RESUMO
Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disease of presenile onset. A better characterization of neurodegenerative disorders has been sought by using tools such as genome-wide association studies (GWAS), where associations between single nucleotide polymorphisms (SNPs) and cognitive profiles could constitute predictive biomarkers for these diseases. However, in FTD, associations between genotypes and cognitive phenotypes are yet to be explored. Here, we evaluate a possible relationship between genetic variants and some cognitive functions in an FTD population. Methodology: A total of 47 SNPs in genes associated with neurodegenerative diseases were evaluated using the Sequenom MassARRAY platform along with their possible relationship with performance in neuropsychological tests in 105 Colombian patients diagnosed with FTD. Results and discussion: The SNPs rs429358 (APOE), rs1768208 (MOBP), and rs1411478 (STX6), were identified as risk factors for having a low cognitive performance in inhibitory control and phonological verbal fluency. Although the significance level was not enough to reach the corrected alpha for multiple comparison correction, our exploratory data may constitute a starting point for future studies of these SNPs and their relationship with cognitive performance in patients with a probable diagnosis of FTD. Further studies with an expansion of the sample size and a long-term design could help to explore the predictive nature of the potential associations we identified.
RESUMO
Major Depression is a complex disorder with a growing incidence worldwide and multiple variables have been associated with its etiology. Nonetheless, its diagnosis is continually changing and the need to understand it from a multidimensional perspective is clear. The purpose of this study was to identify risk factors for depression in a case-control study with 100 depressive inpatients and 87 healthy controls. A multivariate logistic regression analysis was performed including psychosocial factors, cognitive maladaptive schema domains, and specific epigenetic marks (BDNF methylation levels at five CpG sites in promoter IV). A family history of depression, the cognitive schemas of impaired autonomy/performance, impaired limits, other-directedness, and the methylation level of a specific CpG site were identified as predictors. Interestingly, we found a mediating effect of those cognitive schemas in the relationship between childhood maltreatment and depression. Also, we found that depressive patients exhibited hypomethylation in a CpG site of BDNF promoter IV, which adds to the current discussion about the role of methylation in depression. We highlight that determining the methylation of a specific region of a single gene offers the possibility of accessing a highly informative an easily measurable variable, which represents benefits for diagnosis. Following complete replication and validation on larger samples, models like ours could be applicable as additional diagnostic tools in the clinical context.
