The AVPR1A Gene and Substance Use Disorders: Association, Replication, and Functional Evidence

Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, USA.
Biological psychiatry (Impact Factor: 10.26). 04/2011; 70(6):519-27. DOI: 10.1016/j.biopsych.2011.02.023
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The liability to addiction has been shown to be highly genetically correlated across drug classes, suggesting nondrug-specific mechanisms.
In 757 subjects, we performed association analysis between 1536 single nucleotide polymorphisms (SNPs) in 106 candidate genes and a drug use disorder diagnosis (DUD).
Associations (p ≤ .0008) were detected with three SNPs in the arginine vasopressin 1A receptor gene, AVPR1A, with a gene-wise p value of 3 × 10(-5). Bioinformatic evidence points to a role for rs11174811 (microRNA binding site disruption) in AVPR1A function. Based on literature implicating AVPR1A in social bonding, we tested spousal satisfaction as a mediator of the association of rs11174811 with the DUD. Spousal satisfaction was significantly associated with DUD in males (p < .0001). The functional AVPR1A SNP, rs11174811, was associated with spousal satisfaction in males (p = .007). Spousal satisfaction was a significant mediator of the relationship between rs11174811 and DUD. We also present replication of the association in males between rs11174811 and substance use in one clinically ascertained (n = 1399) and one epidemiologic sample (n = 2231). The direction of the association is consistent across the clinically-ascertained samples but reversed in the epidemiologic sample. Lastly, we found a significant impact of rs11174811 genotype on AVPR1A expression in a postmortem brain sample.
The findings of this study call for expansion of research into the role of the arginine vasopressin and other neuropeptide system variation in DUD liability.

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Available from: Christian Heidbreder, Oct 01, 2015
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    • "We focused on the single nucleotide polymorphism (SNP) rs11174811 on the AVPR1a gene (located on chromosome 12q), because not only has it been associated with phenotypes related to anxiety/negative emotionality [e.g., stress reactivity, drug addiction, blood pressure , partnership satisfaction, and aggressive behavior (Maher et al., 2011; Nossent et al., 2011; Levran et al., 2014; Malik et al., 2014)], but also the functionality of this gene variant has been demonstrated by means of mRNA expression in postmortem brain tissue. Expression levels in samples homozygous for the major C-allele (genotype CC) were significantly lower than in samples with at least one minor A-allele (genotypes AA or CA; Maher et al., 2011). "
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    ABSTRACT: Jeffrey Gray's Reinforcement Sensitivity Theory (RST) represents one of the most influential biologically-based personality theories describing individual differences in approach and avoidance tendencies. The most prominent self-report inventory to measure individual differences in approach and avoidance behavior to date is the BIS/BAS scale by Carver and White (1994). As Gray and McNaughton (2000) revised the RST after its initial formulation in the 1970/80s, and given the Carver and White measure is based on the initial conceptualization of RST, there is a growing need for self-report inventories measuring individual differences in the revised behavioral inhibition system (BIS), behavioral activation system (BAS) and the fight, flight, freezing system (FFFS). Therefore, in this paper we present a new questionnaire measuring individual differences in the revised constructs of the BIS, BAS and FFFS in N = 1814 participants (German sample). An English translated version of the new measure is also presented and tested in N = 299 English language participants. A large number of German participants (N = 1090) also filled in the BIS/BAS scales by Carver and White (1994) and the correlations between these measures are presented. Finally, this same subgroup of participants provided buccal swaps for the investigation of the arginine vasopressin receptor 1a (AVPR1a) gene. Here, a functional genetic polymorphism (rs11174811) on the AVPR1a gene was shown to be associated with individual differences in both the revised BIS and classic BIS dimensions.
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    • "Also among men but not women, the RS3 repeat polymorphism of the AVP receptor 1a gene (AVPR1a) is associated with less partner bonding, but also fewer marital crises or threats of divorce (Walum et al., 2008). Interestingly, Maher et al. (2011) found that a particular single nucleotide polymorphism, rs11174811, of the AVPR1a gene is associated with men's (but not women's) greater relationship distress in a clinical sample recruited for severe drug use disorders, but the same SNP was associated with men's greater perceived marital warmth in a population-based sample. Thus, sample characteristics, and potentially other individual or contextual/relationship factors, may play a role in the function of AVP's influence on complex social behaviors. "
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    ABSTRACT: Posttraumatic stress disorder (PTSD) is associated with problems in intimate relationships, partly due to deficits in social cognition. In this study, the role of arginine vasopressin (AVP) in the link between PTSD and partner-specific social cognition was examined. Participants were 24 individuals from 12 heterosexual couples in which at least one partner exhibited clinically significant PTSD symptoms. Attention to partner expressions of anger was examined as an indicator of distress and need for affiliative behaviors to repair the relationship bond. AVP administration improved the speed of men's attentional engagement with their partners' expressions of anger and alleviated the negative impact of PTSD on this social cognitive process. Further, men's morning urinary AVP levels were negatively correlated with their PTSD severity. No such effects were found among women or for attention to unfamiliar men's or women's anger expressions. Thus, the AVP system may function in the relationship problems associated with PTSD.
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