Introduction : Certaines études ont démontré que les patients présentant un trouble du déficit de l’attention et de l’hyperactivité (TDAH) ont plus de problèmes respiratoires du sommeil et d’habitudes orales parafonctionnelles. Bien que ces facteurs puissent être liés aux malocclusions dentaires, aucune donnée n’a encore permis de déterminer si la prévalence de malocclusions dentaires et la nécessité d'un traitement orthodontique sont plus élevés chez les enfants atteints d’un TDAH. Ainsi, une étude plus approfondie de la prévalence et de la sévérité des malocclusions dentaires chez ces patients est importante pour favoriser un diagnostic précoce et une planification optimale de leur traitement orthodontique. Objectifs : Les objectifs primaires de la présente étude sont de : (i) comparer la sévérité des malocclusions des patients avec TDAH et des patients sans TDAH et de (ii) déterminer le type de malocclusion le plus fréquent chez les patients avec TDAH. Les objectifs secondaires de l’étude sont d’évaluer le lien entre : (i) les habitudes orales parafonctionnelles et les malocclusions des patients avec TDAH et (ii) la prise de médicaments utilisés dans le traitement du TDAH et les malocclusions dentaires. Matériels et méthodes : Les patients ont été divisés en deux groupes : un groupe de patients avec TDAH (n = 44) et un groupe contrôle (n = 44). Un questionnaire médical et un examen orthodontique ont été complétés pour chaque patient. Résultats : Les patients atteints de TDAH présentaient une plus grande sévérité de malocclusion (p=0,042), un plus grand nombre de rotation dentaire (p=0,021) et plus d’habitudes orales parafonctionnelles (p=0,001) que le groupe contrôle. Les habitudes orales présentent de façon plus significative chez les patients atteints d’un TDAH comparativement au groupe contrôle étaient le bruxisme (p=0,005) et l’utilisation de la suce pendant l’enfance (p=0,009). Conclusion : Il est important de prendre conscience du risque accru d’habitudes orales parafonctionnelles et de malocclusion dentaire chez les patients atteints de TDAH et de développer des programmes de prévention ainsi que des stratégies thérapeutiques à leur égard. / Introduction: Evidence has shown that patients with attention deficit and hyperactivity disorder (ADHD) have more sleep-breathing problems and parafunctional oral habits. Although these factors can be related to dental malocclusion, it is still unclear if the prevalence of malocclusion and need for orthodontic treatment are higher in children with ADHD. Thus, the knowledge about its prevalence and severity in children with ADHD is valuable in their early diagnosis and treatment planning. Objectives: The primary objectives of this study are: (i) to compare the type of malocclusions of patients with ADHD and patients without ADHD and (ii) to determine the most common type of malocclusion in patients with ADHD. The secondary objectives of the study are to assess the link between: (i) parafunctional oral habits and malocclusions of patients with ADHD and (ii) the drugs used in the treatment of ADHD and malocclusions. Materials and Methods: Patients were divided in two groups: ADHD (n=44) and control (n=44). A medical questionnaire and an orthodontic examination were completed for each patient. Results: Compared to the control group, patients with ADHD had a significantly higher severity of malocclusion (p=0.042), more dental rotation (p=0.021) and more parafunctional oral habits (p=0.001), especially bruxism (p=0.005) and history of pacifier use (p=0.009). Conclusion: It is important to be aware of the increased risk of oral habits and dental malocclusion among ADHD patients and to develop preventive programs as well as therapeutic strategies for them.

[pt] O medo é uma parte intrínseca da evolução humana e animal, mas pode se manifestar de forma patológica, como no Transtorno de Ansiedade. Há estudos na literatura que apontam o uso modelos animais para compreender psicopatologias, devido a simplicidade e semelhança neurobiológica. Foram desenvolvidas duas linhagens de ratos, denominadas Cariocas com Alto e Baixo Congelamento (CAC e CBC), que significa os níveis de ansiedade. O objetivo deste estudo foi investigar comportamentos compulsivos e hiperativos nos Cariocas, especificamente o grooming e o rearing de 138 animais (CAC, n=34; CBC, n=36; CTL, n=38). A metodologia foi analítica e descritiva com base em imagens obtidas em gravações do teste do medo contextual, ao longo de 8 minutos antes do choque. Nossos resultados indicaram que os CBC apresentam maior frequência [F(3,60)= 45,94, p<0,0001] e duração [F(3,43)= 21,51, p< 0,0001] do comportamento de rearing quando comparados aos outros grupos, CAC e CTL (rANOVA; P<0,05, teste post hoc de LSD). Do mesmo modo, quanto ao grooming, houve uma diminuição significativa no tempo total [F(2,00)= 6,35, p<0,01]. Portanto, os resultados sugerem que os CBCs exibem um comportamento mais hiperativo, apoiando a hipótese de que podem servir como um modelo animal de TDAH. / [en] Fear is an intrinsic part of human and animal evolution, but it can manifest itself in pathological ways, such as Anxiety Disorder. There are studies in the literature that point to the use of animal models to understand psychopathologies, due to their simplicity and neurobiological similarity. Two strains of rats were developed, called Cariocas with High and Low Freezing (CAC and CBC), which means anxiety levels. The objective of this study was to investigate compulsive and hyperactive behaviors in Cariocas, specifically the grooming and rearing of 138 animals (CAC, n=34; CBC, n=36; CTL, n=38). The methodology was analytical and descriptive based on images obtained from recordings of the contextual fear test, over 8 minutes before the shock. Our results indicated that BCC present a higher frequency [F(3,60)= 45.94, p<0.0001] and duration [F(3,43)= 21.51, p< 0.0001] of behavior rearing when compared to the other groups, CAC and CTL (rANOVA; P<0.05, LSD post hoc test). Likewise, regarding grooming, there was a significant decrease in total time [F(2.00)= 6.35, p<0.01]. Therefore, the results suggest that CBCs exhibit more hyperactive behavior, supporting the hypothesis that they may serve as an animal model of ADHD.

