Abstract

Project 2: Functional Neuroimaging of Alcoholism Vulnerability: Probing Glutamate and Reward, Using the Fyn Kinase Inhibitor Drug, Saracatinib Godfrey Pearlson, M.D. Abstract This project will test the impact of a direct manipulation of a specific, alcoholism risk-relevant mechanism involving intracellular signaling, on functional MRI-measured human reward brain circuit function. It tests the dose-related effects of the Fyn kinase (Fyn) inhibitor drug, saracatinib (AZD0530) in a placebo-controlled, double-blind, randomized, counterbalanced study design. All proposed aims for Project 2 compare family history positive for alcoholism (FHP; i.e., affected parent plus other close relatives, N=40) to matched family history negative (FHN; i.e., no affected first-degree relative, N=40) participants on four fMRI tasks, with the goal of clarifying the interplay of the neurotransmitters dopamine and glutamate via protein kinase A- related signaling pathways in reward circuit dysfunction associated with familial risk for alcoholism.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Specialized Center (P50)
Project #
5P50AA012870-19
Application #
9698243
Study Section
Special Emphasis Panel (ZAA1)
Project Start
Project End
Budget Start
2019-06-01
Budget End
2020-05-31
Support Year
19
Fiscal Year
2019
Total Cost
Indirect Cost

  Institution

Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Leeman, Robert F; Nogueira, Christine; Wiers, Reinout W et al. (2018) A Test of Multisession Automatic Action Tendency Retraining to Reduce Alcohol Consumption Among Young Adults in the Context of a Human Laboratory Paradigm. Alcohol Clin Exp Res 42:803-814
Morean, Meghan E; L'Insalata, Alexa; Butler, Ellyn R et al. (2018) Age at drinking onset, age at first intoxication, and delay to first intoxication: Assessing the concurrent validity of measures of drinking initiation with alcohol use and related problems. Addict Behav 79:195-200
Preller, Katrin H; Burt, Joshua B; Ji, Jie Lisa et al. (2018) Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor. Elife 7:
Zhang, Huiping; Zhou, Hang; Lencz, Todd et al. (2018) Genome-wide association study of cognitive flexibility assessed by the Wisconsin Card Sorting Test. Am J Med Genet B Neuropsychiatr Genet 177:511-519
Vijay, Aishwarya; Cavallo, Dana; Goldberg, Alissa et al. (2018) PET imaging reveals lower kappa opioid receptor availability in alcoholics but no effect of age. Neuropsychopharmacology 43:2539-2547
Polimanti, Renato; Kayser, Manfred H; Gelernter, Joel (2018) Local adaptation in European populations affected the genetics of psychiatric disorders and behavioral traits. Genome Med 10:24
Polimanti, R; Kaufman, J; Zhao, H et al. (2018) A genome-wide gene-by-trauma interaction study of alcohol misuse in two independent cohorts identifies PRKG1 as a risk locus. Mol Psychiatry 23:154-160
Polimanti, R; Kaufman, J; Zhao, H et al. (2018) Trauma exposure interacts with the genetic risk of bipolar disorder in alcohol misuse of US soldiers. Acta Psychiatr Scand 137:148-156
Ide, Jaime S; Zhornitsky, Simon; Chao, Herta H et al. (2018) Thalamic Cortical Error-Related Responses in Adult Social Drinkers: Sex Differences and Problem Alcohol Use. Biol Psychiatry Cogn Neurosci Neuroimaging 3:868-877
D'Souza, Deepak Cyril; Carson, Richard E; Driesen, Naomi et al. (2018) Dose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects. Biol Psychiatry 84:413-421

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