O Transtorno de Déficit de Atenção/Hiperatividade (TDAH) é comum em adultos e caracteriza-se por sintomas persistentes de desatenção, hiperatividade e impulsividade. Clinicamente, o TDAH é um fenótipo bastante heterogêneo e, frequentemente, encontra-se associado a diversos outros transtornos psiquiátricos. A contribuição genética é substancial no TDAH e diversos genes de pequeno efeito têm sido associados com o desenvolvimento do transtorno. O metilfenidato (MPH) representa o principal agente farmacológico usado no tratamento e seu mecanismo de ação parece envolver a potencialização da transmissão catecolaminérgica no córtex pré-frontal. Estudos farmacogenéticos têm investigado o papel de diversas variantes genéticas, principalmente em sistemas de neurotransmissão, na resposta ao tratamento com MPH. No entanto, esses estudos têm focado quase que exclusivamente no tratamento de crianças com TDAH. No presente trabalho foi investigada a associação entre 17 polimorfismos genéticos, em nove genes candidatos (DAT1, ADRA2A, 5-HTT, HTR1B, TPH2, DBH, DRD4, COMT e SNAP25), e a resposta ao tratamento com MPH. A amostra foi composta de 165 adultos com TDAH, diagnosticados de acordo com os critérios do DSM-IV. A gravidade dos sintomas dos pacientes foi avaliada antes e após um mês de uso de MPH através da aplicação das subescalas SNAP-IV e da escala CGI-S. Também avaliamos uma amostra de 136 dependentes de álcool e 237 controles, em um estudo de associação envolvendo o gene HTR1B. A resposta ao MPH foi analisada através de avaliações categórica e dimensional da redução nos sintomas após o uso de MPH. Foi observada uma redução significativa nos escores de gravidade total dos sintomas após o tratamento, sendo que 83% dos pacientes foram classificados como respondedores e 17% como não respondedores. Interpretamos a dificuldade de identificar variantes genéticas envolvidas na resposta ao tratamento como o reflexo da complexidade clínica e etiológica do TDAH. Exemplo disso é o fato de que o gene HTR1B, que apresenta resultados positivos para associação com o TDAH em meta-análises e em um estudo com crianças da nossa população, não se mostrou associado com o TDAH em adultos ou com a resposta ao MPH, mas sim com o alcoolismo nesse estudo. Novas investigações, em amostras maiores, serão necessárias para que seja alcançado maior sucesso nos estudos farmacogenéticos envolvendo o MPH ou outros fármacos no tratamento do TDAH. / Attention deficit/hyperactivity disorder (ADHD) has a high prevalence in adults and it is characterized by pervasive symptoms of inattention, hyperactivity and impulsivity. Clinically, ADHD is a very heterogeneous disorder frequently associated with other psychiatric conditions. The genetic contribution in ADHD is substantial and several genes of small effect have been associated with ADHD susceptibility. Methylphenidate (MPH) is the primary agent used in pharmacological intervention for ADHD. Its mechanism of action is believed to potentiate catecholamine transmission in the pre-frontal cortex. Pharmacogenetic studies have been investigating the role of genetic variants in the response to the treatment with MPH. However, previous studies have focused almost exclusively in the treatment of children with ADHD. In this study, we investigated the association between 17 polymorphisms, in 9 candidate genes (DAT1, ADRA2A, 5- HTT, HTR1B, TPH2, DBH, DRD4, COMT and SNAP25), and the response to MPH. The sample comprised 165 adults with ADHD diagnosed according to DSMIV criteria. We also evaluated a sample of 136 alcohol dependents and 237 control subjects, in an association study involving the HTR1B gene. The response to MPH was assessed by both categorical and dimensional approaches through the SNAP-IV sub-scales and the CGI-S scale, applied at the beginning and after the 30th day of treatment. We detected a significant reduction in SNAP-IV total scores during the follow-up period. According to the categorical definition of MPH response, 83% of the patients were classified as responders and 17% were classified as non-responders. Our results indicated that none of the investigated variants showed significant effects on the MPH response. We interpret the difficulty of identifying genetic variants involved in response to treatment as a reflection of the clinical and etiological complexity of ADHD. For example, we did not find association of the HTR1B gene with ADHD nor with treatment response to MPH in our adult sample, but it was in fact associated with alcohol dependence. However, this gene has previously shown positive results for association with children ADHD in meta-analysis and also in a study with children of the same population of the current work. More investigations with larger sample sizes will be need to achieve greater success in pharmacogenetic studies involving the MPH or other drugs used in the treatment of ADHD.

