Skip to main content Accessibility help
×
Home

Anomalies of asymmetry of pyramidal cell density and structure in dorsolateral prefrontal cortex in schizophrenia

  • Thomas J. Cullen (a1), Mary A. Walker (a1), Sharon L. Eastwood (a1), Margaret M. Esiri (a1), Paul J. Harrison (a1) and Timothy J. Crow (a1)...

Abstract

Background

Studies suggest that neuronal density in left dorsolateral prefrontal cortex is increased in schizophrenia.

Aims

To replicate these findings and extend them to both hemispheres.

Method

Neuronal density, size and shape were estimated in the prefrontal cortex (Brodmann area 9) of the left and right hemispheres of brains taken postmortem from 10 people with schizophrenia and 10 without mental illness (6 men, 4 women in both groups).

Results

Overall neuronal density (individually corrected for shrinkage) did not differ between the groups. In the control brains, density was generally greater in the left than the right hemisphere, the reverse was seen in the schizophrenia brains; this loss or reversal of asymmetry was most significant in cortical layer 3. Pyramidal neurons in this cell layer were significantly larger on the left and more spherical in shape than on the right side in control brains, but size and shape did not differ between the two sides in schizophrenia. Non-pyramidal and glial cell densities were unchanged.

Conclusions

We failed to find an increase in neuronal density, but found evidence at a cellular level of loss or reversal of asymmetry, consistent with the hypothesis of a primary change in the relative development of areas of heteromodal association cortex in the two hemispheres.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Anomalies of asymmetry of pyramidal cell density and structure in dorsolateral prefrontal cortex in schizophrenia
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Anomalies of asymmetry of pyramidal cell density and structure in dorsolateral prefrontal cortex in schizophrenia
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Anomalies of asymmetry of pyramidal cell density and structure in dorsolateral prefrontal cortex in schizophrenia
      Available formats
      ×

Copyright

Corresponding author

Professor T. J. Crow, Prince of Wales International Centre for SANE Research, Warneford Hospital, Oxford OX3 7JX, UK. Tel: +44(0)1865 455917; fax: +44(0)1865 455922; e-mail: tim.crow@psych.ox.ac.uk

Footnotes

Hide All

Declaration of interest

None. Funding details in Acknowledgements.

