Academic literature on the topic 'Attention-deficit/hiperactivity disorder'

Having an attention deficit hyperactivity disorder (ADHD) child is certainly not easy in her care. Mother, as the most dominant figure in her parenting, certainly experienced psychological impact. This study aims to describe the experience of mothers who are parenting with ADHD related to their quality of life. This research is qualitative research with a Phenomenological approach. The study participants consisted of 5 mothers of children with ADHD aged 36-45 years. Data retrieval is done using semi-structured interviews. Data analysis using thematic analysis. The quality of life in mothers of children with ADHD can be described through 23 themes divided into four domains of quality of life: physical, psychological, social, and environmental. In the physical domain, parenting with ADHD affects daily activities that cause mothers to feel tired. In the psychological domain, the mother feels a variety of feelings from the beginning of the diagnosis to during parenting. In the social relation domain, parenting with ADHD affects maternal relationships. In the environment domain, some costs need to be incurred for the child. Mothers are also able to get new information and lessons during parenting with ADHD.

Socioeconomic status of person has an important role to child development. Social economy can affect physical health, mental wellbeing and cognitive development. One of the growing disorders of attention disorder and hyperactivity disorder was characterized by hyperactive, impulsive and lack of attention. The purpose of this study to determine the relationship of socioeconomic status of parents at risk of attention deficit and hyperactivity disorder (ADHD) to preschoolers in Klaten District. This study uses categorical comparative design with cross sectional approach. Respondents of this study were 84, that divided into two places, there were ABA TK Lor Sabrang Trucuk and TKIT Mutiara Hati so that every kindergarten 42 respondents obtained by purposive sampling. Data was collection by filling the instrument. Bivariate analysis using test Chi Square. The results showed the average age of respondents were 5.25 years. The sex of the respondents is mostly male as many as 47 children or 56.0%. Test results Chi square show there is a relationship of socio-economic status of parents with ADHD (p = 0.036) and there is a different between low socioeconomic status and high that lower socioeconomic status is a risk of ADHD (25,6%) compared with high socioeconomic status (6,7%). There is a negative relationship between socioeconomic status and the risk of attention deficit and hyperactivity disorder in pre-school age children.

Subjek bernama DK, (7 tahun/Lk) anak kedua dari 2 bersaudara. Saat ini Subjek bersekolah kelas satu SD di Karangploso. Subjek tinggal bersama ayah, ibu dan kakaknya yang berusia 22 tahun. Subjek seringkali berlari-lari di dalam kelas serta membuang dan melempar alat tulis yang ia miliki. Subjek sulit untuk fokus saat di berikan pelajaran di dalam kelas terutama pada mata pelajaran menulis dan membaca, namun pada saat pelajaran matematika Subjek cukup mampu dalam mengerjakan. Subjek tidak menyukai bermain bersama teman-temannya, ia lebih suka bermain sendiri, karena ia tidak ingin berbagi mainan yang ia miliki. Subjek seringkali merengek, menangis, mengguling-gulingkan badannya saat keinginannya tidak dipenuhi. Berdasarkan asesmen yang telah dilakukan, Subjek mengalami gangguan ADHD (Attention Deficit Hiperactivity Disorder). Intervensi yang dilakukan adalah play therapy menggunakan metode menyusun menara dengan hasil mampu meningkatkan konsentrasi pada anak ADHD.

It was proved by cross-correlational analysis of EEG of the cohort children of 3-11 years with attention deficit/hyperactivity disorder (ADHD), called minimal brain dysfunction (MDM). On the basis of comprehensive diagnostics, including - for the cross-correlation analysis of EEG computer (QEEG) in normal and ADHD construct therapeutic tactics in the treatment of children with this syndrome. Using QEEG data, the authors confirm the violations of interaction between structures of the cerebral cortex with ADHD compared to the norm, especially between the frontal and parietal-occipital region, as well as between the right parietal-occipital region with all the other departments of the cortex.

El trastorno por déficit de atención e hiperactividad (TDAH) es un trastorno del neurodesarrollo caracterizado por síntomas de inatención, hiperactividad e impulsividad. Los modelos clásicos acerca de la neuroanatomía del trastorno apuntan a alteraciones en los circuitos fronto-estriado-cerebelares. Los estudios de neuroimagen estructural apoyan parcialmente estos modelos. Sin embargo, casi todos estos estudios se basan en el análisis de regiones seleccionadas a priori (procedimiento que se conoce como ROI, acrónimo inglés de regiones de interés: "region of interest"). Estudios más recientes basados en aproximaciones globales apuntan a que las alteraciones estructurales no se limitan a los circuitos fronto-estriado-cerebelares, sino que también afectan las regiones temporales, parietales y cinguladas.
El objetivo de la presente tesis es el de redefinir y aplicar dos métodos de análisis estructural complementarios para identificar los circuitos cerebrales alterados en el TDAH así como para relacionar dichos circuitos con los diferentes subtipos clínicos. Para tal fin, presentaremos y discutiremos dos estudios de resonancia magnética estructural (Carmona et al. 2005; Tremols et al. 2008). Estos dos estudios representan una novedad y mejora de estudios de TDAH previos, por dos razones principales: a) la aplicación por primera vez un estudios basado en la morfometría de vóxeles para comparar el cerebro de niños con TDAH con el cerebro de niños controles no relacionados familiarmente; b) el diseño e implementación de un nuevo método, fácil de aplicar, de segmentación manual del núcleo caudado.