La neurofibromatose de type 1 (NF1) est une condition génétique entraînant des répercussions dans différents systèmes, y compris le système nerveux. Les enfants atteints de la NF1 sont à risque de rencontrer différents défis sur le plan cognitif et comportemental. Un chevauchement avec les symptômes associés à d’autres troubles neurodéveloppementaux, notamment le trouble déficitaire de l’attention avec ou sans hyperactivité (TDAH) et le trouble du spectre de l’autisme (TSA), est d’ailleurs présent dans cette condition génétique. Les études réalisées avec des modèles animaux de NF1 ont permis d’identifier des déséquilibres dans la neurotransmission qui pourraient sous-tendre les déficits cognitifs. Comment ces déséquilibres se traduisent sur le plan de l’activité cérébrale chez l’humain ayant la NF1 demeure peu compris à ce jour. L’objectif général de cette thèse est donc d’étudier, à l’aide de l’électroencéphalographie (EEG), les réponses neuronales lors du traitement sensoriel chez les enfants ayant la NF1 ainsi que les associations avec le fonctionnement cognitif et comportemental. Dans le premier article, nous avons étudié l’intégrité de la réponse de synchronisation neuronale lors de stimulations visuelles rythmiques à différentes fréquences. Considérant l’importance des déficits visuo-perceptifs ainsi que les indices de perturbations de la transmission GABAergique au niveau du cortex occipital dans la NF1, nous avons émis l’hypothèse d’une réduction de la synchronisation neuronale dans le groupe NF1 par rapport au groupe d’enfants neurotypiques. Une puissance réduite de la synchronisation neuronale a effectivement été trouvée dans la NF1, particulièrement en réponse à la plus haute fréquence de stimulation. Cette réponse neuronale affaiblie a été corrélée à une plus grande sévérité des symptômes comportementaux du TDAH. Cela soulève la possibilité d’une modulation de la réponse sensorielle par les réseaux attentionnels et soulève également des questions en lien avec l’impact du diagnostic de TDAH en comorbidité avec la NF1. L’impact de la médication psychostimulante, testé avec un sous-groupe de l’échantillon NF1, s’est d’ailleurs révélé par une amélioration de la réponse de synchronisation neuronale à la plus faible fréquence de stimulation. La réponse de synchronisation neuronale apparait donc comme un marqueur à investiguer davantage pour comprendre les mécanismes qui sous-tendent les déficits cognitifs dans la NF1 et pour évaluer l’impact de traitements. Dans le deuxième article, nous avons étudié les oscillations cérébrales dans la réponse de suppression neuronale et de détection du changement, toujours en comparant un groupe d’enfants ayant la NF1 à un groupe d’enfants neurotypiques. Une modulation atypique des oscillations cérébrales était attendue dans la NF1 en réponse à la répétition et au changement dans la séquence de stimuli audio-visuels. Les résultats ont démontré une réponse de suppression neuronale préservée dans le groupe NF1, mais une puissance accrue des oscillation thêta dans la condition de détection du changement. Les symptômes comportementaux du TDAH ont été associés à une réduction de la puissance des oscillations dans la réponse de détection du changement et ne contribueraient donc pas à la réponse accrue identifiée dans le groupe NF1. En somme, les résultats de la thèse ont permis d’identifier des particularités dans les réponses électrophysiologiques du traitement sensoriel chez les enfants ayant la NF1 et de mettre de l’avant des mesures dont le potentiel translationnel pourrait faciliter le transfert des connaissances accumulées dans les modèles animaux de NF1. Les résultats soulignent la complexité d’établir les bases neuronales des déficits cognitifs dans la NF1 compte tenu de l’hétérogénéité du profil cognitif. Cela dit, les associations établies entre les réponses neuronales et les symptômes comportementaux du TDAH suggèrent la possibilité de considérer le profil électrophysiologique pour guider le développement de traitements et interventions visant à améliorer le fonctionnement cognitif chez les enfants ayant la NF1. / Neurofibromatosis type 1 (NF1) is a genetic condition that has implications across different systems, including the nervous system. Children with NF1 are at risk of facing various cognitive and behavioral challenges. An overlap with symptoms associated with other neurodevelopmental disorders, including attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), is also present in this genetic condition. Studies conducted using animal models of NF1 have identified imbalances in neurotransmission that may underlie cognitive deficits. However, how these imbalances translate into human brain activity in individuals with NF1 remains poorly understood to date. The overall objective of this thesis is to investigate, using electroencephalography (EEG), neural responses during sensory processing in children with NF1 and their associations with cognitive and behavioral functioning. In the first article, we studied the integrity of the neural synchronization response during rhythmic visual stimulation at different frequencies. Given the significance of visuo-perceptual deficits as well as indications of disrupted GABAergic