Polygenic Interactions with Environmental Adversity in the Aetiology of Major Depressive Disorder

Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD. The RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them. PRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10−6). SLEs and CT were also associated with MDD status (p = 2.19 × 10−4 and p = 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples. CT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.

Harmonised framework for ecological risk assessment of sediments from ports and estuarine zones of North and South Atlantic

This paper presents a harmonised framework of sediment quality assessment and dredging material characterisation for estuaries and port zones of North and South Atlantic. This framework, based on the weight-of-evidence approach, provides a structure and a process for conducting sediment/dredging material assessment that leads to a decision. The main structure consists of step 1 (examination of available data); step 2 (chemical characterisation and toxicity assessment); decision 1 (any chemical level higher than reference values? are sediments toxic?); step 3 (assessment of benthic community structure); step 4 (integration of the results); decision 2 (are sediments toxic or benthic community impaired?); step 5 (construction of the decision matrix) and decision 3 (is there environmental risk?). The sequence of assessments may be interrupted when the information obtained is judged to be sufficient for a correct characterisation of the risk posed by the sediments/dredging material. This framework brought novel features compared to other sediment/dredging material risk assessment frameworks: data integration through multivariate analysis allows the identification of which samples are toxic and/or related to impaired benthic communities; it also discriminates the chemicals responsible for negative biological effects; and the framework dispenses the use of a reference area. We demonstrated the successful application of this framework in different port and estuarine zones of the North (Gulf of Cadiz) and South Atlantic (Santos and Paranagua Estuarine Systems).

Distribution and behavior of manganese in the Alto do Paranapanema Basin

This paper reports manganese (Mn) fractionation in samples collected from the water column and sediments in an environmental protection area in the Alto do Paranapanema Basin (Sao Paulo State, Brazil). The three locations studied showed equivalent Mn levels, with moderate seasonal differences (p < 0.05). The sediment samples contained five Mn species (p < 0.05): iron and manganese (hydr)oxides > Mn bound to carbonates approximate to exchangeable Mn approximate to Mn bound to silicates > Mn bound to organic matter (p < 0.05). The water samples contained three species (p < 0.05): particulate Mn > labile Mn approximate to non-labile Mn. The data suggest that Mn has a natural origin (Enrichment Factor EF < 2; Geoaccumulation Index I(geo) < 0) and moderate environmental risk (Risk Assessment Code RAC similar to 30%). At the same time, under certain conditions some manganese species could be present in a state of equilibrium between the water column and sediment. These results could provide a basis for Mn management in the Alto do Paranapanema Basin.

Prevalence of Parkinson’s disease in metropolitan and rural Queensland: A general practice survey

The prevalence of idiopathic Parkinson’s disease (IPD) in Australia is unclear. We estimated the prevalence of IPD, and other forms of parkinsonism, through the study of typical caseloads in general practice. A random sample of general practitioners (GPs) throughout Queensland (401 responses from 528 validated practice addresses) was asked to estimate the numbers of patients with IPD and parkinsonism seen in the preceding year. The estimated prevalence of diagnosed IPD in Queensland was 146 per 100 000 (95% CI = 136–155). A further 51 per 100 000 in the population were suspected by doctors to have IPD without formal diagnosis, whereas another 51 per 100 000 people may have non-idiopathic parkinsonism. Idiopathic Parkinson’s disease was more common in rural than metropolitan areas. Although most GPs were confident in making diagnoses of IPD, the majority had little or no confidence in their ability to treat the disease, especially in its later stages. Support from neurologists was perceived by GPs to be very good in cities, but poor in remote areas.

Development of an IgG4-Based Predictor of Endemic Pemphigus Foliaceus (Fogo Selvagem)

Fogo selvagem (FS) is mediated by pathogenic, predominantly IgG4, anti-desmoglein 1 (Dsg1) autoantibodies and is endemic in Limao Verde, Brazil. IgG and IgG subclass autoantibodies were tested in a sample of 214 FS patients and 261 healthy controls by Dsg1 ELISA. For model selection, the sample was randomly divided into training (50%), validation (25%), and test (25%) sets. Using the training and validation sets, IgG4 was chosen as the best predictor of FS, with index values above 6.43 classified as FS. Using the test set, IgG4 has sensitivity of 92% (95% confidence interval (95% CI): 82-95%), specificity of 97% (95% CI: 89-100%), and area under the curve of 0.97 ( 95% CI: 0.94-1.00). The IgG4 positive predictive value (PPV) in Limao Verde (3% FS prevalence) was 49%. The sensitivity, specificity, and PPV of IgG anti-Dsg1 were 87, 91, and 23%, respectively. The IgG4-based classifier was validated by testing 11 FS patients before and after clinical disease and 60 Japanese pemphigus foliaceus patients. It classified 21 of 96 normal individuals from a Limao Verde cohort as having FS serology. On the basis of its PPV, half of the 21 individuals may currently have preclinical FS and could develop clinical disease in the future. Identifying individuals during preclinical FS will enhance our ability to identify the etiological agent(s) triggering FS.

