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Stereological analysis of the mediodorsal thalamic nucleus in schizophrenia: Volume, neuron number, and cell types

Identifieur interne : 00B650 ( Main/Merge ); précédent : 00B649; suivant : 00B651

Stereological analysis of the mediodorsal thalamic nucleus in schizophrenia: Volume, neuron number, and cell types

Auteurs : Karl-Anton Dorph-Petersen [États-Unis] ; Joseph N. Pierri [États-Unis] ; Zhuoxin Sun [États-Unis] ; Allan R. Sampson [États-Unis] ; David A. Lewis [États-Unis]

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RBID : ISTEX:950F0CC20497A779371856CBF0191A82D8EA3863

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English descriptors

Abstract

The mediodorsal thalamic nucleus (MD) is the principal relay nucleus for the prefrontal cortex, a brain region thought to be dysfunctional in schizophrenia. Several, but not all, postmortem studies of the MD in schizophrenia have reported decreased volume and total neuronal number. However, it is not clear whether the findings are specific for schizophrenia nor is it known which subtypes of thalamic neurons are affected. We studied the left MD in 11 subjects with schizophrenia, 9 control subjects, and 12 subjects with mood disorders. Based on morphological criteria, we divided the neurons into two subclasses, presumably corresponding to projection neurons and local circuit neurons. We estimated MD volume and the neuron number of each subclass using methods based on modern unbiased stereological principles. We also estimated the somal volumes of each subclass using a robust, but biased, approach. In addition, we investigated the left MD in four cynomolgus monkeys chronically exposed to haloperidol and in four control monkeys in order to assess the possible effects of antipsychotic medications. The three human subject groups did not differ in any of the measures. In addition, no differences were observed between the two groups of monkeys. Thus, these findings do not support the hypothesis that the MD is a locus of pathology in schizophrenia, although they cannot rule out important functional or structural changes in parameters not measured. Like other studies, this investigation is subject to the limitations involved in sampling from a heterogeneous population emphasizing the need to continue to improve the application of robust, unbiased techniques to quantitative studies of this complex brain disorder. J. Comp. Neurol. 472:449–462, 2004. © 2004 Wiley‐Liss, Inc.

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DOI: 10.1002/cne.20055

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<term>Other subjects</term>
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<term>Unbiased stereological estimation</term>
<term>Unbiased techniques</term>
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<term>Unshrunken section</term>
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<term>Adobe photoshop</term>
<term>Alcohol dependence</term>
<term>Antipsychotic</term>
<term>Antipsychotic medication</term>
<term>Antipsychotic medications</term>
<term>Ascvd</term>
<term>Axon terminals</term>
<term>Block advance</term>
<term>Brain region</term>
<term>Byne</term>
<term>Calibration study</term>
<term>Camera software</term>
<term>Clinical features</term>
<term>Cohort differences</term>
<term>Color balance</term>
<term>Comorbid mood</term>
<term>Comp neurol</term>
<term>Complex brain disorder</term>
<term>Control monkeys</term>
<term>Control subjects</term>
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<term>Coronal sections</term>
<term>Cryostat sections</term>
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<term>Cynomolgus monkeys</term>
<term>Densocellular region</term>
<term>Dewulf</term>
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<term>Local section thickness</term>
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<term>Nissl stain</term>
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<term>Normal control subjects</term>
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<term>Nucleolus</term>
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<term>Optical fractionator</term>
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<term>Other subjects</term>
<term>Other substance abuse</term>
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<term>Partial sections</term>
<term>Pilot calibration study</term>
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<term>Postmortem study</term>
<term>Potential impact</term>
<term>Prefrontal</term>
<term>Prefrontal cortex</term>
<term>Present study</term>
<term>Previous reports</term>
<term>Previous studies</term>
<term>Previous study</term>
<term>Projection neurons</term>
<term>Psychiatry</term>
<term>Putative projection</term>
<term>Quantitative studies</term>
<term>Random sampling</term>
<term>Reference volume</term>
<term>Retrograde degeneration</term>
<term>Robust</term>
<term>Sampling sites</term>
<term>Schizophrenia</term>
<term>Section thickness</term>
<term>Shot suicide</term>
<term>Shrinkage</term>
<term>Somal</term>
<term>Somal volume</term>
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<term>Somal volumes</term>
<term>Specimen selection</term>
<term>Stereological</term>
<term>Stereological analysis</term>
<term>Storage time</term>
<term>Subject groups</term>
<term>Surface area</term>
<term>Systematic sampling</term>
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<term>Thalamic mediodorsal nucleus</term>
<term>Thalamus</term>
<term>Tiff format</term>
<term>Tissue processing</term>
<term>Tissue shrinkage</term>
<term>Tissue storage time</term>
<term>Total neuron number</term>
<term>Total number</term>
<term>Total volume</term>
<term>Trough serum levels</term>
<term>Unbiased</term>
<term>Unbiased stereological estimation</term>
<term>Unbiased techniques</term>
<term>Undifferentiated schizophrenia</term>
<term>Unshrunken section</term>
<term>Upper guard zone</term>
<term>Vertical sections</term>
<term>Vibratome sections</term>
<term>Volume estimates</term>
<term>White matter tracts</term>
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<div type="abstract" xml:lang="en">The mediodorsal thalamic nucleus (MD) is the principal relay nucleus for the prefrontal cortex, a brain region thought to be dysfunctional in schizophrenia. Several, but not all, postmortem studies of the MD in schizophrenia have reported decreased volume and total neuronal number. However, it is not clear whether the findings are specific for schizophrenia nor is it known which subtypes of thalamic neurons are affected. We studied the left MD in 11 subjects with schizophrenia, 9 control subjects, and 12 subjects with mood disorders. Based on morphological criteria, we divided the neurons into two subclasses, presumably corresponding to projection neurons and local circuit neurons. We estimated MD volume and the neuron number of each subclass using methods based on modern unbiased stereological principles. We also estimated the somal volumes of each subclass using a robust, but biased, approach. In addition, we investigated the left MD in four cynomolgus monkeys chronically exposed to haloperidol and in four control monkeys in order to assess the possible effects of antipsychotic medications. The three human subject groups did not differ in any of the measures. In addition, no differences were observed between the two groups of monkeys. Thus, these findings do not support the hypothesis that the MD is a locus of pathology in schizophrenia, although they cannot rule out important functional or structural changes in parameters not measured. Like other studies, this investigation is subject to the limitations involved in sampling from a heterogeneous population emphasizing the need to continue to improve the application of robust, unbiased techniques to quantitative studies of this complex brain disorder. J. Comp. Neurol. 472:449–462, 2004. © 2004 Wiley‐Liss, Inc.</div>
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