Intervenção psicomotora nas perturbações do espectro do autismo na Associação Portuguesa para as Perturbações do Desenvolvimento e Autismo, APPDA, de Lisboa

O presente relatório descreve as atividades de estágio desenvolvidas no âmbito do Mestrado em Reabilitação Psicomotora, Ramo de Aprofundamento de Competências Profissionais, da Faculdade de Motricidade Humana, realizado na Associação Portuguesa para as Perturbações do Desenvolvimento e Autismo (APPDA) - Lisboa, justamente no Centro de Atividades Ocupacionais (CAO) com 47 jovens e adultos e no Centro de Recursos para a Inclusão (CRI) com 21 crianças e jovens, alunos de seis escolas do ensino regular, integrados em Unidades de Ensino Estruturado para o Autismo (UEEA). O estágio profissionalizante desenrolou-se mediante sessões de intervenção psicomotora em ginásio e meio aquático, em contexto de grupo ou individual acompanhando crianças, jovens e adultos com Perturbações do Desenvolvimento e da Aprendizagem, com maior incidência com Perturbações do Espectro do Autismo. O relatório apresenta o enquadramento teórico, legal e institucional e realização da prática profissional, sendo descritos cinco estudos de caso, enquanto modelos exemplificativos do trabalho desenvolvido, adicionando-se uma reflexão acerca da experiência de estágio. Para cada estudo-caso encontra-se descrito o processo de avaliação, estabelecimento de objetivos, programa pedagógico-terapêutico, resultados e respetiva análise. Da referida intervenção foi possível constatar melhorias, tanto a nível psicomotor como emocional e comportamental, sugerindo os benefícios do contributo da intervenção psicomotora nas Perturbações do Desenvolvimento e Aprendizagem.