Childhood Trauma and Children`s Emerging Psychotic Symptoms: A Genetically Sensitive Longitudinal Cohort Study

Objective: Using longitudinal and prospective measures of trauma during childhood, the authors assessed the risk of developing psychotic symptoms associated with maltreatment, bullying, and accidents in a nationally representative U. K. cohort of young twins. Method: Data were from the Environmental Risk Longitudinal Twin Study, which follows 2,232 twin children and their families. Mothers were interviewed during home visits when children were ages 5, 7, 10, and 12 on whether the children had experienced maltreatment by an adult, bullying by peers, or involvement in an accident. At age 12, children were asked about bullying experiences and psychotic symptoms. Children`s reports of psychotic symptoms were verified by clinicians. Results: Children who experienced maltreatment by an adult (relative risk=3.16, 95% CI=1.92-5.19) or bullying by peers (relative risk=2.47, 95% CI=1.74-3.52) were more likely to report psychotic symptoms at age 12 than were children who did not experience such traumatic events. The higher risk for psychotic symptoms was observed whether these events occurred early in life or later in childhood. The risk associated with childhood trauma remained significant in analyses controlling for children`s gender, socioeconomic deprivation, and IQ; for children`s early symptoms of internalizing or externalizing problems; and for children`s genetic liability to developing psychosis. In contrast, the risk associated with accidents was small (relative risk=1.47, 95% CI=1.02-2.13) and inconsistent across ages. Conclusions: Trauma characterized by intention to harm is associated with children`s reports of psychotic symptoms. Clinicians working with children who report early symptoms of psychosis should inquire about traumatic events such as maltreatment and bullying.

Effects of childhood development on late-life mental disorders

Purpose of review To explore recent findings bridging childhood development and common late-life mental disorders in the elderly. Recent findings We addressed aging as a part of the developmental process in central nervous system, typical and atypical neurodevelopment focusing on genetic and environmental risk factors and their interplay and links between psychopathology from childhood to the elderly, unifying theoretical perspectives and preventive intervention strategies. Summary Current findings suggest that childhood development is strictly connected to psychiatric phenotypes across the lifespan. Although we are far from a comprehensive understanding of mental health trajectories, some initial findings document both heterotypic and homotypic continuities from childhood to adulthood and from adulthood to the elderly. Our review also highlights the urgent need for investigations on preventive interventions in individuals at risk for mental disorders.

An integrative approach for studying the etiology of alcoholism and other addictions

Studies of alcoholism etiology often focus on genetic or psy-chosocial approaches, but not both. Greater understanding of the etiology of alcohol, tobacco and other addictions will come from integration of these research traditions. A research approach is outlined to test three models for the etiology of addictions — behavioral undercontrol, pharmacologic vulnerability, negative affect regulation — addressing key questions including (i) mediators of genetic effects, (ii) genotype-environment correlation effects, (iii) genotype x environment interaction effects, (iv) the developmental unfolding of genetic and environmental effects, (v) subtyping including identification of distinct trajectories of substance involvement, (vi) identification of individual genes that contribute to risk, and (vii) the consequences of excessive use. By using coordinated research designs, including prospective assessment of adolescent twins and their siblings and parents; of adult substance dependent and control twins and their MZ and DZ cotwins, the spouses of these pairs, and their adolescent offspring; and of regular families; by selecting for gene-mapping approaches sibships screened for extreme concordance or discordance on quantitative indices of substance use; and by using experimental (drug challenge) as well as survey approaches, a number of key questions concerning addiction etiology can be addressed. We discuss complementary strengths and weaknesses of different sampling strategies, as well as methods to implement such an integrated approach illustrated for the study of alcoholism etiology. A coordinated program of twin and family studies will allow a comprehensive dissection of the interplay of genetic and environmental risk-factors in the etiology of alcoholism and other addictions.

Applying statistical approaches in the dissection of genes versus environment for asthma and allergic disease

Now that some of the genes involved in asthma and allergy have been identified, interest is turning to how genetic predisposition interacts with exposure to environmental risk factors. These questions are best answered by studies in which both genotypes and other risk factors are measured, but even simpler studies, in which family history is used as a proxy for genotype, have made suggestive findings. For example, early breast feeding may increase the risk of allergic disease in genetically susceptible children, and decrease the risk of 'sporadic' allergy. This review also addresses the overall importance of genetic causes of allergic disease in the general population.

