Background: Abstinent woman, former alcohol user, who is in marriage with active alcohol user. Concept co-dependency (Kudrle, 2003, Whitfield, 1991). Determination, agreement and the will of the married couple for participation in this case study concerning alcohol use and its effects on their coexistence. Objectives and research questions: The main objective of this thesis was to investigate the coexistence of an alcohol-dependent husband with abstinent wife. The main research question was: How is the coexistence of dependent partner with abstinent wife? Additional research questions were: 1) Does, the coexistence look as harmonic in the eyes of the couple and does it fulfil the image of the ideal partnership? 2) What is the role of the respondents in the partnership - is there a sign of co-dependency? 3) Which are the relaps prevention techniques the wife use for maintaining the abstinence? 4) What circumstance or situations may motivate the husband to quit alcohol use? Methodology: The gathering of data for this case study was done by qualitative approach. The main collection methods were the semi-structures in-depth interviews (Miovský, 2006). As the additional methods the study of the medical records of respondents, Quality of Life questionnaire (WHOQOL-BREF) (WHO, 1996), Alcohol Use Disorders...

Introduction : La dépendance à l'alcool est un problème majeur et mondial de santé publique. Pour tenter d'en comprendre les déterminants individuels, plusieurs études se sont centrées sur l'examen de la personnalité, des styles défensifs, des stratégies de coping et de la symptomatologie anxio-dépressive au sein de populations alcoolo-dépendantes. En revanche, à notre connaissance, aucune recherche n'a étudié l'ensemble de ces facteurs simultanément. En conséquence, dans le cadre d'une approche intégrative, le but de cette thèse a été d'évaluer ces variables et d'étudier leurs relations afin d'apporter des éléments de compréhension à l'installation et au maintien de la dépendance à l'alcool. Méthode : Au cours de cette étude multicentrique (5 centres de recrutement) et transversale, 122 patients consultants pour une problématique alcoolique et 185 témoins ont répondu à un questionnaire sociodémographique et centré sur la consommation de substances, au Big Five Inventory (BFI) pour évaluer la personnalité, au Defense Style Questionnaire - 40 (DSQ-40) pour relever les styles défensifs, au Brief Cope pour estimer les stratégies de coping et à l'Hospital Anxiety and Depression Scale (HADS) pour mesurer la symptomatologie anxio-dépressive. Dans un premier temps, des analyses statistiques descriptives, comparatives et de corrélations ont été réalisées. Dans un second temps, des tests de régressions linéaires et logistiques, d'analyse en composantes principales et une analyse discriminante ont permis d'approfondir les résultats en lien avec l'objectif de la thèse (logiciel SPSS). Résultats : Les personnes alcoolo-dépendantes obtiennent des scores significativement différents pour la personnalité (névrosisme élevé, extraversion et conscience basses), pour les styles défensifs (style mature bas, styles névrotique et immature élevés), pour les stratégies de coping (stratégies centrées sur le problème basses, stratégies centrées sur les émotions et évitantes élevées) et pour la symptomatologie anxio-dépressive (symptômes anxieux et dépressifs importants) que les sujets du groupe contrôle. Les relations entre ces variables montrent le rôle des dimensions de personnalité dans l'utilisation de style défensif et/ou de stratégies de coping pouvant conduire à l'installation et au maintien d'une alcoolo-dépendance. En effet, le névrosisme entraîne l'utilisation d'un fonctionnement défensif inadapté. L'extraversion, la conscience et plus particulièrement l'ouverture à l'expérience sont associées à une activité défensive efficace. L'agréabilité, quant à elle, affiche des liens plus complexes avec l'organisation défensive. La présence de liens cohérents entre les styles défensifs et les stratégies de coping confirme l'intérêt de considérer le fonctionnement défensif de manière intégrative et globale. L'analyse discriminante, réalisée sur les facteurs principaux, permet de prédire l'appartenance au groupe « Alcool » pour 3 sujets sur 4. Les analyses de régressions linéaires multiples, exécutées selon un regroupement théorique, montrent que