Acta Neuropathologica

, 112:287 | Cite as

Minicolumnar abnormalities in autism

  • Manuel F. CasanovaEmail author
  • Imke A. J. van Kooten
  • Andrew E. Switala
  • Herman van Engeland
  • Helmut Heinsen
  • Harry W. M. Steinbusch
  • Patrick R. Hof
  • Juan Trippe
  • Janet Stone
  • Christoph Schmitz
Original Paper


Autism is characterized by qualitative abnormalities in behavior and higher order cognitive functions. Minicolumnar irregularities observed in autism provide a neurologically sound localization to observed clinical and anatomical abnormalities. This study corroborates the initial reports of a minicolumnopathy in autism within an independent sample. The patient population consisted of six age-matched pairs of patients (DSM-IV-TR and ADI-R diagnosed) and controls. Digital micrographs were taken from cortical areas S1, 4, 9, and 17. The image analysis produced estimates of minicolumnar width (CW), mean interneuronal distance, variability in CW (V CW), cross section of Nissl-stained somata, boundary length of stained somata per unit area, and the planar convexity. On average CW was 27.2 μm in controls and 25.7 μm in autistic patients (P = 0.0234). Mean neuron and nucleolar cross sections were found to be smaller in autistic cases compared to controls, while neuron density in autism exceeded the comparison group by 23%. Analysis of inter- and intracluster distances of a Delaunay triangulation suggests that the increased cell density is the result of a greater number of minicolumns, otherwise the number of cells per minicolumns appears normal. A reduction in both somatic and nucleolar cross sections could reflect a bias towards shorter connecting fibers, which favors local computation at the expense of inter-areal and callosal connectivity.


Autistic disorder/pathology Child development disorders Pervasive Neocortex Neuropil Pyramidal cells 



We are grateful to the following institutions for the provision of the specimens: Mount Sinai School of Medicine (New York, NY, USA), University of Würzburg Morphological Brain Research Unit (Würzburg, Germany), University of Maryland Brain and Tissue Bank for Developmental Disorders (Baltimore, MD, USA), Harvard Brain Tissue Research Center (Belmont, MA, USA), New York State Institute for Basic Research in Developmental Disabilities (Staten Island, NY, USA) and the US Autism Tissue Program (Princeton, NJ, USA). We thank E.K. Broschk and A. Bahrkel for their technical support. This article is based upon work supported by the Stanley Medical Research Foundation (H.H., C.S., P.R.H. and M.F.C.), the Korczak Foundation (H.v.E.), the National Alliance for Autism Research (C.S. P.R.H. and M.F.C.), the McDonnell Foundation (P.R.H.) and NIMH grants MH61606 (M.F.C.), MH62654 (M.F.C.), MH69991 (M.F.C), NIH MH66392 (P.R.H).


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Manuel F. Casanova
    • 1
    Email author
  • Imke A. J. van Kooten
    • 2
    • 4
  • Andrew E. Switala
    • 3
  • Herman van Engeland
    • 2
  • Helmut Heinsen
    • 5
  • Harry W. M. Steinbusch
    • 4
  • Patrick R. Hof
    • 6
  • Juan Trippe
    • 3
  • Janet Stone
    • 3
  • Christoph Schmitz
    • 4
  1. 1.Department of Psychiatry and Behavioral SciencesUniversity of LouisvilleLouisvilleUSA
  2. 2.Department of Child and Adolescent PsychiatryUniversity Medical CenterUtrechtThe Netherlands
  3. 3.Department of Psychiatry and Behavioral SciencesUniversity of LouisvilleLouisvilleUSA
  4. 4.Department of Psychiatry and Neuropsychology, Division of Cellular NeuroscienceMaastricht University, and European Graduate School of Neuroscience (EURON)MaastrichtThe Netherlands
  5. 5.Morphologic Brain Research UnitUniversity of WürzburgWürzburgGermany
  6. 6.Department of NeuroscienceMount Sinai School of MedicineNew YorkUSA

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