Los resultados confirman los datos obtenidos en estudios previos acerca de menor volumen cerebral en niños con TDAH, y localizan esta reducción en determinadas regiones de sustancia gris. A parte de confirmar las alteraciones fronto-estriado-cerebelares hayamos reducciones en áreas parietales, cingulares y temporales. En concreto observamos decrementos volumétricos de sustancia gris en la corteza frontal inferior, el estriado dorsal, la corteza parietal inferior y la corteza cingulada posterior, regiones clásicamente relacionadas con problemas de inhibición, deficits de memoria de trabajo y alteraciones en tareas de atención visuoespacial, respectivamente. También observamos reducciones volumétricas en áreas típicamente emocionales, como la corteza orbitofrontal, el estriado ventral y las estructurales temporales mediales deficits que podrían explicar las disfunciones motivacionales así como las alteraciones en el procesamiento del refuerzo. Curiosamente, las reducciones de sustancia gris en áreas relacionadas con el procesamiento emocional son más pronunciadas en el subtipo hiperactivo-impulsivo, algo menos en el subtipo combinado y casi inexistentes en el subtipo inatento. Esta diferente afectación en función de los subtipos va en la línea de teorías neuroanatómicas actuales acerca del TDAH (Castellanos and Tannock 2002). También observamos déficits de sustancia gris en áreas sensorio-motoras (específicamente en la corteza perirrolándica y el área motora suplementaria), y en el cerebelo. Por un lado, los déficits en áreas sensorio-motoras probablemente reflejan los problemas de psicomotricidad fina que presentan muchos de los niños con TDAH. Sin embargo, el hecho de que estas reducciones sean especialmente prominentes en los subtipos combinado e inatento, sugieren la posibilidad de que estas alteraciones estén especialmente relacionadas con los déficits atencionales. En base a esto, hipotetizamos que las alteraciones en estas regiones producirían un déficit para integrar y actualizar la información procedente del mundo exterior y, a su vez darían lugar a un sesgo a favor del procesamiento de los estados internos resultando en inatención. Por otro lado, las reducciones cerebelares (extensamente observadas en la literatura del TDAH) parecen están relacionadas con los déficits cognitivos, los afectivos y los emocionales. Creemos que la implicación del cerebelo en estas disfunciones estaría vehiculada por el papel de esta estructural como moduladora del flujo de información entre los circuitos fronto-estriatales. Finalmente nuestros hallazgos son los primeros en demostrar alteraciones diferenciales en la cabeza y el cuerpo del núcleo caudado en el TDAH. Esta desigual implicación de las diferentes partes del núcleo caudado explicaría en parte la heterogeneidad de los estudios previos.
Como conclusión, las reducciones volumétricas de sustancia gris en áreas cognitivas y emocionales apoyan la implicación de disfunciones en los circuitos fronto-estriatales llamados cool (cognitivos) y hot (emocionales) respectivamente. Hasta la fecha este es el primer estudio neuroanatómico que apoya la existencia de disfunciones tanto cognitvas como emocionales en niños con TDAH. Nuestros hallazgos constituyen la primera evidencia neuroanatómica a favor de los modelos de doble ruta porpuestos por Sonuga-Barke (Sonuga- Barke 2002; Sonuga-Barke 2003).
REFERENCIAS:
1. Tremols V, Bielsa A, Soliva JC, Raheb C, Carmona S, Tomas J, et al. (2008): Differential abnormalities of the head and body of the caudate nucleus in attention deficit-hyperactivity disorder. Psychiatry Res. 163:270-278.
2. Carmona S, Vilarroya O, Bielsa A, Tremols V, Soliva JC, Rovira M, et al. (2005): Global and regional gray matter reductions in ADHD: a voxel-based morphometric study. Neurosci Lett. 389:88-93.
3. Castellanos FX, Tannock R (2002): Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes. Nat Rev Neurosci. 3:617-628.
4. Sonuga-Barke EJ (2003): The dual pathway model of AD/HD: an elaboration of neuro-developmental characteristics. Neurosci Biobehav Rev. 27:593-604.
5. Sonuga-Barke EJ (2002): Psychological heterogeneity in AD/HD--a dual pathway model of behaviour and cognition. Behav Brain Res. 130:29-36.
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disease characterized by symptoms of inattention, hyperactivity and impulsivity. Data from different studies point to ADHD abnormalities in fronto-striatal circuits. Structural neuroimaging studies partially support fronto-striatal abnormalities and suggest an important role of the cerebellum. However, nearly all these studies are based on the analysis of apriori selected regions of interest (known as ROI approaches). Recent studies, using more global approaches, found that ADHD structural abnormalities were not limited to fronto-striatal-cerebellar circuits, but also affect temporal, parietal and cingulate regions.
The aim of the present dissertation is to refine and apply two complementary methods of structural neuroimaging, in order to identify the brain circuits altered in
ADHD and relate them to different clinical ADHD subtypes and to known ADHD neuropsychological deficits. For that purpose, two structural MRI studies will be presented and discussed (Carmona et al. 2005; Tremols et al. 2008). The differential contributions of these studies, which represent a novelty and an improvement of previous ADHD studies, are: a) the application for the first time of
voxel-based morphometry analysis to compare ADHD children with non family related control children; b) the design and application of a new, easy to apply, manual method of caudate nucleus segmentation.
The results confirm previous findings about smaller brain volume in ADHD children, and refine this reduction by attributing it to grey matter (GM) volume. We also confirm abnormalities in fronto-striatal-cerebellar circuits as well as in parietal, cingulate and temporal regions. Specifically, we observed reductions in inferior frontal cortex, dorsal striatum, inferior parietal cortex and posterior cingulate cortex; thus explaining inhibition problems, spatial working memory deficits and visuospatial attentional alterations. We also observed GM volume reductions in emotionally driven areas such as orbitofrontal cortex, ventral striatum and middle temporal structures; thus accounting for dysfunctional delayed reward and motivational deficits. Interestingly, GM volume reductions, related to emotional processes are more prominent in H-I subtype, more preserved in combined subtypes, and relatively undisrupted in inattentive subtypes, which is in agreement with previous ADHD theories (Castellanos and Tannock 2002). We have also found GM deficits in "sensori-motor" areas (specifically in perirolandic cortex and supplementary motor area), and in the cerebellum. On the one hand, deficits in sensori-motor areas probably reflect problems in fine motor coordination. However, the fact that these reductions are especially prominent in combined and inattentive subtypes brings up the possibility that they may be related to attentional dysfunctions.
I hypothesized that deficits in these regions may produce a deficit when integrating and updating information from the external world and, in turn, produce a bias toward internal world focusing, thus, resulting in inattention. On the other hand, cerebellar reductions (which are extensively reported in ADHD literature) seem to be related to all cognitive, affective and sensorimotor deficits. The implication of cerebellum in all these dysfunctions may arise from its role as a modulator of the flow of information between fronto-strital circuits. Finally, our findings are also the first to show caudate head and body differential abnormalities in ADHD, which explain previous heterogeneous results, providing a new and reliable method to study striatal structures.
As a conclusion, GM volume reductions in emotional and cognitive areas support the implication of both hot (emotional) and cool (cognitive) functions, which agrees with most neuropsychological accounts of ADHD. To our knowledge this is the first time that a neuroanatomical study provides support for the existence of both cognitive and emotional dysfunctions in ADHD children. If these findings are replicated, they will constitute critical evidence for Sonuga-Barke's theory (Sonuga- Barke 2002; Sonuga-Barke 2003) about the dual route model.
REFERENCIAS:
1. Tremols V, Bielsa A, Soliva JC, Raheb C, Carmona S, Tomas J, et al. (2008): Differential abnormalities of the head and body of the caudate nucleus in attention deficit-hyperactivity disorder. Psychiatry Res. 163:270-278.