le style immature et les stratégies de coping évitantes prédisent le maintien d'une alcoolo-dépendance. L'ensemble des analyses, étayées par l'apport de différents modèles théoriques, permet de proposer un modèle théorico-clinique de l'installation et du maintien d'une dépendance à l'alcool. Des analyses comparatives complémentaires, exécutées sur les facteurs principaux, indiquent des scores significativement différents selon le genre chez les personnes alcoolo-dépendantes. Conclusion : Cette recherche montre la présence d'une association de déterminants individuels favorisant l'installation d'une alcoolo-dépendance en termes de personnalité, de style défensif, de stratégies de coping et de symptomatologie anxio-dépressive. Cette étude souligne l'intérêt d'appréhender le fonctionnement défensif globalement et permet de proposer un modèle théorico-clinique de l'alcoolo-dépendance et de son maintien. / Introduction: Alcohol dependence is a major and global public health problem. To try to understand the individual determinants, several studies have focused on the examination of personality, defense styles, coping strategies, anxiety and depressive symptoms in alcohol-dependent populations. However, to our knowledge, no research has studied all these factors simultaneously. Accordingly, as part of an integrative approach, the aim of this thesis was to evaluate these variables and study their relationships to bring elements of understanding the installation and the maintenance of alcohol dependence. Method: In this multicenter (5 recruitment centers) and cross-sectional study, 122 consultants patients with alcohol dependence and 185 controls answered a sociodemographic and focused on the substance questionnaire, the Big Five Inventory (BFI) to assess personality, the Defense Style Questionnaire - 40 (DSQ-40) to raise the defense styles, the Brief Cope to assess coping strategies and the Hospital Anxiety and Depression Scale (HADS) to measure anxiety and depressive symptoms. Initially, descriptive, comparative statistics and correlations were performed. Secondly, linear and logistic regression tests, principal component analysis and discriminant analysis have deepened the results related to the goal of this thesis (SPSS). Results: The alcohol-dependent obtain significantly different scores for personality (high neuroticism, low extraversion and conscientiousness), for defense styles (low mature style, high neurotic and immature styles), for coping strategies (low problem-focused strategies, high emotion-focused and avoidant strategies) and for anxiety and depressive symptoms (significant anxiety and depressive symptoms) than control subjects. The relationship found between these variables show the role of personality dimensions in adapting defense style and/or effective coping strategies to deal or not with stress. Neuroticism involves the use of an unsuitable defensive operation may lead to the alcohol dependence installation. The extraversion, conscientiousness, and particularly openness to experience are associated with effective defense activity. The agreeableness, meanwhile, appears more complex connections with the defensive organization. The presence of coherent links between defense styles and coping strategies confirms the interest in considering the defensive operation of integrative and comprehensive manner. The discriminant analysis performed on the main factors predicts group membership "Alcohol" subjects for 3 to 4. Analyses of multiple linear regressions, performed according to a theoretical regrouping show that immature style and avoidant coping strategies predict the maintenance of alcohol dependence. All analysis, supported by the contribution of different theoretical models allows proposing a theoretical-clinical model of the installation and maintenance of alcohol dependence. Further analyses comparing the main factors indicate significantly different scores by gender among alcohol-dependent people. Conclusion: This research shows the presence of a combination of individual determinants favoring the emergence of alcohol dependence in terms of personality, defense style, coping strategies and anxiety-depressive symptomatology. This study emphasizes the importance of understanding the overall defensive functioning and allows proposing a theoretical-clinical model of alcohol dependence and its maintenance.