Craving is thought to play a predominant role in the persistence of alcohol dependence, which seems to bear a substantial genetic component. Based on previous results highlighting the influence of serotonergic and dopaminergic nerotransmissions in both dependence and craving for alcohol, we investigated the impact of three specific polymorphisms on craving in male abstinent alcohol dependent patients. Our results show that alcohol craving may be influenced by genetic differences in alcohol dependent patients. There seems to be a dual serotonergic and dopaminergic modulation of craving. During acute withdrawal, desire to drink is predominantly influenced by the C1019 allele of the 5-HT1A receptor. Conversely, carrying the A1 allele of the DRD2 increases craving only when patients are no longer hospitalized and protected from drinking cues. Furthermore, we showed that craving partially influenced relapse and that the S allele of the 5-HTTpro, responsible for a 5-HT hypo-functioning, was significantly associated with relapse in abstinent alcohol dependent patients, possibly through intermediate phenotypes such as personality features or lack of behavioral inhibition. Our results may be useful in evaluating and developing novel pharmacogenetic approaches to treat alcohol dependence and one of its core symptoms, namely craving. Le craving semble jouer un rôle prédominant dans la persistance des comportements dalcoolisation et de rechute chez les sujets alcoolo-dépendants. Cette pathologie semble par ailleurs très nettement influencée par des facteurs dordre génétique. Sur base détudes préliminaires illustrant linfluence des neurotransmissions dopaminergique et sérotoninergique dans lalcoolo-dépendance et le craving pour lalcool, notre objectif a été dévaluer limpact de trois polymorphismes génétiques spécifiques sur le craving chez des patients masculins alcoolo-dépendant sevrés. Nos résultats montrent que le craving est bien influencé par des différences génétiques interindividuelles et quune modulation bimodale sérotoninergique et dopaminergique semble sexercer sur le craving pour lalcool. Pendant la phase aiguë du sevrage, lenvie de boire est nettement influencée par la présence de lallèle C du polymorphisme C-1019G du récepteur sérotoninergique 5-HT1A. A linverse, la présence de lallèle A1 du récepteur dopaminergique D2 ninfluence le craving quà distance du sevrage, lorsque les patients sont à nouveau dans leur milieu habituel et soumis à des stimuli déclanchant une envie de boire. De plus, nous avons pu montrer que le craving influençait partiellement la survenue dune rechute et que lallèle court du polymorphisme du promoteur du transporteur de la sérotonine (5-HTTpro) exerçait une influence significative sur la rechute, peut-être au travers de phénotypes intermédiaires de type traits de personnalité ou carence dinhibition comportementale. Ces résultats pourraient savérer utiles dans lévaluation et le développement de stratégies pharmacogénétiques destinées à traiter lalcoolo-dépendance et lun de symptômes les principaux : le craving.

First use and initiation of regular alcohol use has been frequently found to start in adolescence. However, only few studies have also investigated how many adolescents proceed during ages 14–24 to harmful drinking or even develop alcohol use disorders. This paper – using the EDSP baseline sample of 3,021 community respondents from the Munich area – examines the prevalence of use, abuse and dependence and investigates the dose/disorder relationship. Alcohol abuse was reported by 9.7% of respondents and alcohol dependence by 6.2%. Men were more likely to report an alcohol disorder than women, prevalence also increased in the older age cohorts. However, even among 14- to 17-year-olds a substantial proportion of respondents report high and regular consumption rates, the occurrence of abuse and dependence criteria and even a full dependence syndrome. There is however only a moderate association between average number of standard drinks consumed with the risk of developing abuse and dependence. In light of the substantial rates among adolescents and young adults the validity of DSM-IV alcohol disorder criteria is discussed.

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.