2. Carmona S, Vilarroya O, Bielsa A, Tremols V, Soliva JC, Rovira M, et al. (2005): Global and regional gray matter reductions in ADHD: a voxel-based morphometric study. Neurosci Lett. 389:88-93.
3. Castellanos FX, Tannock R (2002): Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes. Nat Rev Neurosci. 3:617-628.
5. Sonuga-Barke EJ (2003): The dual pathway model of AD/HD: an elaboration of neuro-developmental characteristics. Neurosci Biobehav Rev. 27:593-604.
6. Sonuga-Barke EJ (2002): Psychological heterogeneity in AD/HD--a dual pathway model of behaviour and cognition. Behav Brain Res. 130:29-36.

Orientador: Rubens Nelson Amaral de Assis Reimão
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Esse estudo avalia a associação entre Transtorno do Déficit de Atenção e Hiperatividade (TDAH) e distúrbios do sono para caracterizar fatores clínicos e problemas associados. No primeiro artigo nós revisamos diversas pesquisas sobre alterações do sono em crianças com Transtorno do Déficit de Atenção e Hiperatividade (TDAH) com ou sem o tratamento com psicoestimulantes. No segundo artigo fizemos revisão de prontuários de 50 crianças e adolescentes com idade de 4 a 17 anos e consecutivo diagnóstico de TDAH sem diagnóstico de retardo mental ou transtornos invasivos do desenvolvimento. Resultados: estudos do sono têm sido realizados e anormalidades durante o sono como Síndrome das Pernas Inquietas (SPI), Movimentos Periódicos dos Membros Durante o Sono (MPMS), Distúrbios Respiratórios do Sono (DRS) podem ser responsáveis por muitos sintomas de TDAH. Crianças com distúrbios de sono nos primeiros meses de vida foram associados com desenvolvimento de sintomas de TDAH ainda na infância. Foram encontradas associações significativas entre alterações do sono e farmacoterapia (p<0,01), comorbidade (p<0,01) e maior aderência ao tratamento prescrito para sintomas de TDAH (p<0,05). Conclusões: avaliação de distúrbios do sono deve ser considerada antes de iniciar tratamento farmacológico para TDAH porque os critérios diagnósticos baseados no DSM-IV ou CID-10 não diferenciam entre crianças com ou sem distúrbios do sono. O conhecimento sobre os distúrbios do sono pode trazer uma nova oportunidade de tratamento para algumas crianças com TDAH. Serão necessárias novas pesquisas para clarear a relação entre distúrbios do sono e TDAH, ou os efeitos dos estimulantes no sono de crianças com TDAH. Descritores: Transtornos do Sono, Transtornos do Comportamento Infantil, Sono, Transtorno da Falta de Atenção com Hiperatividade, Literatura de Revisão
Abstract: This study examined the relationship between Attention Deficit Hyperactivity Disorder (ADHD) and sleeps disorders to chacterize clinical features and associated problems. In the first paper we review several researches about sleep disturbances in children with Attention-Deficit Hyperactivity Disorder (ADHD) with or without psychostimulant treatment. In the second paper we performed a record review for 50 consecutive children and adolescents aged 4 to 17 years with ADHD who do not have mental retardation or pervasive developmental disorders. Results: sleep studies have been performed and abnormalities during the sleep such Restless Legs Syndrome (RLS), Periodic Limbs Moviments in Sleep (PLMS), Sleep-Disorder Breathing (SDB) could be responsible for severe diurnal ADHD symptoms. Infants with sleep disorders were associated with development of ADHD in later childhood. Significant relationship were found between sleep disturbances and pharmacotherapy (p<0.01), comorbidity (p<0.01) and greatest adherence to treatment prescribed for symptoms of ADHD (p<0.05). Conclusions: evaluation of sleep disorders should be considered before starting drug treatment for ADHD because diagnostic criteria for ADHD based on DSM-IV or ICD-10 do not differentiate between children with or without sleep disorders. Assessment for sleep disorders may provide a new treatment opportunity for some ADHD children. Future researchs will need to clarify the relationship between sleep disorders and ADHD or the effects of stimulants on sleep de children with ADHD
Mestrado
Saude da Criança e do Adolescente
Mestre em Pediatria

Essa dissertação é o resultado de um projeto de pesquisa desenvolvido no Programa de Pós Graduação Stricto Sensu da Faculdade de Educação da Universidade Federal de Uberlândia, como requisito parcial para a obtenção do título de mestre em educação. Tivemos como objetivo analisar como a escola e os professores atuavam frente ao diagnóstico multiprofissional do TDAH e como a psicopedagogia poderia auxiliar na práxis docente junto à criança diagnosticada. No primeiro capítulo, intitulado “O quebra cabeça de uma vida”, apresentamos o meu caminhar profissional, que fez compreender os questionamentos que nortearam a pesquisa atual. Em seguida, com intuito de respaldar teoricamente as análises deste trabalho, apresentamos o segundo capítulo – “Começando o quebra cabeça do TDAH: as primeiras peças”. Abordamos os aportes teóricos sobre o transtorno e sobre temas relevantes que auxiliaram na melhor compreensão do universo ao qual o TDAH se inseria: a importância dos vínculos, dentre eles o do professor-aluno, o diagnóstico multiprofissional, conceitos sobre aprendizagem e avaliação dentro do viés psicopedagógico, o papel da escola frente ao TDAH, e a medicalização/ patologização advindos com o transtorno. Para obtenção dos dados da pesquisa realizamos entrevistas semi estruturadas com professores, pedagogos, diretores e com as crianças diagnósticas inseridas nas escolas às quais estavam matriculadas. Também foram realizadas duas técnicas projetivas (Par Educativo e Planta da Sala de Aula) com as respectivas crianças para que pudéssemos entender como elas representavam o espaço escolar e os vínculos com suas aprendizagens. Na realização das análises dos dados, utilizamos o recurso da análise categorial, onde os dados foram organizados em três categorias: “Peça um: as concepções e o trabalho da instituição escolar em prol da criança diagnosticada com TDAH”, onde pudemos observar quais eram as visões dos profissionais acerca do transtorno e quais os procedimentos realizados pela escola enquanto instituição para viabilizar a educação das crianças diagnosticadas; “Peça dois: As contribuições pedagógicas voltadas para a criança com TDAH no contexto da sala de aula”, que apresentou a forma com que as ações pedagógicas são oportunizadas no contexto da sala de aula para a criança diagnosticada com TDAH; e “Peça três: O olhar da criança diagnosticada com o TDAH frente às ações direcionadas ao seu ensino e aprendizagem”, que buscou compreender a visão da criança diagnosticada em relação a escola e suas ações. Como resposta aos questionamentos iniciais, concluímos que mesmo com o laudo da criança a escola ainda não possui formação nem informação que a respalde para desenvolver um trabalho específico para a criança com TDAH, assim como as crianças diagnosticadas com TDAH não compreendem que as ações desenvolvidas são para a melhoria de seu processo de aprendizagem apesar do transtorno. Dessa forma a psicopedagogia seria uma alternativa para compreender os processos do aprender, o como avaliar, conhecer e atuar em conjunto com a escola, criança e família, oportunizando uma abordagem mais ampla e além do transtorno, com melhorias na qualidade da educação, não somente para as crianças diagnosticadas, mas a todas inseridas no contexto escolar.
