oucos estudos avaliaram a associação da ingestão de ácidos graxos ômega 3 e transtornos de ansiedade. O presente estudo utilizou dados transversais do exame de linha de base (2008-2010) do Estudo Longitudinal Brasileiro de Saúde do Adulto - ELSA-Brasil para avaliar essa associação. A exposição dietética foi medida por um questionário quantitativo de frequência alimentar validado para a população brasileira e adaptado para o estudo, e os diagnósticos mentais foram avaliados pelo Clinical Interview Schedule-Revised Version - CIS-R, diagnosticando transtornos mentais de acordo com a Classificação Internacional de Doenças - CID-10. Modelos de regressão logística foram construídos utilizando quintis do consumo de ácidos graxos ômega 3, ácidos graxos ômega 6, razão de consumo n-6/n-3, e ácidos graxos poli-insaturados, usando o primeiro quintil como referência. Dos 15.105 sujeitos participantes do ELSA-Brasil, foram excluídos aqueles que relataram ingestão de menos de 500 ou mais de 4000 kcal, aqueles que relataram ingestão de suplementos n-3 ou n-6 e aqueles que foram submetidos a cirurgia bariátrica. Após as exclusões, 12268 participantes permaneceram na análise, dos quais 1893 (15,4%) apresentaram transtornos de ansiedade. Os indivíduos com transtorno de ansiedade eram mais jovens, de sexo feminino, menor escolaridade e renda, referiram tabagismo atual e atividade física mais leve. Valores mais altos de IMC e de proteína C reativa de alta sensibilidade foram observados nos indivíduos com ansiedade. A ingestão diária média de ácido eicosapentaenoico (EPA), ácido docosapentanoico (DPA) e ácido docosaexaenoico (DHA) foi significativamente menor em participantes com ansiedade. Um maior consumo desses três ácidos graxos da família ômega-3 foi observado em indivíduos com mais idade, maior renda e escolaridade, com dislipidemia, consumo de álcool e tabagismo atuais, e prática de atividade física vigorosa. Após o ajuste para variáveis sociodemográficas (idade, sexo, etnia e educação) fatores de risco cardiovascular (hipertensão, diabetes, dislipidemia, tabagismo, ingestão de álcool e atividade física), calorias totais, qualidade da dieta e depressão, os participantes do quinto quintil de ingestão de EPA, DHA e DPA mostraram associação inversa com transtornos de ansiedade: OR 0,82 (IC 95%, 0,69-0,98), OR 0,83 (IC 95%, 0,69-0,98) e OR 0,82 (IC 95%, 0,69-0,98), respectivamente. Participantes no quinto quintil de razão ômega-6/ômega-3 tiveram associação positiva com transtornos de ansiedade. Nenhuma associação foi encontrada com a ingestão de PUFA, ou ômega-3 e ômega-6 isoladamente com ansiedade após os ajustes. Nesta análise, uma alta ingestão de ômega-3 EPA, DHA e DPA foi inversamente associada com a presença de transtornos de ansiedade, enquanto que a alta razão ômega-6/ômega-3 foi diretamente associada à presença desses transtornos, sugerindo um possível efeito protetor dos ácidos graxos omega-3 EPA, DPA e DHA contra a ansiedade / Few studies have evaluated the association of omega-3 fatty acids intake and anxiety disorders. The present study used cross-sectional data from the baseline (2008-2010) examination of the Brazilian Longitudinal Study of Adult Health - ELSA-Brazil to evaluate this association. The dietary exposure was measured by a quantitative food frequency questionnaire validated for the brazilian population and adapted for the study, and the mental diagnoses were assessed by the Clinical Interview Schedule-Revised Version (CIS-R), diagnosing mental disorders according to the International Classification of Diseases - ICD-10. Logistic regression models were built using quintiles of omega-3 fatty acids, omega-6 fatty acids, omega-6/omega-3 ratio, and polyunsaturated fatty acids consumption, using the first quintile as a reference. Of the 15,105 subjects participating in ELSA-Brazil, those who reported ingestion of less than 500 or more than 4000 kcal, those who reported ingestion of omega-3 or omega-6 supplements and those had undergone bariatric surgery were excluded. After exclusions, 