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

Lester, K. J., Coleman, J. R. I., Roberts, S., Keers, R., Breen, G., Bogels, S., Creswell, C., Hudson, J. L., McKinnon, A., Nauta, M., Rapee, R. M., Schneider, S., Silverman, W. K., Thastum, M., Waite, P. ORCID: https://orcid.org/0000-0002-1967-8028, Wergeland, G. J. H. and Eley, T. C. (2017) Genetic variation in the endocannabinoid system and response to cognitive behavioural therapy for child anxiety disorders. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 174 (2). pp. 144-155. ISSN 1552-485X doi: 10.1002/ajmg.b.32467

Abstract/Summary

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.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/65725
Identification Number/DOI	10.1002/ajmg.b.32467
Refereed	Yes
Divisions	Life Sciences > School of Psychology and Clinical Language Sciences > Department of Psychology Life Sciences > School of Psychology and Clinical Language Sciences > Development Life Sciences > School of Psychology and Clinical Language Sciences > Psychopathology and Affective Neuroscience Life Sciences > School of Psychology and Clinical Language Sciences > Anxiety and Depression in Young People (AnDY)
Publisher	Wiley
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