Associations between psychiatric disorders and cardiovascular risk factors

Bien que de nombreuses études suggèrent des liens entre les troubles psychiatriques et les maladies cardiovasculaires (MCV), peu ont utilisé des investigations somatique, biologique et psychiatrique adéquates. Pour déterminer les potentiels mécanismes impliqués dans ces associations, plusieurs études ont investigué le lien entre les troubles psychiatriques et les facteurs de risque des maladies cardiovasculaires (FRCV) (surpoids, diabète, dyslipidémie, hypertension artérielle, inactivité, consommation de cigarettes). De plus, des biomarqueurs (régulateurs du métabolisme, marqueurs hépatiques et inflammatoires) pouvant être associés à la fois aux troubles psychiatriques et aux FRCV ont été étudiés mais avec des résultats contradictoires. Basée sur un large échantillon de la population générale de la Ville de Lausanne et des investigations somatique et psychiatrique adéquates, cette thèse comporte deux articles: le premier étudie l'association entre les troubles psychiatriques majeurs et les FRCV; le second établit les liens entre certains biomarqueurs et le développement du diabète de type 2. Appliquant une méthodologie rigoureuse sur un échantillon de 3716 sujets de la population lausannoise âgés de 35 à 66 ans, les résultats du premier article ont montré que 1) le sous-type atypique de la dépression était associé à une augmentation du risque de souffrir de plusieurs FRCV (surpoids, diabète et syndrome métabolique), contrairement à d'autres sous-types de dépression, 2) les problèmes d'alcool étaient associés à un risque accru de souffrir de diabète et de dyslipidémie, 3) presque tous les troubles psychiatriques étaient associés à une consommation régulière de cigarettes. Quant au deuxième article, parmi les différents biomarqueurs testés, seul un niveau bas d'adiponectine (une hormone produite par le tissu adipeux qui affecte la sensibilité à l'insuline) était associé à un risque accru de souffrir de diabète par la suite. Ces résultats soulignent la nécessité pour les spécialistes de distinguer les sous-types de dépression pour le risque cardiovasculaire et de donner une attention particulière au sous-type atypique. Un problème d'alcool comorbide pourrait accroître le risque cardiovasculaire. De plus, des efforts pour diminuer la cigarette chez les sujets souffrant de troubles psychiatriques seraient une mesure préventive importante contre le développement des MCV. Le rôle de l'adiponectine dans l'association entre les troubles psychiatriques et les FRCV restant incertain, une prochaine analyse devrait déterminer le lien entre ce biomarqueur et la dépression atypique. - Despite the fact that several studies have highlighted associations between psychiatric disorders and cardiovascular diseases (CVD), few have used adequate somatic, biological and psychiatric measures. To determine potential mechanisms implicated in these associations, several studies have assessed the relationship between psychiatric disorders and cardiovascular risk factors (CVRFs), such as overweight, diabetes, dyslipidemia, hypertension, physical inactivity and smoking. Moreover, biomarkers such as metabolic regulators, hepatic and inflammatory markers, which could be associated with both psychiatric disorders and CVRFs, have been studied yielding contradictory results. Based on a population-based sample from the city of Lausanne and using adequate somatic and psychiatric investigations, this dissertation encompasses two articles: the first studies the associations between major psychiatric disorders established for lifetime and CVRFs; the second studies the associations between certain biomarkers and the development of type 2 diabetes. Using standardized contemporary methodology in a sample composed of 3716 individuals aged from 35 to 66 years, the first article revealed associations between 1) the atypical depression subtype and an increased risk of several CVRFs (overweight, diabetes and the metabolic syndrome) in contrast to other depression subtypes; 2) alcohol disorders and an increased risk of diabetes and dyslipidemia; 3) almost all psychiatric disorders and a lifetime history of regular cigarette smoking. The second article showed, among the various biomarkers tested, that only lower levels of adiponectin (a hormone produced by adiposity which affects sensitivity to insulin) were associated with an increased risk of subsequent type 2 diabetes. Our results highlight the need for specialists to subtype depression when studying the cardiovascular risk and to pay particular attention to the atypical subtype. A comorbid alcohol misuse may further increase the cardiovascular risk. Moreover, efforts to diminish smoking in subjects suffering from psychiatric disorders could be an important tool for preventing subsequent CVD. The role of adiponectin in the association between psychiatric disorders and CVRFs should still be elucidated, and future analyses should focus in particular on the relationship between this biomarker and atypical depression.

Regression, developmental trajectory and associated problems in disorders in the autism spectrum: the SNAP study

We report rates of regression and associated findings in a population derived group of 255 children aged 9-14 years, participating in a prevalence study of autism spectrum disorders (ASD); 53 with narrowly defined autism, 105 with broader ASD and 97 with non-ASD neurodevelopmental problems, drawn from those with special educational needs within a population of 56,946 children. Language regression was reported in 30% with narrowly defined autism, 8% with broader ASD and less than 3% with developmental problems without ASD. A smaller group of children were identified who underwent a less clear setback. Regression was associated with higher rates of autistic symptoms and a deviation in developmental trajectory. Regression was not associated with epilepsy or gastrointestinal problems.

Families with Children with Autism, Developmental Delay, and Typical Development: The Relationships of Parenting Self-Efficacy, Parenting Strategies, and Child Problem Behaviour

Parents of children with autism spectrum disorders (ASD) and developmental delays (DD) may experience more child problem behaviours, report lower parenting selfefficacy (PSE), and be more reactive than proactive in their parenting strategies than those who have children with typical development (TD). Differences in PSE and parenting strategies may also influence the extent to which child problem behaviours are experienced by parents who have children with ASD and DD, compared to those who have children with TD. Using a convenience sample of parents of children with ASD (n = 48), DD (n = 51), and TD (n = 72), this study examined group differences on three key variables: PSE, parenting strategies, and child problem behaviour. Results indicated that those in the DD group scored lower on PSE in preventing child problem behaviour than the ASD group. The TD group used fewer reactive strategies than the DD group, and fewer proactive strategies than both the ASD and DD groups. For the overall sample, higher reactive strategies use was found to predict higher ratings of child problem behaviour, while a greater proportion of proactive to reactive strategies use predicted lower ratings of child problem behaviour. PSE was found to moderate DD diagnosis and child problem behaviour. Implications for a behavioural (i.e., parenting strategies) or cognitive (i.e., PSE) approach to parenting are discussed.

