Long-term chronic alcohol abuse is associated with structural brain changes and neuro-cognitive impairment. Few studies have shown a convincing correlation between these phenomena and it appears likely that neurosubstrates other than structural alterations underlie the cognitive changes associated with heavy drinking and recovery. The overall goal of this project is to test the hypothesis that axonal/dendritic and membrane phospholipid ( and possibly perfusion) changes in white matter underlie the reversible structural and neurocognitive changes associated with long-term chronic alcohol abuse and recovery. Subjects: 50 light drinkers (LD) and 100 heavy drinkers. LD will be studied at baseline and 9-12 months later, HD will be studied at entry into alcohol abuse treatment (to capture the full extent of brain damage due to heavy drinking), at 2-4 weeks of abstinence, and at 9-12 months after treatment entry during abstinence or relapse. Measurements: Cognition by neuropsychological testing; brain structures by MRI, axonal/dendritic and neuronal viability by 1H MR spectroscopic imaging (N-acetyl aspartate, a putative neuronal/axonal marker); lipids by choline-containing compounds (Cho) and myo-inositol (ml) and by phosphorus-31 MRS (via membrane phospholipids and their breakdown products and precursors); regional cerebral blood flow will be measured with exploratory spin-tagged perfusion MRI. The specific focus of the study will be on white matter, but cortical and subcortical gray matter, cerebellum, hippocampus, corpus callosum, and brain stem, intracranial volume and volumes of various brain nuclei will also be assessed. We expect that initially low regional NAA and phospholipid measures and initially high Cho and mI measures correlate with specific measures of cognitive impairment and that these outcome measures will recover during abstinence in association with cognitive improvements; relapse will arrest structural, metabolic, and cognitive improvements. The significance of these results is several fold: First, this project will develop non invasive outcome measures which provide objective quantitative measurements of alcohol-induced brain damage. This may be useful in future clinical trials in which drugs or treatments are used to reduce drinking, or to monitor effects of drugs aimed at reducing brain damage, or facilitating recovery. Second, these results may also provide information, which can lead to the development of specific drug treatments, aimed at preventing brain damage at the neuron or membrane or at facilitating recovery.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA010788-07
Application #
6532365
Study Section
Special Emphasis Panel (ZAA1-BB (01))
Program Officer
Witt, Ellen
Project Start
1996-08-01
Project End
2006-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
7
Fiscal Year
2002
Total Cost
$560,995
Indirect Cost
Name
Northern California Institute Research & Education
Department
Type
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94121
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; 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
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
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

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