Bakgrund: Alkoholberoende är en medicinsk diagnos som skiljer sig från risk- samt skadligt bruk. Beroende utvecklas i samspel med belöningssystemet och har en ärftlig komponent. Personer med alkoholberoende är en stigmatiserad grupp i samhället såväl som i sjukvården, och diagnosen innebär ett stort lidande för den enskilde personen. Därför är det viktigt att belysa personernas egna erfarenheter av vårdrelationer. Syfte: Att belysa erfarenheter av vårdrelationer hos personer med alkoholberoende. Metod: Litteraturstudie med sökorden Alcohol dependence, care, patient experiences. alcohol addiction, phenomenological, alcohol, treatment barriers, patient satisfaction, nursing, experiences och qualitative. Tio kvalitativa studier hämtade från databaserna Cinahl Complete, PubMed, Nursing and allied health source, PsycINFO och Psychology and Behavioral Sciences Collection analyserades och tematiserades. Resultat: Det övergripande temat som formades från resultatartiklarna var Vårdrelationens olika aspekter med fyra underteman. Dessa underteman var 1) Vikten av ömsesidig tillit och bekräftelse, 2) Betydelsen av kunskap och professionalitet, 3) Makt och delaktighet i vårdrelationen, samt 4) Att känna sig dömd och diskriminerad. Diskussion: Resultatet diskuteras mot Barkers Tidal-modell. Det diskuteras kring att mycket som framkom i resultatet var positiva erfarenheter och vad det kan bero på. Vidare avhandlas vad negativa attityder gentemot personer med alkoholberoende kan innebära för den enskilde personen och huruvida det är möjligt att utökade kunskaper kan förbättra attityderna. / Background: Alcohol dependence is a medical diagnosis and differs from alcohol abuse and harmful drinking. Dependence develops in interaction with the reward system and has a hereditary component. People with alcohol dependence are a stigmatized group in society as well as within healthcare, and the diagnosis means great suffering. It is therefore important to shed light on these individuals own experiences of caring relationships. Aim: To illuminate experiences of caring relationships in people with alcohol dependence. Method: A literature review with the keywords Alcohol dependence, care, patient experiences, alcohol addiction, phenomenological, alcohol, treatment barriers, patient satisfaction, nursing, experiences and qualitative. Ten qualitative studies collected from Cinahl Complete, PubMed, Nursing and allied health source, PsycINFO and Psychology and Behavioral Sciences Collection were analyzed and thematized. Results: The overarching theme that was formed from the results was Different aspects of the caring relationship with four subthemes. These subthemes were 1) The importance of mutual trust and affirmation, 2) The meaning of knowledge and professionalism, 3) Power and involvement in the caring relationship, and 4) To feel judged and discriminated. Discussions: The results are discussed in relation to Barkers Tidal model. In the discussion it is noted that much that emerged in the results were positive experiences and what this may be due to. Further discussed is what negative attitudes towards people with alcohol dependence can mean for the person, and whether it's possible that extended knowledge can improve these attitudes.

Chronic ethanol (EtOH) exposure produces neuroadaptations within the NMDA receptor system and alterations in HPA axis functioning that contribute to neurodegeneration during ethanol withdrawal (EWD). Chronic EtOH exposure and EWD, as well as corticosteroids, also promote increased synthesis and release of polyamines, which allosterically potentiate NMDA receptor open-channel time at the NR2B subunit. The current studies investigated effects of 10 day EtOH and corticosterone (CORT) co-exposure on toxicity during EWD in rat organotypic hippocampal slice cultures, and alterations in function and/or density of the NR2B subunit of the NMDA receptor that may mediate CORT-potentiation of toxicity during EWD. We hypothesized that toxicity during withdrawal following EtOH and CORT co-exposure would be greatest in the CA1 region due to increased NMDA NR2B receptor abundance and/or function. Cultures were exposed to CORT (0.01–1 μM) during 10 day EtOH exposure (50 mM) and 1 day EWD. Additional EtOH-naïve cultures were exposed to CORT for 11 days. Propidium iodide (PI) was used to measure toxicity in the CA1, CA3, and DG hippocampal regions. In EtOH-naïve cultures, 11 day exposure to CORT (0.01 – 1 μM) produced modest toxicity and in all regions. Exposure to CORT during EtOH exposure/EWD potentiated CORT-toxicity at all concentrations in the CA1 region. Ifenprodil, an NR2B polyamine site antagonist, significantly reduced toxicity from EtOH and CORT (0.1 μM) co-exposure during withdrawal. Immunohistochemistry and Western blot analyses were conducted for measurement of NR2B immunoreactivity in organotypic cultures, and autoradiography studies were conducted for measurement of polyamine-sensitive NR2B subunits with [3H]ifenprodil. Consistent increases in NR2B subunit protein were not detected with use of any methodology. Additional studies exposed cultures to a membrane impermeable form of CORT (BSA-conjugated CORT; 0.1 μM) with or without EtOH exposure and withdrawal. BSA-CORT exposure did not produce toxicity in any hippocampal region, suggesting that CORT toxicity was not mediated by membrane bound substrates. These data suggest that CORT and EtOH co-exposure result in increased function of polyamine-sensitive NR2B subunits, but this toxicity does not appear dependent on the number of hippocampal NMDA NR2B subunits.