Research review: reading comprehension in developmental disorders of language and communication

Background: Deficits in reading airment (SLI), Down syndrome (DS) and autism spectrum disorders (ASD). Methods: In this review (based on a search of the ISI Web of Knowledge database to 2011), the Simple View of Reading is used as a framework for considering reading comprehension in these groups. Conclusions: There is substantial evidence for reading comprehension impairments in SLI and growing evidence that weaknesses in this domain are common in DS and ASD. Further, in these groups reading comprehension is typically more impaired than word recognition. However, there is also evidence that some children and adolescents with DS, ASD and a history of SLI develop reading comprehension and word recognition skills at or above the age appropriate level. This review of the literature indicates that factors including word recognition, oral language, nonverbal ability and working memory may explain reading comprehension difficulties in SLI, DS and ASD. In addition, it highlights methodological issues, implications of poor reading comprehension and fruitful areas for future research.

Molecular and Cytogenetic Analyses on Brazilian Youths with Pervasive Developmental Disorders

The Pervasive Developmental Disorders (PDDs) constitute a group of behavioral and neurobiological impairment conditions whose main features are delayed communicative and cognitive development. Genetic factors are reportedly associated with PDDs and particular genetic abnormalities are frequently found in specific diagnostic subgroups such as the autism spectrum disorders. This study evaluated cytogenetic and molecular parameters in 30 youths with autism or other PDDs. The fragile X syndrome was the most common genetic abnormality detected, presented by 1 patient with autism and 1 patient with PPD not-otherwise specified (PPD-NOS). One girl with PDD-NOS was found to have tetrasomy for the 15q11-q13 region, and one patient with autism exhibited in 2/100 metaphases an inv(7)(p15q36), thus suggesting a mosaicism 46,XX/46,XX,inv(7)(p15q36) or representing a coincidental finding. The high frequency of chromosomopathies support the hypothesis that PDDs may develop as a consequence to chromosomal abnormalities and justify the cytogenetic and molecular assessment in all patients with PDDs for establishment of diagnosis.

[association Between Physical And Psychosocial Impacts Of Oral Disorders And Quality Of Life Among The Elderly].

This study sought to evaluate the association between the impact of oral disorders in terms of physical/psychosocial dimensions and quality of life among the elderly. It involved a cross-sectional study conducted among the elderly (65-74 years) in 2008/2009. The social impact was assessed using the Oral Health Impact Profile (OHIP 14) and the quality of life using the SF 12 Short-Form Health Survey. Descriptive, univariate and multivariate (logistic regression) analysis was conducted with correction for the design effect, using SPSS(r)18.0 software. Of the 800 individuals approached, 736 elderly individuals participated (TR = 92%), with a mean age of 67.77 years, the majority of whom showed no impact based on the measurement of the prevalence of OHIP. The functional limitation dimension of the OHIP was associated with the physical domain of the SF12, irrespective of the other variables investigated. However, the seriousness of OHIP and its psychological discomfort and disability dimensions was associated with the mental domain of the SF12. The conclusion reached is that some impacts of oral disorders were associated with unsatisfactory quality of life in the physical and mental domains.

Anxiety Disorders and Rheumatic Fever: Is There an Association?

Introduction: Findings suggest that obsessive-compulsi e disorder (OCD) and related disorders, referred to as obsessive-compulsive spectrum disorders (OCSDs), are more common in patients with rheumatic fever (RF). Objectives: To determine whether RF or Sydenham`s chorea increases the probability of anxiety disorders in the relatives of individuals with RF with and without SC. Methods: This was a case-Control family study in which 98 probands and 389 first-degree relatives (FDRs) were assessed using structured psychiatric interviews. A Poisson regression model was used to determine whether the presence of any disorder in one family member influences the rate of disorders in the remaining family members. Results: Generalized anxiety disorder (GAD) occurred more frequently in the FDRs of RF probands than in those of control probands (P=.018). The presence of RF,GAD, or separation anxiety disorder in one family member significantly increased the chance of OCSDs in another member of the family.

