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 [11C]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.
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08 September 2020
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Acknowledgements
We acknowledge the excellent work of the staff of the Yale PET Center and the nursing support from Brenda Breault, Cynthia D’Amico, Michelle San Pedro, Jamie Cyr, and Deborah Campbell for their contributions with patient care during the PET scans. This project was supported by the National Institutes of Health (NIH) through the following awards: R21MH096105, R21MH085627, RO1MH096876, and RO1MH102566. This publication was also made possible by CTSA Grant Number UL1 RR024139 from the National Center for Research Resources (NCRR) and the National Center for Advancing Translational Science (NCATS), components of the National Institutes of Health (NIH), NIH Roadmap for Medical Research, and Clinical Neurosciences Division of the United States Department of Veterans Affairs National Center for Posttraumatic Stress Disorder. Dr Neumeister has received grant support from Lilly. The work of Drs Neumeister, Huang, Potenza, and Carson was funded by the NIH.
The NIH or VA played no role in the design of the study, collection and analysis of the data, and decision to publish. Contents of this publication are solely the responsibility of the authors and do not necessarily represent the official view of NIH or VA.
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Pietrzak, R., Huang, Y., Corsi-Travali, S. et al. RETRACTED ARTICLE: Cannabinoid Type 1 Receptor Availability in the Amygdala Mediates Threat Processing in Trauma Survivors. Neuropsychopharmacol 39, 2519–2528 (2014). https://doi.org/10.1038/npp.2014.110
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DOI: https://doi.org/10.1038/npp.2014.110
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