Neuroinflammation and -function in alcohol dependence

• Applicant: Dr. Corinde Wiers
• Subject Area: Biological Psychiatry ; Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry ; Human Cognitive and Systems Neuroscience
• Term: from 2015 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 270915269

Alcohol dependence is a chronic relapsing disorder and a devastating problem in the world today. The abuse of high doses of alcohol has been associated with cognitive impairment that in extreme cases can result in dementia. However, the mechanisms underlying the neurotoxic effects of alcohol to the human brain remain poorly understood. The aim of the research proposed in this application is to examine whether alcohol-induced neuroinflammation contributes to its neurotoxic effects in humans. Alcohol-dependent (AD) patients and social drinking healthy control (HC) participants undergo two positron emission tomography (PET) scans, one with [11C]PBR28 (a marker of neuroinflammation) and one with 18FDG (a marker of brain glucose metabolism), magnetic resonance imaging (MRI) scans to assess brain structure, functional reactivity, functional connectivity, and neuropsychological testing. After three weeks, participants who show evidence of inflammatory changes (both AD patients and HC) undergo the same procedure as before. In AD patients, this phase is performed after alcohol abstinence, whereas no intervention takes place in the HC group. The main outcome measure is to assess whether neuroinflammation is present in AD patients and whether it recovers after detoxification. Secondary outcome measures are: to assess if neuroinflammation is associated with markers of brain function which include (1) regional brain glucose metabolism; (2) MRI based voxel-based morphometry (VBM) to assess cortical atrophy; (3) blood-oxygenation level-dependent (BOLD) activation during cognitive tasks; (4) brain functional connectivity; (5) myo-inositol concentrations measured with Magnetic Resonance Spectroscopy (MRS); (6) neuropsychological testing to assess cognitive performance, and to evaluate if neuroinflammation predicts relapse in AD over a 3 month follow-up period. If neuroinflammation can be documented in the brain of AD patients, this could be a possible target of therapeutic intervention to improve brain function and enhance success in recovery (e.g., with anti-inflammatory drugs).

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professorin Dr. Nora Volkow