Association between sleep bruxism and temporomandibular disorders: A polysomnographic pilot study

The aim of this study was to verify the association between sleep bruxism (SB) and temporomandibular disorders (TMD) in a sample of 14 TMD patients and 12 healthy control subjects. All participants were evaluated using a clinical questionnaire, visual analog scale (VAS) for TMJ/muscle palpation, and by functional examination. The experimental group was divided into three TMD subgroups: joint sounds and pain, muscular tenderness, and mixed diagnosis. All participants underwent polysomnographic recording (PSG). A second clinical examination was then carried out to verify the relationship between rhythmic masticatory muscle activity and pain/tenderness on the following morning. e experimental and control groups presented VAS mean scores of 36.85 +/- 23.73 mm and 0 mm, respectively. The presence of SB was neither associated with TMD (p>0.05) nor with pain on palpation (p>0.05). Further research with a more representative sample of each TMD subgroup is necessary to elucidate its interaction with SB.

Long-term effects of developmental exposure to di-n-butyl-phthalate (DBP) on rat prostate: Proliferative and inflammatory disorders and a possible role of androgens

In the present study we evaluated the toxic effects on the male adult rat prostate of DBP exposure during fetal and lactational periods, because although many studies have addressed the influence of phthalates on the male reproductive system, only a few have discussed their possible effects on prostate development. Pregnant females were distributed into two experimental groups: Control (C) and Treated (T). The females of the T group received DBP (100 mg/kg, by gavage) from gestation day 12 to postnatal day 21, while C rats received the vehicle (corn oil). In adulthood (90 days old), the animals were euthanized. The serum and testicular testosterone levels were measured. Ventral prostate was removed and weighed. Distal segment fragments of the ventral prostate were fixed and processed for histochemistry and immunohistochemistry to detect androgen receptor (AR) and Ki67 antigens. Protein extraction from ventral prostate fragments was performed for AR immunoblotting and Gelatin zymography for MMP-2 and MMP-9 (MMP, metalloproteinase). Stereological and histopathological analyses were also performed. Serum and testicular testosterone levels and prostate weight were comparable between groups. In the T group the relative proportions (%) of epithelial (C=32.86; T=42.04*) and stromal (C=21.61; T=27.88*) compartments were increased, while the luminal compartment was decreased (C=45.54; T=30.08*), *p < 0.05. In T, disseminated inflammatory infiltrate in the stroma, associated or not with epithelial dysplasia and PIN (Prostatic Intraepithelial Neoplasia), was observed. Increases in AR expression, proliferation index and metalloproteinase 9 (MMP-9) activity were noted in T animals. In some T animals, collagen fibrils accumulated adjacent to the epithelium. As far as we are aware, this is the first report in the literature showing that phthalates could play a role in proliferative and inflammatory disorders of the rat prostate. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Imitation, mirror neurons and autism

Various deficits in the cognitive functioning of people with autism have been documented in recent years but these provide only partial explanations for the condition. We focus instead on an imitative disturbance involving difficulties both in copying actions and in inhibiting more stereotyped mimicking, such as echolalia. A candidate for the neural basis of this disturbance may be found in a recently discovered class of neurons in frontal cortex, 'mirror neurons' (MNs). These neurons show activity in relation both to specific actions performed by self and matching actions performed by others, providing a potential bridge between minds. MN systems exist in primates without imitative and 'theory of mind' abilities and we suggest that in order for them to have become utilized to perform social cognitive functions, sophisticated cortical neuronal systems have evolved in which MNs function as key elements. Early developmental failures of MN systems are likely to result in a consequent cascade of developmental impairments characterised by the clinical syndrome of autism. Crown Copyright (C) 2001 Published by Elsevier Science Ltd. All rights reserved.

