title: The fatty acid amide hydrolase C385A variant affects brain binding of the positron emission tomography tracer [11C]CURB.
abstract: The common functional single-nucleotide polymorphism (rs324420, C385A) of the endocannabinoid inactivating enzyme fatty acid amide hydrolase (FAAH) has been associated with anxiety disorder relevant phenotype and risk for addictions. Here, we tested whether the FAAH polymorphism affects in vivo binding of the FAAH positron emission tomography (PET) probe [(11)C]CURB ([(11)C-carbonyl]-6-hydroxy-[1,10-biphenyl]-3-yl cyclohexylcarbamate (URB694)). Participants (n=24) completed one [(11)C]CURB/PET scan and were genotyped for rs324420. Relative to C/C (58%), A-allele carriers (42%) had 23% lower [(11)C]CURB binding (λk3) in brain. We report evidence that the genetic variant rs324420 in FAAH is associated with measurable differences in brain FAAH binding as per PET [(11)C]CURB measurement.
authors.affiliation: 1] Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Human Brain Lab, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [3] Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [4] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [5] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada [6] Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boileau
authors.affiliation: 1] Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada [3] Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Tyndale
authors.affiliation: 1] Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Human Brain Lab, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [3] Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [4] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Belinda
authors.initials: B
authors.lastname: Williams
authors.affiliation: 1] Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Human Brain Lab, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [3] Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [4] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Esmaeil
authors.initials: E
authors.lastname: Mansouri
authors.affiliation: 1] Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Human Brain Lab, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [3] Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [4] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [5] Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Westwood
authors.affiliation: 1] Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada [3] Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada [4] Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Le Foll
authors.affiliation: 1] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Pablo M
authors.initials: PM
authors.lastname: Rusjan
authors.affiliation: 1] Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [3] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada [4] Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Romina
authors.initials: R
authors.lastname: Mizrahi
authors.affiliation: 1] Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada [3] Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: 1] Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.affiliation: 1] Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.affiliation: 1] Human Brain Lab, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [3] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [4] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada [5] Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada [6] Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kish
authors.affiliation: 1] Human Brain Lab, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [3] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [4] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Junchao
authors.initials: J
authors.lastname: Tong
mesh_terms: D000328:Adult; D000483:Alleles; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D001008:Anxiety Disorders / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D011859:Radiography; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D019275:Radiopharmaceuticals; D000099252:Fatty Acid Amide Hydrolases