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Increased grey matter densities in schizophrenia patients with negative symptoms after treatment with quetiapine: a voxel-based morphometry study

Stip, Emmanuela b c h; Mancini-Marïe, Adhama b c; Letourneau, Genevièvea b c; Fahim, Chérinec e; Mensour, Boualemd; Crivello, Fabricef; Dollfus, Soniaf g

International Clinical Psychopharmacology: January 2009 - Volume 24 - Issue 1 - p 34-41
doi: 10.1097/YIC.0b013e32831daf6c

Among new-generation antipsychotics, quetiapine was found to be associated with a partial ‘normalization’ of reduced functional activation in prefrontal and temporal areas and studies conducted by our group found a clinical improvement in negative symptoms in addition to restoration of frontal activation in schizophrenia patients with blunted affect after treatment with quetiapine. Here we investigated the parallelism between improved clinical symptoms and grey mater density (GMD) changes in the frontal region after quetiapine treatment in 15 schizophrenia patients. We hypothesize that improvement in clinical symptoms will be associated with change in GMD in prefrontal regions of interest. By using voxel-based morphometry, paired t-test random-effect analysis showed a significant increase in GMD bilaterally in the inferior frontal cortex/orbitofrontal gyrus and anterior cingulate cortex after 5.5 months of treatment with quetiapine. This GMD increase was associated with a significant improvement in negative symptoms. When GMD was correlated with psychiatric assessment scores, there was a negative correlation between GMD in the anterior cingulate cortex and the Rating Scale for Emotional Blunting score (r=−665, P=0.008) and between the orbitofrontal gyrus and the total Positive and Negative Syndrome Scale negative score (r=−764, P=0.001). Results suggest that increased GMD in some frontal regions are associated with an improvement of negative symptoms. Although not unique to quetiapine, it would be reasonable to attribute the GMD changes in the study to treatment.

aDepartment of Psychiatry, Fernand-Seguin Research Center

bDepartment of Psychiatry, L-H. Lafontaine Hospital

cDepartment of Psychiatry

dDepartment of Radiology, Centre Hospitalier de l'Université de Montréal (CHUM), Notre Dame Hospital, University of Montreal

eMcConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, Canada

fCNRS, Centre Cyceron

gCHU Côte de Nacre, Department of Psychiatry, Caen, France

hDepartment of Psychiatry, Sacre-coeur Hospital, Montreal, Quebec, Canada

Correspondence to Dr Emmanuel Stip, MD, MSc, CSPQ, Centre de recherche Fernand-Seguin, Rue Hochelaga 7331, Montreal, Quebec, Canada

Tel: +514 251 4015; fax: +514 251 2617;


Received 26 March 2008 Accepted 14 October 2008

© 2009 Lippincott Williams & Wilkins, Inc.