This text is the result of a research developed at EducationalStrictu Sensu’s Post Graduation Program at Uberlândia’s Federal University, as a partial requirement to the Educational Master Degree. Our goal was to analyze how school and teachers worked with ADHD’s mutiprofessional diagnosis and how psychopedagogy could help on teacher’s praxis with ADHD’s children. At the first chapter, titled as “A puzzle of a life” we presented my professional construction, which made understand the questions that guided this research.Then, with the intuitto back up theoretically this work’s analysis, we presented the second chapter – “Starting the ADHD’s puzzle: first pieces”. There we found the theoretical support about the disorder and relevant themes that helped to better understand ADHD’s universe: the importance of bounds, specially teacher and students ones, the multiprofessional diagnosis, learning and evaluation concepts based on psychopedagogy understanding, school’s role into ADHD children’s education, the disturb’s medicalization/ pathologisation. To get the research’s data we did semi-structured interviews with teachers, teachers’ supervisors, principals and children diagnosed into their schools. It was also done two projective techniques (Educative Couple and Classroom’s floor plant) with the related children so we could understand how they represented school’s space and their learning bounds. Into the analysis, we decided to use categorical analysis, where the data was divided in 3 parts: “Piece one: the school’s conceptions and work with ADHD’s children”, where we could see which was the professional’s understanding about the disorder and the procedures as an institution to support diagnosed ADHD’s children education; “Piece two: the pedagogical contributions inside the classroom to ADHD’s children”, that presented how pedagogical acts was done inside the classroom to them; and “Piece three: the way ADHD’s children see the actions done to their education and learning process”, which tried to understand how children saw their school and the actions done by them. As an answer to our initial questions, we realized that, even with the diagnosis, school still haven’t have enough information and the right educative formation to help develop an specific work with ADHD’s children, as children don’t realize specifically the actions that has been done to make their learning process better instead of the disorder. Because of it, psychopedagogy would be a bridge to understand learning processes, as to evaluate, understand and act together with the school, the child and the family, bringing a new approach beyond the disorder itself, with better education quality not just for diagnosed children, but to all students in the scholar context.
Dissertação (Mestrado)

Introdução: Em crianças e adolescentes, o Transtorno de Humor Bipolar (THB) é associado a danos devastadores no desenvolvimento. O Transtorno de Déficit de Atenção/Hiperatividade (TDAH), caracterizado por sintomas de desatenção, hiperatividade e impulsividade também causa prejuízo funcional significativo. O diagnóstico diferencial entre os dois transtornos é puramente clínico e, até o momento, há poucos estudos avaliando diferenças neurobiológicas. Diversas pesquisas sugerem a participação do Fator Neurotrófico Derivado do Cérebro (BDNF), cujo papel não foi elucidado em crianças e adolescentes com THB e com TDAH. Apesar das altas taxas de comorbidade entre o THB e o TDAH, de uma pior resposta ao tratamento e de um pior funcionamento psicossocial quando da comorbidade, apenas dois estudos avaliaram a resposta ao tratamento especificamente neste grupo de pacientes. Objetivos: O objetivo principal deste trabalho é avançar no entendimento do papel do BDNF na psicopatologia do THB e do TDAH, visando sua diferenciação. O tratamento da comorbidade com estimulantes tambem foi estudado. Métodos: A transmissão do alelo Val66 do BDNF foi avaliada em famílias de crianças e adolescentes com THB e TDAH, assim como o efeito do gene no nível sérico da proteína do BDNF entre os grupos. Foi realizada a comparação dos níveis séricos entre pacientes com THB em comorbidade com TDAH e TDAH isolado. Um estudo clínico cruzado com estimulantes foi realizado em crianças e adolescentes com THB e TDAH em comorbidade que tinham apresentado remissão dos sintomas de humor com o uso de aripiprazol, mas persistência dos sintomas de TDAH. Os sintomas de mania, depressão, desatenção e hiperatividade foram acompanhados ao longo de quatro semanas de tratamento, duas com placebo ou metilfenidato e duas com o tratamento inverso. Resultados: Na investigação da transmissão do gene do BDNF em crianças e adolescentes não foi detectada diferença significativa na transmissão do alelo Val66. Tampouco foi observada diferença significativa nos níveis séricos da proteína do BDNF entre os pacientes com THB em comorbidade com TDAH, quando comparados aos pacientes com TDAH e controles. No estudo cruzado com crianças e adolescentes com THB em comorbidade com TDAH, não houve diferenças entre os grupos com placebo ou estimulantes na resposta ao tratamento nos sintomas de TDAH. Os sintomas de humor mantiveram-se estáveis a despeito do uso de metilfenidato. Conclusões: Os achados quanto ao gene do BDNF não sugerem sua participação na neurobiologia do THB ou no TDAH, ou que devido à herança poligênica característica dos transtornos mentais, sua participação seja pequena. O achado de diferença significativa entre os níveis séricos do BDNF de crianças e adolescentes com THB+TDAH e TDAH indica que esse tema deve ser mais estudado, e, caso seja também encontrado de forma consistente por outros grupos, possa vir a ser utilizado como marcador biológico na diferenciação diagnóstica entre essas condições. No estudo de tratamento da comorbidade entre THB e TDAH, a ausência de resposta ao metilfenidato nos sintomas de TDAH em pacientes que apresentam a comorbidade reforça a evidência de que há pior resposta ao tratamento neste grupo, dado o elevado tamanho de efeito do metilfenidato no tratamento do TDAH em isolado O estudo de fatores biológicos para um melhor entendimento da psicopatologia e conseqüente diferenciação dos transtornos mentais tem extrema relevância porque a identificação destes fatores pode auxiliar na elaboração de tratamentos mais precisos, urgentemente necessários devido às graves conseqüências do THB e do TDAH nas vidas dos pacientes e de suas famílias. A criação de um programa específico para Crianças e Adolescentes com Transtorno Bipolar (ProCAB) e de uma linha de pesquisa com foco na etiologia e tratamento possibilitam uma constante geração de conhecimento nesta área, onde poucos estudos estão disponíveis.