O Transtorno de Déficit de Atenção/Hiperatividade (TDAH) é comum em adultos e caracteriza-se por sintomas persistentes de desatenção, hiperatividade e impulsividade. Clinicamente, o TDAH é um fenótipo bastante heterogêneo e, frequentemente, encontra-se associado a diversos outros transtornos psiquiátricos. A contribuição genética é substancial no TDAH e diversos genes de pequeno efeito têm sido associados com o desenvolvimento do transtorno. O metilfenidato (MPH) representa o principal agente farmacológico usado no tratamento e seu mecanismo de ação parece envolver a potencialização da transmissão catecolaminérgica no córtex pré-frontal. Estudos farmacogenéticos têm investigado o papel de diversas variantes genéticas, principalmente em sistemas de neurotransmissão, na resposta ao tratamento com MPH. No entanto, esses estudos têm focado quase que exclusivamente no tratamento de crianças com TDAH. No presente trabalho foi investigada a associação entre 17 polimorfismos genéticos, em nove genes candidatos (DAT1, ADRA2A, 5-HTT, HTR1B, TPH2, DBH, DRD4, COMT e SNAP25), e a resposta ao tratamento com MPH. A amostra foi composta de 165 adultos com TDAH, diagnosticados de acordo com os critérios do DSM-IV. A gravidade dos sintomas dos pacientes foi avaliada antes e após um mês de uso de MPH através da aplicação das subescalas SNAP-IV e da escala CGI-S. Também avaliamos uma amostra de 136 dependentes de álcool e 237 controles, em um estudo de associação envolvendo o gene HTR1B. A resposta ao MPH foi analisada através de avaliações categórica e dimensional da redução nos sintomas após o uso de MPH. Foi observada uma redução significativa nos escores de gravidade total dos sintomas após o tratamento, sendo que 83% dos pacientes foram classificados como respondedores e 17% como não respondedores. Interpretamos a dificuldade de identificar variantes genéticas envolvidas na resposta ao tratamento como o reflexo da complexidade clínica e etiológica do TDAH. Exemplo disso é o fato de que o gene HTR1B, que apresenta resultados positivos para associação com o TDAH em meta-análises e em um estudo com crianças da nossa população, não se mostrou associado com o TDAH em adultos ou com a resposta ao MPH, mas sim com o alcoolismo nesse estudo. Novas investigações, em amostras maiores, serão necessárias para que seja alcançado maior sucesso nos estudos farmacogenéticos envolvendo o MPH ou outros fármacos no tratamento do TDAH. / Attention deficit/hyperactivity disorder (ADHD) has a high prevalence in adults and it is characterized by pervasive symptoms of inattention, hyperactivity and impulsivity. Clinically, ADHD is a very heterogeneous disorder frequently associated with other psychiatric conditions. The genetic contribution in ADHD is substantial and several genes of small effect have been associated with ADHD susceptibility. Methylphenidate (MPH) is the primary agent used in pharmacological intervention for ADHD. Its mechanism of action is believed to potentiate catecholamine transmission in the pre-frontal cortex. Pharmacogenetic studies have been investigating the role of genetic variants in the response to the treatment with MPH. However, previous studies have focused almost exclusively in the treatment of children with ADHD. In this study, we investigated the association between 17 polymorphisms, in 9 candidate genes (DAT1, ADRA2A, 5- HTT, HTR1B, TPH2, DBH, DRD4, COMT and SNAP25), and the response to MPH. The sample comprised 165 adults with ADHD diagnosed according to DSMIV criteria. We also evaluated a sample of 136 alcohol dependents and 237 control subjects, in an association study involving the HTR1B gene. The response to MPH was assessed by both categorical and dimensional approaches through the SNAP-IV sub-scales and the CGI-S scale, applied at the beginning and after the 30th day of treatment. We detected a significant reduction in SNAP-IV total scores during the follow-up period. According to the categorical definition of MPH response, 83% of the patients were classified as responders and 17% were classified as non-responders. Our results indicated that none of the investigated variants showed significant effects on the MPH response. We interpret the difficulty of identifying genetic variants involved in response to treatment as a reflection of the clinical and etiological complexity of ADHD. For example, we did not find association of the HTR1B gene with ADHD nor with treatment response to MPH in our adult sample, but it was in fact associated with alcohol dependence. However, this gene has previously shown positive results for association with children ADHD in meta-analysis and also in a study with children of the same population of the current work. More investigations with larger sample sizes will be need to achieve greater success in pharmacogenetic studies involving the MPH or other drugs used in the treatment of ADHD.