Estimating Two-Stage Models for Genetic Influences on Alcohol, Tobacco or Drug Use Initiation and Dependence Vulnerability in Twin and Family Data

Genetic research on risk of alcohol, tobacco or drug dependence must make allowance for the partial overlap of risk-factors for initiation of use, and risk-factors for dependence or other outcomes in users. Except in the extreme cases where genetic and environmental risk-factors for initiation and dependence overlap completely or are uncorrelated, there is no consensus about how best to estimate the magnitude of genetic or environmental correlations between Initiation and Dependence in twin and family data. We explore by computer simulation the biases to estimates of genetic and environmental parameters caused by model misspecification when Initiation can only be defined as a binary variable. For plausible simulated parameter values, the two-stage genetic models that we consider yield estimates of genetic and environmental variances for Dependence that, although biased, are not very discrepant from the true values. However, estimates of genetic (or environmental) correlations between Initiation and Dependence may be seriously biased, and may differ markedly under different two-stage models. Such estimates may have little credibility unless external data favor selection of one particular model. These problems can be avoided if Initiation can be assessed as a multiple-category variable (e.g. never versus early-onset versus later onset user), with at least two categories measurable in users at risk for dependence. Under these conditions, under certain distributional assumptions., recovery of simulated genetic and environmental correlations becomes possible, Illustrative application of the model to Australian twin data on smoking confirmed substantial heritability of smoking persistence (42%) with minimal overlap with genetic influences on initiation.

A critique of evaluated adolescent smoking cessation programmes

Rates of adolescent smoking appear to be on the increase, with a number of authors documenting increases in the 1990's. However, the issue of prevention rather than cessation has received greater attention in tobacco control programmes among youth. This review provides details of published school based and other tobacco cessation programmes for adolescents and compares their efficacy. Variations in outcome measures were noted with the programmes. Environmental risk factors such as economic deprivation, concurrent use of alcohol and illicit substances and a minority ethnic background have been associated with greater smoking rates among youth. It is suggested that tobacco cessation initiatives need to be considered in the context of improving adolescents lifestyle choices. Specific cessation programmes should also address issues such as appropriate follow-up and validation. (C) 2002 The Association for Professionals in Services for Adolescents. Published by Elsevier Science Ltd. All rights reserved.

The genetics of coronary heart disease: the contribution of twin studies

Despite the decline in coronary heart disease in many European countries, the disease remains an enormous public health problem. Although we know a great deal about environmental risk factors for coronary heart disease, a heritable component was recognized a long time ago. The earliest and best known examples of how our genetic constitution may determine cardiovascular risk relate to lipoprotein(a), familial hypercholesterolaemia and apolipoprotein E. In the past 20 years a fair number of polymorphisms assessed singly have shown strong associations with the disease but most are subject to poor repeatability. Twins constitute a compelling natural experiment to establish the genetic contribution to coronary heart disease and its risk factors. GenomEUtwin, a recently funded Framework 5 Programme of the European Community, affords the opportunity of comparing the heritability of risk factors in different European Twin Registries. As an illustration we present the heritabilities of systolic and diastolic blood pressure, based on data from over 4000 twin pairs from six different European countries and Australia. Heritabilities for systolic blood pressure are between 52 and 66% and for diastolic blood pressure between 44 and 66%. There is no evidence of sex differences in heritability estimates and very little to no evidence for a significant contribution of shared family environment. A non-twin based prospective case/cohort study of coronary heart disease and stroke (MORGAM) will allow hypotheses relating to cardiovascular disease, generated in the twin cohorts, to be tested prospectively in adult populations. Twin studies have also contributed to our understanding of the life course hypothesis, and GenomEUtwin has the potential to add to this.

Qualidade da água da lagoa Juara (Serra/ES) : avaliações físicas, químicas e respostas fisiológicas e citogenéticas em plantas

