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

• Final Report Year: 2016

Final Report Abstract

The central aim of the research was to examine whether there was increases inflammation in patients with alcohol dependence (AD) compared to socially drinking healthy controls (HC). To study this, n=7 AD patients and n=7 socially drinking controls were scanned with neuroinflammation Positron Emission Tomography (PET) tracer [11 C]PBR28, within 7 days of their last drinking episode. Groups were matched for age, gender, IQ, and TSPO genotype (which is known to influence [11C]PBR28). AD subjects drank alcohol for at least 10 years, at least 5 days a week, at least 4 drinks a day; whereas controls did not meet current or past AD criteria, and did not drink more than 3 drinks on one occasion in the past 6 months. Preliminary results show that AD subjects had lower whole brain [11C]PBR28 uptake (SUV) compared to controls. However, when correcting for whole brain uptake, there was a regional difference in white matter uptake in that AD subjects had increased [11C]PBR28 uptake in frontal white matter compared to HC(SPM p<.001 uncorrected). Similar results were corroborated in alcoholic Wistar rats: while SUVs showed lower uptake in the brains of alcoholic compared to healthy rats; regional differences showed increased PBR28 uptake in the anterior cingulate cortex of AD vs control rats. These findings provide preliminary evidence for increased PBR28 uptake in white matter structures in human patients with AD, and in the anterior cingulate cortex of alcoholic rats. Human and rat studies therefore suggest that whiter matter might be vulnerable to neuroinflammation in alcohol use disorders.

Publications

• (2015). Effects of depressive symptoms and peripheral DAT methylation on neural reactivity to alcohol cues in alcoholism. Transl Psychiatry;5:e648
  Wiers, C. E.; Shumay, E.; Volkow, N. D.; Frieling, H.; Kotsiari, A.; Lindenmeyer, J.; Walter, H. & Bermpohl, F.
  
• (2016). Cannabis Abusers Show Hypofrontality and Blunted Brain Responses to a Stimulant Challenge in Females but not in Males. Neuropsychopharmacology. 41(10):2596-60
  Wiers, Corinde E.; Shokri-Kojori, Ehsan; Wong, Christopher T.; Abi-Dargham, Anissa; Demiral, Şükrü B.; Tomasi, Dardo; Wang, Gene-Jack & Volkow, Nora D.
  
• (2016). PET imaging for addiction medicine: From neural mechanisms to clinical considerations. Prog Brain Res 224. 175-201
  Wiers, Corinde E.; Cabrera, Elizabeth; Skarda, Emily; Volkow, Nora D. & Wang, Gene-Jack
  
• (2016). Socioeconomic status is associated with striatal dopamine D2/D3 receptors in healthy volunteers but not in cocaine abusers. Neurosci Lett., 617:27-31
  Wiers, Corinde E.; Shokri-Kojori, Ehsan; Cabrera, Elizabeth; Cunningham, Samantha; Wong, Christopher; Tomasi, Dardo; Wang, Gene-Jack & Volkow, Nora D.
  
• Alcohol affects brain functional connectivity and its coupling with behavior: greater effects in male heavy drinkers. Molecular Psychiatry volume 22, pages 1185–1195 (2017)
  Shokri-Kojori, E.; Tomasi, D.; Wiers, C. E.; Wang, G.-J. & Volkow, N. D.
  
• Reduced sleep duration mediates decreases in striatal D2/D3 receptor availability in cocaine abusers. Translational Psychiatry volume 6, page e752 (2016)
  Wiers, C. E.; Shumay, E.; Cabrera, E.; Shokri-Kojori, E.; Gladwin, T. E.; Skarda, E.; Cunningham, S. I.; Kim, S. W.; Wong, T. C.; Tomasi, D.; Wang, G.-J. & Volkow, N. D.