transmission in the occipital cortex of individuals with NF1, we hypothesized a reduction in neural synchronization in the NF1 group compared to neurotypical children. Reduced power of neural synchronization was indeed found in NF1, particularly in response to the highest stimulation frequency. This weakened neural response was correlated with greater severity of ADHD behavioral symptoms. These results suggest a possible modulation of this sensory response by attentional networks and raise questions regarding the impact of comorbid ADHD diagnosis on neural activity in NF1. The intake of psychostimulant medication, in a subgroup of the NF1 sample, resulted in an increased neural synchronization at the lowest stimulation frequency. Neural synchronization should be further investigated as a potential biomarker in NF1 and could help understand the underlying mechanisms of cognitive deficits and assess the impact of treatments. In the second article, we studied brain oscillations in the repetition suppression and change detection response, again comparing a group of children with NF1 to a group of neurotypical children. Atypical modulation of brain oscillations was expected in NF1 in response to repetition and change in the audio-visual stimuli sequence. Results showed preserved repetition suppression response in the NF1 group, but increased power of theta oscillations in the change detection condition. Behavioral symptoms of ADHD were associated with reduced oscillatory power in the change detection response, which suggest that the ADHD comorbidity did not contribute to the increased response identified in the NF1 group. In summary, results of this thesis have demonstrated distinct electrophysiological responses during sensory processing in children with NF1 and have highlighted measures with translational potential that could facilitate the transfer of knowledge gained from animal models of NF1. The results emphasize the complexity of establishing the neural basis of cognitive deficits in NF1, given the heterogeneity of the cognitive profile. However, the associations established between neural responses and ADHD behavioral symptoms suggest the possibility of considering the electrophysiological profile to guide the development of treatments and interventions aimed at improving cognitive functioning in children with NF1.

[pt] O estudo tem como foco a negociação de identidades em situação de conflito em contexto de consulta médica pediátrica de crianças e adolescentes com diagnóstico de Transtorno de Déficit de Atenção e Hiperatividade (TDAH), em atendimento de rotina conduzido pela médica. O objetivo consiste em criar inteligibilidades sobre os conflitos familiares consequentes do transtorno e as identidades projetadas/negociadas por pais, crianças e adolescentes com TDAH, para si e para o outro. A pesquisa está ancorada em linhas teóricas da fala-em-interação em atendimento clínico. Situa-se na Linguística Aplicada das Profissões, em articulação com a Análise da Conversa Etnometodológica, em contexto institucional, com a Sociolinguística Interacional e com os estudos discursivos sobre identidades. A metodologia da pesquisa, de natureza qualitativa e interpretativista, com gravação em vídeo de quatro consultas pediátricas, tem caráter etnográfico, mediante observação participante na antessala de atendimento. Os dados foram transcritos de acordo com convenções da Análise da Conversa Etnometodológica. Os resultados das análises mostram a prática profissional da médica nos enquadres de consulta clínica e de orientação psicoeducativa. A médica realiza tanto atividades relacionadas a tarefas de avaliação física e comportamental das crianças e dos adolescentes, em ações que visam ao tratamento medicamentoso e psicológico do TDAH, quanto atos comunicativos como formuladora, mediadora e conselheira na intermediação de conflitos emergentes da inter-relação TDAH, família e escola, resultantes do comportamento dos filhos nas relações familiares e do baixo rendimento acadêmico destes no contexto escolar. Os pais se alinham junto à médica, no enquadre de transtornos escolares dos filhos, e estabelecem enquadres conflitantes junto aos filhos; projetam para si identidades cujos atributos oscilam entre participativos, compreensivos e responsáveis, e impacientes, frustrados e esgotados. As identidades que projetam para os filhos apresentam-se, por vezes, contraditórias, entre filhos amorosos, perspicazes e irritantes; e alunos inteligentes, ineptos e displicentes. As crianças e os adolescentes, embora se alinhem com a médica, nos enquadres de consulta e orientação, rejeitam o estigma de TDAH e projetam para si identidades de alunos e filhos respeitosos e intelectualmente capazes; e para seus pais, na maioria das vezes, de pais impacientes e exigentes em sua educação. O estudo proporciona maior entendimento da complexidade e das múltiplas atividades da atuação profissional da médica na consulta pediátrica, e contribui para uma melhor compreensão das experiências cotidianas de pais, crianças e adolescentes com TDAH, marcadas por conflitos desestruturantes da harmonia entre esses atores sociais nos contextos da escola e da família. / [en] The study focuses on the negotiation of