Introduction: Bipolar Disorder (BD) in children and adolescents is associated to devastating developmental deficits. Attention-Deficit/Hyperactivity Disorder (ADHD), characterized by inattention, hyperactivity, and impulsivity, also promotes significant impairment. Differential diagnosis between both conditions is purely clinical – currently, there are scarce investigations on neurobiological differences. Several studies suggest the participation of the Brain-Derived Neurotrophic Factor (BDNF) in these disorders, whose role has not been elucidated in BD and ADHD in children and adolescents. Despite high comorbidity rates between BD and ADHD, worse psychosocial functioning, and worse response to treatment, only two studies addressed treatment response specifically in this group of patients. Objectives: promote advances in understanding the role of BDNF in the psychopathology of BD and ADHD. The treatment of the comorbidity was also studied. Methods: Transmission of the Val66 allele at the BDNF was assessed in children and adolescents with BD and ADHD, as well as the effect of the gene on the serum levels of BDNF protein in both conditions. BDNF serum levels were compared between patients with BD comorbid with ADHD, and ADHD. A crossover clinical trial with stimulants and placebo was performed with children and adolescents preseting BD and comorbid ADHD. Manic, depressive, inatention and hyperactivity symptoms were assessed along a 4-week treatment, 2 weeks in each treatment arm (placebo or stimulants). Results: There was no significant transmission of the Val66 allele at the BDNF gene in children and adolescents with BD or ADHD. A significant difference in BDNF protein serum levels between BD+ADHD when compared to ADHD alone and controls. In the crossover trial with children and adolescents with BD and comorbid ADHD, we did not observe differences between the placebo and stimulant treatment groups in the response of ADHD symptoms. Mood symptoms remained stable despite the use of methylphenidate. Conclusions: our results regarding the BDNF gene do not suggest its participation in the neurobiology of BD or ADHD, or that due to the polygenic characteristic of mental disorders, that this gene confers a only a small risk, undetectable in our sample. The finding of a significant difference in BDNF serum levels between BD comorbid with ADHD, and ADHD alone warrants further investigation, and in case replication studies with larger samples from other groups are positive, BDNF serum levels might be used as a biological marker in the diagnostic difference between these conditions. In the investigation of the treatment of the comorbidity between BD and ADHD, the absence of different responses between placebo and methylphenidate in ADHD symptoms strengthens the evidence that there is a worse response to treatment in this group, given the large effect size of methylphenidate response in the treatment of ADHD alone. The quest for biological markers for a better understanding of the psychopathology and subsequent differentiation of mental disorders is extremely relevant. The identification of these factors may facilitate the creation of more accurate treatment regimens, urgently needed due to the severe developmental consequences of BD and ADHD in the patients’ and families’ lives. In this sense, the creation of a specific outpatient program for children and adolescent BD (ProCAB), a research line with focus on risk factors and treatment, will enable a Constant generation of knowledge in this área, where scarce data is available.

Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in early childhood and adolescence and its consequences can persist through adulthood. It is characterized by continuous inattention and/or hyperactivity- impulsivity. Cognitive impairments are also associated with this disorder. The etiology of ADHD continues to be debated, although several contributing factors have been acknowledged, including diet and sleep. Several studies have analyzed the association between dietary patterns and ADHD. The common result is that unhealthy dietary patterns (i.e. high in saturated fat, refined sugars and low in fruits and vegetables) are associated with ADHD. Although the mechanisms linking low quality diet and ADHD are still unknown, an unbalanced diet, can lead to deficiencies in essential nutrients or higher intakes of certain food components. For instance, low levels of serum iron, ferritin, and long-chain omega-3 seem to have a relationship with ADHD. Specifically, iron deficiency has been reported to be a possible risk factor in the pathophysiology of ADHD. However, to date, the results regarding the potential relationship between iron deficiency and ADHD have shown some inconsistency. On the other hand, sleep disturbances are particularly widespread in ADHD and they contribute to ADHD symptomatology. Moreover, there is evidence that suggest an additional and independent relationship between diet and sleep. The data on this topic are really scarce but associations between more sleep disturbance and higher intakes of carbohydrates, fat, and, most particularly, sugar have been reported. Serum iron levels and long-chain polyunsaturated fatty acid also seem to play a role in the sleep quality of children and adolescents with ADHD. Therefore, the aim of the present thesis project is to assess the possible relationship between our characteristic and healthy dietary pattern, the Mediterranean diet, and the incidence of ADHD. Moreover, the influence of the dietary intake and nutrient deficiencies in children and adolescents with ADHD on their behavioral symptoms and their cognitive abilities as well as their sleep quality will be also analyzed

El trastorn per dèficit d’atenció amb hiperactivitat (TDAH) és un trastorn del neurodesenvolupament caracteritzat per símptomes d’inatenció i/o hiperactivitat/impulsivitat. Nombrosos estudis suggereixen un important component genètic en l’etiologia del TDAH, amb una heretabilitat estimada del 70-80%. Tanmateix, la majoria de variants genètiques identificades només expliquen una petita proporció de la variabilitat fenotípica observada i la seva associació, en general, no ha estat replicada consistentment. A més, s’han descrit diversos factors ambientals que tendeixen a incrementar el risc de presentar TDAH i que sovint contribueixen a agreujar-ne les manifestacions. Les discrepàncies en els resultats obtinguts, per tant, podrien ser degudes, entre d’altres, a la influència de variables ambientals, capaces de modular els efectes dels factors genètics a través d’interaccions gen × ambient. Pel que fa a l’abordatge terapèutic del TDAH, el principal tractament farmacològic consisteix en l’administració de psicoestimulants com el metilfenidat (MPH), un potent inhibidor de la recaptació de dopamina. No obstant això, aproximadament un 30% dels pacients no respon adequadament al fàrmac, fet que podria estar determinat, en part, per influències genètiques. La recerca farmacogenètica del MPH s’ha centrat de forma quasi exclusiva en gens suposadament relacionats amb el seu mecanisme d’acció, entre els quals destaquen el transportador de dopamina (SLC6A3) i el receptor dopaminèrgic D4 (DRD4), malgrat que els resultats aportats han estat predominantment negatius o discordants. La majoria d’investigacions, a més, han avaluat un únic o un nombre molt reduït de polimorfismes en base a la seva presumpta rellevància funcional, sense tenir en compte la possible interacció entre ells o amb influències ambientals. L’objectiu de la present tesi doctoral fou, per una banda, aprofundir en els processos etiològics implicats en el TDAH mitjançant un estudi d’associació amb vuit gens candidats (DRD4, SLC6A3, COMT, ADRA2A, CES1, CYP2D6, LPHN3 i OPRM1) en què s’avaluaren dotze polimorfismes potencialment funcionals en una mostra de sis-cents quatre pacients adults i sis-cents onze individus control. A continuació, s’investigà la influència d’experiències estressants durant la infantesa