Universidade de Lisboa Repositório da Universidade de Lisboa

Repositório da Universidade de Lisboa >
Faculdade de Ciências (FC) >
FC - Teses de Doutoramento >

Please use this identifier to cite or link to this item: http://hdl.handle.net/10451/1616

Título: Genetic factors in autism spectrum disorders (ASD) and in variability in individual response to risperidone therapy
Autor: Correia, Catarina Alexandra Tavares, 1980-
Orientador: Fialho, Maria da Graça Monteiro de Azevedo, 1943-
Vicente, Astride Carolina Lentz de Moura
Palavras-chave: Autismo
Teses de doutoramento
Issue Date: 2009
Resumo: Autism is a complex neurodevelopmental disorder resulting from a combination of genetic, environmental, and immunological factors. This work aimed at the characterization of autism-associated phenotypes and the identification of genes regulating such phenotypes and contributing to autism risk. A second objective was the identification of genetic factors underlying the variability in individual response of autistic patients to risperidone therapy. Association studies performed with genes ITGA4 and SLC25A12, mapping to the autism linkage region on 2q31-33, confirmed that the ITGA4 gene is a susceptibility gene for autism. Further, this gene may be involved in the process of neuroinflammation suggested by the observation of a widespread occurrence of autoreactivities to brain tissue in a subset of patients. On the contrary, the SLC25A12 gene was not associated with autism or with mitochondrial dysfunction markers frequently observed in our sample. Increased circulating levels of brain derived neurotrophic factor (BDNF) were observed in 25% of our patients, and this trait mapped to the chromosome 5q11.2-q13 region, likely to the RNF180 gene. Taken together with the association of NTRK2 genetic variants with autism, our results provide strong evidence for an alteration of the BDNF/TrkB signalling in autism. Association with autism of the BDNF regulatory genes CADPS2 and SLC1A2 was not fully conclusive, requiring replication in larger populations. Risperidone, administered to forty-five patients for one year, was very effective in reducing some autism symptoms and caused few serious adverse effects. Although association results should be taken as suggestive, we identified for the first time several genes implicated in risperidone efficacy and safety in autism patients. Overall, the results of this work contribute to the identification of susceptibility genes for autism. In particular, it defined a disruption of the BDNF/TrkB signalling pathway as contributing to autism. Additionally, our pharmacogenetic study constitutes a step toward individualized therapy in autism.
Descrição: Tese de doutoramento, Biologia (Genética), 2009, Universidade de Lisboa, Faculdade de Ciências
URI: http://catalogo.ul.pt/F/?func=item-global&doc_library=ULB01&type=03&doc_number=000558258
Appears in Collections:FC - Teses de Doutoramento

Files in This Item:

File Description SizeFormat
18242_ulsd_re380_Tese_dout_Catarina_Correia.pdf2,34 MBAdobe PDFView/Open
Restrict Access. You can request a copy!

Please give feedback about this item
FacebookTwitterDeliciousLinkedInDiggGoogle BookmarksMySpace
Formato BibTex MendeleyEndnote Logotipo do DeGóis 

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.


  © Universidade de Lisboa / SIBUL
Alameda da Universidade | Cidade Universitária | 1649-004 Lisboa | Portugal
Tel. +351 217967624 | Fax +351 217933624 | repositorio@reitoria.ul.pt - Feedback - Statistics
Promotores do RCAAP   Financiadores do RCAAP

Fundação para a Ciência e a Tecnologia Universidade do Minho   Governo Português Ministério da Educação e Ciência PO Sociedade do Conhecimento (POSC) Portal oficial da União Europeia