It has been proposed that schizophrenia is a consequence of the lateralization of the brain in conjunction with the evolution of human language. Differences have been found between normal and schizophrenic brains in the size and lateralization of temporal lobes. Most work, however, has concentrated on gross structures while ignoring the potential for anatomical differences that may be found in relevant cytoarchitectonic areas. Furthermore, it would be profitable to examine anatomical components that correlate with known functional significance. Such a structure is the minicolumn, a fundamental anatomical and physiological unit of the cortex. The morphology of the minicoiumn has been shown to differ between small architectonic regions, reflecting variation in input, output, and local organization. For this reason, it was chosen as the ideal anatomical marker for the investigation of asymmetrical differences. In our preliminary studies, we examined five morphological features of minicolumns in 11 normal and 5 schizophrenic brains. The results revealed that: 1) differences between normal and schizophrenic brains are found not in the horizontal spacing that separate cell columns internalized structure of the cell columns, and 2) asymmetry of cell columns involves more than one anatomical variable. This project will examine possible differences in lateralization patterns of minicolumns in selected areas of cortex, including a part of Wernicke's language area, in 40 normal and 52 schizophrenic brains derived from the Runwell III collection. Magnified images (1 100x) of Nissl-stained cell columns in Lamina III will be analyzed by powerful computer imaging hardware and software enabling researchers to precisely quantify details of cell column morphology. If the preliminary findings of this study are confirmed, they will demonstrate that the reported differences of the temporal lobe in schizophrenia involve not only size but also a reorganization of a basic unit of function. Another possible outcome is that the number of minicolumns in the temporal lobe may differ without a concomitant change in the structural reorganization.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
7R01MH061606-04
Application #
6942822
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Meinecke, Douglas L
Project Start
2001-09-25
Project End
2006-08-31
Budget Start
2004-09-01
Budget End
2006-08-31
Support Year
4
Fiscal Year
2004
Total Cost
$330,750
Indirect Cost
Name
University of Louisville
Department
Psychiatry
Type
Schools of Medicine
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40292
Casanova, Manuel F; Trippe 2nd, Juan; Tillquist, Christopher R et al. (2010) Dolphin insula reflects minicolumnar organization of mammalian isocortex. Transl Neurosci 1:37-42
Casanova, Manuel F; Trippe 2nd, Juan; Tillquist, Christopher et al. (2009) Morphometric variability of minicolumns in the striate cortex of Homo sapiens, Macaca mulatta, and Pan troglodytes. J Anat 214:226-34
Chance, Steven A; Casanova, Manuel F; Switala, Andy E et al. (2008) Auditory cortex asymmetry, altered minicolumn spacing and absence of ageing effects in schizophrenia. Brain 131:3178-92
Casanova, Manuel F; Kreczmanski, Pawel; Trippe 2nd, Juan et al. (2008) Neuronal distribution in the neocortex of schizophrenic patients. Psychiatry Res 158:267-77
Casanova, Manuel F; Switala, Andrew E; Trippe, Juan (2007) A comparison study of the vertical bias of pyramidal cells in the hippocampus and neocortex. Dev Neurosci 29:193-200
Casanova, Manuel F (2007) Schizophrenia seen as a deficit in the modulation of cortical minicolumns by monoaminergic systems. Int Rev Psychiatry 19:361-72
Casanova, Manuel F; Trippe 2nd, Juan; Switala, Andrew (2007) A temporal continuity to the vertical organization of the human neocortex. Cereb Cortex 17:130-7
Casanova, Manuel F (2006) Neuropathological and genetic findings in autism: the significance of a putative minicolumnopathy. Neuroscientist 12:435-41
Casanova, Manuel F; van Kooten, Imke A J; Switala, Andrew E et al. (2006) Minicolumnar abnormalities in autism. Acta Neuropathol 112:287-303
Seelan, Ratnam S; Janckila, Anthony J; Parthasarathy, Ranga N et al. (2006) The importance of using equimolar DNA for transfection analysis of the 5' flanking promoter regions of genes. Anal Biochem 349:306-8

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