en la gravetat del trastorn, així com la possible interacció entre l’adversitat ambiental i les variants genètiques de risc identificades. Els resultats de l’esmentat estudi revelaren la contribució de DRD4 en la persistència del TDAH a l’edat adulta i proporcionaren evidències preliminars sobre el seu paper com a mediador de l’efecte que els esdeveniments vitals adversos exerceixen en la gravetat de la simptomatologia. Per altra banda, es proposà identificar marcadors genètics de la resposta i la tolerabilitat al MPH. Per a aquesta finalitat, s’empraren dues estratègies complementàries. En primer lloc, s’examinaren cinquanta-set polimorfismes distribuïts al llarg dels principals gens de la neurotransmissió dopaminèrgica (DRD1-5, SLC6A3, TH, COMT i DBH) en una mostra de cent set pacients pediàtrics amb TDAH. A més, s’explorà la influència de variables ambientals pre i perinatals en els efectes del tractament, així com la presència d’interaccions gen × gen i gen × ambient. Els resultats de la segona investigació suggeriren la implicació de DRD3, DBH, TH i l’exposició prenatal al tabac en l’eficàcia clínica del MPH. Concretament, s’observà un major risc de resistència al tractament en individus susceptibles genèticament i amb mares fumadores durant l’embaràs mentre que l’aparició d’efectes adversos s’associà a la variabilitat a DBH i DRD2. En segon lloc, s’analitzà l’associació amb la resposta al MPH a escala genòmica en cent setanta-tres infants amb el trastorn. Les dades obtingudes es combinaren amb evidències biològiques i bioinformàtiques, fet que posà de manifest la participació de gens relacionats amb el desenvolupament i funció del sistema nerviós, malalties neurològiques i psiquiàtriques, com el dèficit d’aprenentatge, o la conducta, com el comportament hiperactiu. En definitiva, els resultats que conformen la present tesi doctoral aporten informació innovadora i rellevant al camp de l’etiologia i la farmacogenètica del TDAH a través de la identificació de loci genètics implicats en el sistema dopaminèrgic i el neurodesenvolupament, i de factors ambientals com els esdeveniments vitals estressants o el consum matern de tabac durant l’embaràs.
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a strong genetic component. However, most of the identified genetic variants explain only a small proportion of the phenotypic variance. Additionally, several environmental factors have been reported to increase the risk and severity of ADHD. Thus, the absence of clear conclusions might be caused by environmental influences that moderate the effects of genetic factors through gene-environment interactions. Stimulant medications such as methylphenidate (MPH), a dopamine reuptake inhibitor, are generally the first-line choice in ADHD pharmacological treatment. Nevertheless, approximately 30% of ADHD patients do not respond favorably to treatment, which may reflect underlying genetic influences. Pharmacogenetic studies of MPH have focused on genes presumably related to its mechanism of action, especially the dopamine transporter (SLC6A3) and the dopamine receptor D4 (DRD4), although findings have been predominantly negative or inconsistent. Furthermore, the majority of investigations have evaluated a single or few polymorphisms based on their putative functional implications, without considering the possible interaction between them or with environmental factors. The objective of the present doctoral thesis was to elucidate the etiological processes implicated in ADHD through an association study with eight candidate genes (DRD4, SLC6A3, COMT, ADRA2A, CES1, CYP2D6, LPHN3 and OPRM1), which examined 12 potentially functional polymorphisms in a sample of 604 adult patients and 611 controls. We subsequently investigated the impact of childhood stressful experiences on the severity of ADHD, as well as the possible interaction between environmental adversity and the identified genetic risk variants. On the other hand, the doctoral thesis aimed to identify pharmacogenetic markers of MPH response and tolerability. Firstly, we analyzed 57 polymorphisms across the main genes of the dopaminergic neurotransmission (DRD1-5, SLC6A3, TH, COMT and DBH) in a sample of 107 ADHD pediatric patients. We also explored the influence of prenatal and perinatal risk factors on treatment effects, as well as the presence of gene-gene and gene-environment interactions. Secondly, we conducted a genome-wide association study of MPH response in 173 children with ADHD and we combined the data obtained with bioinformatic and biological evidence. The results of the present doctoral thesis provide innovative and relevant information to the field of ADHD etiology and pharmacogenetics through the identification of genetic loci implicated in the dopaminergic system and neurodevelopment, and environmental factors such as stressful life events or maternal smoking during pregnancy.

El Trastorno por Déficit de Atención e Hiperactividad (TDAH) es el trastorno psiquiátrico infantil más estudiado en la actualidad, suscitando un enorme interés en las dos últimas décadas debido en gran parte a su elevada prevalencia. Se trata de un trastorno con diferentes formas de expresión a lo largo de la infancia, la adolescencia y la edad adulta, con un gran impacto en el paciente, la familia y la sociedad. Sus consecuencias se traducen en un alto coste económico por la necesidad de recursos educativos, sanitarios y sociales que genera. Los estudios científicos internacionales respaldan que el TDAH es un trastorno complejo del neurodesarrollo con múltiples causas, siendo la genética una de las más determinantes. Sin embargo, para tener una comprensión transversal y adecuada del trastorno, es imprescindible contemplar la influencia biológica desde un enfoque interactivo, teniendo en cuenta el importante papel modulador que ejerce el ambiente psicosocial. Los subsistemas sociales, familiares y escolares en los que se desarrolla el niño van a tener una gran influencia en el curso del TDAH, tanto en su detección como en su evolución. Sabemos por la bibliografía previa que el nivel socioeconómico, la presencia de psicopatología en alguno de los progenitores y el nivel de estrés psicosocial familiar van a influir en las actitudes y pautas educativas de los padres, y en general en el desarrollo del ejercicio de la paternidad. El estudio que aquí se presenta pretende analizar la psicopatología presente en los progenitores de niños diagnosticados de TDAH, puesto que éste puede considerarse un problema familiar que se da en un marco de relaciones donde todos los miembros de la familia se ven influenciados, y la presencia de enfermedad mental o de psicopatología en los padres va a influir notablemente en la detección, la evolución y la aparición de comorbilidades. En este estudio se ha analizado y comparado la presencia de psicopatología parental general, así como la presencia de sintomatología propia del TDAH en los progenitores de 60 niños con dicho trastorno, frente a progenitores de 60 niños no afectos de TDAH. Así mismo, también se ha analizado y comparado la percepción de malestar emocional en los progenitores de niños con diagnóstico reciente de TDAH, frente a progenitores de niños sin TDAH. Como resultados de nuestro estudio se encontraron entre los progenitores de niños con TDAH prevalencias más elevadas de antecedentes de TDAH en la infancia (20,33% en las madres y 25% en los padres), trastorno por consumo de sustancias (6,67%) y, en el límite de la significación para la depresión postparto (15%). En cuanto a la psicopatología activa se encontraron mayores prevalencias de TDAH actual (25,42% en las madres y del 21,43% en los padres). Por otro lado, los progenitores de niños con TDAH informaron de mayor malestar emocional en comparación a los progenitores de niños sin TDAH (42,37% en las madres y 26,79% en los padres). En conclusión, los progenitores de niños con TDAH presentan mayor psicopatología en comparación a los progenitores de niños sin TDAH.
