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

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.

[1]  Sabine Landau,et al.  Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder. , 2002, Cerebral cortex.

[2]  Sabine Landau,et al.  Evidence for orbitofrontal pathology in bipolar disorder and major depression, but not in schizophrenia. , 2005, Bipolar disorders.

[3]  E. G. Jones,et al.  Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. , 1995, Archives of general psychiatry.

[4]  P. Goldman-Rakic,et al.  Abnormally high neuronal density in the schizophrenic cortex. A morphometric analysis of prefrontal area 9 and occipital area 17. , 1995, Archives of general psychiatry.

[5]  R. McCarley MRI anatomy of schizophrenia: A review and update , 2001, European Neuropsychopharmacology.

[6]  T. Crow Temporal lobe asymmetries as the key to the etiology of schizophrenia. , 1990, Schizophrenia bulletin.

[7]  R. Kahn,et al.  Handedness, language lateralisation and anatomical asymmetry in schizophrenia: meta-analysis. , 2001, The British journal of psychiatry : the journal of mental science.

[8]  T. L. Hayes,et al.  Anatomical Specialization of the Anterior Motor Speech Area: Hemispheric Differences in Magnopyramidal Neurons , 1995, Brain and Language.

[9]  T. Crow Schizophrenia as failure of hemispheric dominance for language. , 1997, Trends in neurosciences.

[10]  Paul J. Harrison,et al.  Low medial and lateral right pulvinar volumes in schizophrenia: a postmortem study. , 2003, The American journal of psychiatry.

[11]  P. Goldman-Rakic,et al.  Regional specificity in the neuropathologic substrates of schizophrenia: a morphometric analysis of Broca's area 44 and area 9. , 2003, Archives of general psychiatry.

[12]  F. Benes,et al.  Quantitative cytoarchitectural studies of the cerebral cortex of schizophrenics. , 1986, Archives of general psychiatry.

[13]  Daniel R. Weinberger,et al.  Schizophrenia and the frontal lobe , 1988, Trends in Neurosciences.

[14]  Paul J. Harrison,et al.  The distribution and morphology of prefrontal cortex pyramidal neurons identified using anti-neurofilament antibodies SMI32, N200 and FNP7. Normative data and a comparison in subjects with schizophrenia, bipolar disorder or major depression. , 2003, Journal of psychiatric research.

[15]  R. Mohs,et al.  Consortium to establish a registry for Alzheimer's disease (CERAD) clinical and neuropsychological assessment of Alzheimer's disease. , 2002, Psychopharmacology bulletin.

[16]  P. Södersten,et al.  Schizophrenia as failure of hemispheric dominance forlanguage , 1998, Trends in Neurosciences.

[17]  D. Buxhoeveden,et al.  Lateralization of Minicolumns in Human Planum temporale Is Absent in Nonhuman Primate Cortex , 2001, Brain, Behavior and Evolution.

[18]  N. Geschwind,et al.  Human Brain: Left-Right Asymmetries in Temporal Speech Region , 1968, Science.

[19]  E. Tanabe,et al.  65-152 Working memory dysfunction in schizophrenia , 1997, Biological Psychiatry.

[20]  R. Petty,et al.  Structural asymmetries of the human brain and their disturbance in schizophrenia. , 1999, Schizophrenia bulletin.

[21]  P. Goldman-Rakic,et al.  Elevated neuronal density in prefrontal area 46 in brains from schizophrenic patients: Application of a three‐dimensional, stereologic counting method , 1998, The Journal of comparative neurology.

[22]  P. Rakic,et al.  Three‐dimensional counting: An accurate and direct method to estimate numbers of cells in sectioned material , 1988, The Journal of comparative neurology.

[23]  B. Pakkenberg,et al.  Total nerve cell number in neocortex in chronic schizophrenics and controls estimated using optical disectors , 1993, Biological Psychiatry.

[24]  Paul J. Harrison,et al.  Schizophrenia and the frontal lobes: post-mortem stereological study of tissue volume. , 2001, The British journal of psychiatry : the journal of mental science.

[25]  A. Sampson,et al.  Decreased somal size of deep layer 3 pyramidal neurons in the prefrontal cortex of subjects with schizophrenia. , 2001, Archives of general psychiatry.

[26]  T. J. Crow,et al.  Anomalies of cerebral asymmetry in schizophrenia interact with gender and age of onset: a post-mortem study , 1998, Schizophrenia Research.

[27]  P S Goldman-Rakic,et al.  Cytoarchitectonic definition of prefrontal areas in the normal human cortex: I. Remapping of areas 9 and 46 using quantitative criteria. , 1995, Cerebral cortex.

[28]  C V Howard,et al.  The total number of neurons in the human neocortex unbiasedly estimated using optical disectors , 1990, Journal of microscopy.

[29]  Jordan Grafman,et al.  Handbook of Neuropsychology , 1991 .

[30]  M M Esiri,et al.  Schizophrenia and temporal lobe asymmetry. A post-mortem stereological study of tissue volume. , 1999, The British journal of psychiatry : the journal of mental science.

[31]  S. M. Sumi,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) , 1991, Neurology.

[32]  T. Crow,et al.  Anomalous asymmetry of fusiform and parahippocampal gyrus gray matter in schizophrenia: A postmortem study. , 2000, The American journal of psychiatry.