The fatty acid amide hydrolase C385A variant affects brain binding of the positron emission tomography tracer [11C]CURB

Isabelle Boileau; Rachel F Tyndale; Belinda Williams; Esmaeil Mansouri; Duncan J Westwood; Bernard Le Foll; Pablo M Rusjan; Romina Mizrahi; Vincenzo De Luca; Qian Zhou; Alan A Wilson; Sylvain Houle; Stephen J Kish; Junchao Tong

doi:10.1038/jcbfm.2015.119

The fatty acid amide hydrolase C385A variant affects brain binding of the positron emission tomography tracer [11C]CURB

J Cereb Blood Flow Metab. 2015 Aug;35(8):1237-40. doi: 10.1038/jcbfm.2015.119. Epub 2015 Jun 3.

Authors

Affiliations

¹ 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.
² 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.
³ 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.
⁴ 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.
⁵ 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.
⁶ 1] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
⁷ 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.
⁸ 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.
⁹ Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
¹⁰ 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.
¹¹ 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.
¹² 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.

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.

Publication types

Clinical Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Alleles*
Amidohydrolases* / genetics
Amidohydrolases* / metabolism
Anxiety Disorders* / diagnostic imaging
Anxiety Disorders* / genetics
Anxiety Disorders* / metabolism
Female
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide*
Positron-Emission Tomography*
Radiography
Radiopharmaceuticals* / administration & dosage
Radiopharmaceuticals* / pharmacokinetics

Substances

Radiopharmaceuticals
Amidohydrolases
fatty-acid amide hydrolase

Abstract

Publication types

MeSH terms

Substances

Grants and funding