Introdução: A ocorrência de episódios depressivos e abuso ou dependência de álcool após um evento agudo de insuficiência coronariana pode representar um marcador independente de mau prognóstico. Portanto, investigamos a presença de sintomas depressivos, transtorno depressivo maior (TDM) e abuso ou dependência de álcool em uma subamostra de uma coorte prospectiva de Síndrome Coronariana Aguda (SCA), Estratégia de Registro de Insuficiência Coronariana Aguda (ERICO) em andamento no pronto-socorro do Hospital Universitário. Métodos: Foi realizado um estudo observacional em 146 participantes do estudo ERICO. A gravidade dos sintomas depressivos foi avaliada em três momentos: 1ª) na admissão hospitalar pelo Patient Health Questionnaire (PHQ-9 itens); 2º) 30 dias pós-SCA pelo PHQ-9, Inventário de Depressão de Beck (BDI) e Escala de Depressão de Hamilton (HDRS-21 itens); e 3º) 180 dias pós-SCA pelo PHQ-9 e BDI. O abuso e uso nocivo de álcool foram avaliados pelo AUDIT e CAGE em 30 e 180 dias pós-SCA. Resultados: Ao longo do estudo as frequências de sintomas depressivos variaram entre 40% e 60% e de TDM entre 28% e 33%. Na admissão hospitalar houve maior predominância de sintomas depressivos entre os homens (58%; p=0,03) e sedentários (72,1%; p=0,02), entretanto, TDM foi mais frequente na população feminina (55,1%; p < 0,001) com uma razão de chances [(RC) 4,5; intervalo de confiança IC 95% 1,85-10,98]. Após 30 dias do evento agudo constatou-se um maior risco de sintomas depressivos entre os tabagistas (RC 5,8; IC 95% 1,81-18,72) e diabéticos (RC 3,6; IC 95% 1,40-9,60). Os diabéticos também apresentaram (RC 3,5; IC 95% 1,39-8,71) para desenvolver TDM. No seguimento de 180 dias verificou-se que indivíduos com angina instável (AI) (RC 4, 46; IC 95% 1,39-14,32) e infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMCST) (RC 3,40; IC 95% 1,30-8,87) apresentaram maior probabilidade de desenvolverem sintomas depressivos em relação aos indivíduos que apresentaram IAMSST. Os únicos fatores de risco que se mantiveram associados a um maior risco de sintomas depressivos após 180 dias foi o sexo feminino (RC 3,9; IC 95% 1,54-9,73) e o tabagismo (RC 5,34; IC 95% 1,64-17,44). Em relação à TDM, encontramos uma RC de 14 (IC 95% 2,94-67,51) para associação com tabagismo. Quanto ao abuso e uso nocivo de álcool as frequências variaram ao longo do estudo pelo AUDIT e CAGE entre 18,3% e 33,6%. Verificamos na populacão masculina uma frequência de 88,2% (p=0,001) e entre os tabagistas de 55,9% (p=0,003) e foi encontrada uma RC de 51,64 para população mais jovem (35-44 anos) e uma RC de 42,95 para tabagistas. Finalmente, não foi encontrada nenhuma associação entre abuso de álcool e depressão de acordo com os subtipos de SCA nos períodos analisados. Conclusão: A frequência de depressão variou entre 40% e 60% da admissão até 180 dias pós-SCA. Indivíduos que desenvolveram AI ou IAMCST, além de mulheres e tabagistas apresentaram maiores chances de desenvolver depressão ao longo do seguimento de 180 dias e indivíduos entre 35 e 44 anos e tabagistas apresentaram maior possibilidade de abusar do álcool / Introduction: The occurrence of depression and alcohol abuse or dependence after an acute coronary insufficiency may represent an independent marker of poor prognosis. Therefore, we investigated the presence of depressive symptoms, major depressive disorder (MDD) and alcohol abuse or dependence in a subsample of a prospective cohort of Acute Coronary Syndrome (ACS), Strategy of Registry of Acute Coronary Syndrome Study (ERICO study), which is still ongoing in the emergency room of the Hospital Universitário. Methods: We conducted an observational study in 146 participants of the ERICO study. The severity of depressive symptoms was evaluated in 3 moments: 1st) at the hospital admission using The Patient Health Questionnaire (PHQ-9 items); 2nd) 30 days post-ACS using the PHQ-9, the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS -21 items), and 3rd) 180 