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Monoacylglycerol lipase (MGLL) polymorphism rs604300 interacts with childhood adversity to predict cannabis dependence symptoms and amygdala habituation: Evidence from an endocannabinoid system-level analysis.
Despite evidence for heritable variation in cannabis involvement and the discovery of cannabinoid receptors and their endogenous ligands, no consistent patterns have emerged from candidate endocannabinoid (eCB) genetic association studies of cannabis involvement. Given interactions between eCB and stress systems and associations between childhood stress and cannabis involvement, it may be important to consider childhood adversity in the context of eCB-related genetic variation. We employed a system-level gene-based analysis of data from the Comorbidity and Trauma Study (N = 1,558) to examine whether genetic variation in six eCB genes (anabolism: DAGLA, DAGLB, NAPEPLD; catabolism: MGLL, FAAH; binding: CNR1; SNPs N = 65) and childhood sexual abuse (CSA) predict cannabis dependence symptoms. Significant interactions with CSA emerged for MGLL at the gene level (p = .009), and for rs604300 within MGLL (ΔR2 = .007, p < .001), the latter of which survived SNP-level Bonferroni correction and was significant in an additional sample with similar directional effects (N = 859; ΔR2 = .005, p = .026). Furthermore, in a third sample (N = 312), there was evidence that rs604300 genotype interacts with early life adversity to predict threat-related basolateral amygdala habituation, a neural phenotype linked to the eCB system and addiction (ΔR2 = .013, p = .047). Rs604300 may be related to epigenetic modulation of MGLL expression. These results are consistent with rodent models implicating 2-arachidonoylglycerol (2-AG), an endogenous cannabinoid metabolized by the enzyme encoded by MGLL, in the etiology of stress adaptation related to cannabis dependence, but require further replication.
(c) 2015 APA, all rights reserved).
2015 Nov
entrez 2015/11/24 06:00
pubmed 2015/11/26 06:00
medline 2015/11/26 06:00
pmc-release 2016/11/01 00:00
Carey CE Carey Caitlin E CE Department of Psychology, Washington University in St. Louis.
Agrawal A Agrawal Arpana A Department of Psychiatry, Washington University in St. Louis.
Zhang B Zhang Bo B Department of Genetics, Washington University in St. Louis.
Conley ED Conley Emily D ED 23andMe.
Degenhardt L Degenhardt Louisa L National Drug and Alcohol Research Centre, University of New South Wales.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University in St. Louis.
Li D Li Daofeng D Department of Genetics, Washington University in St. Louis.
Lynskey MT Lynskey Michael T MT Institute of Psychiatry, Kings College London.
Martin NG Martin Nicholas G NG Berghofer Medical Research Institute.
Montgomery GW Montgomery Grant W GW Berghofer Medical Research Institute.
Wang T Wang Ting T Department of Genetics, Washington University in St. Louis.
Bierut LJ Bierut Laura J LJ Department of Psychiatry, Washington University in St. Louis.
Hariri AR Hariri Ahmad R AR Department of Psychology and Neuroscience, Duke University.
Nelson EC Nelson Elliot C EC Department of Psychiatry, Washington University in St. Louis.
Bogdan R Bogdan Ryan R Department of Psychology, Washington University in St. Louis.
TITLE: Journal of abnormal psychology
YEAR: 2015
ISSN: 1939-1846
ISSNTYPE: Electronic
MEDLINETA: J Abnorm Psychol
COUNTRY: United States
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
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