Cannabis-Dependence Risk Relates to Synergism between Neuroticism and Proenkephalin SNPs Associated with Amygdala Gene Expression: Case-Control StudyReport as inadecuate




Cannabis-Dependence Risk Relates to Synergism between Neuroticism and Proenkephalin SNPs Associated with Amygdala Gene Expression: Case-Control Study - Download this document for free, or read online. Document in PDF available to download.

Background

Many young people experiment with cannabis, yet only a subgroup progress to dependence suggesting individual differences that could relate to factors such as genetics and behavioral traits. Dopamine receptor D2 DRD2 and proenkephalin PENK genes have been implicated in animal studies with cannabis exposure. Whether polymorphisms of these genes are associated with cannabis dependence and related behavioral traits is unknown.

Methodology-Principal Findings

Healthy young adults 18–27 years with cannabis dependence and without a dependence diagnosis were studied N = 50-group in relation to a priori-determined single nucleotide polymorphisms SNPs of the DRD2 and PENK genes. Negative affect, Impulsive Risk Taking and Neuroticism-Anxiety temperamental traits, positive and negative reward-learning performance and stop-signal reaction times were examined. The findings replicated the known association between the rs6277 DRD2 SNP and decisions associated with negative reinforcement outcomes. Moreover, PENK variants rs2576573 and rs2609997 significantly related to Neuroticism and cannabis dependence. Cigarette smoking is common in cannabis users, but it was not associated to PENK SNPs as also validated in another cohort N = 247 smokers, N = 312 non-smokers. Neuroticism mediated 15.3%–19.5% the genetic risk to cannabis dependence and interacted with risk SNPs, resulting in a 9-fold increase risk for cannabis dependence. Molecular characterization of the postmortem human brain in a different population revealed an association between PENK SNPs and PENK mRNA expression in the central amygdala nucleus emphasizing the functional relevance of the SNPs in a brain region strongly linked to negative affect.

Conclusions-Significance

Overall, the findings suggest an important role for Neuroticism as an endophenotype linking PENK polymorphisms to cannabis-dependence vulnerability synergistically amplifying the apparent genetic risk.



Author: Didier Jutras-Aswad, Michelle M. Jacobs, Georgia Yiannoulos, Panos Roussos, Panos Bitsios, Yoko Nomura, Xun Liu, Yasmin L. Hurd

Source: http://plos.srce.hr/



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