It has been postulated that the prefrontal cortices of schizophrenic patients have less interneuronal space than controls, specifically in areas 9 and 46. This is thought to reflect an alteration in the neuronal circuitry of these areas that according to Selemon et al. (1995) is a possible component of the pathology of schizophrenia. This study, and those that followed, were based on measures of neuronal density. Our goal is two-fold: one is to examine this finding based on the cortical minicolumn, and secondly, to elucidate the distribution of interneuronal space in regards to the morphology of the cell column. Our preliminary study used a small population of normal controls (n = 16) and schizophrenic patients (n = 9), diagnosed according to DSM ffl-R criteria. Our test revealed smaller values for all spacing distances and neuropil space in area 9 of schizophrenic brains. The greatest reduction occurred in the minicolumn compartment where the majority of apical dendrite bundles, thalamocortical, and cortico-cortical fibers are found. This study will examine columnar differences in 40 schizophrenic (DSM IV diagnosis) and 52 controls derived from the Runwell ifi collection. Specimens will be derived from areas 9, 46, 17, and 4 (Brodmann). Magnified images (lOOx) of Nissi-stained cell columns in layers III-VI will be analyzed by powerful computer imaging hardware and software enabling researchers to precisely quantify details of cell column morphology. Stereological techniques will be used to estimate neuronal density. If our preliminary findings are corroborated, the smaller than normal minicolumns will demonstrate a reorganization of brain circuitry most probably defined during development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH062654-01A2
Application #
6473555
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Meinecke, Douglas L
Project Start
2002-06-04
Project End
2006-05-31
Budget Start
2002-06-04
Budget End
2003-05-31
Support Year
1
Fiscal Year
2002
Total Cost
$216,546
Indirect Cost
Name
Medical College of Georgia (MCG)
Department
Psychiatry
Type
Schools of Medicine
DUNS #
City
Augusta
State
GA
Country
United States
Zip Code
30912
Casanova, Manuel F; El-Baz, Ayman S; Giedd, Jay et al. (2010) Increased white matter gyral depth in dyslexia: implications for corticocortical connectivity. J Autism Dev Disord 40:21-9
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
Bychkov, E R; Gurevich, V V; Joyce, J N et al. (2008) Arrestins and two receptor kinases are upregulated in Parkinson's disease with dementia. Neurobiol Aging 29:379-96
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
Ahmed, Mohamed Rafiuddin; Gurevich, Vsevolod V; Dalby, Kevin N et al. (2008) Haloperidol and clozapine differentially affect the expression of arrestins, receptor kinases, and extracellular signal-regulated kinase activation. J Pharmacol Exp Ther 325:276-83
Casanova, Manuel F; Tillquist, Christopher R (2008) Encephalization, emergent properties, and psychiatry: a minicolumnar perspective. Neuroscientist 14:101-18
Casanova, Manuel F (2008) The minicolumnopathy of autism: A link between migraine and gastrointestinal symptoms. Med Hypotheses 70:73-80
Casanova, Manuel F; Kreczmanski, Pawel; Trippe 2nd, Juan et al. (2008) Neuronal distribution in the neocortex of schizophrenic patients. Psychiatry Res 158:267-77
Ahmed, M Rafiuddin; Bychkov, Evgeny; Gurevich, Vsevolod V et al. (2008) Altered expression and subcellular distribution of GRK subtypes in the dopamine-depleted rat basal ganglia is not normalized by l-DOPA treatment. J Neurochem 104:1622-36

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