days post -ACS through PHQ-9 and BDI. The abuse and harmful alcohol consumption were assessed by the AUDIT and the CAGE 30 and 180 days post-ACS. Results: Along the study, the frequencies of depressive symptoms ranged from 40% to 60% and MDD from 28% to 33%. At the hospital admission there was a higher prevalence of depressive symptoms among men (58%, p= 0.03) and sedentary patients (72.1%, p= 0.02), however, MDD was higher among women (55.1%, p < 0.001) with an increased risk of [odds ratio [(OR) 4.5; confidence interval CI 95% 1.85-10.98]. After 30 days of the acute event, we observed an increased risk of depressive symptoms among smokers (OR 5.8; CI 95%, 1.81-18.72) and among diabetics (OR 3.6; CI 95%, 1.40-9.60) the diabetics were also more likely to develop MDD (OR 3.5; IC 95% 1,39-8,71). At 180 days follow-up, individuals with unstable angina (UA) (OR 4.46; CI 95% 1.39-14.32) and ST elevation myocardial infarction (STEMI) (OR 3.40; CI 95% 1.30-8.87) were more likely to develop depressive symptoms compared with patients who had NSTEMI. The only two factors that remained associated with a higher risk of depressive symptoms after 180 days were female gender (OR 3.9; CI 95% 1.54-9.73) and smokers (OR 5.34; CI 95% 1.64-17.44). Regarding MDD we found an OR of 14 (CI 95% 2.9-67.51) for smokers. In relation to abuse and hazardous consumption of alcohol, the frequencies for CAGE and AUDIT ranged from 18.3% to 33.6% along the study. We found among the male population a frequency of 88.2% (p=0.001) and smokers 55.9% (p=0.003). We also found OR of 51.64 among younger (aged 35-44 years) and OR of 42.95 for smokers. Finally, no association between alcohol abuse and depression according to ACS subtypes was observed. Conclusion: The prevalence of depression post-ACS ranged from 40% to 60% during the follow-up (admission hospital to 180 days). Individuals who developed UA or STEMI, besides women and smokers were more likely to develop depression during follow-up of 180 days and individual aged between 35-44 years and smokers were more likely to abuse of alcohol

Hintergrund. In klinischen und epidemiologischen Untersuchungen wurden retrospektiv Assoziationen zwischen Angst- und Alkoholstörungen bestätigt. Bei Personen, die von beiden Störungen betroffen waren, fand man restrospektiv meist einen früheren Beginn der Angststörungen im Vergleich zu den Alkoholstörungen, was kausal im Sinne der Selbstmedikationshypothese interpretiert wurde. Diese konnte bisher nicht eindeutig bestätigt werden. Zur Aufklärung notwendige prospektive Untersuchungen, die Angststörungen auf diagnostischer Ebene erfassen, zwischen verschiedenen Angststörungen unterscheiden und sich auf Jugendliche beziehen, fehlen bisher. Fragestellung. Die Bedeutung von Angststörungen für die Entwicklung von erhöhtem Alkoholkonsum und Alkoholstörungen bei Jugendlichen und jungen Erwachsenen. Methodik. Die Analysen basieren auf den Daten der prospektiv-longitudinalen EDSP-Studie (Follow-Up: insg. 4 Jahre) mit einer epidemiologischen, repräsentativen Stichprobe von 3021 Personen im Alter zwischen 14 und 24 Jahre zu T0 aus München und Umland. Zur Erhebung von DSM-IV-Diagnosen wurde das M-CIDI verwendet. Ergebnisse. Primäre Panikstörungen, Panikattacken und Soziale Phobie erwiesen sich prospektiv als spezifische Prädiktoren für Beginn und Aufrechterhaltung von Alkoholproblemen. Umgekehrt waren Alkoholprobleme mit einem erhöhten Risiko für den Beginn von Sozialer Phobie und GAS assoziiert. Bezüglich DSM-IV Diagnosekriterien fanden sich phobische Ängste sowie Episoden intensiver Angst als Risikofaktoren für den Beginn von Alkoholproblemen. Vermeidungsverhalten war mit einem verminderten Risiko für nachfolgende Alkoholprobleme verbunden. Schlussfolgerungen. Maßnahmen zur Prävention von Alkoholproblemen können sich zielgruppenorientiert an Jugendliche mit Sozialer Phobie und Paniksymptomatik richten. Bei Patienten, die sich wegen Alkoholproblemen in Behandlung begeben, ist eine umfassende