Genetic variation in the endocannabinoid system and response to cognitive behavior therapy for child anxiety disorders

Kathryn J. Lester*, Jonathan R. I. Coleman, Susanna Roberts, Robert Keers, Gerome Breen, Susan Bögels, Cathy Creswell, Jennifer L. Hudson, Anna Mckinnon, Maaike Nauta, Ronald M. Rapee, Silvia Schneider, Wendy K. Silverman, Mikael Thastum, Polly Waite, Gro Janne H. Wergeland, Thalia C. Eley

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)
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Extinction learning is an important mechanism in the successful psychological treatment of anxiety. Individual differences in response and relapse following Cognitive Behavior Therapy may in part be explained by variability in the ease with which fears are extinguished or the vulnerability of these fears to re-emerge. Given the role of the endocannabinoid system in fear extinction, this study investigates whether genetic variation in the endocannabinoid system explains individual differences in response to CBT. Children (N = 1,309) with a primary anxiety disorder diagnosis were recruited. We investigated the relationship between variation in the CNR1, CNR2, and FAAH genes and change in primary anxiety disorder severity between pre- and post-treatment and during the follow-up period in the full sample and a subset with fear-based anxiety disorder diagnoses. Change in symptom severity during active treatment was nominally associated (P < 0.05) with two SNPs. During the follow-up period, five SNPs were nominally associated with a poorer treatment response (rs806365 [CNR1]; rs2501431 [CNR2]; rs2070956 [CNR2]; rs7769940 [CNR1]; rs2209172 [FAAH]) and one with a more favorable response (rs6928813 [CNR1]). Within the fear-based subset, the effect of rs806365 survived multiple testing corrections (P < 0.0016). We found very limited evidence for an association between variants in endocannabinoid system genes and treatment response once multiple testing corrections were applied. Larger, more homogenous cohorts are needed to allow the identification of variants of small but statistically significant effect and to estimate effect sizes for these variants with greater precision in order to determine their potential clinical utility.

Original languageEnglish
Pages (from-to)144-155
Number of pages12
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Issue number2
Early online date27 Jun 2016
Publication statusPublished - Mar 2017

Bibliographical note

Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


  • anxiety
  • children
  • Cognitive Behavior Therapy
  • endocannabinoids
  • fear extinction


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