A gestão dos recursos hídricos necessita da integração entre os critérios físicos e químicos, e os aspectos bióticos, os quais possibilitam identificar os efeitos combinados de substâncias e avaliar suas influências. Os sistemas testes Allium cepa e Tradescantia pallida, são utilizados para o estudo da poluição aquática a partir de aspectos citogenéticos. Além destes biomarcadores, os teores de clorofila também são utilizados em estudos de estresse devido ao reflexo a múltiplos fatores. Assim, o objetivo deste trabalho foi avaliar a qualidade da água da lagoa Juara (Município de Serra/ES) pela análise integrada de aspectos físicos, químicos e ecotoxicológicos a partir de estudos citogenéticos em A. cepa e T. pallida, e fotossintéticos nesta última espécie. Foram definidas três estações amostrais ao longo da lagoa e a partir de amostras de água foram analisados parâmetros tais como condutividade, oxigênio dissolvido, concentração de nutrientes e metais. A determinação dos metais ocorreu por análises de espectrometria de massa. O teste do A. cepa foi realizado a partir sementes germinadas em amostras de água da lagoa. Com plantas de T. pallida, foi realizado o ensaio da mitose em ponta de raiz de T. pallida e dosado os teores de pigmentos cloroplastídicos em folhas totalmente expandidas. Para tanto, foi realizado ensaio utilizando-se a água da lagoa como solvente para solução de Hoagland onde estacas previamente enraizadas de T. pallida foram expostas durante 24 horas e 40 dias para as avaliações citogenéticas e fotossintéticas, respectivamente. Foi realizado novo teste do A. cepa nas águas da lagoa após os 40 dias de ensaio para aferir a manutenção das propriedades químicas das amostras. A avaliação citogenética nas duas espécies envolveu a análise dos índice mitótico (IM), índice de aberrações cromossômicas (AC) e frequência de micronúcleos (MN). Para a análise estatística foi utilizada a análise de variância seguida pelo teste de Tukey (p < 0.05) para a comparação dos tratamentos durante a mesma campanha, e teste de Bonferroni (p < 0,05) para a comparação entre as campanhas. Os resultados físicos e químicos mensurados demonstram que a lagoa Juara apresenta indícios de eutroficação artificial. Duas estações amostrais, em pelo menos uma campanha amostral, apresentaram potenciais citotóxico, genotóxico e mutagênico. Todavia, esses potenciais não demonstram relação com os teores de Fe e Mn quantificados, levando a crer que tais pontos apresentam outros potenciais poluentes. Os danos citogenéticos observados apresentaram efeitos maximizados durante a segunda campanha, demostrando o efeito do período de chuva na intensificação da poluição nesse ambiente. O estudo do metabolismo fotossintético em T. pallida, demonstrou os teores de pigmentos cloroplastídicos relacionados ao elevado aporte de nutrientes presentes nas estações J2 e J3. Sendo o excesso destes, o provável responsável pelo teor inferior de pigmentos em J3. Observa-se que os ensaios com A. cepa e T. pallida responderam de maneira fidedigna ao risco potencial do ambiente, complementando as análises físicas e químicas usualmente utilizadas na avaliação da qualidade da água de ambientes lacustres.

Estudo do sobre o impacto do risco biológico e ambiental na qualidade da interacção mãe-filho(a)

O presente estudo exploratório tem como principais objectivos: averiguar o impacto do risco biológico e ambiental, ou ambos, na interacção mãe-filho(a), e contribuir para a adaptação de uma escala de observação da qualidade da interacção mãe-filho(a) em interacção livre. Para o efeito observámos 40 díades mãe-filho(a) em jogo livre distribuídas por 4 grupos de estudo: o primeiro grupo composto por 14 díades sem condições assinaláveis de risco, o segundo grupo composto por 8 díades assinaláveis de risco biológico, o terceiro grupo composto por 7 díades em risco ambiental e por fim, o quarto grupo por 10 díades em risco ambiental e biológico. A recolha de dados foi realizada nos concelhos do Porto e Viseu. A qualidade de interacção foi inicialmente observada em 50 casos com a Escala de Comportamentos Interactivos dos bebés e das mães em jogo livre (Fuertes, Faria, Oliveira-Costa & Soares, 2010), tendo sido posteriormente adaptada para condições de risco tomando a designação de escala Escala de Avaliação de Comportamentos Interactivos mãe-filho(a)-Adaptada para Condições de Risco (Fuertes & Canelhas, 2011). Os comportamentos maternos e infantis foram cotados, independentemente, relativamente à expressão facial, expressão vocal, expressão afectiva, posicionamento, directividade e jogo. Os resultados foram analisados com recurso a estatística descritiva e multinominal. Os resultados do nosso estudo sugerem que as díades sem condições de risco tinham interacções mais positivas, recíprocas e ajustadas à idade das crianças, do que as díades sujeitas, quer a situações de risco biológico, quer a condições de risco ambiental. Adicionalmente, verificámos que alguns factores demográficos (e.g., risco na gravidez, área de residência, estabilidade profissional das mães e a frequência de creche (em oposição a amas) afectam a qualidade da interacção mãe-filho(a). Por fim, encontramos uma forte concordância entre as duas escalas, sugerindo que a nossa escala (Escala de Avaliação de Comportamentos Interactivos mãe-filho(a)-Adaptada para Situações de Risco), tem indicadores capazes de captar a natureza interactiva do jogo mãe-filho(a) e deverá ser validada.

Síndroma dos edifícios doentes: estudo da qualidade do ar interior e despiste da eventual existência de SED entre a população do edifício “E” de um estabelecimento de ensino superior

Mestrado em Segurança e Higiene no Trabalho.