Association between child-care and acute diarrhea: a study in Portuguese children

OBJECTIVE: To quantify the influence of the type of child-care on the occurrence of acute diarrhea with special emphasis on the effect of children grouping during care. METHODS: From October 1998 to January 1999 292 children, aged 24 to 36 months, recruited using a previously assembled cohort of newborns, were evaluated. Information on the type of care and occurrence of diarrhea in the previous year was obtained from parents by telephone interview. The X² and Kruskal-Wallis tests were used to compare proportions and quantitative variables, respectively. The risk of diarrhea was estimated through the calculation of incident odds ratios (OR) and their respective 95% confidence intervals (95% CI), crude and adjusted by unconditional logistic regression. RESULTS: Using as reference category children cared individually at home, the adjusted ORs for diarrhea occurrence were 3.18, 95% CI [1.49, 6.77] for children cared in group at home, 2.28, 95% CI [0.92, 5.67] for children cared in group in day-care homes and 2.54, 95% CI [1.21, 5.33] for children cared in day-care centers. Children that changed from any other type of child-care setting to child-care centers in the year preceding the study showed a risk even higher (OR 7.65, 95% CI [3.25, 18.02]). CONCLUSIONS: Group care increases the risk of acute diarrhea whatsoever the specific setting.

PsyCoLaUS: santé mentale et maladies cardiovasculaires: association fortuite [PsyCoLaus: mental disorders and cardiovascular diseases: spurious association?].

Cardio-vascular diseases (CVD), their well established risk factors (CVRF) and mental disorders are common and co-occur more frequently than would be expected by chance. However, the mechanisms underlying this association are still poorly understood. The main study questions of PsyCoLaus, the psychiatric arm of CoLaus, are: 1) Do mental disorders increase vulnerability to CVRF and CVD? 2) Do CVRF and CVD promote the development of mental disorders? 3) Do CVRF/ CVD and mental disorders share common pathogenetic processes? The longitudinal project adds a comprehensive psychiatric evaluation to the CoLaus investigation. A better understanding of the psychological, physiological and behavioral links underlying CVD/ CVRF and mental disorders will result in the development of more specific and efficient strategies of prevention and treatment for both psychiatric and CVD/CVRF, two major elements of burden of disease.

Computational analysis of the genetic and environmental contributions to disease-related human phenotypes: From predicting adverse lipid response of HIV patients receiving antiretroviral therapy to genome-wide association studies of cardiovascular and lipid related disorders