The attention-deficit hyperactivity disorder (ADHD) is the most reviewed children’s psychiatric disorder nowadays. It has aroused great interest in the last two decades due to its high prevalence. This disorder has several forms of levelled appearances during childhood, adolescence and adulthood, with a great impact on the patient, family and society. Its consequences involve a high economical cost due to the essential need of educational, healthcare and social resources that it demands. The international scientific studies support that ADHD is a complex neurodevelopmental disorder with several causes, having genetics as one of the most decisive ones. Nevertheless, to achieve an adequate transversal comprehension of the disorder it is essential to contemplate the biological influences from an interactive perspective, taking into account the important modulating role that the psychosocial environment exerts. The social, family and scholar subsystems where the child develops are going to have a great influence in the progress of the ADHD. In both aspects: its detection and evolution. Previous studies and bibliography suggest that socio- economic status, where the presence of psychopathology in one of the parents and the domestic psycho-social stress; are going to influence the educational attitudes and behavioral patterns of the parents, as well as the delivered parenthood. The study presented in this document, simulates the analyze of the psychopathology in 60 families with ADHD diagnosed children since this might be considered a family matter, appearing in a relationship framework; where all family members are influenced and the presence of mental disease of psychopathology in the parents will influence relevantly in the detection, evolution and appearance of comorbidities. The study has analyzed and compared the presence of general parental psychopathology, as well as the presence of ADHD specific symptomatology in the progenitors of 60 children with that disorder compared to progenitors of 60 children not affected by ADHD. In addition, it has been analyzed the perception of emotional discomfort in the parents of children with and without ADHD. As result of our study, the parents of children with ADHD were found to have higher prevalence of ADHD in childhood (20.33% in mothers and 25% in fathers), history of substance use disorder (6.67%) and, at the limit of significance for postpartum depression (15%). Regarding the active psychopathology, higher current ADHD prevalence was found. The 25.42% of the mothers suffered current ADHD and the 21.43% of the fathers. On the other hand, parents of children with ADHD reported increased emotional discomfort compared to parents of children without ADHD (42.37% in mothers and 26.79% in fathers). In conclusion, parents of children with ADHD have greater psychopathology compared to parents of children without ADHD.

Antecedentes y objetivos: el tempo cognitivo lento (TCL) se ha asociado, desde su definición, al trastorno por déficit de atención con hiperactividad subtipo inatento (TDAH-I). Se han hallado síntomas TCL en el trastorno por déficit de atención con hiperactividad subtipo combinado (TDAH-C), en otros trastornos psiquiátricos y en grupos clínicos sin trastorno mental. Existen correlaciones entre los síntomas de TCL y síntomas de ansiedad, depresión, dificultades de regulación emocional de emociones negativas, mayor sensibilidad al castigo, evitación social, bajo rendimiento académico y con un peor funcionamiento social. La validez estadística de los síntomas TCL ha quedado demostrada diferenciándose del TDAH y presentando unas características propias. Los estudios de población general sugieren que probablemente los síntomas TCL presenten diferentes correlatos socio-demográficos, asociación con determinados déficits de funciones ejecutivas y diferentes ámbitos de discapacidad psicosocial en relación al TDAH. Los objetivos de esta tesis son: realizar una revisión del concepto TCL, determinar su prevalencia, características clínicas y sociodemográficas en la población general y clínica infanto-juvenil, estudiar la relación entre TDAH y TCL y finalmente delimitar el perfil neuropsicológico específico para los síntomas TCL. Métodos: para llevar a cabo los objetivo se han realizado 4 estudios. El primero, se trata de una revisión sistemática de la literatura. Para determinar las prevalencias, características clínicas, y conductuales tanto en población general infanto-juvenil como clínica se realizaron el segundo y tercer estudio, respectivamente. Y, finalmente, el cuarto estudio, en la muestra de población general infantil, se estudió el perfil neuropsicológico asociado a los síntomas TCL. Resultados: se han hallado síntomas TCL tanto en población general como clínica, duplicándose en esta última. Se asocian a genero masculino, a población clínica y a mayor edad. La exposición al tabaco (peri-natal y a terceros) son factores asociados a los síntomas TCL así como una elevada vulnerabilidad socioeconómica. El perfil clínico viene caracterizado por sintomatología internalizante, problemas con iguales, problemas emocionales, síntomas de inatención con mayor afectación en la población clínica. En el ámbito escolar presentan más problemas académicos y mayor número de síntomas de dislexia. Parece ser que esto se traduce en la población clínica en más síntomas de TCL en los trastornos del aprendizaje que en el TDAH. Siendo un factor de riesgo los síntomas TCL a padecer un trastorno del aprendizaje. Los niños de la población general con síntomas TCL presentan más diagnósticos de TDAH y en la población clínica de TDAH-I. Sin embargo, los síntomas TCL están presentes en otros trastornos psiquiátricos a parte del TDAH. Finalmente, los niños con síntomas TCL presentan un perfil neuropsicológico específico que puede diferenciarse del TDAH. Presentan mayores tiempos de reacción, peor memoria de trabajo y mayor afectación de la red de conflicto. Cuando estudiamos los mismos niños excluyendo los que tienen diagnóstico de TDAH el perfil emergente se caracteriza por: mayores tiempos de reacción y peor memoria de trabajo. Conclusiones: Los síntomas TCL se asocian a unas características sociodemográficas, clínicas y neuropsicológicas específicas. EL perfil neuropsicológico asociado a los síntomas TCL es distinto al del TDAH. Se recomienda su valoración tanto en ámbito escolar y clínico para poder realizar evaluaciones y tratamientos más precisos para estos niños.