BACKGROUND: Alcohol dependence is more common among men than among women. Potential explanations for this include the role of genes in sex chromosomes (X and Y). In the present study, we scanned the entire Y chromosome and its homologs on the X chromosome in men to identify male-specific risk genes for alcohol dependence. METHODS: Two thousand nine hundred and twenty-seven individuals in two independent cohorts were analyzed. The European-American male cohort (883 cases with alcohol dependence and 445 controls) served as the discovery cohort and the European-American female cohort (526 cases and 1073 controls) served as a contrast group. All individuals were genotyped on the Illumina Human 1M beadchip. Two thousand two hundred and twenty-four single nucleotide polymorphisms (SNPs) on the Y chromosome or in the homologs on the X chromosome were analyzed. The allele frequencies were compared between cases and controls within each cohort using logistic regression analysis. RESULTS: We found that, after experiment-wide correction, two SNPs on the X chromosome were associated significantly with alcohol dependence in European-American men (P=1.0×10 for rs5916144 and P=5.5×10 for rs5961794 at 3′ UTR of NLGN4X), but not in the women. A total of 26 SNPs at 3′UTR of or within NLGN4X were nominally associated with alcohol dependence in men (5.5×10≤P≤0.05), all of which were not statistically significant in women. CONCLUSION: We conclude that NLGN4X was a significant male-specific risk gene for alcohol dependence in European-Americans. NLGN4X might harbor a causal variant(s) for alcohol dependence. A defect of synaptogenesis in neuronal circuitry caused by NLGN4X mutations is believed to play a role in alcohol dependence.

Variants (such as rs9939609) in the fat mass- and obesity-associated (FTO) gene have been associated with obesity, type 2 diabetes, some cancers, and alcohol consumption. This study tested the associations of 167 single-nucleotide polymorphisms (SNPs) within FTO gene with alcohol dependence (AD) using two Caucasian samples: the Collaborative Study on the Genetics of Alcoholism (COGA) sample (660 AD cases and 400 controls) and the Study of Addiction: Genetics and Environment (SAGE) sample (623 cases and 1,016 controls). Logistic regression analysis of AD as a binary trait was performed using the PLINK software. For the SAGE sample, the top three SNPs showing associations with AD were rs8062891, rs1108086, and rs1420318 (p = 0.00088, 0.00086 and 0.00086, respectively). Two SNPs (rs12597786 and rs7204609) associated with AD in the SAGE sample (p = 0.017 and 0.034, respectively) were replicated in the COGA sample (p = 0.017 and 0.014, respectively). Through meta-analysis of two samples using PLINK, the top three SNPs associated with AD were rs8062891, rs12597786, and rs7204609 (p = 0.00064, 0.00076 and 0.0011, respectively). Haplotype analysis in the SAGE sample further supported the associations with AD in single-marker analysis. In addition, we found association of rs17817449 (which has a strong linkage disequilibrium with rs9939609) with AD in the SAGE sample (p = 0.00339). The findings provide evidence of joint intervention and prevention of AD and obesity.

Objective: We aimed to identify novel, functional, replicable and genome-wide significant risk regions specific for alcohol dependence using genome-wide association studies (GWASs). Methods: A discovery sample (1409 European-American cases with alcohol dependence and 1518 European-American controls) and a replication sample (6438 European-Australian family subjects with 1645 alcohol dependent probands) underwent association analysis. Nineteen other cohorts with 11 different neuropsychiatric disorders served as contrast groups. Additional eight samples underwent expression quantitative locus (eQTL) analysis. Results: A genome-wide significant risk gene region (NKAIN1-SERINC2) was identified in a meta-analysis of the discovery and replication samples. This region was enriched with 74 risk SNPs (unimputed); half of them had significant cis-acting regulatory effects. The distributions of -log(p) values for the SNP-disease associations or SNP-expression associations in this region were consistent throughout eight independent samples. Furthermore, imputing across the NKAIN1-SERINC2 region, we found that among all 795 SNPs in the discovery sample, 471 SNPs were nominally associated with alcohol dependence (1.7×10-7≤p≤0.047); 53 survived region- and cohort-wide correction for multiple testing; 92 SNPs were replicated in the replication sample (0.002≤p≤0.050). This region was neither significantly associated with alcohol dependence in African-Americans, nor with other non-alcoholism diseases. Finally, transcript expression of genes in NKAIN1-SERINC2 was significantly (p<3.4×10-7) associated with expression of numerous genes in the neurotransmitter systems or metabolic pathways previously associated with alcohol dependence. Conclusion: NKAIN1-SERINC2 may harbor a causal variant(s) for alcohol dependence. It may contribute to the disease risk by way of neurotransmitter systems or metabolic pathways.