Diagnostik zur Identifikation zusätzlicher Angststörungen ratsam. / Background. Many clinical and epidemiological studies have documented significant cross-sectional comorbidities between anxiety disorders and alcohol use disorders. Analysis of retrospective age-of-onset reports suggests that the anxiety disorders often start earlier than the alcohol disorders. These data have often been interpreted in terms of a self-medication-model implying a causal mechanism. Overall, in former studies this model couldn't definitely be proofed. Prospective studies that follow a sample of adolescents into adulthood assessing different anxiety disorders on an diagnostic level are needed to confirm these associations. Methods. Baseline and four-year-follow-up data from the EDSP-Study, a prospective community survey of 3021 (2548 at follow-up) adolescents and young adults aged 14 to 24 years at baseline carried out in Munich, were used. DSM-IV anxiety disorders, alcohol use and alcohol use disorders were assessed with the M-CIDI. Results. While in retrospective analyses strong associations between nearly all anxiety disorders and alcohol problems, especially harmful use and dependence, were found, prospective analyses showed that only primary panic disorder, panic attack and social phobia are specific predictors of subsequent onset and persistence of alcohol problems. Contrary, primary alcohol problems were related to subsequent onset of social phobia and GAD. Considering the different DSM-IV-criteria, phobic anxiety as well as episodes of intensive anxiety were found to be risk factors for the following onset of alcohol problems. Avoidance behavior was associated with a lower risk for subsequent alcohol problems. Conclusions. Alcohol prevention programs could be directed to target groups with social phobia and panic. Patients with alcohol problems should carefully be screened for comorbid anxiety disorders. In order to prevent relapses the treating of social phobia and panic should be part of the therapy with comorbid alcohol patients.

One fifth of Sweden's children growing up have under their childhood had at least one parent who had an alcohol use disorder. Children are individually affected in different ways by the circumstances of their upbringing and it is not something that is always apparent to those outside the family circle.  It becomes a dilemma when these children's voices aren't heard. Another compounding factor can be an absence of social support and intervention often carried out by social workers. Social programs adapted to these children’s situation can help break the silence and reach the individuals hiding behind the masks put on to shield off the world outside. We were interested how individuals who had been subjected to having a parent with an alcohol disorder described their experiences and how they felt they had been affected by that circumstance. We wanted to leverage this to reach a deeper understanding of how to better support children living with this situation. This formed the purpose of the of this study and gave rise to the questions investigated. The method employed to conduct the study was a thematic analysis on six swedish autobiographies within this framework. After the autobiographies had been read, four different themes to further investigate emerged: escape from reality, consequences embodied as adults, socioeconomic situation, and relevant social work. Analyses showed that the authors were affected by difficult childhoods impacted by parental alcohol use disorders in a multitude of different ways.  By example, they devised different methods to flee their predicament as children. The results also showed these children could be found in different types of homes and strata across the spectrum of socioeconomic statuses. The now grown children also believed that their childhoods would have been improved if they had had more caring, secure adults in their vicinity to their lives otherwise filled with chaos.

