NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION INC
Grant: $232,500 - National Institutes of Health - Aug. 14, 2009
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Award Description: The main goals of our parent grant (R01AA10788) are to test in alcohol dependent individuals (i) if chronic smoking influences brain injury, (ii) if chronic smoking effects ares functionally significant, and (iii) to what extent chronic smoking modulates recovery of alcohol-induced brain injury and neurocognitive dysfunction during abstinence from alcohol. We study brain injury and cognitive dysfunction in smoking and non-smoking alcoholics in treatment with state-of-the-art Magnetic Resonance Imaging (MRI) methodology and nerocognitive testing. To better understand the wide-reaching implications of concurrent chronic cigarette smoking and alcohol dependence, we quantitate regional brain structure (by volumetric MRI), brain metabolites reflecting neuronal and glial viability as well as amino acids such as y-aminobutyric acid (GABA) and glutamate (Glu) (by MR spectroscopy), regional cerebral blood flow (by arterial spin label perfusion MRI), and neurocognitive performance during abstinence from alcohol. The amino acids play critical roles in the mesocorticolimbic reward pathway that has been implicated in alcohol and nicotine dependence. In alcoholism, the altered concentrations of these amino acids are associated with neurotoxicity and clinically significant functional cognitive abnormalities such as memory and executive function deficits. We request supplemental funds to respond to gaps in current knowledge about cognitively and behaviorally significant brain effects and their confounds in smoking and non-smoking alcoholics. Specifically, we will focus additional MR data acquisition and analyses on specific regions of the reward system, which we believe to be more sensitive and relevant to drug-use behavior and relapse than our lobar measurements, which have been the focus of our parent grant. The MR-based neurobiological measures will then be related to the proposed reward processing, decision-making and impulsivity measures reported to be compromised in substance use disorders. Assessment of the integrity of the brain reward system, decision-making and impulse control will allow us to better understand the neurobiological and neurocognitive correlates of relapse in alcoholism than our initially proposed lobar measurements. In addition, we will expang our genotyping efforts to also include genes which have been found to be associated with endophenotypic indicators of reward system dysfunction. We believe that these additions to our parent R01 are not only responsive to the recovery program, but ultimately also to clinicians' needs to improve patient-treatment matching for more efficient spending of scarce treatment resources.
Project Description: Little is known about the effects of chronic smoking on neuroimaging and cognitive measures of brain injury in alcohol-dependance. By focusing our data acquisition and analyses on the brain reward system and specific genetic variations, we will improve our understanding of mechanisms and genotypes that underlie alcohol and smoking induced brain injury and its potential reversibility with abstinence from alcohol. The results can be used directly for public education, policy making, in new approaches to pharmacologic and behavioral treatments for substance dependence, and in predicting and monitoring treatment outcome.
Infrastructure Description: NA
Jobs Summary: Retention of employees if reward is granted (1) Wendy Ooteman, PhD (Postdoctoral Researcher). Dr Ooteman is a new postdoctoral researcher, who joined the PI in February 2009. She is currently being trained on all MR procedures associated with the parent grant. She will perform the additional studies that are requested through this supplement. She will also participate in processing and analyze the newly acquired MR data. (2) Linda Abadjian, PhD (Study Coordinatory and Clinical Assessor). She will perform and score the addtional evaluations and cognitive tests proposed in this supplement. (3) Soo Shin (Administrative Support). Due to the extraordinary administrative oversight and reporting associated with the American Recovery and Reinvestment Act, we request 0.6 calendar months salary support for the additional administrative services required by the Act should an award be issued. (Total jobs reported: 0)
Project Status: Not Started
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