Genetic variants influence the risk to develop certain diseases or give rise to differences in drug response. Recent progresses in cost-effective, high-throughput genome-wide techniques, such as microarrays measuring Single Nucleotide Polymorphisms (SNPs), have facilitated genotyping of large clinical and population cohorts. Combining the massive genotypic data with measurements of phenotypic traits allows for the determination of genetic differences that explain, at least in part, the phenotypic variations within a population. So far, models combining the most significant variants can only explain a small fraction of the variance, indicating the limitations of current models. In particular, researchers have only begun to address the possibility of interactions between genotypes and the environment. Elucidating the contributions of such interactions is a difficult task because of the large number of genetic as well as possible environmental factors.In this thesis, I worked on several projects within this context. My first and main project was the identification of possible SNP-environment interactions, where the phenotypes were serum lipid levels of patients from the Swiss HIV Cohort Study (SHCS) treated with antiretroviral therapy. Here the genotypes consisted of a limited set of SNPs in candidate genes relevant for lipid transport and metabolism. The environmental variables were the specific combinations of drugs given to each patient over the treatment period. My work explored bioinformatic and statistical approaches to relate patients' lipid responses to these SNPs, drugs and, importantly, their interactions. The goal of this project was to improve our understanding and to explore the possibility of predicting dyslipidemia, a well-known adverse drug reaction of antiretroviral therapy. Specifically, I quantified how much of the variance in lipid profiles could be explained by the host genetic variants, the administered drugs and SNP-drug interactions and assessed the predictive power of these features on lipid responses. Using cross-validation stratified by patients, we could not validate our hypothesis that models that select a subset of SNP-drug interactions in a principled way have better predictive power than the control models using "random" subsets. Nevertheless, all models tested containing SNP and/or drug terms, exhibited significant predictive power (as compared to a random predictor) and explained a sizable proportion of variance, in the patient stratified cross-validation context. Importantly, the model containing stepwise selected SNP terms showed higher capacity to predict triglyceride levels than a model containing randomly selected SNPs. Dyslipidemia is a complex trait for which many factors remain to be discovered, thus missing from the data, and possibly explaining the limitations of our analysis. In particular, the interactions of drugs with SNPs selected from the set of candidate genes likely have small effect sizes which we were unable to detect in a sample of the present size (<800 patients).In the second part of my thesis, I performed genome-wide association studies within the Cohorte Lausannoise (CoLaus). I have been involved in several international projects to identify SNPs that are associated with various traits, such as serum calcium, body mass index, two-hour glucose levels, as well as metabolic syndrome and its components. These phenotypes are all related to major human health issues, such as cardiovascular disease. I applied statistical methods to detect new variants associated with these phenotypes, contributing to the identification of new genetic loci that may lead to new insights into the genetic basis of these traits. This kind of research will lead to a better understanding of the mechanisms underlying these pathologies, a better evaluation of disease risk, the identification of new therapeutic leads and may ultimately lead to the realization of "personalized" medicine.

The PsyCoLaus study: methodology and characteristics of the sample of a population-based survey on psychiatric disorders and their association with genetic and cardiovascular risk factors.

ABSTRACT: BACKGROUND: The Psychiatric arm of the population-based CoLaus study (PsyCoLaus) is designed to: 1) establish the prevalence of threshold and subthreshold psychiatric syndromes in the 35 to 66 year-old population of the city of Lausanne (Switzerland); 2) test the validity of postulated definitions for subthreshold mood and anxiety syndromes; 3) determine the associations between psychiatric disorders, personality traits and cardiovascular diseases (CVD), 4) identify genetic variants that can modify the risk for psychiatric disorders and determine whether genetic risk factors are shared between psychiatric disorders and CVD. This paper presents the method as well as somatic and sociodemographic characteristics of the sample. METHODS: All 35 to 66 year-old persons previously selected for the population-based CoLaus survey on risk factors for CVD were asked to participate in a substudy assessing psychiatric conditions. This investigation included the Diagnostic Interview for Genetic Studies to elicit diagnostic criteria for threshold disorders according to DSM-IV and algorithmically defined subthreshold syndromes. Complementary information was gathered on potential risk and protective factors for psychiatric disorders, migraine and on the morbidity of first-degree family members, whereas the collection of DNA and plasma samples was part of the original somatic study (CoLaus). RESULTS: A total of 3,691 individuals completed the psychiatric evaluation (67% participation). The gender distribution of the sample did not differ significantly from that of the general population in the same age range. Although the youngest 5-year band of the cohort was underrepresented and the oldest 5-year band overrepresented, participants of PsyCoLaus and individuals who refused to participate revealed comparable scores on the General Health Questionnaire, a self-rating instrument completed at the somatic exam. CONCLUSIONS: Despite limitations resulting from the relatively low participation in the context of a comprehensive and time-consuming investigation, the PsyCoLaus study should significantly contribute to the current understanding of psychiatric disorders and comorbid somatic conditions by: 1) establishing the clinical relevance of specific psychiatric syndromes below the DSM-IV threshold; 2) determining comorbidity between risk factors for CVD and psychiatric disorders; 3) assessing genetic variants associated with common psychiatric disorders and 4) identifying DNA markers shared between CVD and psychiatric disorders.