identities during conflict situations in the context of pediatric appointments for children and teenagers diagnosed with Attention Deficit Hyperactivity Disorder (ADHD), in routine care conducted by the doctor. The main purpose consists on creating intelligibilities about the family conflicts resultant from the disorder and the identities projected/negotiated by the parents, children and teenagers with ADHA, for themselves and others. The research is based on theoretical lines of speech-in-interaction regarding clinical care. It is situated on Professions Applied Linguistics, in articulation with the Ethnomethodological Conversation Analysis, in an institutional context, in Interational Sociolinguistics and on discursive studies about identities. The research methodology, of a qualitative and interpretive nature, with video recording of four pediatric appointments, has an ethnographic character, by a participant observation in the Doctor’s office waiting room. Data were transcribed in accordance with conventions of the Ethnomethodological Conversation Analysis. The analyzes results indicate the professional practice of the Doctor concerning clinical care and the psycho-educative orientation. The Doctor carries out activities related to physical evaluation and behavior tasks of children and teenagers, in actions that aim at the ADHA medicated and psychological treatment, and also the communicative acts as a formulator, mediator and advisor when intermediating conflicts emerging from the ADHA, family and school inter-relation, resultant from the behavior of the children in family relation and the their low academic performance in the school context. The parents align with the Doctor, in the framings of their children school disorders, and stablish conflicting framings together with their children; they project to themselves the identities whose attributes oscillate between participative, comprehensive and responsible, and impatient, frustrated and exhausted. The identities that project toward children are occasionally presented as contradictory, among the children considered lovely, insightful and annoying; and intelligent, inept and ungracious students. Children and teenagers, although being aligned with the Doctor, in the framings of appointments and orientation reject the ADHA stigma and project to themselves the identities of students and children considered to be respectful and intellectually capable; and for their parents, most of the time, identities of impatient and demanding parents regarding education. The study provides a greater understanding of the complexity and the multiple activities of the professional performance of the Doctor during the pediatric care, and contributes for a better understanding of the daily experiences of parents, children and teenagers with ADHA, marked by destabilizing conflicts of harmony between these social authors in the school and family contexts.

Le neurofeedback (NF) suscite actuellement un vif intérêt dans la prise en charge du trouble déficitaire de l’attention avec hyperactivité (TDAH) chez l’enfant. Proposée comme méthode alternative à la médication par de nombreux cliniciens, notamment aux États-Unis, le NF est une intervention non-invasive de type électrophysiologique qui repose sur l’apprentissage par conditionnement opérant de l’autorégulation d’ondes cérébrales déviantes. Les études empiriques qui étayent cette pratique font toutefois l’objet de virulentes critiques de la part de spécialistes dans le domaine du TDAH en raison de résultats systématiquement positifs mais non spécifiques, auxquels s’ajoutent de nombreuses lacunes méthodologiques. Les travaux de cette thèse visent à appliquer une méthodologie stricte de type essai clinique contrôlé avec assignation aléatoire afin d’isoler les effets particuliers du NF, en appliquant un protocole d’entraînement propre au déficit primaire sous-tendant le TDAH, soit l’inhibition motrice, dans le but d’évaluer la spécificité de cette intervention. Dans un premier temps, les connaissances relatives à la nosologie du TDAH, à ses principaux traitements, au NF et aux capacités d’inhibition chez l’enfant ayant un TDAH sont présentées (Chapitre 1). Ensuite, les études réalisées dans le cadre de cette thèse sont exposées. Dans l’étude initiale, la spécificité du NF est évaluée sur les capacités d’inhibition grâce à des mesures subjectives, soit des questionnaires de comportements complétés par les parents, ainsi que des mesures objectives, à savoir des tâches neuropsychologiques (Chapitre 2). Afin de préciser davantage les conséquences d’un entraînement à l’autorégulation d’ondes cérébrales, l’étude subséquente s’est intéressée à l’impact neurophysiologiques de l’amélioration des capacités d’inhibition, par le biais d’une étude en potentiels évoqués employant une tâche de performance continue de type Stop-signal (Chapitre 3). Les principaux résultats reflètent un recrutement sous optimal, avec une puissance statistique insuffisante pour réaliser des statistiques quantitatives de groupe. Néanmoins, l’appréciation des données selon une approche d’étude de cas multiples permet de mettre en évidence la présence d’une réponse placebo sur les capacités d’inhibition suite à un entraînement