology of schizophrenia, though he went on to study more tractable brain diseases. The results of subsequent neuropathological studies were disappointing because of conflicting findings. Research interest thus waned and did not flourish again until 1976, following the pivotal computer assisted tomography (CT) finding of lateral ventricular enlargement in schizophrenia by Johnstone and colleagues. Since that time significant progress has been made in brain imaging, particularly with the advent of magnetic resonance imaging (MRI), beginning with the first MRI study of schizophrenia by Smith and coworkers in 1984 (Smith, R.C., Calderon, M., Ravichandran, G.K., et al. (1984). Nuclear magnetic resonance in schizophrenia: A preliminary study. Psychiatry Res. 12, 137-147). MR in vivo imaging of the brain now confirms brain abnormalities in schizophrenia. The 193 peer reviewed MRI studies reported in the current review span the period from 1988 to August, 2000. This 12 year period has witnessed a burgeoning of MRI studies and has led to more definitive findings of brain abnormalities in schizophrenia than any other time period in the history of schizophrenia research. Such progress in defining the neuropathology of schizophrenia is largely due to advances in in vivo MRI techniques. These advances have now led to the identification of a number of brain abnormalities in schizophrenia. Some of these abnormalities confirm earlier post-mortem findings, and most are small and subtle, rather than large, thus necessitating more advanced and accurate measurement tools. These findings include ventricular enlargement (80% of studies reviewed) and third ventricle enlargement (73% of studies reviewed). There is also preferential involvement of medial temporal lobe structures (74% of studies reviewed), which include the amygdala, hippocampus, and parahippocampal gyrus, and neocortical temporal lobe regions (superior temporal gyrus) (100% of studies reviewed). When gray and white matter of superior temporal gyrus was combined, 67% of studies reported abnormalities. There was also moderate evidence for frontal lobe abnormalities (59% of studies reviewed), particularly prefrontal gray matter and orbitofrontal regions. Similarly, there was moderate evidence for parietal lobe abnormalities (60% of studies reviewed), particularly of the inferior parietal lobule which includes both supramarginal and angular gyri. Additionally, there was strong to moderate evidence for subcortical abnormalities (i.e. cavum septi pellucidi-92% of studies reviewed, basal ganglia-68% of studies reviewed, corpus callosum-63% of studies reviewed, and thalamus-42% of studies reviewed), but more equivocal evidence for cerebellar abnormalities (31% of studies reviewed). The timing of such abnormalities has not yet been determined, although many are evident when a patient first becomes symptomatic. There is, however, also evidence that a subset of brain abnormalities may change over the course of the illness. The most parsimonious explanation is that some brain abnormalities are neurodevelopmental in origin but unfold later in development, thus setting the stage for the development of the symptoms of schizophrenia. Or there may be additional factors, such as stress or neurotoxicity, that occur during adolescence or early adulthood and are necessary for the development of schizophrenia, and may be associated with neurodegenerative changes. Importantly, as several different brain regions are involved in the neuropathology of schizophrenia, new models need to be developed and tested that explain neural circuitry abnormalities effecting brain regions not necessarily structurally proximal to each other but nonetheless functionally interrelated. (ABSTRACT TRUNCATED)