Footnotes

References

Hide All
Akbarian, S., Kim, J. J., Potkin, S. G., et al (1995) Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Archives of General Psychiatry, 52, 258289.
American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM-IV). Washington, DC: APA.
Benes, F. M., Davidson, J. & Bird, E. D. (1986) Quantitative cytoarchitectural studies of the cerebral cortex of schizophrenics. Archives of General Psychiatry, 43, 3135.
Braendgaard, H., Evans, S. M., Howard, C. V., et al (1990) The total number of neurons in the human neocortex unbiasedly estimated using optical disectors. Journal of Microscopy, 157, 285304.
Buxhoeveden, D., Switala, A. E., Litaker, M., et al (2001) Lateralization of minicolumns in human planum temporale is absent in nonhuman primate cortex. Brain, Behavior and Evolution, 57, 349358.
Cotter, D., Mackay, D., Chana, G., et al (2002) Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder. Cerebral Cortex, 12, 386394.
Cotter, D., Hudson, L. & Landau, S. (2005) Evidence for orbitofrontal pathology in bipolar disorder and major depression, but not in schizophrenia. Bipolar Disorder, 7, 358369.
Crow, T. J. (1990) Temporal lobe asymmetries as the key to the etiology of schizophrenia. Schizophrenia Bulletin, 16, 433443.
Crow, T. J. (1997) Schizophrenia as failure of hemispheric dominance for language. Trends in Neurosciences, 20, 339343.
Eberstaller, O. (1884) Zur Oberflächenanatomie des Grosshirnhemisphären. Wiener Medizinische Blätter, 7, 479482.
Geschwind, N. & Levitsky, W. (1968) Human brain: left-right asymmetry in temporal speech region. Science, 161, 186187.
Goldman-Rakic, P. S. (1994) Working memory dysfunction in schizophrenia. Journal of Neuropsychiatry and Clinical Neuroscience, 6, 348357.
Hayes, T. L. & Lewis, D. A. (1995) Anatomical specialization of the anterior motor speech area: hemispheric differences in magnopyramidal neurons. Brain and Language, 37, 497499.
Highley, J. R., Esiri, M. M., Cortina-Borja, M., et al (1998) Anomalies of cerebral asymmetry in schizophrenia interact with gender and age of onset: a post mortem study. Schizophrenia Research, 34, 1325.
Highley, J. R., McDonald, B., Walker, M. A., et al (1999) Schizophrenia and temporal lobe asymmetry. A post-mortem stereological study of tissue volume. British Journal of Psychiatry, 175, 127134.
Highley, J. R., Walker, M. A., Crow, T. J., et al (2003) Low medial and lateral right pulvinar volumes in schizophrenia: a post-mortem study. American Journal of Psychiatry, 160, 11771179.
Law, A. J. & Harrison, P. J. (2003) The distribution and morphology of prefrontal cortex neurons identified using anti-neurofilament antibodies SM132, N200 and FNP7. Normative data and a comparison in subjects with schizophrenia, bipolar disorder or major depression. Journal of Psychiatric Research, 37, 497499.
McCarley, R. W., Wible, C. G., Frumin, M., et al (1991) MRI anatomy of schizophrenia. Biological Psychiatry, 45, 10991119.
McDonald, B., Highley, J. R., Walker, M. A., et al (2000) Anomalous asymmetry of fusiform and parahippocampal gyrus grey matter in schizophrenia: a post-mortem study. American Journal of Psychiatry, 157, 4047.
Mirra, S. S., Heyman, A., McKeel, D., et al (1991) The consortium to establish a registry for Alzheimer's disease (CERAD) Part II. Standardisation of the neuropathologic assessment of Alzheimer's disease. Neurology, 41, 479486.
Pakkenberg, B. (1993) Total nerve cell number in neocortex in chronic schizophrenics and controls estimated using optical dissectors. Biological Psychiatry, 34, 768772.
Petty, R. G. (1999) Structural asymmetries of the human brain and their disturbance in schizophrenia. Schizophrenia Bulletin, 25, 121139.
Pierri, J., Volk, C. L., Auh, S., et al (2001) Decreased somal size of deep layer 3 pyramidal neurons in the prefrontal cortex of subjects with schizophrenia. Archives of General Psychiatry, 58, 466473.
Rajkowska, G. & Goldman-Rakic, P. S. (1995) Cytoarchitectonic definition of prefrontal areas in the normal human cortex. I Remapping of areas 9 and 46 using quantitative criteria. Cerebral Cortex, 5, 307322.
Selemon, L. D., Rajkowska, G. & Goldman-Rakic, P. S. (1995) Abnormally high neuronal density in the schizophrenic cortex: a morphometric analysis of prefrontal area 9 and occipital area 17. Archives of General Psychiatry, 52, 805818.
Selemon, L. D., Rajkowska, G. & Goldman-Rakic, P. S. (1998) Elevated neuronal density in prefrontal area 46 in brains from schizophrenic patients: application of a three-dimensional stereological counting method. Journal of Comparative Neurology, 392, 402412.
Selemon, L. D., Mrzljak, J., Kleinman, J. E., et al (2003) Regional specificity in the neuropathologic substrates of schizophrenia: a morphometric analysis of Broca's area 44 and area 9. Archives of General Psychiatry, 60, 6977.
Sommer, I., Ramsey, N., Khan, R., et al (2001) Handedness, language lateralisation and anatomical asymmetry in schizophrenia. Meta-analysis. British Journal of Psychiatry, 178, 344351.
Weinberger, D. R. (1988) Schizophrenia and the frontal lobes. Trends in Neurosciences, 11, 367370.
Williams, R. W. & Rakic, P. (1988) Three-dimensional counting: an accurate and direct method to estimate numbers of cells in sectioned material. Journal of Comparative Neurology, 278, 344352.
Witelson, S. F. & Kigar, D. L. (1988) Asymmetry of brain function follows asymmetry in anatomical form: gross, microscopic, postmortem and imaging studies. In Handbook of Neuropsychology (eds Boller, F. & Grafman, J.), pp. 111142. Amsterdam: Elsevier.

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed

Anomalies of asymmetry of pyramidal cell density and structure in dorsolateral prefrontal cortex in schizophrenia

  • Thomas J. Cullen (a1), Mary A. Walker (a1), Sharon L. Eastwood (a1), Margaret M. Esiri (a1), Paul J. Harrison (a1) and Timothy J. Crow (a1)...
Submit a response

eLetters

No eLetters have been published for this article.

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *