Genetic Vulnerability and Susceptibility to Substance Dependence

Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA.
Neuron (Impact Factor: 15.05). 02/2011; 69(4):618-27. DOI: 10.1016/j.neuron.2011.02.015
Source: PubMed

ABSTRACT The development of substance dependence requires the initiation of substance use and the conversion from experimental use to established use before development of dependence. Numerous large twin studies have indicated a significant genetic contribution to this process. Genetic studies to date have been most successful at identifying genetic factors that influence the transition from regular use to dependence. The availability of large cohort samples for nicotine and alcohol dependence has resulted in significant progress being made in understanding at least some of the genetic contributions to these addictions. Fewer studies have replicated specific genetic contributions to illicit drug use, though it is clear that there is a strong genetic component involved here as well. Substance dependence can be thought of as a pharmacogenetic illness, and most likely hundreds and more probably thousands of genetic variants will be required to fully explain the genetic input to this disease.

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    • "t al . , 2008 ) . Despite these independent lines of support for a role of GABRA2 variants in the etiology of alcohol dependence , addictions and other externalizing problems in samples from var - ied developmental epochs and with differing ascer - tainment protocols , no GWAS to date has identified these SNPs at genome - wide significant levels ( Bierut et al . , 2010 ; Frank et al . , 2011 ; Gelernter et al . , 2014 ; Heath et al . , 2011 ; McGue et al . , 2013 ; Treutlein et al . , 2009 ) . Did all these studies get it wrong ? If we strictly adhere to the statistical gold standard of GWAS p values , then the extant GABRA2 signals should be considered false positives . This might also"
    Psychological Inquiry 07/2015; 26(3):231-238. DOI:10.1080/1047840X.2015.1039930 · 4.73 Impact Factor
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    • "Key words: extracellular signal-regulated kinase (ERK); nucleus accumbens; prefrontal cortex; psychogenetic selection; Roman high-and low-avoidance rats Clinical studies indicate that genetically determined personality traits, such as sensation seeking and impulsivity (Zuckerman, 1996; Bierut, 2011), are associated with increased drug addiction liability (Kreek et al., 2005; Meyer et al., 2010; Dalley et al., 2011; Ersche et al., 2013). These findings have stimulated the use of selected strains and lines of rodents as models to investigate genetically determined differences in behavioral and neurochemical traits related to addictive disorders (Flagel et al., 2010; Crabbe et al., 1994). "
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    • "These areas were targeted because we assumed that grant applications within each of these areas would study related topics, and that there would be a tendency for similarity in the constructs and measures. Furthermore, investigators in these areas increasingly recognize the importance of data comparability, interoperability, and integration across multiple studies (Curran and Hussong, 2009), particularly in the area of gene-environment interactions (Bennett et al., 2011; Bierut, 2011; Cornelis et al., 2010; Duncan and Keller, 2011), a research portfolio that is largely housed within the epidemiology domain. "
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    ABSTRACT: The need for comprehensive analysis to compare and combine data across multiple studies in order to validate and extend results is widely recognized. This paper aims to assess the extent of data compatibility in the substance abuse and addiction (SAA) sciences through an examination of measure commonality, defined as the use of similar measures, across grants funded by the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Data were extracted from applications of funded, active grants involving human-subjects research in four scientific areas (epidemiology, prevention, services, and treatment) and six frequently assessed scientific domains. A total of 548 distinct measures were cited across 141 randomly sampled applications. Commonality, as assessed by density (range of 0-1) of shared measurement, was examined. Results showed that commonality was low and varied by domain/area. Commonality was most prominent for (1) diagnostic interviews (structured and semi-structured) for substance use disorders and psychopathology (density of 0.88), followed by (2) scales to assess dimensions of substance use problems and disorders (0.70), (3) scales to assess dimensions of affect and psychopathology (0.69), (4) measures of substance use quantity and frequency (0.62), (5) measures of personality traits (0.40), and (6) assessments of cognitive/neurologic ability (0.22). The areas of prevention (density of 0.41) and treatment (0.42) had greater commonality than epidemiology (0.36) and services (0.32). To address the lack of measure commonality, NIDA and its scientific partners recommend and provide common measures for SAA researchers within the PhenX Toolkit.
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