Brain Advance Access published online on February 15, 2007
Brain, doi:10.1093/brain/awl386
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Volume, neuron density and total neuron number in five subcortical regions in schizophrenia
1Department of Psychiatry and Neuropsychology, Division of Cellular Neuroscience, Maastricht University, 2European Graduate School of Neuroscience (EURON), Maastricht, The Netherlands, 3Morphological Brain Research Unit, University of Wuerzburg, Wuerzburg, Germany, 4Department of Psychiatry, Section of Clinical Neuropharmacology, Institute of Psychiatry, Kings College London, London, UK, 5Department of Psychiatric Sciences and Psychological Medicine, Psychiatric Clinic III, University of Rome La Sapienza, Rome, Italy, 6Department of Anatomy, University of Rostock, Rostock, 7Department of Anatomy and Cell Biology, RWTH Aachen University, Aachen, Germany and 8Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA
Correspondence to:
Dr Christoph Schmitz, Department of Psychiatry and Neuropsychology, Division of Cellular Neuroscience, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands E-mail: c.schmitz{at}np.unimaas.nl
Several studies have pointed to alterations in mean volumes, neuron densities and total neuron numbers in the caudate nucleus (CN), putamen, nucleus accumbens (NA), mediodorsal nucleus of the thalamus (MDNT) and lateral nucleus of the amygdala (LNA) in schizophrenia. However, the results of these studies are conflicting and no clear pattern of alterations has yet been established in these subcortical regions, possibly due to differences in quantitative histological methods used as well as differences in the investigated case series. The present study investigates these subcortical regions in both hemispheres of the same post-mortem brains for volume, neuron density and total neuron number with high-precision design-based stereology. The analysed case series consisted of 13 post-mortem brains from male schizophrenic patients [age range: 22–64 years; mean age 51.5 ± 3.3 years (mean ± SEM)] and 13 age-matched male controls (age range: 25–65 years; mean age 51.9 ± 3.1 years). A general linear model multivariate analysis of variance with diagnosis and hemisphere as fixed factors and illness duration (schizophrenic patients) or age (controls), post-mortem interval and fixation time as covariates showed a number of statistically significant alterations in the brains from schizophrenic patients compared with the controls. There was a reduced mean volume of the putamen [–5.0% on the left side (l) and –4.1% on the right side (r)] and the LNA (l: –12.1%, r: –17.6%), and a reduced mean total neuron number in the CN (l: –10.4%, r: –10.2%), putamen (l: –8.1%, r: –11.6%) and the LNA (l: –15.9%, r: –16.2%). These data show a previously unreported, distinct pattern of alterations in mean total neuron numbers in identified subcortical brain regions in a carefully selected sample of brains from schizophrenic patients. The rigorous quantitative analysis of several regions in brains from schizophrenic patients and matched controls is crucial to provide reliable information on the neuropathology of schizophrenia as well as insights about its pathogenesis.
Key Words: amygdala; design-based stereology; schizophrenia; striatum; thalamus
Abbreviations: ABNA, accessory basal nuclei of the amygdala; BNA, basal nuclei of the amygdala; CGM, cortical grey matter; CN, caudate nucleus; LNA, lateral nucleus of the amygdala; MDNT, mediodorsal nucleus of the thalmus; NA, nucleus accumbens
Received September 7, 2006. Revised December 7, 2006. Accepted December 8, 2006.
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