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The AVPR1A gene and substance use disorders: association, replication, and functional evidence.

ABSTRACT: 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.

SUBMITTER: Maher BS

PROVIDER: S-EPMC4083653 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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The AVPR1A gene and substance use disorders: association, replication, and functional evidence.

Maher Brion S BS Vladimirov Vladimir I VI Latendresse Shawn J SJ Thiselton Dawn L DL McNamee Rebecca R Kang Moonsu M Bigdeli Tim B TB Chen Xiangning X Riley Brien P BP Hettema John M JM Chilcoat Howard H Heidbreder Christian C Muglia Pierandrea P Murrelle E Lenn EL Dick Danielle M DM Aliev Fazil F Agrawal Arpana A Edenberg Howard J HJ Kramer John J Nurnberger John J Tischfield Jay A JA Devlin Bernie B Ferrell Robert E RE Kirillova Galina P GP Tarter Ralph E RE Kendler Kenneth S KS Vanyukov Michael M MM

Biological psychiatry 20110422 6

<h4>Background</h4>The liability to addiction has been shown to be highly genetically correlated across drug classes, suggesting nondrug-specific mechanisms.<h4>Methods</h4>In 757 subjects, we performed association analysis between 1536 single nucleotide polymorphisms (SNPs) in 106 candidate genes and a drug use disorder diagnosis (DUD).<h4>Results</h4>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(- ...[more]

PMID: 21514569

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Project description:ImportanceThe United States is currently facing an epidemic of deaths related to substance use disorder (SUD), with totals exceeding those due to motor vehicle crashes and gun violence. The epidemic has led to decreased life expectancy in some populations. In recent years, Medicaid eligibility has expanded in some states, and the association of this expansion with SUD-related deaths is yet to be examined.ObjectiveTo examine the association between eligibility thresholds for state Medicaid coverage and SUD-related deaths.Design, setting, and participantsEconomic evaluation study using a retrospective analysis of state-level data between 2002 and 2015 to determine the association between the Medicaid eligibility threshold and SUD-related deaths, controlling for other relevant policies, state socioeconomic characteristics, fixed effects, and a time trend. Policy variables were lagged by 1 year to allow time for associations to materialize. Data were collected and analyzed from 2016 to 2017.ExposuresThe policy of interest was the state Medicaid eligibility threshold, ie, the highest allowed income that qualifies a person for Medicaid, expressed as a percentage of the federal poverty level. State policies related to mental health, overdose treatment, and law enforcement of drug crimes were included as controls.Main outcomes and measuresThe primary outcome was number of SUD-related deaths, obtained from data provided by the Centers for Disease Control and Prevention.ResultsAcross 700 state-year observations, the mean (SD) number of SUD-related deaths was 21.15 (6.05) per 100 000 population. Between 2002 and 2015, the national SUD-related death rate increased from 16.0 to 27.5 per 100 000, while the average Medicaid eligibility threshold increased from 87.2% to 97.1% of the federal poverty level. Over this period, every 100-percentage point increase in the Medicaid eligibility threshold (eg, from 50% to 150% of the federal poverty level) was associated with 1.373 (95% CI, -2.732 to -0.014) fewer SUD-related deaths per 100 000 residents, a reduction of 6.50%. In the 22 states with net contractions in eligibility thresholds between 2005 and 2015, an estimated increase of 570 SUD-related deaths (95% CI, -143 to 1283) occurred. In the 28 states that increased eligibility thresholds, an estimated 1045 SUD-related deaths (95% CI, -209 to 2299) may have been prevented.Conclusions and relevanceThese findings suggest that the overall increase in SUD-related deaths between 2002 and 2015 may have been greater had the average eligibility threshold for Medicaid not increased over this period. Broader eligibility for Medicaid coverage may be one tool to help reduce SUD-related deaths.

Project description:BackgroundWhilst effective treatments exist for substance use and alcohol use disorders, they are not commonly practised. Studies have shown that only a small percentage of services provide evidence-based treatments such as addiction medications or psychosocial therapies. Although there is a growing body of literature on evidence-based treatment, no synthesis of research on the implementation of evidence-based addiction treatment exists. This proposed systematic review will synthesise and evaluate the effectiveness of implementation programmes in the treatment of patients with drug and alcohol problems using the Consolidated Framework for Implementation Research (CFIR) framework.MethodsWe will search (from inception onwards) PubMed/MEDLINE, Cochrane Library, PsycINFO, Web of Science and CINAHL. Eligible studies will be clinical trials (e.g. randomised controlled trials, non-randomised controlled trials) and observational studies (e.g. before-and-after studies, interrupted time series) evaluating strategies used to implement evidence-based psychosocial treatments for alcohol and substance use disorders. The primary outcomes will be related to the implementation, service system, or clinical practice (e.g. acceptability, implementation costs, feasibility). Two researchers will independently screen all citations, full-text articles and abstract data. Risk of bias of individual studies will be appraised using appropriate tools. A narrative synthesis will be provided.DiscussionThis project aims to provide evidence to help guide the design of translational research programmes to improve implementation of evidence-based care in drug and alcohol settings. Findings from the study will specify effective strategies for domains of influence including (1) intervention characteristics (e.g. evidence strength and quality, adaptability), (2) outer setting (e.g. patient needs and resources, external policies and incentives), (3) inner setting (e.g. implementation climate, readiness for implementation), (4) individuals involved (e.g. self-efficacy, knowledge and beliefs about the intervention) and (5) the implementation process (e.g. engaging members of the organisation, executing the innovation). Identified gaps in knowledge will guide further study.Systematic review registrationPROSPERO CRD42019123812.

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The AVPR1A gene and substance use disorders: association, replication, and functional evidence.

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The AVPR1A gene and substance use disorders: association, replication, and functional evidence.

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