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Schizophrenia Bulletin Advance Access published online on June 19, 2009

Schizophrenia Bulletin, doi:10.1093/schbul/sbp058
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© The Author 2009. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Hippocampi, Thalami, and Accumbens Microstructural Damage in Schizophrenia: A Volumetry, Diffusivity, and Neuropsychological Study

Ilaria Spoletini2, Andrea Cherubini2, Giulia Banfi2, Ivo Alex Rubino3, Patrice Peran2, Carlo Caltagirone2,3 and Gianfranco Spalletta1,3
2 Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Rome, Italy
3 Department of Neuroscience, Tor Vergata University, Rome, Italy

1 To whom correspondence should be addressed; Laboratory of Clinical and Behavioural Neurology, Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Via Ardeatina 306. 00179 Rome, Italy; tel: +39-06-51501575, fax: +39-06-51501575, e-mail: g.spalletta{at}hsantalucia.it.

Volumetric abnormalities in the subcortical structures have been described in schizophrenia. However, it still has to be clarified if subtle microstructural damage is also present. Thus, we aimed to detect subcortical volume and mean diffusivity (MD) alterations in 45 patients with diagnosis of schizophrenia compared with 45 age-, gender-, and educational attainment–matched healthy comparison (HC) participants, by using a combined volumetry and diffusion tensor imaging (DTI) method. A secondary aim was to identify the neuropsychological correlates of subcortical abnormalities in the schizophrenic group. We found thalami and hippocampi bilaterally and left accumbens to show MD increase in the schizophrenic group. No volumetric decrease was found. Moreover, significant correlations between the MD values in subcortical structures (right thalamus and hippocampus and left accumbens) and working memory performance were found. Thus, subcortical microstructural alterations are present in schizophrenia even in absence of volumetric abnormalities. Furthermore, microstructural damage in subcortical areas is linked to working memory, suggesting the presence of a subtle microstructural subcortical dysfunction in the pathoetiological mechanism underlying high cognitive load performances in schizophrenia. Finally, our findings indicate that MD is a more sensitive marker of brain tissue deficits than signal intensity variations measured in T1-weighted imaging data, consistently with previous reports. Thus, DTI appears to be an invaluable tool to investigate subcortical pathology in schizophrenia, greatly enhancing the ability to detect subtle brain changes in this complex disorder.

Keywords: subcortical structure / mean diffusivity / volume / working memory


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