1. ¹Inserm U.797, CEA–INSERM Research Unit 'Neuroimaging & Psychiatry', Institute for Health and Medical Research (INSERM) and Atomic Energy Commission (CEA) Hospital Department Frédéric Joliot, IFR49, Univ Paris-sud, Univ Paris 5, Orsay, France
2. ²APHP, Department of Psychiatry and Addictology, Paul Brousse Hospital, Villejuif, France
3. ³APHP, Addiction Treatment Center, Emile Roux Hospital, Limeil-Brevannes, France
4. ⁴URA CNRS-CEA 2210, Frédéric Joliot Department (SHFJ), Orsay, France

Correspondence: Jean-Luc Martinot, U797 INSERM-CEA, Service Hospitalier Frédéric Joliot, CEA, 4, place du Général Leclerc, 91401 Orsay, France. Tel: +33 1 6986 7742; Fax: +33 1 6986 7810; E-mail: jean-luc.martinot@cea.fr

Received 24 May 2006; Revised 28 July 2006; Accepted 28 August 2006; Published online 18 October 2006.

Abstract

The extent of structural brain damage and related cognitive deficits has been little described in alcohol-dependent individuals with preserved social functioning. Thus, we investigated the relationship between regional alterations, executive performance, and drinking history. Volumes of gray and white matter were assessed using magnetic resonance imaging voxel-based morphometry in healthy men and in detoxified alcohol-dependent men with good psychosocial functioning. Their executive performance was assessed using neuropsychological tests. Regression analyses were carried out in the regions in which volume differences were detected. Decreases in gray matter were detected bilaterally in alcohol-dependents in the dorsolateral frontal cortex (up to 20% lower), and to a lesser extent in the temporal cortex, insula, thalamus, and cerebellum. Decreases in white matter volume were widespread, being up to 10% in corpus callosum. The degradation of neuropsychological performance correlated with gray matter volume decreases in the frontal lobe, insula, hippocampus, thalami and cerebellum, and with white matter decrease in the brainstem. An early age at first drinking was associated with decreased gray matter volumes in the cerebellum, brainstem (pons), and frontal regions. Regional alteration in gray and white matter volume was associated with impairment of executive function despite preserved social and somatic functioning in detoxified patients. Besides involving frontal regions, these findings are consistent with a cerebello-thalamo-cortical model of impaired executive functions in alcohol-dependent individuals.