Saturday, September 05, 2015

Cannabis Dependence Risk Factors: Neuroticism

Posted 30th July 2012
Bill Yates
Brain Posts

Cannabis appears to have a lower risk of dependence in users than other drugs such as heroin, cocaine or nicotine.  Despite this lower risk, some cannabis users do go on to develop typical substance dependence signs and symptoms like daily high-dose use and impairment in social and occupational function.

Genetic factors appear to influence risk for a variety types of drug dependence.  I will review some of the genetic studies of cannabis dependence in a future post.

A recent study suggests the possibility that the trait neuroticism may interact with genotype to increase risk of cannabis dependence.

Jutras-Aswad and colleagues recently summarized results from a case-control study of 50 subjects with cannabis dependence compared to 50 subjects without cannabis dependence.  Subjects completed extensive psychological assessment and single nucleotide polymorphism (SNP) genotyping related to the dopamine 2 receptor gene and the proenkephalin genes.  These two genes are felt to be important in modulating addictive behaviors.

Neuroticism is considered to be a lifelong trait describing the anxiety proneness or vulnerability in individuals.  High neuroticism individuals have higher rates of anxiety symptoms as well as specific anxiety disorders such  as panic disorder.  The current study found a interaction between neuroticism scores and proenkephalin SNP genotype.  When individuals were grouped in four groups by neuroticism and proenkephalin SNP rs2609997 status the risk for cannabis dependence (odds ratio) was estimated to be:
  • Low neuroticism/low risk genotype (1.0)
  • High neuroticism/low risk gentotype (1.3)
  • Low neuroticism/high risk genotype (1.8)
  • High neuroticism/high risk genotype (9.2)

One potential confounding variable in this study was daily nicotine use.  Daily nicotine use was present in 54% of the cannabis dependence group compared to only 4% of the control group.  The authors conducted two analysis to examine the potential confounding effect of nicotine use on neuroticism and proenkephalin SNP genotype. Although nicotine dependence was linked to higher neuroticism scores it did not appear related to proenkephalin SNP gene status.

So this study supports a significant elevation in cannabis risk for individuals with both high neuroticism trait scores and a vulnerability genotype of the proenkepalin gene.  Future studies might examine the benefit of pharmacological or psychological interventions for high neuroticism individuals with a high-risk genotype for cannabis dependence.

Photo of cannabis leaf from Wikimedia Commons public domain images authored by Christopher Thomas.

Jutras-Aswad D, Jacobs MM, Yiannoulos G, Roussos P, Bitsios P, Nomura Y, Liu X, & Hurd YL (2012). Cannabis-Dependence Risk Relates to Synergism between Neuroticism and Proenkephalin SNPs Associated with Amygdala Gene Expression: Case-Control Study. PloS one, 7 (6) PMID: 22745721.

See the original article:

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