O Transtorno de Déficit de Atenção/Hiperatividade (TDAH) é comum em adultos e caracteriza-se por sintomas persistentes de desatenção, hiperatividade e impulsividade. Clinicamente, o TDAH é um fenótipo bastante heterogêneo e, frequentemente, encontra-se associado a diversos outros transtornos psiquiátricos. A contribuição genética é substancial no TDAH e diversos genes de pequeno efeito têm sido associados com o desenvolvimento do transtorno. O metilfenidato (MPH) representa o principal agente farmacológico usado no tratamento e seu mecanismo de ação parece envolver a potencialização da transmissão catecolaminérgica no córtex pré-frontal. Estudos farmacogenéticos têm investigado o papel de diversas variantes genéticas, principalmente em sistemas de neurotransmissão, na resposta ao tratamento com MPH. No entanto, esses estudos têm focado quase que exclusivamente no tratamento de crianças com TDAH. No presente trabalho foi investigada a associação entre 17 polimorfismos genéticos, em nove genes candidatos (DAT1, ADRA2A, 5-HTT, HTR1B, TPH2, DBH, DRD4, COMT e SNAP25), e a resposta ao tratamento com MPH. A amostra foi composta de 165 adultos com TDAH, diagnosticados de acordo com os critérios do DSM-IV. A gravidade dos sintomas dos pacientes foi avaliada antes e após um mês de uso de MPH através da aplicação das subescalas SNAP-IV e da escala CGI-S. Também avaliamos uma amostra de 136 dependentes de álcool e 237 controles, em um estudo de associação envolvendo o gene HTR1B. A resposta ao MPH foi analisada através de avaliações categórica e dimensional da redução nos sintomas após o uso de MPH. Foi observada uma redução significativa nos escores de gravidade total dos sintomas após o tratamento, sendo que 83% dos pacientes foram classificados como respondedores e 17% como não respondedores. Interpretamos a dificuldade de identificar variantes genéticas envolvidas na resposta ao tratamento como o reflexo da complexidade clínica e etiológica do TDAH. Exemplo disso é o fato de que o gene HTR1B, que apresenta resultados positivos para associação com o TDAH em meta-análises e em um estudo com crianças da nossa população, não se mostrou associado com o TDAH em adultos ou com a resposta ao MPH, mas sim com o alcoolismo nesse estudo. Novas investigações, em amostras maiores, serão necessárias para que seja alcançado maior sucesso nos estudos farmacogenéticos envolvendo o MPH ou outros fármacos no tratamento do TDAH. / Attention deficit/hyperactivity disorder (ADHD) has a high prevalence in adults and it is characterized by pervasive symptoms of inattention, hyperactivity and impulsivity. Clinically, ADHD is a very heterogeneous disorder frequently associated with other psychiatric conditions. The genetic contribution in ADHD is substantial and several genes of small effect have been associated with ADHD susceptibility. Methylphenidate (MPH) is the primary agent used in pharmacological intervention for ADHD. Its mechanism of action is believed to potentiate catecholamine transmission in the pre-frontal cortex. Pharmacogenetic studies have been investigating the role of genetic variants in the response to the treatment with MPH. However, previous studies have focused almost exclusively in the treatment of children with ADHD. In this study, we investigated the association between 17 polymorphisms, in 9 candidate genes (DAT1, ADRA2A, 5- HTT, HTR1B, TPH2, DBH, DRD4, COMT and SNAP25), and the response to MPH. The sample comprised 165 adults with ADHD diagnosed according to DSMIV criteria. We also evaluated a sample of 136 alcohol dependents and 237 control subjects, in an association study involving the HTR1B gene. The response to MPH was assessed by both categorical and dimensional approaches through the SNAP-IV sub-scales and the CGI-S scale, applied at the beginning and after the 30th day of treatment. We detected a significant reduction in SNAP-IV total scores during the follow-up period. According to the categorical definition of MPH response, 83% of the patients were classified as responders and 17% were classified as non-responders. Our results indicated that none of the investigated