HLA-DRA gene polymorphisms might play an important role in alcohol dependence (AD). We examined genetic associations of 29 single-nucleotide polymorphisms (SNPs) within the HLA-DRA gene with AD using two Caucasian samples - the Collaborative Study on the Genetics of Alcoholism (COGA) sample (660 AD cases and 400 controls) and the Study of Addiction: Genetics and Environment (SAGE) sample (623 cases and 1,016 controls). Logistic regression analysis using PLINK showed that 16 SNPs were associated with AD in the COGA sample and 13 SNPs were associated with AD in the SAGE sample (p < 0.05). The best novel signal was SNP rs2239803 associated with AD in both samples (p = 0.000817 for the COGA sample and p = 0.0026 for the SAGE sample, respectively) while one flanking SNP rs4935356 also showed strong association in both samples (p = 0.00219 and 0.0026 for the COGA and SAGE samples, respectively). Furthermore, these two SNPs revealed stronger associations in meta-analysis of these two samples (p = 8.97 × 10-6 and 2.02 × 10-5 for rs2239803 and rs4935356, respectively). In addition, the G-A haplotype from these two SNPs revealed a significant association with AD in both the COGA and SAGE samples (p = 0.0007 and 0.0019, respectively). These findings highlight the novel associations with HLA-DRA that may play an important role in the etiology of AD.

OBJECTIVES: We have previously reported a top-ranked risk gene [i.e., serine incorporator 2 gene (SERINC2)] for alcohol dependence in individuals of European descent by analyzing the common variants in a genome-wide association study. In the present study, we comprehensively examined the rare variants [minor allele frequency (MAF)<0.05] in the NKAIN1-SERINC2 region to confirm our previous finding. MATERIALS AND METHODS: A discovery sample (1409 European-American patients with alcohol dependence and 1518 European-American controls) and a replication sample (6438 European-Australian family participants with 1645 alcohol-dependent probands) were subjected to an association analysis. A total of 39 903 individuals from 19 other cohorts with 11 different neuropsychiatric and neurological disorders served as contrast groups. The entire NKAIN1-SERINC2 region was imputed in all cohorts using the same reference panels of genotypes that included rare variants from the whole-genome sequencing data. We stringently cleaned the phenotype and genotype data, and obtained a total of about 220 single-nucleotide polymorphisms in individuals of European descent and about 450 single-nucleotide polymorphisms in the individuals of African descent with 0

BACKGROUND: Alcohol dependence is more common among men than among women. Potential explanations for this include the role of genes in sex chromosomes (X and Y). In the present study, we scanned the entire Y chromosome and its homologs on the X chromosome in men to identify male-specific risk genes for alcohol dependence. METHODS: Two thousand nine hundred and twenty-seven individuals in two independent cohorts were analyzed. The European-American male cohort (883 cases with alcohol dependence and 445 controls) served as the discovery cohort and the European-American female cohort (526 cases and 1073 controls) served as a contrast group. All individuals were genotyped on the Illumina Human 1M beadchip. Two thousand two hundred and twenty-four single nucleotide polymorphisms (SNPs) on the Y chromosome or in the homologs on the X chromosome were analyzed. The allele frequencies were compared between cases and controls within each cohort using logistic regression analysis. RESULTS: We found that, after experiment-wide correction, two SNPs on the X chromosome were associated significantly with alcohol dependence in European-American men (P=1.0×10 for rs5916144 and P=5.5×10 for rs5961794 at 3′ UTR of NLGN4X), but not in the women. A total of 26 SNPs at 3′UTR of or within NLGN4X were nominally associated with alcohol dependence in men (5.5×10≤P≤0.05), all of which were not statistically significant in women. CONCLUSION: We conclude that NLGN4X was a significant male-specific risk gene for alcohol dependence in European-Americans. NLGN4X might harbor a causal variant(s) for alcohol dependence. A defect of synaptogenesis in neuronal circuitry caused by NLGN4X mutations is believed to play a role in alcohol dependence.

