Early detection and intervention are theorized to facilitate better outcomes in autistic children. However, response to early intervention varies considerably between individuals, some children show significant improvement, while others show minimal response to the intervention. Some pre-treatment individualized characteristics as well as intervention-specific factors were theorized to moderate outcomes, but literature revealed often mixed findings making difficult to understand whether and to what extent these factors facilitate learning during treatment. To parse the heterogeneity of the autistic population, recent studies have also attempted to investigate biological factors related to clinical and behavioral profiles. However, to date it is unknown whether and how biological information can provide insight into the variability of treatment outcomes. With this in mind, we attempted to expand the current knowledge by first investigating whether pre-treatment child’s characteristics and blood leukocyte gene expression patterns could predict developmental trajectories during treatment. Leveraging a cohort of 41 autistic toddlers who received the same early intervention and provided a blood sample, we were able to analyze the effect of starting treatment very early (i.e., <24 months) on treatment trajectories. We also provided for the first-time evidence that both pre-treatment blood leukocyte gene expression patterns and clinical-behavioral characteristics are important for predicting developmental change during intervention, and that pretreatment epigenetic mechanisms such as histone acetylation may be a key biological process that influence how a child respond to early intervention. Lastly, we carried out a mega-analysis of a large international consortium, isolating individual child characteristics and treatment related factors to examine their key role in moderating child developmental trajectories throughout the course of early intervention. The final dataset comprised 645 autistic toddlers who received two types of interventions either Early Start Denver Model (ESDM) or other treatment as usual/community interventions (TAU/COM). This mega-analysis provided strong evidence that individual factors, such as cognitive level and age at treatment start, predict most outcomes, and on-average, ESDM may promote some developmental skills better than COM/TAU. Taken together, these results advance our understanding of “what works, for whom, for what and why” questions, identifying new biological predictors and providing an alternative methodology that can effectively examine the individual variability of treatment outcomes.

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Made available in DSpace on 2014-12-17T14:36:46Z (GMT). No. of bitstreams: 1 ElianaRA_DISSERT_noPW.pdf: 5125022 bytes, checksum: 73f55cf802af39eb44b559aad107292f (MD5) Previous issue date: 2012-09-28 / In the last decades, studies on early intervention involving children with autism have suggested that there is no single intervention model capable of addressing the needs of all individuals in the spectrum. The role of parents as active intervention agents is, however, highly recommended. The More Than Words-HANEN Program has been specifically created for parents of children, under five years of age, who are in the autism spectrum. This intervention aims at improving the social competence and language comprehension of the child, as well as their parents empowerment. Until now only three studies have been performed in order to evaluate the effectiveness of the HMTW program. The purpose of this investigation is to evaluate the effects of an early intervention program inspired on HMTW model on the level of caregiver responsiveness and child communication skills. The present study adds to the existing research literature on family-centered early intervention that uses a developmental paradigm. A two year boy in risk for autism, his mother and nanny took part in this investigation, which was carried out in the child?s home in Mossor?, Rio Grande do Norte. The caretakers were given one fifty-two hours of training, divided into thirteen weekly meetings. A quasi-experimental A-B-C design (baselineintervention- follow-up) showed improvement in the caretakers level of responsiveness and meaningful social-communicative gains in the child?s response / Nas ?ltimas d?cadas, estudos em interven??o precoce realizados com crian?as com risco de autismo concluem n?o haver uma abordagem ?nica que possa ser aplicada a todas as crian?as com essa s?ndrome. Recomenda-se, no entanto, que os pais sejam envolvidos como agentes ativos nas interven??es de tratamento. O More Than Words-HANEN (HMTW) ? um programa de capacita??o criado especificamente para pais de crian?as menores de cinco anos de idade, as quais apresentam caracter?sticas de Transtornos do Espectro do Autismo TEA. A interven??o tem como objetivo a melhoria da compet?ncia social e da compreens?o da linguagem da crian?a, bem como a responsividade das cuidadoras. At? a atualidade, foram produzidos apenas tr?s estudos com o objetivo de avaliar a efic?cia da capacita??o HMTW. A presente pesquisa visa ampliar o campo de investiga??o em interven??o precoce focada na fam?lia sob a abordagem desenvolvimentista, avaliando os efeitos da implementa??o de um programa de interven??o precoce, inspirado na capacita??o do modelo HMTW. Participaram do estudo um menino de dois anos, com risco de autismo, sua m?e e sua bab?. A pesquisa, conduzida na resid?ncia da crian?a, localizada na cidade de Mossor?/RN, utilizou delineamento quase experimental do tipo A-B-C (linha de base, tratamento e acompanhamento). As cuidadoras participaram de cinquenta duas horas de capacita??o, distribu?das em treze encontros semanais. Os resultados do estudo evidenciaram ganhos nos n?veis de responsividade das cuidadoras durante a intera??o social com o menino, e indicaram aumento na frequ?ncia de turnos comunicativos

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