en NF. Finalement, les implications de la taille de l’échantillon, ainsi que les limites et les critiques de ces études sont discutées au Chapitre 4. / In recent years, there has been a lively interest in the use of neurofeedback (NF) as an alternative treatment to pharmacotherapy in pediatric Attention-deficit hyperactivity disorder (ADHD). NF is defined as an operant conditioning procedure whereby an individual learns to self-regulate electrical brain activity. Yet, empirical studies supporting its practice are harshly criticized in the field of ADHD research due to systematic unspecific positive results associated to numerous methodological flaws. Studies presented in this dissertation aim at applying a randomized placebo-controlled clinical trial to the investigation of NF specific effects. In order to further establish treatment specificity, we trained the participants using a NF protocol characteristic to motor-inhibition functioning since it has repeatedly been described as the core deficit in ADHD. The fist part of this thesis comprises a brief review of knowledge concerning ADHD, principal treatments offered for this disorder, NF research in pediatric ADHD and inhibition abilities in these children (Chapter 1). Following are the two studies conducted as part of this dissertation. In the initial study, effects of NF training are investigated on inhibition capacities by means of behavior rating scales and neuropsychological tests (Chapter 2). With the aim of further defining the consequence of training to self-regulate ones brain activity, the subsequent study looks at the neurophysiologic impact of improving inhibition capacities with an event-related potential study using a Stop-signal continuous performance task (Chapter 3). The principal results reveal a non optimal recruitment, with insufficient statistical power, thus precluding quantitative group statistics. Nevertheless, appreciating the data from a multiple case study perspective enables to suggest that a placebo response could be at play following NF training, such as measured by improvements on inhibition capacities. Finally, the implications of such a small sample size, limits and critics of these studies are discussed in Chapter 4.

Le trouble du déficit de l’attention avec ou sans hyperactivité (TDAH) est de plus en plus reconnu chez l'adulte. Les psychostimulants représentent la première ligne de traitement, mais ceux-ci ne sont parfois pas tolérés, peuvent être contrindiqués ou ne pas être efficaces. Les médicaments non stimulants constituent une alternative mais ont été insuffisamment explorés. Cette thèse présente un essai clinique randomisé contrôlé de 30 sujets souffrant de TDAH qui ont reçu soit la duloxétine 60 mg par jour ou le placebo pendant une période de 6 semaines. Le Conners’ Adult ADHD Rating Scale (CAARS) et le Clinical Global Impression scale (CGI) ont été utilisés pour mesurer la sévérité des symptômes et l'amélioration clinique. Le Hamilton Anxiety Rating Scale (HARS) et le Hamilton Depression Rating Scale (HDRS) ont été choisis pour vérifier l'impact sur la symptomatologie anxio-dépressive. Les résultats démontrent que les sujets ayant reçu la duloxétine avait un score au CGI-Severity (CGI-S) inférieur au groupe contrôle à 6 semaines de traitement et une amélioration plus importante au CGI-Improvement (CGI-I). Ce groupe démontre également des diminutions supérieures des scores à plusieurs sous-échelles du CAARS. Aucun effet n'a été observé sur le HARS et le HDRS. Le taux de retrait du bras duloxetine remet par contre en question la dose initiale choisie dans ce protocole. La duloxétine semble donc une option prometteuse dans le traitement du TDAH chez l'adulte et la réplication des données cliniques serait la prochaine étape pour confirmer ces résultats. / Attention-deficit/hyperactivity disorder (ADHD) is increasingly recognized in adults. Stimulants are first-line treatment options but can be ineffective, poorly tolerated or contraindicated in some patients. For these patients, non-stimulants can be an interesting option; however, this heterogeneous class has been insufficiently studied. This thesis presents the results of a pilot study. In this randomized controlled clinical trial, thirty adults with ADHD received either placebo or duloxetine 60 mg daily for 6 weeks. The Conners’ Adult ADHD Rating Scale (CAARS) and the Clinical Global Impression scale (CGI) were chosen to assess symptom severity and clinical improvement. The Hamilton Anxiety Rating Scale (HARS) and the Hamilton Depression Rating Scale (HDRS) were used to measure the effect on anxiety and depressive symptoms. In summary, the duloxetine group showed a lower score on CGI-Severity at week 6, greater improvement on CGI-Improvement and greater decreases on multiple subscales of the CAARS. There was no treatment group effect on HDRS or HARS scores. Tolerability was an issue with participants in the duloxetine group and the dose titration schedule chosen in this study should be revised. This is the first clinical trial of duloxetine in adults with ADHD. This medication seams to improve symptoms in this condition but further studies are required to replicate these findings in larger samples of ADHD adults.