12,268 participants remained in the analysis, of whom 1893 (15.4%) had anxiety disorders. Subjects with anxiety disorder were younger, female, had lower education and income, reported current smoking and mild physical activity. Higher values of BMI and high sensibility C reactive protein were observed in subjects with anxiety. The mean daily intakes of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) were significantly lower in subjects with anxiety. A higher intake of these three omega-3 fatty acids was observed in older individuals with higher income and education, with current dyslipidemias, alcohol consumption and smoking, and vigorous physical activity. After adjustment for socio-demographic variables (age, sex, ethnicity and education), cardiovascular risk factors (hypertension, diabetes, dyslipidemia, smoking, alcohol intake and physical activity), total calories, diet quality and depression, EPA, DHA and DPA intakes showed an inverse association with anxiety disorders: OR 0.82 (95% CI, 0.69-0.98), OR 0.83 (95% CI, 0.69-0.98) and OR 0.82 (95% CI, 0.69-0.98), respectively. Participants in the fifth quintile of omega-6/omega-3 ratio had a positive association with anxiety disorders. No association was found with ingestion of PUFA, or omega-3 and omega-6 alone with anxiety after adjustments. In this analysis, a high intake of omega-3 EPA, DHA and DPA was inversely associated with the presence of anxiety disorders, while the higher omega-6 omega-3 ratio was directly associated with the presence of these disorders, suggesting a possible protector effect of omega-3 fatty acids EPA, DPA and DHA against anxiety

OBJETIVOS: Estimar a prevalência de transtornos mentais comuns (TMC) e transtornos de abuso e dependência de álcool (TADA) em população atendida por Estratégia Saúde da Família (ESF) do município de Santa Cruz do Sul, Brasil; estudar as associações entre TMC e TADA com variáveis sociodemográficas. METODOLOGIA: Todos moradores acima de 14 anos de 3 áreas atendidas por ESF foram convidados a participar no período de 10 de fevereiro de 2006 a 10 de fevereiro de 2007. RESULTADOS: Dos 2921 participantes, as prevalências de TMC e TADA foram de 29,93% (IC95%29,30%-30,56%) e 12,07% (IC95%11,63%-12,52%), respectivamente. Sexo feminino, situação ocupacional desfavorável, baixa escolaridade e baixa renda mostraram associação positiva e independente com TMC. Sexo masculino, situação ocupacional desfavorável e TMC apresentaram associação independente com TADA. DISCUSSÃO: Foram encontradas prevalências de TMC e TADA acima das relatadas em outros estudos brasileiros. Grupos com condições socioeconômicas desfavoráveis são os de maior risco para TMC e TADA. CONCLUSÕES: Os grupos de maior risco para TMC e TADA deveriam ser levados em consideração quando se planejam políticas públicas em saúde mental. / OBJECTIVE: Estimate the prevalence of common mental disorders (CMD) as well as alcohol abuse and dependence disorders (AADD) in a population assisted by Programa de Saúde da Família (PSF or Family Health Program) in the City of Santa Cruz do Sul, Southern Brazil; estimate the associations between CMD and AADD with socio-demographic variables. METHOD: All residents over 14 years of age from 3 areas assisted by the PSF were invited to participate between February 10, 2006 to February 10, 2007. RESULTS: Of 2,921 participants, the prevalence estimates of CMD and AADD were 29.93% (IC95%29.30%-30.56%) e 12.07% (IC95%11.63%-12.52%), respectively. Female, unfavorable employment situation, low schooling and low income showed a positive and independent association with CMD. Male, unfavorable employment situation and CMD showed an independent association with AADD. DISCUSSION: We found higher prevalence estimates of CMD and AADD in relation to the observed prevalence estimates in other Brazilian studies. Groups with unfavorable socioeconomic conditions present the highest risk. CONCLUSIONS: The groups with the highest risk for CMD and AADD should be taken into account when planning public mental health policies.

