Annual Report of Activities CNC 2008 - Center for Neuroscience and ...

Biomedical Inter‐Institutional Research Programme1. Psychiatry ResearchMolecular Genetics Studies of Complex Disorders(Carlos Pato, Michele Pato (University of Southern California.), M.H. Azevedo (HUC, FMUC, CNC) C.R. Oliveira(HUC, FMUC, CNC)These studies are focused on the identification of candidate genes for Schizophrenia and Bipolar Disorderthrough the use of linkage and association analysis. For this purpose two populations have been analyzed:a relatively homogenous population from Azores, augmented by a similarly homogenous subsample fromMadeira, and a mainland Portuguese population. To date we have collected over 3000 DNA samples,including 700 schizophrenic patients, 500 bipolar patients, and 1400 unaffected family members.Additionally, 350 unaffected (i.e. no history of psychiatric disorder) subjects of Azorean descent have beencollected as a control group. The schizophrenic sample includes 100 multiplex (2 or more affectedmembers) families, and the bipolar sample includes 120 multiplex families.These studies have utilized ʺstate of the artʺ DNA and RNA microarray technology to identifychromosomal regions of linkage to each disorder, as well as areas of increased expression in the presenceof illness. This convergent genetic‐genomic approach has led to the identification of several areas in thehuman genome to target for follow‐up study, most notably on Chromosome 5 for schizophrenia andpsychosis, and on Chromosome 6 for Bipolar Disorder. Additionally, collaborators from the BroadInstitute in the United States and from the Centre on Addiction and Mental Health (CAMH) in Toronto,Canada have been using the sample, collectively known as the “Portuguese Island Collection,” toinvestigate specific candidate genes for schizophrenia, including neuregulin 1, syntaxin 1A, and genesfrom the dopaminergic and serotonergic systems. We have also formed the International Shizophreniacollaborative to use whole genome approaches to define the genomics of this disorder.851.1 Clinical Research – Phenotypic Studies of Complex DisordersIn parallel with the genetic studies of schizophrenia and bipolar disorder, we have developed a range ofclinical investigations in areas in which a more clear understanding of the phenotypic definitions andboundaries were needed. These studies have focused in the area of personality, namely studying theperfectionism and the relationship between this trait and some disorders of the obsessive‐compulsivespectrum (eating disorders and OCD) and sleep problems. Another important area under investigation isthe postpartum depression, and for this purpose a funded project from the Fundação para a Ciência eTecnologia has been completed. One of the areas of expertise of our team is in the field of diagnosticmethodologies and tools, and in this context several scales have been validated to be used in the abovementioned studies.PublicationsCarvalho Bos S, Pereira AT, Marques M, Maia B, Soares MJ, Valente J, Gomes A, Macedo A, Azevedo MH(2008) The BDI‐II factor structure in pregnancy and postpartum: two or three factors? European Psychiatrydoi:10.1016/j.eurpsy.2008.10.003.International Schizophrenia Consortium 1 . (2008) Rare chromosomal deletions and duplications increaserisk of schizophrenia. Nature; 455:237‐41.1 128 autores contribuintes – para a Faculdade de Medicina de Coimbra: António Macedo, Maria Helena Pinto deAzevedo