Cette étude vise à examiner la relation entre les pratiques parentales utilisées durant la période de l'enfance et les dimensions principales du du trouble déficitaire de l'attention avec hyperactivité (TDAH) à l'adolescence, soit l’inattention, l’hyperactivité et l’impulsivité. Les pratiques spécifiques parentales (engagement, pratiques parentales appropriée, supervision, punitions corporelles, discipline appropriée, discipline sévère et incohérente, discipline verbale positive, félicitations et récompenses, et les attentes claires) et les aspects du fonctionnement familial (communication, résolution de problèmes, rôles dans la famille, sensibilité affective, engagement affectif, contrôle comportemental) ont été examinés par rapport à l'inattention et d'hyperactivité. Trente-six enfants de 6 à 9 ans et leurs parents ont participé à une étude longitudinale de 5 ans. Il y a un manque d'études longitudinales dans ce domaine et cette étude vise à combler cette lacune. Les résultats ne montrent pas de résultats significatifs dans la relation entre les pratiques parentales utilisées dans l'enfance et les symptômes principaux de l'hyperactivité et l'inattention à l'adolescence. Les études futures devraient se concentrer sur la relation entre la psychopathologie parentale et les principaux symptômes du TDAH de l'enfance à l'adolescence, ainsi que l'impact des pratiques parentales sur ces principaux symptômes. / This study aims to examine the relationship between parenting practices used in childhood on one hand and the core symptoms of Attention deficit hyperactivity disorder (ADHD) in adolescence on the other hand. Specific parenting practices ( involvement, positive parenting, monitoring/supervision, corporal punishment, appropriate discipline, harsh and inconsistent discipline, positive verbal discipline, praise and incentives and clear expectations) and aspects of family functioning were examined ( communication, problem solving, roles, affective responsiveness, affective involvement, behavioural control and general functioning) in relation to inattention and hyperactivity. The sample consisted of 36 participants involved in a 5 year study from childhood (6 to 9 years old) to adolescence (11 to 14 years old). The results do not show significant results in the relationship between parenting practices used in childhood and the core symptoms of hyperactivity and inattention in adolescence. There is a lack of longitudinal studies in this area and this study attempts to fill in this gap. However despite a lack of significant results, past research suggests an important relationship between parental psychopathology, which has been linked with ineffective parenting practices and the persistence of ADHD from childhood to adolescence. Future studies should focus on the relationship between parental psychopathology and the core symptoms of ADHD from childhood to adolescence, as well as the impact of parenting practices on these core symptoms.

O Transtorno de Déficit de Atenção e Hiperatividade (TDAH) é a doença do neurodesenvolvimento mais comum na infância, afetando cerca de 5,8% de crianças e adolescentes no mundo. Muitos estudos vêm tentando investigar a suscetibilidade genética em TDAH, mas sem muito sucesso. Este estudo teve como objetivo analisar variantes raras e comuns contribuindo para a arquitetura genética do TDAH. Foram gerados os primeiros dados de exoma de TDAH de 30 trios brasileiros em que o filho foi diagnosticado com TDAH esporádico. Foram analisados tanto variações de único nucleotídeo (ou SNVs, single-nucleotide variants) quanto variações de número de cópias (ou CNVs, copy-number variants), tanto nesses trios quanto em outros conjuntos de dados, incluindo uma amostra brasileira de 503 crianças/adolescentes controles, bem como resultados previamente publicados em quatro estudos com variação de número de cópias e uma meta-análise de estudos de associação ao longo do genoma. Tanto os trios quanto os controles fazem parte da Coorte de Escolares de Alto Risco para o desenvolvimento de Psicopatologia e Resiliência na Infância do Instituto Nacional de Psiquiatria do Desenvolvimento (INPD). Os resultados de trios brasileiros mostraram três padrões marcantes: casos com variações herdadas e somente SNVs de novo ou CNVs de novo, e casos somente com variações herdadas. Embora o tamanho amostral seja pequeno, pudemos ver que diferentes comorbidades são mais frequentes em casos somente com variações herdadas. Após explorarmos a composição de variações nos probandos brasileiros, foram selecionados genes recorrentes entre amostras do nosso estudo ou em bancos de dados públicos. Além disso, usando somente genes expressos no cérebro (amostras pós-mortem dos projetos Brain Atlas e Genotype-Tissue Expression), construímos uma rede de interação proteína-proteína \"in silico\" com interações físicas confirmadas por pelo menos duas fontes. Análises topológicas e funcionais dos genes da rede mostraram genes relacionados a sinapse, adesão celular, vias glutamatérgicas e serotonérgicas, o que confirma achados de trabalhos independentes na literatura indicando ainda novos genes e variantes genéticas nessas vias. / Attention-Deficit/Hyperactivity Disorder (ADHD) is the most common neuro-developmental disorder in children, affecting 5.8% of children and adolescents in the world. Many studies have attempted to investigate the genetic susceptibility of ADHD without much success. The present study aimed to analyze rare and common variants contributing to the genetic architecture of ADHD. We generated exome data from 30 Brazilian trios where the children were diagnosed with sporadic ADHD. We analyzed both single-nucleotide variants (SNVs) and copy-number variants (CNVs) in these trios and across multiple datasets, including a Brazilian sample of 503 children/adolescent controls from the High Risk Cohort Study for the Development of Childhood Psychiatric Disorders, and also previously published results of four CNV studies of ADHD involving children/adolescent Caucasian samples. The results from the Brazilian trios showed 3 major patterns: cases with inherited variations and de novo SNVs or de novo CNVs and cases with only inherited variations. Although the sample size is small, we could see that various comorbidities are more frequent in cases with only inherited variants. After exploring the rare variant composition in our 30 cases we selected genes with variations (SNVs or located in CNV regions) in our trio analysis that are recurrent in the families analyzed or in public data sets. Moreover, using only genes expressed in brain (post-mortem samples from Brain Atlas and The Genotype-Tissue Expression project), we constructed an in silico protein-protein interaction (PPI) network, with physical interactions confirmed by at least two sources. Topological and functional analyses of genes in this network uncovered genes related to synapse, cell adhesion, glutamatergic and serotoninergic pathways, both confirming findings of previous studies and capturing new genes and genetic variants in these pathways.