O presente trabalho tem por objetivo refletir sobre a atuação/inserção dos trabalhadores em saúde mental na implantação da rede substitutiva de saúde mental do município de São Paulo, entre os anos de 1989 e 1992. A discussão, orientada pelas contribuições da Psicologia Social como descrita por Pichon-Rivière, apoia-se em dados coletados a partir da observação grupos de supervisão clínica/institucional. Estes grupos são parte do Projeto de Formação Permanente em Recursos Humanos na Área de Saúde Mental, resultado do convênio entre a Prefeitura do Município de São Paulo e a Universidade de São Paulo (PMSP/USP), através do termo aditivo entre Secretaria Municipal de Saúde e Instituto de Psicologia (SMS/PST-IPUSP), cuja realização se deu paralelamente à implantação da rede referida. Ressignificar e construir/superar limites conceituais, teóricos, técnicos, práticos; e problematizar as contradições, conflitos e dúvidas decorrentes da prática são fundamentais na substituição de práticas antimanicomiais. Ao enfocar a contradição entre saberes e práticas do modelo psiquiátrico tradicional X modelo antimanicomial, analisou-se os conflitos de natureza objetiva e/ou subjetiva, emergentes no contexto de trabalho e relacionados principalmente à concepção de loucura, constituição da equipe multiprofissional e formação dos trabalhadores em saúde mental na construção de práticas inspiradas nos princípios antimanicomiais. Constatou-se que contradições ('loucura/doença mental x saúde mental’, ‘loucura/desrazão X razão’, ‘anormalidade/patologia x normalidade’, ‘saber x não saber’, ‘modelo médico x não médico’, ‘terapêutico x não terapêutico’) provenientes da quebra do modelo manicomial desencadeiam processos de indiscriminação, emergentes nas relações intersubjetivas, tendo como efeito a perda de limites (‘trabalhadores x usuários’, ‘técnicos x não técnicos’, ‘neurose x psicose’, ‘eficiência x ineficiência’ de técnicas, ‘público x privado). Assim, a construção destes novos modelos, ligada a desconstrução do manicômio, apresenta-se como uma tarefa complexa, cuja realização não se restringe ao âmbito das práticas, pois carrega consigo contradições inerentes ao sistema social do qual advém (burguesia X proletariado, movimentos sociais x Estado, sociedade global x instituição de saúde, instituição x trabalhadores, trabalhadores em saúde mental x usuário/familiares e usuários x familiares). / The aim of the present study is to analyse the performance of mental health workers in the implementation of a new model of mental health care is the municipality of São Paulo, in the years 1989 to 1992. This study is based on data collected from the observation of groups of clinical/institutional supervision and is guided by the contributions of the Social Psychology as proposed by Pichon-Rivière. These groups were part of a Project for Continued Education in Human Resources in the Mental Health Area, agreed between the Municipality of São Paulo and the University of São Paulo (PMSP/USP), through the Municipal Health Secretarial and the Institute of Psychology (SMS/PST-IPUSP). The Project was developed at the same time as a new model for mental health care was implemented. An analyses indicate that to substitute the asylum practice it’s essential to give a new meaning to conceptual, theoretical, technical and practical limits and to bring to discussion the contradictions, conflicts and doubts which emerge in action. Focusing the contradiction between knowledge and practice in the traditional psychiatric model and in the anti-asylum model, we analysed the objective/subjective conflict emerging in the context of work and related mainly to the conception of madnees, the building-up of a multiprofessional team and the education of mental health workers in the developement of a practice based on the anti-asylum principles. Our findings show that the contradictions (madness/mental illness X mental health, madness/unreason X reason, abnormality/pathology X normality, knowledge X non-knowledge, medical X non medical model, therapeutic X non therapeutic) that result from the break of the asylum model foster a process of indiscrimination emerging in the inter subjective relationship and have the effect of loss of limits (workers X users, technician X non-technician, neurosis X psychosis, efficiency X inefficiency of techiniques, public X private). Thus the construction of these new model, linked to the ‘disconstruction’ of an asylum model, is a complexe task that cannot be restricted to the bounds of practice, since it has contradiction which are inherente to the social system from which it derives (bourgeoisie X workers, social movements X state, global society X health institution, institution X workers, workers in mental health X users/family and users X family).

