title: Interactions Between Anandamide and Corticotropin-Releasing Factor Signaling Modulate Human Amygdala Function and Risk for Anxiety Disorders: An Imaging Genetics Strategy for Modeling Molecular Interactions.
abstract: Preclinical models reveal that stress-induced amygdala activity and impairment in fear extinction reflect reductions in anandamide driven by corticotropin-releasing factor receptor type 1 (CRF1) potentiation of the anandamide catabolic enzyme fatty acid amide hydrolase.
  
  
  
  Here, we provide clinical translation for the importance of these molecular interactions using an imaging genetics strategy to examine whether interactions between genetic polymorphisms associated with differential anandamide (FAAH rs324420) and CRF1 (CRHR1 rs110402) signaling modulate amygdala function and anxiety disorder diagnosis.
  
  
  
  Analyses revealed that individuals with a genetic background predicting relatively high anandamide and CRF1 signaling exhibited blunted basolateral amygdala habituation, which further mediated increased risk for anxiety disorders among these same individuals.
  
  
  
  The convergence of preclinical and clinical data suggests that interactions between anandamide and CRF1 represent a fundamental molecular mechanism regulating amygdala function and anxiety. Our results further highlight the potential of imaging genetics to powerfully translate complex preclinical findings to clinically meaningful human phenotypes.
authors.affiliation: Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, Missouri.
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Demers
authors.affiliation: 23andMe, Inc., Mountain View, California.
authors.forename: Emily
authors.initials: E
authors.lastname: Drabant Conley
authors.affiliation: Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, Missouri; Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, Missouri. Electronic address: rbogdan@wustl.edu.
authors.forename: Ryan
authors.initials: R
authors.lastname: Bogdan
authors.affiliation: Department of Psychology and Neuroscience, Laboratory of NeuroGenetics, Duke University, Durham, North Carolina.
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Hariri
mesh_terms: D000581:Amidohydrolases / Q000235:genetics; D000679:Amygdala / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D001007:Anxiety / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D001095:Arachidonic Acids / Q000235:genetics*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D063388:Endocannabinoids / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D053284:Polyunsaturated Alkamides; D011569:Psychiatric Status Rating Scales; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics; D012189:Retrospective Studies; D015398:Signal Transduction / Q000235:genetics*; D055815:Young Adult; D000099052:CRF Receptor, Type 1; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D003346:Corticotropin-Releasing Hormone; D063388:Endocannabinoids; D010100:Oxygen; D053284:Polyunsaturated Alkamides; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D000099252:Fatty Acid Amide Hydrolases; C078814:anandamide
keywords: Amygdala; Anxiety; CRHR1; FAAH; Habituation; Imaging genetics