Efecte de la variabilitat genètica de DDR1 en la matèria blanca cerebral i en la velocitat de processament en pacients amb un trastorn de l'espectre de l'esquizofrènia i altres psicosis

Identificador:  TDX:3165

Handle: https://hdl.handle.net/20.500.11797/TDX3165

Autores:  Gas Prades, Cinta

Resumen:
Our research group observed that the discoidin domain receptor 1 (DDR1) gene is linked to myelination and schizophrenia. In this work we studied whether the rs1264323 and rs2267641 DDR1 variants were associated with the diagnosis of schizophrenia spectrum and other psychotic disorders (SSOPD) in other samples and also whether they were associated with a decrease in the integrity of white matter and cognitive processing speed (PS). 1) We conducted a systematic literature review on the role of DDR1 in the central nervous system. 2) The case-control association study between SSOPD and the DDR1 genotype was replicated and a genotypic combination (rs1264323AA-rs2267641AC/CC) of risk was observed. 3) The relation between DDR1 single nucleotide polymorphisms (SNPs) and PS was explored in a SSOPD sample, finding that patients with rs2267641CC genotype, compared to AA and AC, had a decreased PS. 4) By exploring the relation between DDR1 SNPs and PS in two independent samples of patients in the early phases of psychosis, we found that the genotypic combination of risk was associated with an increase in PS in patients but not in controls. 5) In a subgroup of patients with SSOPD using neuroimaging by diffusion tensor imaging, we observed that carriers of the rs1264323AA genotype showed a decrease in fractional anisotropy in white matter regions associated with a decrease in PS. The results confirm the interaction between SNP-type variants of DDR1 and the risk of developing a SSOPD, and suggest that they are associated with alterations in myelin microstructure that are in turn associated with PS.