La consommation de cannabis durant l'adolescence est associée à des risques accrus de problèmes de santé mentale, y compris la toxicomanie et la psychose. Tout en considérant qu'une partie de l'étiologie de ces troubles est héréditaire, nous avons étudié le risque génétique de psychose et de troubles liés à l'usage de substances et leurs relations avec le cannabis et le système endocannabinoïde. Dans notre premier travail, nous avons étudié la relation entre les marqueurs génétiques endocannabinoïdes et les troubles d’usage d'alcool (TUA) pour deux cohortes d'adolescents. À l’aide d’approches de gènes candidats, nous avons démontré une relation significative entre ces gènes endocannabinoïdes et les TUA, mais ces résultats n'ont pas été répliqués chez une deuxième cohorte indépendante. Lors d’une seconde étude, nous avons examiné si la relation entre le score de risque polygénique pour la schizophrénie (PRS-Sz) et les expériences prépsychotiques (PLE) est médiée et/ou modérée par la consommation de cannabis, pour deux cohortes indépendantes. Des modèles de régression de médiation et de modération ont été utilisés pour examiner dans quelle mesure la relation prospective entre PRS-Sz et PLE est expliquée par la consommation de cannabis. Les résultats des analyses de médiation et de modération n'étaient pas significatifs, bien que le PRS-Sz et la consommation de cannabis aient tous deux prédit indépendamment les PLE. Ces résultats suggèrent que la consommation de cannabis reste un facteur de risque de psychose, au-delà de la vulnérabilité génétique connue pour la schizophrénie et qu’il n'y a pas de preuve que les individus génétiquement vulnérables étaient plus sensibles aux conséquences psychotiques de la consommation de cannabis. Le travail décrit démontre que les risques posés par la consommation de cannabis chez les adolescents pourraient ne pas être associés à une prédisposition génétique aux maladies psychiatriques, nonobstant l’implication du système endocannabinoïde dans la pathogenèse de ces mêmes maladies. / Cannabis consumption during adolescence, increases the likelihood of adverse mental health outcomes, including substance abuse and psychosis. Considering that part of the etiology of these disorders are heritable, we aimed to elucidate the genetic risk for psychosis and substance use disorders and their relationships to cannabis and the endocannabinoid system. In our first work, we investigated the relationship between endocannabinoid genetic markers and alcohol use disorder in two adolescent cohorts. Through candidate gene approaches we demonstrated a significant relationship between these endocannabinoid genes and AUD, but the results were not replicated in the second cohort. In a second work, we examined if the relationship between polygenic risk score for schizophrenia (PRS-Sz) and psychotic like experiences (PLE) is mediated and/or moderated by cannabis use, in two cohorts. Mediation and moderation regression models were used to examine the extent to which the prospective relationship between PRS-Sz and PLE is accounted for by cannabis use. The results of both the mediation and moderation analyses were not significant, although PRS-Sz and cannabis use both independently predicted PLE. These results suggest that cannabis use remains a risk factor for psychotic-like experiences, over and above known genetic vulnerability for schizophrenia and there was no evidence that genetically vulnerable individuals were more susceptible to the psychosis-related outcomes of adolescent onset cannabis use. The work described demonstrates that the risks posed by adolescent cannabis consumption may be unrelated to one’s genetic predisposition to psychiatric disease, notwithstanding the involvement of the endocannabinoid system in the pathogenesis of these same diseases.

