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VOLUMETRIC DIFFERENCES IN GREY AND WHITE MATTER OF ALCOHOL ABUSERS

Romero FJ, Romero MJ, Asensio S, *Beltran MA, Senabre I, Morales JL, Lopez-Pedrajas R. Instituto de Drogas y Conductas Adictivas (IDYCA), Universidad CEU-Cardenal Herrera, Valencia, Spain. * Agencia Valenciana de Salud, Spain.

IntroductionAddiction has a multifactorial origin. Genetic load may predispose towards impulsive behaviors facilitating drug use, abuse and finally drug dependence. Although an increased impulsivity trait has been observed in addicted patients, it still remains unclear whether this alteration, as many others like structural, functional or neuropsychological, are previous or posterior to toxic drug effects of long term drug administration1.Ethanol toxic effects may decrease the volume of sensitive brain regions of alcoholic patients2 and a number of behavioral/functional MRI studies have also revealed alterations of the reward sensitivity, inhibitory control and its neural correlates in addicted patients3,4. However, much less research has linked this reward circuit impairment to structural abnormalities. Here we aimed to study brain structural abnormalities of alcohol abusers (before chronic ethanol intake may alter white and grey matters) and the association with impulsivity. In so doing, we can study the neural correlates of high impulsivity disorder that could be previous to alcohol dependence.

MethodsMorphometric imaging was applied to 21 subjects with alcohol abuse diagnosis and 21 controls in a 1.5 T MRI scanner. Optimized VBM protocole was employed to study local volumetric differences between groups using SPM2 software (Segmentation and HMRF model of 0.3, normalization to a own template, Jacobian modulation, 10mm FWHM kernel smoothing). Subjects completed the Barratt Impulsivity Scale v.11 (BIS) which was correlated with each between-group differential cluster of WM and GM of the VBM analysis.

WM

ResultsAlcohol abusers rated a significant higher BIS score than controls (Cognitive, Motor and Total Impulsivity: p<0.01). Compared to controls, alcohol abusers showed lower GM regional volume in the mPFC, and greater volume in the left ventral stritaum. They also showed lower WM volume in the bilateral inferior frontal WM and greater in the bilateral ventral striatum (telencephalic medial fascicle, a WM stream connecting midbrain and striatum). Significant correlations were observed between ACC GM, and inferior frontal and ventral striatum WM and impulsivity scores, including all subjects. Only the positive correlation between WM of ventral striatum and motor/total impulsivity remained significant in the patients group (p<0.05).

C>P P>C T-Score: 3 7 -3 -7

GM

DiscussionMedial PFC is involved in cognitive control and performance monitoring. Given that a GM reduction of this region has been linked to impulsivity5, the low mPFC GM and WM observed in this population of alcohol abusers may contribute to the higher impulsivity score and the inability to inhibit compulsive drinking behavior. Furthermore, some studies that showed an altered ventral striatum recruitment by rewarding cues suggested an increased limbic system sensitivity to reward and loss delivery, consistent with the role of impulsivity in addiction3. Therefore, these results of greater GM and WM volume in the ventral striatum of alcohol abusers and the positive correlation with impulsivity scores support the hypothesis of a enhanced sensitivity to reward in drug addiction which could be present before alcohol dependence even before alcohol abuse. This brain alterations could make harder to refuse immediate rewards, may underlie the compulsive drug use and, indirectly, could drive these subjects to keep abusing alcohol and to develop alcohol addiction.

Acknowledgements: This work was partially supported by a grant SAF2007-66801 from Plan Nacional de Biomedicina, Madrid, Spain, and funds from FEPAD, Red de Trastornos Adictivos RTA,Dirección General de Drogodependencias Generalitat Valenciana and COPERNICUS-SANTANDER program of the Universidad CEU Cardenal Herrera.

References: [1] Volkow ND. et al. (2004) Dopamine in drug abuse and addiction: results from imaging studies and treatment implications. Mol Psychiatry 9:557-69. [2] Mechtcheriakov S. et al. (2007) A widespread distinct pattern of cerebral atrophy in patients with alcohol addiction revealed by voxel-based morphometry. J Neurol Neurosurg Psychiatry 78:610-614. [3] Bjork JM et al. (2008) Striatal sensitivity to reward deliveries and omissions in substance dependent patients. Neuroimage. 42(4):1609-21. [4] Goldstein RZ, Volkow ND: Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am J Psychiatry 2002; 159(10):1642-52 [5] Matsuo K. et al. (2009) A voxel-based morphometry study of frontal gray matter correlates of impulsivity. Hum Brain Mapp 30:1188-95