Cocaine is a plant-based illicit drug commonly involved in substance use disorder. Although cocaine overdose and cocaine use disorders cause adverse health consequences to individuals and the economic burden on their family and society, there are no FDA (Food and Drug Administration) approved medications for treatment. Recently, it has been recognized that delivery of cocaine hydrolase (CocH) is a promising therapeutic strategy. Human butyrylcholinesterase (hBChE), the primary enzyme involved in cocaine metabolism in human, have advantages over other candidates for the development of CocH. Previous studies in our laboratory have designed and characterized hBChE mutants that have ~4,000-fold improved catalytic efficiency against naturally occurring (-)-cocaine as compared to the wild-type hBChE. Besides the catalytic efficiency, the biological half-life is another essential factor that influences the desired therapeutic value in the long-term treatment of cocaine use disorder. In order to provide prolonged effects to reduce administration frequency in clinical use, efforts have been made to increase the retention time of CocHs in blood circulation by fusing CocHs with other thermostable proteins or their mutants, including human serum albumin (Albu) or the Fc region of the human IgG (Fc). In this dissertation, we demonstrated the clinical potential and the benefits of long-lasting CocHs for cocaine overdose treatment. We used rodent models to show the ability of AlbuCocH1 to block or reverse manifestations of toxic effects of cocaine. In addition, a concomitant LC-MS/MS-based analysis was conducted to investigate the pharmacokinetic profile of a lethal dose of cocaine with the presence of AlbuCocH1. These experimental data demonstrated AlbuCocH1 as an effective cocaine detoxification agent by accelerating the metabolism of cocaine. In order to examine the potential therapeutic value of Fc-fused CocHs in the treatment of cocaine use disorder, we conducted a series of behavioral experiments in rats to evaluate the effectiveness and duration of Fc-fused CocHs in blocking or attenuating cocaine-induced psychostimulant and discriminative stimulus effects. In addition, the intravenous self-administration model was used to investigate the long-term effectiveness of Fc-fused CocHs in blocking or attenuating the reinforcing effects of cocaine. It has been shown that a single dose of E30-6-Fc (3 mg/kg) was able to effectively alter the cocaine dose-response curve and attenuate the reinforcing efficacy of cocaine for at least a month in both male and female rats. In summary, AlbuCocH1 (TV-1380), which failed to meet the primary efficacy endpoint in clinical trials for facilitating abstinence in cocaine-dependent subjects with a weekly dosing schedule (due to the short biological half-life), is more suitable to be developed as a cocaine detoxification agent. On the contrary, the newly designed Fc-fused CocH (e.g. CocH3-Fc, E30-6-Fc) with higher catalytic efficiency and longer biological half-life will be beneficial for long-term abstinence management in cocaine-dependent individuals.

Adolescence and young adulthood are the periods of development associated with the highest amount of risk-taking. One theory, the Dual-Systems model, suggests that this could be due to an imbalance in the maturation of two brain systems: reward appraisal, which matures first, and cognitive control, which matures later. This imbalance may be the cause of adolescents’ tendency to favor immediate rewards, disregarding consequences. Depressed adolescents, however, behave differently. While it is not exactly clear whether they take more risks or fewer risks, depressed adolescents display different interactions and decision making with their peers than non-depressed adolescents. This study attempted to use these patterns of behavior already identified in previous research to predict where an adolescent would fall on a depression continuum based on their Self-Focused and Other-Focused risk behaviors. Results did not find a link between depression and either type of risk. Results may be inconclusive due to issues within the data and data collection process.