Diese Dissertation fasst drei wissenschaftliche Arbeiten (Artikel) zusammen, welche sich mit veränderten Entscheidungsprozessen bei substanzgebundenen- und substanzungebundenen Abhängigkeitserkrankungen beschäftigen. In Artikel I wurde beobachtet, dass Probanden mit Alkoholkonsumstörung (AD) und Probanden mit Glücksspielstörung (GD) eine ähnlich reduzierte Verlustaversion gegenüber gesunden Kontrollen (HC) aufweisen. Beide Gruppen zeigten jedoch unterschiedliche neuronale Korrelate dieser reduzierten Verlustaversion: Während AD-Probanden eine unterschiedliche funktionelle Aktivität im dorsal-lateralen-präfrontalen Kortex im Vergleich zu HC aufwiesen, zeigten GD-Probanden eine veränderte funktionelle Konnektivität zwischen Amygdala und orbito-frontalem Kortex (OFC) bzw. medial-präfrontalem Kortex. In den Artikeln II und III wurde untersucht, ob das Verhalten und die neuronale Aktivität bei einer Verlustaversionsaufgabe bei GD-Probanden moduliert wird, wie dies in ähnlichen Studien bei AD-Probanden beobachtet wurde. Tatsächlich konnten GD-Probanden von HC-Probanden auf Grundlage ihrer veränderten Glücksspielannahme während der Präsentation spielbezogener Hinweisreize unterschieden werden. Auf neuronaler Ebene (Artikel III) konnten GD-Probanden von HC-Probanden durch die neuronalen Korrelate der reizinduzierten Veränderungen im Spielverhalten in einem Netzwerk aus Amygdala, Nucleus Accumbens und OFC unterschieden werden. Da in den Studien der Fokus auf Glücksspielabhängigkeit lag, also auf einer Abhängigkeit, welche unabhängig von Substanzmissbrauch existiert, deuten die hier diskutierten Ergebnisse darauf hin, dass verminderte Verlustaversion, sowie erhöhte reizinduzierte Veränderungen im Entscheidungsverhalten – welches beides bekannte Phänomene von Substanzabhängigkeiten sind – nicht durch Substanzmissbrauch zustande kommen. Beide Phänomene scheinen vielmehr erlernte Merkmale oder sogar prädisponierende Faktoren von Abhängigkeitserkrankungen zu sein. / This dissertation summarizes three papers concerned with decision-making impairments in a substance-based and a non-substance-based addictive disorder. In Paper I, it was observed that subjects with alcohol use disorder (AD) and subjects with gambling disorder (GD) show similarly reduced loss aversion. Both groups, however, showed different neural correlates of this reduced loss aversion: While AD subjects showed different functional activity in dorsal-lateral-prefrontal cortex compared to healthy controls (HC), GD subjects showed different amygdala-orbital-frontal and amygdala-medial-prefrontal connectivity. Paper II and III investigated whether behavior and neural activity in a loss aversion task is modulated in GD subjects, as has been observed in similar studies in AD subjects. The data showed that GD subjects can be distinguished from HC subjects using a behavioral pattern of increased cue-induced gamble increase when gambling-related cues are presented in the background. On neural level (Paper III), GD subjects could be distinguished from HC subjects by neural correlates of cue-induced changes in gambling behavior in a network of amygdala, nucleus accumbens and orbital-frontal cortex. Since the focus of the studies was GD, an addiction that is independent of substance abuse, the results suggest that reduced loss aversion and increased cue-induced changes in gambling behaviors, two phenomena related to substance-based addictions, are not dependent on a substance of abuse but rather on learned characteristics or even on predisposing traits of addictive disorders.

No description available.

Alcohol use disorder (AUD) is characterized by excessive habitual drinking and loss of control over alcohol intake despite negative consequences. Both of these aspects foster uncontrolled drinking and high relapse rates in AUD patients. Yet, common interventions mostly focus on the phenomenological level, and prioritize the reduction of craving and withdrawal symptoms. Our review provides a mechanistic understanding of AUD and suggests alternative therapeutic approaches targeting the mechanisms underlying dysfunctional alcohol-related behaviours. Specifically, we explain how repeated drinking fosters the development of rigid drinking habits and is associated with diminished cognitive control. These behavioural and cognitive effects are then functionally related to the neurobiochemical effects of alcohol abuse. We further explain how alterations in fronto-striatal network activity may constitute the neurobiological correlates of these alcohol-related dysfunctions. Finally, we discuss limitations in current pharmacological AUD therapies and suggest non-invasive brain stimulation (like TMS and tDCS interventions) as a potential addition/alternative for modulating the activation of both cortical and subcortical areas to help re-establish the functional balance between controlled and automatic behaviour.