Chronic cigarette smoking is very common in alcohol use disorders (AUD). Nevertheless, the effects of chronic smoking on in-vivo measures of brain injury in alcohol-dependent individuals have not been studied. Thus, it is unknown if the full extent of brain atrophy, cell membrane and microstructural injury, derangement of neurometabolism, low cerebral blood flow, and neurocognitive dysfunction described in alcohol dependence are solely attributable to chronic alcohol use, or if chronic smoking influences these measures. Preliminary results from our ongoing magnetic resonance (MR) and cognitive studies indicate that chronic smoking appears to exacerbate alcohol-induced abnormalities in brain morphology, neurochemistry, and blood flow, and may adversely affect recovery of surrogate markers of neuronal and cell membrane/myelin integrity as well as aspects of neurocognition during short-term abstinence from alcohol. The main goal of this competing continuation is therefore to test in treated alcohol dependent individuals (i) if chronic smoking compounds alcohol-induced neurobiological brain injury, (ii) if chronic smoking effects are functionally significant, and (iii) if chronic smoking influences recovery of alcohol-induced neurobiological and neurocognitive dysfunction during abstinence from alcohol. We will continue to apply an integrative approach of combining information from different MR modalities and neurocognitive testing in the same individual longitudinally to assess the neurobiological and functional consequences of chronic smoking in treated alcohol-dependent individuals. Specifically, we will continue our longitudinal 1.5 Tesla MR studies to quantitate regional brain structure, brain metabolites (reflecting neuronal and myelin viability), and regional cerebral blood flow as well as repeat comprehensive neurocognitive testing. In addition, new MR studies at high magnetic field (4T) will improve the quality of cerebral blood flow and diffusion data, and will measure cortical levels of glutamate and Y-aminobutyric acid, amino acids critically involved in the initiation and maintenance of substance dependence. Relationships of MR-derived and neurocognitive measures will determine the functional relevance of neurobiological measures and their changes over time and test the effects of chronic smoking on functional neurocircuitry in alcoholism. This application is responsive to PA-05-074 in that the proposed research will improve our understanding of the mechanisms underlying alcohol- and smoking induced brain injury and its potential reversibility with abstinence from alcohol. Chronic smoking may have hitherto unrecognized but significant contributions to these neurobiological processes and their cognitive and clinical consequences. The knowledge to be gained from this translational research can be used directly for public education, in new approaches to pharmacologic and behavioral interventions for AUD, and in monitoring treatment outcome. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA010788-12
Application #
7285687
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Matochik, John A
Project Start
1996-08-01
Project End
2011-07-31
Budget Start
2007-08-01
Budget End
2008-07-31
Support Year
12
Fiscal Year
2007
Total Cost
$688,094
Indirect Cost
Name
Northern California Institute Research & Education
Department
Type
DUNS #
613338789
City
San Francisco
State
CA
Country
United States
Zip Code
94121
Meyerhoff, Dieter J; Murray, Donna E; Durazzo, Timothy C et al. (2018) Brain GABA and Glutamate Concentrations Following Chronic Gabapentin Administration: A Convenience Sample Studied During Early Abstinence From Alcohol. Front Psychiatry 9:78
Zou, Yukai; Murray, Donna E; Durazzo, Timothy C et al. (2018) White matter microstructural correlates of relapse in alcohol dependence. Psychiatry Res Neuroimaging 281:92-100
Murray, Donna E; Durazzo, Timothy C; Schmidt, Thomas P et al. (2018) Regional cerebral blood flow in opiate dependence relates to substance use and neuropsychological performance. Addict Biol 23:781-795
Zou, Xiaowei; Durazzo, Timothy C; Meyerhoff, Dieter J (2018) Regional Brain Volume Changes in Alcohol-Dependent Individuals During Short-Term and Long-Term Abstinence. Alcohol Clin Exp Res 42:1062-1072
Meyerhoff, Dieter J (2017) Structural Neuroimaging in Polysubstance Users. Curr Opin Behav Sci 13:13-18
Schmidt, Thomas P; Pennington, David L; Cardoos, Stephanie L et al. (2017) Neurocognition and inhibitory control in polysubstance use disorders: Comparison with alcohol use disorders and changes with abstinence. J Clin Exp Neuropsychol 39:22-34
Durazzo, Timothy C; Meyerhoff, Dieter J (2017) Psychiatric, Demographic, and Brain Morphological Predictors of Relapse After Treatment for an Alcohol Use Disorder. Alcohol Clin Exp Res 41:107-116
Durazzo, Timothy C; Mon, Anderson; Gazdzinski, Stefan et al. (2017) Regional brain volume changes in alcohol-dependent individuals during early abstinence: associations with relapse following treatment. Addict Biol 22:1416-1425
Zou, Yukai; Murray, Donna E; Durazzo, Timothy C et al. (2017) Effects of abstinence and chronic cigarette smoking on white matter microstructure in alcohol dependence: Diffusion tensor imaging at 4T. Drug Alcohol Depend 175:42-50
Durazzo, Timothy C; Murray, Donna E; Meyerhoff, Dieter J (2017) Reply to: On the Correction of Effects of Flip Angle in 1H Magnetic Resonance Spectroscopy Signal Acquired Using Stimulated Echo Acquisition Mode Sequence. Biol Psychiatry 81:e17

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