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  1. Anderson J, Umans C, Halle M, et al. Anatomy Browser: Java based interactive teaching tool for learning human neuro-anatomy. RSNA Electronic Journal. 1998;2:50–97. http://ej.rsna.org/ej2/0050-97.fin/index.html. [Google Scholar]
  2. Carpenter M. Core Text of Neuroanatomy. Human Neuroanatomy. Baltimore, MD: Williams and Wilkins; 1983. [Google Scholar]
  3. Dunlap C. Dementia praecox: Some preliminary observations on brains from carefully selected cases, and a consideration of certain sources of error. Am. J. Psychiatry. 1924;80:403–421. [Google Scholar]
  4. Frumin M, Golland P, McCarley RW, et al. Shape differences in the corpus callosum in first episode schizophrenia and affective disorder. 37th Annual Meeting of the American College of Neuropsychopharmacology; Puerto Rico. 1998. Dec, [Google Scholar]
  5. Glass G, McGraw B, Smith M. Metaanalysis in Social Research. Newbury Park, CA: Sage Publications; 1981. [Google Scholar]
  6. Gruzelier JH. Hemispheric imbalance: syndromes of schizophrenia, premorbid personality, and neurodevelopmental influences. In: Steinhauer SR, Gruzelier JH, Zubin J, editors. Handbook of Schizophrenia: Neuropsychology, Psychophysiology and Information Processing. vol. 5. New York, NY: Elsevier; 1991. pp. 599–650. [Google Scholar]
  7. Hecker E. Die hebephrenic. Arch. Patholiche Anat. und fur Physiol. Klinische Medicin. 1871;52:394–429. [Google Scholar]
  8. Hier D, LeMay M, Rosenberger P. Autism-association with reversed cerebral asymmetry. Neurology. 1978;28:348–349. [Google Scholar]
  9. Hunter J, Schmidt F. Methods of Metaanalysis. Newbury Park, CA: Sage Publications; 1990. [Google Scholar]
  10. Jones EG. The Thalamus. New York, NY: Plenum Press; 1985. [Google Scholar]
  11. Kahlbaum K. Die Katatonie oder der Spannungsirresein. Berlin: Hirshwald; 1874. [PubMed] [Google Scholar]
  12. Komuro H, Rakic P. Orchestration of neural migration by activity of ion channels, neurotransmitter receptors, and intra-cellular Ca2 + fluctuations. J. Neurobiol. 1998;37:110–130. [PubMed] [Google Scholar]
  13. Kraepelin E. Dementia Praecox. New York: Churchill Livingston Inc; 1919–1971. [Google Scholar]
  14. LeMay M. Leftright temporal region asymmetry in infants and children [letter] AJNR Am. J. Neuroradiol. 1986;7:974. [PMC free article] [PubMed] [Google Scholar]
  15. Pearlson GD, Marsh L. MRI in psychiatry. In: Oldham J, B R, A T, editors. American Psychiatric Association Press Review of Psychiatry. Washington DC: American Psychiatric Association; 1993. pp. 347–381. [Google Scholar]
  16. Pinel P. Traite medico philosophique sur l’alienation mentale boulamania. Paris: Richard Caille et Ravier; 1801. [Google Scholar]
  17. Rosenthal R. Design, Analysis, and Meta-analysis. Cambridge, MA: Cambridge University Press; 1987. Judgement Studies. [Google Scholar]
  18. Scheibel AB, Kovelman JA. Dendritic disarray in the hippocampus of paranoid schizophrenia. Annual Meeting of the Society of Biological Psychiatry. 1979 [Google Scholar]
  19. Scheibel AB, Kovelman JA. Disorientation of the hippocampal pyramidal cell and its processes in the schizophrenic patient. Biol. Psychiatry. 1981;16:101–102. [Google Scholar]
  20. Selemon LD, Rajkowska G, Goldman-Rakic PS. Elevated neuronal density in prefrontal area 46 in brains from schizophrenic patients: application of a three-dimensional, stereologic counting method. J. Comp. Neurol. 1998;392:402–412. [PubMed] [Google Scholar]
  21. Shelton RC, Weinberger DR. X-ray computerized tomography studies in schizophrenia: a review and synthesis. In: Nasrallah HA, Weinberger DR, editors. Handbook of Schizophrenia: The Neuropathology of Schizophrenia. vol. I. New York: Elsevier Science Publishers; 1986. pp. 207–225. [Google Scholar]
  22. Shenton M, Frumin M, McCarley R, et al. Morphometric MRI studies: Findings in schizophrenia. In: Dougherty D, Rauch S, Rosen J, et al., editors. Psychiatric Neuroimaging Strategies: Research and Clinical Applications. Washington, DC: American Psychiatric Association; 2001. (in press) [Google Scholar]
  23. Weinberger DR. The pathogenesis: a neurodevelopmental theory. In: Nasrallah HA, Weinberger DR, editors. Handbook of Schizophrenia: The Neuropathology of Schizophrenia. vol. I. New York: Elsevier Science Publishers; 1986. pp. 397–406. [Google Scholar]
  24. Wernicke C. De aphasische symptomenkomplex. Breslau: Cohen and Weigart; 1874. [Google Scholar]

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Authors
Shenton, M. E., Dickey, C. C., Frumin, M., & McCarley, R. W.
Affiliations
Harvard University (US)
Corresponding author
  • Shenton, Martha E.
  • McCarley, Robert W.
Venue
Schizophrenia Research
Publisher
Elsevier BV
Published
2001-04
Volume
49
Issue
1-2
Pages
1-52
ISSN
0920-9964 (ISSN-L)
OpenAlex
W1985994929
Cited by
2,346
References
480
Citations by year
2026: 21 · 2025: 47 · 2024: 35 · 2023: 52 · 2022: 51 · 2021: 69 · 2020: 57 · 2019: 72 · 2018: 62 · 2017: 99 · 2016: 81 · 2015: 110 · 2014: 98 · 2013: 107 · 2012: 143
FWCI
16.51
Type
journal article
Language
en
Open access
Locations
  • Schizophrenia Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders
  • U.S. Department of Veterans Affairs
  • University of Cambridge
  • National Institute of Mental Health (MH-01110, MH-50740, MH40799, K02MH001110, R01MH050740, R01MH040799)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Hallucinations in medical conditions
Keywords
schizophrenia, brain abnormalities
MeSH terms
Brain, Humans, Magnetic Resonance Imaging, Psychotic Disorders, Schizophrenia

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