<p>In this study, we have addressed the serotonergic and the opioid system within the CNS. Both systems are of outmost importance in the etiology of disease states, especially mental disorders. </p><p>In our investigation of the serotonergic system, we have synthesized novel enantiomerically pure 6-aryl-3-amino- and 8-aryl-3-aminochromans as ligands for the 5-HT₇ receptor. One reason for the lack of understanding of the physiological functionality of the serotonin 5-HT₇ receptor, the most recently discovered member of the serotonin receptor family, is the absence of partial agonists and agonists. In this series, we have identified partial agonists with more than189 fold selectivity over the 5-HT_1Areceptor and one agonist with 29 fold greater selectivity over the serotonin 5-HT_1Areceptor. Thus the present series constitutes a starting point for developing highly selective ligands for the 5-HT₇ receptor. </p><p>In our investigation of the opioid system, our focus has been on the natural product salvinorin A, which is a highly selective kappa opioid receptor agonist. In the total synthesis of salvinorin A, we have accomplished the synthesis of a key intermediate, 6-(3-furyl)-4-methyl-5,6-dihydro-pyran-2-one via ring closing metathesis. Furthermore, synthetic methodologies have been developed as a part of the total synthesis. Several lipases have been screeened for their ability to generate enantiomerically pure 1-(3-Furyl)-3-buten-1-ol via bio-catalyzed hydrolysis of the corresponding acetate. The lipase from <i>Pseudomonas fluorescens</i> was identified as having stereoselectivity high enough to generate a % <i>ee </i>value above 98%. We have also developed a route for the introduction of a hydroxyl functionality in the γ position of α,β-unsaturated cyclic ketones by the regioselective oxidation of 1-silyloxy-1,3-dienes using dimethyldioxirane. We have initiated the investigation of the pharmacophore responsible for the kappa opioid activity by synthesizing simplified analogues of salvinorin A. A synthetic route providing easy access to simplified analogues of salvinorin A have been established.</p>

In this study, we have addressed the serotonergic and the opioid system within the CNS. Both systems are of outmost importance in the etiology of disease states, especially mental disorders. In our investigation of the serotonergic system, we have synthesized novel enantiomerically pure 6-aryl-3-amino- and 8-aryl-3-aminochromans as ligands for the 5-HT7 receptor. One reason for the lack of understanding of the physiological functionality of the serotonin 5-HT7 receptor, the most recently discovered member of the serotonin receptor family, is the absence of partial agonists and agonists. In this series, we have identified partial agonists with more than189 fold selectivity over the 5-HT1A receptor and one agonist with 29 fold greater selectivity over the serotonin 5-HT1A receptor. Thus the present series constitutes a starting point for developing highly selective ligands for the 5-HT7 receptor. In our investigation of the opioid system, our focus has been on the natural product salvinorin A, which is a highly selective kappa opioid receptor agonist. In the total synthesis of salvinorin A, we have accomplished the synthesis of a key intermediate, 6-(3-furyl)-4-methyl-5,6-dihydro-pyran-2-one via ring closing metathesis. Furthermore, synthetic methodologies have been developed as a part of the total synthesis. Several lipases have been screeened for their ability to generate enantiomerically pure 1-(3-Furyl)-3-buten-1-ol via bio-catalyzed hydrolysis of the corresponding acetate. The lipase from Pseudomonas fluorescens was identified as having stereoselectivity high enough to generate a % ee value above 98%. We have also developed a route for the introduction of a hydroxyl functionality in the γ position of α,β-unsaturated cyclic ketones by the regioselective oxidation of 1-silyloxy-1,3-dienes using dimethyldioxirane. We have initiated the investigation of the pharmacophore responsible for the kappa opioid activity by synthesizing simplified analogues of salvinorin A. A synthetic route providing easy access to simplified analogues of salvinorin A have been established.

This article examines the stability of symptoms, syndromes, and diagnoses of specific anxiety and depressive disorders, as well as diagnostic shifts from one syndrome to another over time. Using retrospective and longitudinal prospective data from the baseline and first follow-up investigation (19.7 months later) of the Early Developmental Stages of Psychopathology Study (EDSP), we focus on establishing stability measures for early stages of mental disorders in a community sample of adolescents aged 14 to 17 years at baseline. The results are as follows: (1) Although only about 30% developed a full-blown DSM-IV disorder, psychopathological syndromes are widespread in adolescents: 15% of the population aged 14 to 17 at baseline were not affected by at least some clinically relevant symptoms of mental disorders either throughout their previous life or throughout the follow-up period. (2) The likelihood of staying free of symptoms and threshold disorders during follow-up was highest among subjects who were completely well at baseline. The probability of a positive outcome decreased as a function of severity of baseline diagnostic status. (3) There was a considerable degree of fluctuation not only in the diagnostic status and severity of specific disorders, but also in terms of complete remissions and shifts from one syndrome and disorder to another. (4) Anxiety disorders, overall, slightly differ with regard to the persistence and stability of the diagnostic status from depressive disorders. (5) However, there were remarkable differences between specific types of anxiety and depressive disorders. Consistent with other longitudinal epidemiological studies in the general population, this study finds that the syndromes and diagnoses of mental disorders have a strong tendency to wax and wane over time in this age group.