variants showed significant effects on the MPH response. We interpret the difficulty of identifying genetic variants involved in response to treatment as a reflection of the clinical and etiological complexity of ADHD. For example, we did not find association of the HTR1B gene with ADHD nor with treatment response to MPH in our adult sample, but it was in fact associated with alcohol dependence. However, this gene has previously shown positive results for association with children ADHD in meta-analysis and also in a study with children of the same population of the current work. More investigations with larger sample sizes will be need to achieve greater success in pharmacogenetic studies involving the MPH or other drugs used in the treatment of ADHD.

Background: Alcohol use disorders belong among the ten leading causes of Years Lost due to Disability in high-income countries. Poland, Czech Republic, and the Slovak Republic are countries with high alcohol consumption. The specific inpatient psychotherapeutic program is basic treatment approach in patients suffering from alcohol dependency. The theory of change assumes that therapeutic approaches should be adapted to the stage of change in which the patient actually is. Aim: To examine the state of readiness to change at the beginning and the end of inpatient short (six weeks) and long (12 weeks) therapeutic program in Slovak Republic, Poland, and the Czech Republic. To compare readiness to change with insight and motivation. To find, whether patients change and how patients change advances in alcohol treatment. Methods: Total 380 alcohol dependent inpatients (282 men and 98 women) were examined using International Statistical Classification of Diseases and Related Health Problems- 10th Revision (ICD- 10), World Health Organization (1992). Alcohol Use Disorders Identification Test (AUDIT), The Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES), Readiness to Change Questionnaire (RCQ), and Demographic Questionnaire. All analyses were calculated using the SPSS (Statistical Packages...

Magister Psychologiae - MPsych / Increased rates of alcohol abuse and childhood trauma have been reported in previous studies of anxiety disorders, and social anxiety disorder (SAD) in particular. Yet the exact nature of this relationship remains unclear. This study aimed to assess whether SAD is a risk factor for later development of alcohol use disorders (AUD) and to investigate the association of childhood trauma with the prospective SAD-AUD comorbidity in adults with SAD. Data from fifty seven adult participants (N=57) with a primary diagnosis of SAD (mean age 36.7; 60% male) completed the self-rated Childhood Trauma Questionnaire (CTQ) as well as the Liebowitz Social Anxiety Scale (LSAS), a measure of SAD symptom severity. Alcohol abuse and dependence information were assessed with the Structured Clinical Interview for Axis I Disorders-Patient Version (SCID-I/P). Data from sixty two adult age and gender match controls were used as a comparison group. A Cognitive Behavioural Model and the Social Learning Model are the theoretical frameworks utilised in the conceptualisation of this research. The data is quantitative in nature and will be statistically analysed using descriptive statistics, logistic regression and ANOVA using the Statistical Package for the Social Sciences (SPSS) version 17.0. Informed consent was obtained in writing from all participants. The findings of the study were that 73.7% of the SAD sample met severity criteria for at least one type of childhood abuse or neglect as measured by the CTQ subscales using previously established thresholds. Physical neglect was found to be significantly associated with increased SAD symptom severity.17.5% of the SAD sample had a comorbid lifetime alcohol use disorder (AUD) and of those 80% reported experiencing childhood trauma. In conclusion there was a high rate of childhood trauma in individuals with SAD and there is a strong association between childhood trauma and comorbid AUDs in those with SAD.Thus screening for childhood trauma in SAD individuals is clinically prudent.