title: Cannabinoid type 1 receptor availability in the amygdala mediates threat processing in trauma survivors.
abstract: Attentional bias to threat is a key endophenotype that contributes to the chronicity of trauma-related psychopathology. However, little is known about the neurobiology of this endophenotype and no known in vivo molecular imaging study has been conducted to evaluate candidate receptor systems that may be implicated in this endophenotype or the phenotypic expression of trauma-related psychopathology that comprises threat (ie, re-experiencing, avoidance, and hyperarousal) and loss (ie, emotional numbing, depression/dysphoria, generalized anxiety) symptomatology. Using the radioligand [(11)C]OMAR and positron emission tomography (PET), we evaluated the relationship between in vivo cannabinoid receptor type 1 (CB1) receptor availability in the amygdala, and performance on a dot-probe measure of attentional bias to threat, and clinician interview-based measures of trauma-related psychopathology. The sample comprised adults presenting with a broad spectrum of trauma-related psychopathology, ranging from nontrauma-exposed, psychiatrically healthy adults to trauma-exposed adults with severe trauma-related psychopathology. Results revealed that increased CB1 receptor availability in the amygdala was associated with increased attentional bias to threat, as well as increased severity of threat, but not loss, symptomatology; greater peripheral anandamide levels were associated with decreased attentional bias to threat. A mediation analysis further suggested that attentional bias to threat mediated the relationship between CB1 receptor availability in the amygdala and severity of threat symptomatology. These data substantiate a key role for compromised endocannabinoid function in mediating both the endophenotypic and phenotypic expression of threat symptomatology in humans. They further suggest that novel pharmacotherapies that target the CB1 system may provide a more focused, mechanism-based approach to mitigating this core aspect of trauma-related psychopathology.
authors.affiliation: 1] Clinical Neurosciences Division, National Center for Posttraumatic Stress Disorder, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA [2] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Pietrzak
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Departments of Psychiatry and Radiology, New York University School of Medicine, New York, NY, USA.
authors.forename: Stefani
authors.initials: S
authors.lastname: Corsi-Travali
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Ming-Qiang
authors.initials: MQ
authors.lastname: Zheng
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Shu-fei
authors.initials: SF
authors.lastname: Lin
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Shannan
authors.initials: S
authors.lastname: Henry
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Marc N
authors.initials: MN
authors.lastname: Potenza
authors.affiliation: Anatomy & Neurobiology School of Medicine, University of California, Irvine, Irvine, CA, USA.
authors.forename: Daniele
authors.initials: D
authors.lastname: Piomelli
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.affiliation: Departments of Psychiatry and Radiology, New York University School of Medicine, New York, NY, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Neumeister
mesh_terms: D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001095:Arachidonic Acids / Q000097:blood; D001288:Attention / Q000502:physiology*; D002250:Carbon Radioisotopes; D063388:Endocannabinoids / Q000097:blood; D005239:Fear / Q000502:physiology*; D005260:Female; D006801:Humans; D007406:Interview, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D053284:Polyunsaturated Alkamides / Q000097:blood; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1; C078814:anandamide