Gene-environment interactions in addictive disorders: epidemiological and methodological aspects.

The gene-environment interactions' approach could explain some epidemiological and clinical factors associated with addictive behaviours. Twin studies first help to disentangle the respective roles of environment and genetic effects, finding convincing evidence for common genetic vulnerability in several addictive behaviours, and helping to delimit what syndrome could belong to the addictive disorder spectrum. Assessing gene x environment interaction (GxE) needs specifically designed studies, using multiplicative or additive approaches. Focusing on this GxE interaction already showed its relevancy in many recent studies, using both epidemiological and molecular approaches. For example, in a non-human primate model of alcohol dependence assessing the respective role of genetic vulnerability (having the short allele located in the promoter region of the gene coding for the serotonin transporter) and severe fostering conditions (as locked up in a cage with other inmates for the first six months of life), the only group of monkeys that has a significant risk of using spontaneously alcohol is the one that gathers both risk factors, i.e. being peer-raised and having the short allele. Such approach could help to more accurately select specific candidate genes, to identify more homogenous subgroups of patients (as sharing the same genetic vulnerability), to understand how genetic factors mediate the risk of associated psychiatric disorders, and ultimately, may lead to more focused, i.e. more efficient, prevention strategies. To cite this article: P. Gorwood et al., C. R. Biologies 330 (2007)

Molecular Genetics of Alcohol Dependence and Related Endophenotypes

Alcohol dependence is a worldwide public health problem, and involves both environmental and genetic vulnerability factors. The heritability of alcohol dependence is rather high, ranging between 50% and 60%, although alcohol dependence is a polygenic, complex disorder

Decision-Making Measured by the Iowa Gambling Task in Patients with Alcohol Use Disorders Choosing Harm Reduction versus Relapse Prevention Program

AIMS: Two main therapeutic programs were offered to patients suffering from alcohol use disorders (AUDs): avoid the alcohol by abstinence or controlling their consumption. After information and motivational sessions, the patient chooses his own therapeutic plan. However, patients with AUD exhibit poor decision-making. The purpose of this study was to investigate the decision-making in AUD by comparing patients who chose to reduce and control their consumption to those who chose abstinence program. METHODS: Sixty-seven subjects with alcohol use disorder were included (AUD group) for treatment, choosing either a relapse prevention program (RPP) or a harm reduction program (HRP). Patients were compared to a healthy control group (n = 31). Cognitive skills were assessed through the Montreal Cognitive Assessment test, the National Adult Reading Test, the Trail Making Test and the Iowa Gambling Task (IGT). RESULTS: Thirty-seven patients with AUD chose the RPP while 30 followed a HRP. The AUD group performed worse than controls on the IGT. The RPP group had significantly lower performance than both HRP and control groups (these later groups being not statistically different). No correlation was observed between the available clinical, cognitive and intellectual measures. CONCLUSION: This study confirms that the decision-making process of patients with an alcohol use disorder is impaired. However, the 2 groups differ on the IGT scores, despite comparable clinical and cognitive profiles. The patients\u27 decision-making abilities could be a useful guide when developing therapeutic programs

5-HT1A gene promoter polymorphism and [18F]MPPF binding potential in healthy subjects: a PET study

<p>Abstract</p> <p>Background</p> <p>Previous Positron Emission Tomography (PET) studies of 5-HT_1Areceptors have shown an influence of several genetic factors, including the triallelic serotonin transporter gene-linked polymorphic region on the binding potential (BP_ND) of these receptors. The aim of our study was to investigate the relationship between a 5-HT_1Apromoter polymorphism and the binding potential of another selective 5-HT_1Areceptor antagonist, [¹⁸F]MPPF, in healthy subjects.</p> <p>Methods</p> <p>Thirty-five volunteers, including 23 women, underwent an [¹⁸F]MPPF scan and were genotyped for both the C(-1019)G 5-HT_1Apromoter polymorphism and the triallelic serotonin transporter gene-linked polymorphic region. We used a simplified reference tissue model to generate parametric images of BP_ND. Whole brain Statistical Parametric Mapping and raphe nuclei region of interest analyses were performed to look for an association of [¹⁸F]MPPF BP_NDwith the C(-1019)G 5-HT_1Apromoter polymorphism.</p> <p>Results</p> <p>Among the 35 subjects, 5-HT_1Apromoter genotypes occurred with the following frequencies: three G/G, twenty-one G/C, and eleven C/C. No difference of [¹⁸F]MPPF BP_NDbetween groups was observed, except for two women who were homozygote carriers for the G allele and showed greater binding potential compared to other age-matched women over the frontal and temporal neocortex. However, the biological relevance of this result remains uncertain due to the very small number of subjects with a G/G genotype. These findings were not modified by excluding individuals carrying the S/S genotype of the serotonin transporter gene-linked polymorphic region.</p> <p>Conclusions</p> <p>We failed to observe an association between the C(-1019)G 5-HT_1Apromoter polymorphism and [¹⁸F]MPPF binding in healthy subjects. However our data suggest that the small number of women homozygote for the G allele might have greater [¹⁸F]MPPF BP_NDrelative to other individuals. This finding should be confirmed in a larger sample.</p

Massively multiplayer online role-playing games: comparing characteristics of addict vs non-addict online recruited gamers in a French adult population

<p>Abstract</p> <p>Background</p> <p>Massively Multiplayer Online Role-Playing Games (MMORPGs) are a very popular and enjoyable leisure activity, and there is a lack of international validated instruments to assess excessive gaming. With the growing number of gamers worldwide, adverse effects (isolation, hospitalizations, excessive use, etc.) are observed in a minority of gamers, which is a concern for society and for the scientific community. In the present study, we focused on screening gamers at potential risk of MMORPG addiction.</p> <p>Methods</p> <p>In this exploratory study, we focused on characteristics, online habits and problematic overuse in adult MMORPG gamers. In addition to socio-demographical data and gamer behavioral patterns, 3 different instruments for screening addiction were used in French MMORPG gamers recruited online over 10 consecutive months: the substance dependence criteria for the Diagnostic and Statistical Manual of Mental Disorder, fourth revised edition (DSM-IV-TR) that has been adapted for MMORPG (DAS), the qualitative Goldberg Internet Addiction Disorder scale (GIAD) and the quantitative Orman Internet Stress Scale (ISS). For all scales, a score above a specific threshold defined positivity.</p> <p>Results</p> <p>The 448 participating adult gamers were mainly young adult university graduates living alone in urban areas. Participants showed high rates of both Internet addiction (44.2% for GIAD, 32.6% for ISS) and DAS positivity (27.5%). Compared to the DAS negative group, DAS positive gamers reported significantly higher rates of tolerance phenomenon (increased amount of time in online gaming to obtain the desired effect) and declared significantly more social, financial (OR: 4.85), marital (OR: 4.61), family (OR: 4.69) and/or professional difficulties (OR: 4.42) since they started online gaming. Furthermore, these gamers self-reported significantly higher rates (3 times more) of irritability, daytime sleepiness, sleep deprivation due to play, low mood and emotional changes since online gaming onset.</p> <p>Conclusions</p> <p>The DAS appeared to be a good first-line instrument to screen MMORPG addiction in online gamers. This study found high MMORPG addiction rates, and self-reported adverse symptoms in important aspects of life, including mood and sleep. This confirms the need to set up relevant prevention programs against online game overuse.</p