Luke J Ney1, Allison Matthews1, Chia-Ming Ken Hsu1, Daniel V Zuj2, Emma Nicholson3, Trevor Steward3, David Nichols4, Bronwyn Graham5, Ben Harrison6, Raimondo Bruno1, Kim Felmingham3. 1. School of Psychology, University of Tasmania, Hobart, Australia. 2. Department of Psychology, Swansea University, Wales, United Kingdom. 3. School of Psychological Sciences, University of Melbourne, Melbourne, Australia. 4. Central Science Laboratory, University of Tasmania, Hobart, Australia. 5. School of Psychology, The University of New South Wales, Kensington, Australia. 6. Department of Psychiatry, Melbourne Neuropsychiatry Center, University of Melbourne & Melbourne Health, Melbourne, Australia.
Abstract
BACKGROUND: The endocannabinoid system is gaining increasing attention as a favorable target for improving posttraumatic stress disorder (PTSD) treatments. Exposure therapy is the gold-standard treatment for PTSD, and fear extinction learning is a key concept underlying successful exposure. METHODS: This study examined the role of genetic endocannabinoid polymorphisms in a fear extinction paradigm with PTSD compared to healthy participants (N = 220). Participants provided saliva for genotyping, completed a fear conditioning and extinction task, with blood samples taken before and after the task (n = 57). Skin conductance was the outcome and was analyzed using mixed models. RESULTS: Results for cannabinoid receptor type 1 polymorphisms suggested that minor alleles of rs2180619 and rs1049353 were associated with poorer extinction learning in PTSD participants. The minor allele of the fatty acid amide hydrolase (FAAH) polymorphism rs324420 was associated with worse extinction in PTSD participants. Subanalysis of healthy participants (n = 57) showed the FAAH rs324420 genotype effect was dependent on plasma arachidonoyl ethanolamide (AEA) level, but not oleoylethanolamide or 2-arachidonoyl glycerol. Specifically, higher but not lower AEA levels in conjunction with the minor allele of FAAH rs324420 were associated with better extinction learning. CONCLUSIONS: These findings provide translational evidence that cannabinoid receptor 1 and AEA are involved in extinction learning in humans. FAAH rs324420's effect on fear extinction is moderated by AEA plasma level in healthy controls. These findings imply that FAAH inhibitors may be effective for targeting anxiety in PTSD, but this effect needs to be explored further in clinical populations.
BACKGROUND: The endocannabinoid system is gaining increasing attention as a favorable target for improving posttraumatic stress disorder (PTSD) treatments. Exposure therapy is the gold-standard treatment for PTSD, and fear extinction learning is a key concept underlying successful exposure. METHODS: This study examined the role of genetic endocannabinoid polymorphisms in a fear extinction paradigm with PTSD compared to healthy participants (N = 220). Participants provided saliva for genotyping, completed a fear conditioning and extinction task, with blood samples taken before and after the task (n = 57). Skin conductance was the outcome and was analyzed using mixed models. RESULTS: Results for cannabinoid receptor type 1 polymorphisms suggested that minor alleles of rs2180619 and rs1049353 were associated with poorer extinction learning in PTSDparticipants. The minor allele of the fatty acid amide hydrolase (FAAH) polymorphism rs324420 was associated with worse extinction in PTSDparticipants. Subanalysis of healthy participants (n = 57) showed the FAAHrs324420 genotype effect was dependent on plasma arachidonoyl ethanolamide (AEA) level, but not oleoylethanolamide or 2-arachidonoyl glycerol. Specifically, higher but not lower AEA levels in conjunction with the minor allele of FAAHrs324420 were associated with better extinction learning. CONCLUSIONS: These findings provide translational evidence that cannabinoid receptor 1 and AEA are involved in extinction learning in humans. FAAHrs324420's effect on fear extinction is moderated by AEA plasma level in healthy controls. These findings imply that FAAH inhibitors may be effective for targeting anxiety in PTSD, but this effect needs to be explored further in clinical populations.
Authors: Daniela Navarro; Ani Gasparyan; Francisco Navarrete; Abraham B Torregrosa; Gabriel Rubio; Marta Marín-Mayor; Gabriela B Acosta; Maria Salud Garcia-Gutiérrez; Jorge Manzanares Journal: Int J Mol Sci Date: 2022-04-26 Impact factor: 6.208
Authors: Luke J Ney; Patrick A F Laing; Trevor Steward; Daniel V Zuj; Simon Dymond; Ben Harrison; Bronwyn Graham; Kim L Felmingham Journal: PLoS One Date: 2022-05-24 Impact factor: 3.752
Authors: G Kastrati; J Rosén; M Fredrikson; X Chen; R Kuja-Halkola; H Larsson; K B Jensen; F Åhs Journal: Transl Psychiatry Date: 2022-03-08 Impact factor: 7.989