Background: When assessing the association between a factor X and a subsequent outcome Y in observational studies, the question that arises is what are the variables to adjust for to reduce bias due to confounding for causal inference on the effect of X on Y. Disregarding such factors is often a source of overestimation because these variables may affect both X and Y. On the other hand, adjustment for such variables can also be a source of underestimation because such variables may be the causal consequence of X and part of the mechanism that leads from X to Y. Methods: In this paper, we present a simple method to compute control variables in the presence of age at onset data on both X and a set of other variables. Using these age at onset data, control variables are computed that adjust only for conditions that occur prior to X. This strategy can be used in prospective as well as in survival analysis. Our method is motivated by an argument based on the counterfactual model of a causal effect. Results: The procedure is exemplified by examining of the relation between panic attack and the subsequent incidence of MDD. Conclusions: The results reveal that the adjustment for all other variables, irrespective of their temporal relation to X, can yield a false negative result (despite unconsidered confounders and other sources of bias).

The aim of this doctoral thesis is to – from a child perspective and with children as informants – describe and analyze childhood conditions for children whose parents suffer from severe mental illness. The method used is qualitative – 28 children, 10 boys and 18 girls, 7–18 years old, were interviewed about their parents’ mental disorder; the family situation and their own personal life – in school and during free time. The analyses are based on Sociology of Childhood and Family Sociology. Previous studies have, to a great extent, focused on the risk the children run of developing mental health- and social problems and what helps them to grow up healthy. The increased risk of mental health- and social problems has been well confirmed, but also that preventive interventions can contribute to resilience in the children. Although some studies have explored children’s experiences of their parents’ mental illness and the challenges they meet, research from a childhood perspective, has so far been scarce. The results of this study reveal different degrees of emotional, physical and social exposure for the children. Their childhood conditions were related to gender, relations, communication, problem load and social situation of the family. If the parent with a mental illness was a woman, the situation for the child was often more exposed than if it was the father – most likely due to parental roles and expectations on men and women in the Swedish society at that time. Girls seemed more emotionally involved in the parents’ problems than boys, especially if the parent with a mental illness was a father. Most of the parents were divorced or had never lived together. Parental conflicts complicated the life of the children, who were expected to have maintained relationships to both parents. Lack of communication about the parent’s mental disorder in - and outside the family - was common. The children were often uninformed about the parent’s problems.  If hindered to pass information between and outside their two homes, they were left to handle difficult, sometimes dangerous, situations with the mentally ill parent, alone. The home was not always the safe place for rest and recovery, as homes are expected to be. The heavier the total problem load of the family, the more exposed was the child. Most exposed were children whose both parents had severe problems – mental illness or addiction. They were often placed in out of home care, for longer or shorter periods. The kind and degree of exposure the children experienced varied. Four kinds of childhood sceneries could be recognized: (1) the well organized childhood, where the parent’s mental health problem was mainly an emotional burden for the children; (2) the complicated childhood, where the parents conflicts and inability to protect the child made the child either too involved or too lonely in handling the problems that the parent’s mental illness caused them; (3) the problematic childhood where the parent’s mental illness was not the only problem in the family, but factors like the other parent’s drinking, siblings’ problems, social and economical difficulties added to the burden and (4) the exposed childhood where none of the parents was able to take care of the child. Knowledge and openness, about the parents’ problems, seemed to increase competence and decrease feelings of guilt and responsibility for the parent. All of the children stood forward, not as passive victims, but as competent agents in their own lives – although often more or less powerless because of their dependence of their parents and other adults around them. It was clear, though, that there is a need for professionals in adult psychiatry, social services, school and preschool, to pay attention to the children of parents with mental health problems and see to that they get the information and support they need. Keywords: Children, childhood conditions, children as agents, parental mental illness/mental disorders, mental health knowledge, exposed life situations, competence.