Background and objectives: Sluggish cognitive tempo (SCT) has been associated, ever since it was first defined, with attention deficit hyperactive disorder, inattentive subtype (ADHD-I). SCT symptoms have been observed in ADHD, combined subtype (ADHD-C), in other psychiatric disorders and in clinical groups with no mental disorder. There are correlations between the symptoms of SCT and symptoms of anxiety disorders, depression, problems controlling negative emotions, heightened sensitivity to punishment, social disengagement, low academic achievement and with impaired social functioning. The statistical validity of SCT symptoms has been demonstrated through their differentiation from ADHD and the presenting of specific characteristics. Studies carried out among the general population (both in adults and in children) suggest that SCT symptoms present different socio-demographic correlates, association with specific executive function deficits and different areas of psychosocial disability related to ADHD. The objectives of this doctoral thesis are: to review the concept of SCT; to determine the prevalence of SCT, its clinical and sociodemographic characteristics in the general population and in the infant-adolescent clinical population; to study the relation between ADHD and SCT; and finally, to delimit the specific neuropsychological profile of SCT symptoms. Methods: In order to achieve those objectives, I have carried out four studies as part of an active research group. The first was a systematic review of the literature. The next two studies aimed to determine the prevalence, and the clinical and behavioural characteristics of SCT in both the general (second study) and clinical (third study) infant-adolescent populations. Finally, in the fourth study, I studied the neuropsychological profile associated with SCT symptoms in the general infant population sample. Results: I found SCT symptoms in both the general and the clinical populations, with the prevalence in the latter being twice that in the former. They are associated with being male, with forming part of the clinical population and with increasing age. Exposure to tobacco smoke (both perinatally and passively) is associated with SCT symptoms as is increased socioeconomic vulnerability. The clinical profile is characterised by an internalising symptomology, problems in peer relations, emotional problems and symptoms of inattention, all more frequently in the clinical population. Within a school setting, children exhibiting SCT symptoms present more academic problems and a greater frequency of dyslexia symptoms. It appears that in the clinical population this translates into more SCT symptoms in learning disorders than in ADHD: SCT symptoms can be seen as a risk factor for suffering from a learning disorder. Children in the general population with SCT symptoms present more ADHD diagnoses and in the clinical population more for ADHD-I. However, SCT symptoms are present in psychiatric disorders other than ADHD. Finally, children with SCT symptoms present a specific neuropsychological profile which can be differentiated from that of ADHD. They have increased reaction times, worse working memory and more problems with their conflict resolution networks. When I studied the same sample of children but excluding those with an ADHD diagnosis, the profile that emerged was characterised by increased reaction times and worse working memory. Conclusions: SCT symptoms are associated with specific sociodemographic, clinical and neuropsychological characteristics. The neuropsychological profile associated with SCT symptoms is different from that of ADHD; and it should be assessed both in school and clinical settings to facilitate more precise evaluation and treatment.

El trastorno de déficit de atención e hiperactividad (TDAH) es el trastorno más común en la infancia y adolescencia y sus consecuencias suelen persistir hasta la edad adulta. La etiología de este trastorno es compleja, sin embargo el TDAH parece presentar anormalidades estructurales y funcionales que responden a una combinación de varios factores ambientales y genéticos, que además se han relacionado con múltiples comorbilidades y problemas de salud que afectan la calidad de vida de quien lo padece. Esta tesis doctoral presenta los resultados obtenidos en un estudio de casos y controles realizado en el Hospital Sant Joan de Déu-Barcelona y en el Departamento de Nutrición, ciencias de la alimentación y gastronomía de la Universidad de Barcelona. Este estudio fue realizado en población pediátrica con TDAH y controles sanos. Se ha planteado como objetivo general, evaluar el impacto de la alteración de ciertos ritmos circadianos, la alimentación y la variabilidad genética en la sintomatología y comorbilidades de este trastorno. Concretamente se obtuvieron resultados de las alteraciones de los ritmos circadianos de la actividad motora y su relación con la sintomatología y subtipos de TDAH. Se evaluó también el papel de la variabilidad de intensidad de la luz en las variables circadianas actividad motora y el papel de la dieta en los problemas y disturbios del sueño de estos pacientes. Se presentan también los resultados del análisis de un polimorfismo funcional de la región promotora de la serotonina (5-HTTLPR) relacionado con los síntomas internalizantes y externalizantes pacientes con TDAH, además se muestra por vez primera la relación de este polimorfismo con la desregulación emocional. Finalmente, se describe el importante papel del estado del hierro en la sintomatología de este desorden. Estos resultados reflejan la importancia del abordaje multidisciplinario y contribuyen a la comprensión de los mecanismos internos y externos que pueden estar relacionados con el TDAH.

In this thesis, the Adaptative Hypermedia Systems (AHS) are used to generate e-Learning processes that consider the characteristics of university students who suffer from Attention Deficit Hyperactivity Disorder (ADHD). Overall, it was proposed a solution that ranges from symptoms detection to academic intervention. Specifically, it was developed a student model based on personal, demographic, academic, behavioral conduct, background and cognitive performance information to create personal student profiles, which indicate if an e-Learning student could have ADHD symptoms. Afther that, considering preferences and strengths of university students suffering from ADHD, three didactic strategies were integrated in the academic environment with the aim of obtaining a better e-Learning experience and academic performance, these strategies are: a serious game, a reusable learning object based on gamification and the use of Universal Design for Learning (UDL).
En esta tesis, los Sistemas Hipermedia Adaptativos (SHA) son usados para generar procesos de formación e-Learning que consideran las características de los estudiantes universitarios que sufren del Trastorno por Déficit de Atención e Hiperactividad (TDAH). De manera general, se desarrolló un proceso que va desde la detección de síntomas hasta al apoyo académico. Específicamente, se desarrolló un modelo del estudiante que considera información personal, demográfica, académica, comportamental, histórica y cognitiva para identificar si un estudiante e-Learning puede tener síntomas del TDAH. Después de ello, considerando las preferencias y fortalezas de los estudiantes con TDAH, se integraron dos estrategias didácticas en el proceso académico, una basada en videojuegos y otra en gamificación. Adicionalmente, se desarrolló una tercera estrategia basada en la implementación del Diseño Universal para el Aprendizaje (DUA) considerando su filosofía de contribuir a disminuir las barreras que no permiten procesos de formación de calidad para todos.