Abstract

Background Major Depressive Disorder (MDD [MIM: 608516]) is a multifactorial disease that affects morbidity, mortality and quality of life. It is a chronic and recurrent phenotype of a complex etiological relationship between genetic and environmental factors where early childhood adversity and stressful life events are recognized environmental risk factors for MDD. However, early-life adversity does not always end in MDD but the individual stress assessment may be a determining factor in the presentation of MDD symptoms. Additionally, Brain-Derived Neurotrophic Factor Gene (BDNF) Val66Met (rs6265) variant has a well-established role in neuronal plasticity and decreased levels have been observed in individuals with MDD. Previous studies present evidence that support the idea that vulnerability to environmental stress is mediated by the rs6265 variant. However, there is still some controversy on the topic, mainly because most of these studies have been carried out in non-clinical populations. This study aimed to stablish if the number and individual response to adverse events together with the Val66Met variant may predict MDD. