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Microvessel length density, total length, and length per neuron in five subcortical regions in schizophrenia

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Abstract

Recent studies (Prabakaran et al. in Mol Psychiat 9:684–697, 2004; Hanson and Gottesman in BMC Med Genet 6:7, 2005; Harris et al. in PLoS ONE 3:e3964, 2008) have suggested that microvascular abnormalities occur in the brains of patients with schizophrenia. To assess the integrity of the microvasculature in subcortical brain regions in schizophrenia, we investigated the microvessel length density, total microvessel length, and microvessel length per neuron using design-based stereologic methods in the caudate nucleus, putamen, nucleus accumbens, mediodorsal nucleus of the thalamus, and lateral nucleus of the amygdala in both hemispheres of 13 postmortem brains from male patients with schizophrenia and 13 age-matched male controls. A general linear model multivariate analysis of variance with diagnosis and hemisphere as fixed factors and illness duration (patients with schizophrenia) or age (controls), postmortem interval and fixation time as covariates showed no statistically significant differences in the brains from the patients with schizophrenia compared to the controls. These data extend our earlier findings in prefrontal cortex area 9 and anterior cingulate cortex area 24 from the same brains (Kreczmanski et al. in Acta Neuropathol 109:510–518, 2005), that alterations in microvessel length density, total length, and particularly length per neuron cannot be considered characteristic features of schizophrenia. As such, compromised brain metabolism and occurrence of oxidative stress in the brains of patients with schizophrenia are likely caused by other mechanisms such as functional disruption in the coupling of cerebral blood flow to neuronal metabolic needs.

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Acknowledgments

We thank E.K. Broschk and H. Steinbusch for expert technical assistance, Dr. M. Schüler (Bayreuth, Germany) for valuable help in retrieving clinical data of the investigated patients, and G. Greene and B. Boehringer (MicroBrightField, Williston, VT, USA) for valuable help in implementing the space balls method. This work was supported by the Stanley Medical Research Institute (#02R-258, #04R-674 to HH, PRH, and CS), the European Community (Quality of Life and Management of Living Resources, QLK6-CT-2000-60042, QLK6-GH-00-60042-46, to PK), and NIH grant MH66392 to PRH.

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Authors and Affiliations

  1. Division of Cellular Neuroscience, School for Mental Health and Neurosciences, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands

    Pawel Kreczmanski, Valentina Mantua, Rainald Schmidt-Kastner, Hubert Korr, Harry W. M. Steinbusch & Christoph Schmitz

  2. European Graduate School of Neuroscience (EURON), Maastricht, The Netherlands

    Pawel Kreczmanski, Hubert Korr, Harry W. M. Steinbusch & Christoph Schmitz

  3. Morphological Brain Research Unit, Psychiatric Clinic, University of Wuerzburg, Wuerzburg, Germany

    Helmut Heinsen

  4. Department of Psychiatry, Section of Clinical Neuropharmacology, Institute of Psychiatry, Kings College London, London, UK

    Valentina Mantua

  5. Department of Psychiatric Sciences and Psychological Medicine, Psychiatric Clinic III, University of Rome La Sapienza, Rome, Italy

    Valentina Mantua

  6. Department of Anatomy, University of Rostock, Rostock, Germany

    Fritz Woltersdorf & Norbert Ulfig

  7. Department of Anatomy and Cell Biology, RWTH Aachen University, Aachen, Germany

    Thorsten Masson

  8. Department of Neuroscience, Mount Sinai School of Medicine, Box 1065, One Gustave L. Levy Place, New York, NY, 10029, USA

    Patrick R. Hof

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  1. Pawel Kreczmanski
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  2. Helmut Heinsen
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  3. Valentina Mantua
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  4. Fritz Woltersdorf
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  7. Rainald Schmidt-Kastner
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  9. Harry W. M. Steinbusch
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  10. Patrick R. Hof
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  11. Christoph Schmitz
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Correspondence to Patrick R. Hof or Christoph Schmitz.

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Kreczmanski, P., Heinsen, H., Mantua, V. et al. Microvessel length density, total length, and length per neuron in five subcortical regions in schizophrenia. Acta Neuropathol 117, 409–421 (2009). https://doi.org/10.1007/s00401-009-0482-7

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