Chronic cigarette smoking in alcohol dependence: associations with cortical thickness and N-acetylaspartate levels in the extended brain reward system

Addict Biol. 2013 Mar;18(2):379-91. doi: 10.1111/j.1369-1600.2011.00407.x. Epub 2011 Nov 9.


Chronic smoking in alcohol dependence is associated with abnormalities in brain morphology and metabolite levels in large lobar regions (e.g. frontal lobe). Here, we evaluated if these abnormalities are specifically apparent in several cortical and select subcortical components of the extended brain reward system (BRS), a network that is critically involved in the development and maintenance of all forms of addictive disorders. We studied 33 non-smoking and 43 smoking alcohol-dependent individuals (ALC) with 1 week of abstinence and 42 non-smoking Controls. At 1.5 Tesla, we obtained regional measures of cortical thickness and N-acetylaspartate (NAA; a surrogate marker of neuronal integrity) concentration in major components of the BRS as well as the corresponding measures throughout the cortex. Smoking ALC and non-smoking ALC demonstrated decreased thickness compared with Controls in the dorsolateral prefrontal cortex (DLPFC), insula, orbitofrontal cortex (OFC), the total BRS, total frontal cortex and global cortex. Smoking ALC had significantly decreased thickness compared to non-smoking ALC in the ACC, insula, the total BRS and total frontal cortex. Smoking ALC had also lower NAA concentrations than both non-smoking ALC and Controls in the DLPFC, insula, superior corona radiata and the total BRS. Alcohol consumption and common medical and psychiatric co-morbidities did not mediate differences between smoking and non-smoking ALC. This dual modality magnetic resonance (MR) study indicated that chronic smoking in ALC was associated with significant cortical thinning and NAA abnormalities in anterior brain regions that are implicated in the development and maintenance of addictive disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alcoholism / epidemiology
  • Alcoholism / metabolism
  • Alcoholism / pathology*
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Behavior, Addictive / epidemiology
  • Behavior, Addictive / metabolism
  • Behavior, Addictive / pathology*
  • Brain Mapping
  • Case-Control Studies
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology*
  • Chronic Disease
  • Comorbidity
  • Executive Function
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Reward*
  • Smoking / epidemiology
  • Smoking / metabolism
  • Smoking / pathology*


  • Aspartic Acid
  • N-acetylaspartate