Made available in DSpace on 2016-04-28T20:38:05Z (GMT). No. of bitstreams: 1 Helena Maria Daquanno Martins Testi.pdf: 2024967 bytes, checksum: 4a9ae508bfb6deb8424fb9530dba9133 (MD5) Previous issue date: 2012-05-03 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The present study investigates from the point of view of Psychoanalysis a case of attention deficit disorder/hyperactivity disorder (ADHD). Articulate this point of view the research developed by doctors and scientists, like Barkley, Camargos Jr. and Hounie, Cypel, Rohde, Topoczewski, Ajuriaguerra, among others, to investigate the context of diagnosis and onset of that name, and its evolution in the field of Medicine. Guide this work theoretically studies of Freud and Piera Aulagnier, which postulate the psychic constitution of the subject based on conflicts of early childhood. The basic concepts for the analysis of the case were the transfer, identificatory conflicts and maniac defense. The notion of melancholy potentiality, developed by Violante, was also important for this study. The case investigated is that of a six year old child diagnosed as ADHD, the inattentive subtype. Manoel, as it is called the child in this study, was referred by the school because he had difficulty reading and writing, and can not focus and disrupt colleagues in the classroom. Was in attendance at weekly meetings during the year and a half, most of which, alone. Were also individually interviewed the mother (on three separate occasions) and father (in one). The researcher's notes during the meetings served as the basis for the constitution of the case and further analysis. The research questions that guided the research were: a) From the discussion of a clinical case, which conflicts are the basis of somatic manifestation? b) What defenses are mobilized or not for these conflicts? c) What are the implications of changes in family structure and how this affects relations with each parent? The analysis indicated that the identificatory conflicts were those at the base of the somatic manifestations, taken as hyperactivity. The maniac defenses were deployed against a potentiality of melancholy. Furthermore, Manoel was subjected to an environment psychic disturbing / O presente estudo consiste em investigar, sob o ponto de vista da Psicanálise, um caso de transtorno do déficit de atenção/hiperatividade (TDAH). Articulam-se a esse ponto de vista as pesquisas desenvolvidas por médicos e cientistas, como Barkley, Camargos Jr. e Hounie, Cypel, Rohde, Topoczewski, Ajuriaguerra, dentre outros, no sentido de investigar o contexto de aparecimento desse diagnóstico e dessa denominação, bem como a sua evolução na área da Medicina. Norteiam teoricamente este trabalho os estudos de Freud e Piera Aulagnier, dos quais se postula a constituição psíquica do sujeito pautada nos conflitos da primeira infância. Os conceitos basilares para a análise do caso foram os de transferência, conflitos identificatórios e defesa maníaca. A noção de potencialidade melancólica, desenvolvida por Violante, também foi importante para este estudo. O caso clínico investigado é o de uma criança de seis anos, diagnosticada como TDAH, do subtipo desatento. Manoel, como é chamada essa criança neste trabalho, foi encaminhada à análise pela escola, pois tinha dificuldades para ler e escrever, além de não conseguir se concentrar e atrapalhar os colegas em sala de aula. Esteve em atendimento em encontros semanais durante o período de um ano e meio, na maioria dos quais, sozinho. Foram entrevistados individualmente também a mãe (em três ocasiões distintas) e o pai (em uma única). As anotações da pesquisadora durante os encontros serviram de base para a constituição do caso e posterior análise. As perguntas de pesquisa que orientaram a investigação foram: a) A partir da discussão de um caso clínico, que conflitos estão na base dessa manifestação somática?; b) Que defesas são mobilizadas ou não por esses conflitos?; c) Quais são as implicações das mudanças na organização familiar e como isso repercute nas relações vinculares com cada um dos pais? A análise indicou que os conflitos identificatórios eram os que estavam na base da manifestação somática, tida como hiperatividade. As defesas maníacas foram mobilizadas contra uma possível potencialidade melancólica. Além disso, Manoel era uma criança submetida a um meio ambiente psíquico perturbador