Variants (such as rs9939609) in the fat mass- and obesity-associated (FTO) gene have been associated with obesity, type 2 diabetes, some cancers, and alcohol consumption. This study tested the associations of 167 single-nucleotide polymorphisms (SNPs) within FTO gene with alcohol dependence (AD) using two Caucasian samples: the Collaborative Study on the Genetics of Alcoholism (COGA) sample (660 AD cases and 400 controls) and the Study of Addiction: Genetics and Environment (SAGE) sample (623 cases and 1,016 controls). Logistic regression analysis of AD as a binary trait was performed using the PLINK software. For the SAGE sample, the top three SNPs showing associations with AD were rs8062891, rs1108086, and rs1420318 (p = 0.00088, 0.00086 and 0.00086, respectively). Two SNPs (rs12597786 and rs7204609) associated with AD in the SAGE sample (p = 0.017 and 0.034, respectively) were replicated in the COGA sample (p = 0.017 and 0.014, respectively). Through meta-analysis of two samples using PLINK, the top three SNPs associated with AD were rs8062891, rs12597786, and rs7204609 (p = 0.00064, 0.00076 and 0.0011, respectively). Haplotype analysis in the SAGE sample further supported the associations with AD in single-marker analysis. In addition, we found association of rs17817449 (which has a strong linkage disequilibrium with rs9939609) with AD in the SAGE sample (p = 0.00339). The findings provide evidence of joint intervention and prevention of AD and obesity.

Objective: We aimed to identify novel, functional, replicable and genome-wide significant risk regions specific for alcohol dependence using genome-wide association studies (GWASs). Methods: A discovery sample (1409 European-American cases with alcohol dependence and 1518 European-American controls) and a replication sample (6438 European-Australian family subjects with 1645 alcohol dependent probands) underwent association analysis. Nineteen other cohorts with 11 different neuropsychiatric disorders served as contrast groups. Additional eight samples underwent expression quantitative locus (eQTL) analysis. Results: A genome-wide significant risk gene region (NKAIN1-SERINC2) was identified in a meta-analysis of the discovery and replication samples. This region was enriched with 74 risk SNPs (unimputed); half of them had significant cis-acting regulatory effects. The distributions of -log(p) values for the SNP-disease associations or SNP-expression associations in this region were consistent throughout eight independent samples. Furthermore, imputing across the NKAIN1-SERINC2 region, we found that among all 795 SNPs in the discovery sample, 471 SNPs were nominally associated with alcohol dependence (1.7×10-7≤p≤0.047); 53 survived region- and cohort-wide correction for multiple testing; 92 SNPs were replicated in the replication sample (0.002≤p≤0.050). This region was neither significantly associated with alcohol dependence in African-Americans, nor with other non-alcoholism diseases. Finally, transcript expression of genes in NKAIN1-SERINC2 was significantly (p<3.4×10-7) associated with expression of numerous genes in the neurotransmitter systems or metabolic pathways previously associated with alcohol dependence. Conclusion: NKAIN1-SERINC2 may harbor a causal variant(s) for alcohol dependence. It may contribute to the disease risk by way of neurotransmitter systems or metabolic pathways.