O Transtorno de Déficit de Atenção e Hiperatividade (TDAH) é um dos transtornos neuropsiquiátricos mais prevalentes da infância caracterizado pelos sintomas de desatenção, hiperatividade e impulsividade. O TDAH é uma desordem neurocomportamental heterogênea e fenotipicamente complexa e sua etiologia ainda não foi completamente esclarecida, mas sabe-se que a interação de fatores ambientais e genéticos e o acúmulo de seus efeitos possivelmente aumenta a vulnerabilidade ao transtorno. Nesse estudo, foram investigados o imunoconteúdo de proteínas sinápticas e do desenvolvimento a partir de neurônios da região do córtex pré-frontal de animais SHR, um dos modelos animais mais validados para o estudo do TDAH. Também foi realizada uma análise morfomética do padrão de desenvolvimento dessas células ao longo de diferentes dias in vitro e o papel do BDNF, fator neurotrófico crucial para a sobrevivência e maturação das sinapses, no desenvolvimento dos neurônios SHR. A análise do imunoconteúdo da SNAP-25 mostrou aumento nos níveis dessa proteína no 2º DIV e diminuição no 5º DIV nos neurônios SHR em relação ao controle WKY, sem alterações entre as cepas nos outros dias analisados. Em relação aos níveis de sinaptofisina nos neurônios SHR, foi observado aumento somente no 5º DIV. A análise do proBDNF mostrou diminuição nos neurônios SHR no 5º DIV e aumento no 8º DIV. A imunodetecção do CREB mostrou que os neurônios SHR apresentam níveis diminuídos dessa proteína somente no 1º DIV. O receptor TrkB também apresentou alterações no seu imunoconteúdo, com aumento no 2º DIV e diminuição no 5º DIV nos neurônios SHR. O imunoconteúdo do BDNF e do TrkB fosforilado não apresentaram alterações entre as linhagens nos dias analisados. Além disso, foi realizada uma análise morfométrica de diferentes parâmetros de desenvolvimento dos neurônios ao longo de diferentes dias in vitro por meio da marcação da proteína da região somatodendrítica MAP-2. Foi observada diminuição no comprimento total dos neuritos dos neurônios SHR no 5º DIV em relação aos neurônios WKY. Também foi verificado redução no número de raízes no 2º DIV e redução no número de pontos de ramificação no 5º DIV nos neurônios SHR. As alterações observadas em proteínas que são relacionadas aos processos de sinapses e de desenvolvimento neuronal podem auxiliar na compreenssão das diferenças encontradas no padrão de desenvolvimento dos neurônios SHR. Essas modificações a nível proteico podem estar alterando o crescimento e o padrão de arborização dendrítica e implicar em modificações na funcionalidade dessas células importantes para a melhor compreensão das bases neurobiológicas do TDAH. / Attention deficit hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders of childhood characterized by symptoms of inattention, hyperactivity and impulsivity. ADHD is a heterogeneous and phenotypically complex neurobehavioral disorder with unknown etiology, but the interaction between environmental and genetic factors have been described to increase the vulnerability to the disorder. In this study, we investigated the immunocontent of synaptic and development proteins of prefrontal cortex neurons from one of the most validated animal models for the study of ADHD (SHR). We also performed a morphometric analysis along development of these cells at different days in vitro and the role of a neurotrofic factor (BDNF) in neuronal outgrowth. SNAP-25 immunocontent was increased at 2 DIV and decreased at 5 DIV in SHR neurons. Synaptophysin levels show increases only at 5 DIV in SHR neurons. The levels of proBDNF were decreased at 5 DIV and increased at 8 DIV in SHR neurons. CREB immunodetection showed that SHR neurons present decreased levels only at 1 DIV. The TrkB receptor also presented changes in immunocontent, with increase at 2 DIV and decrease at 5 DIV in the SHR neurons. Morphometric analysis during neuronal development by immunostaining with MAP-2 somatodendritic protein show decrease in total length at 5 DIV in SHR neurons in relation to WKY neurons. Besides that, SHR neurons exhibit reduction in number of roots at 2 DIV and number of branch points at 5 DIV. Changes in proteins related to synaptic processes and neuronal during development can help to understand differences found in the pattern of development of the neurons SHR. These changes at protein level may be altering neuronal outgrowth and dendritic arborization and possible involve modifications in functionality of these cells important for better understanding the neurobiological bases of ADHD.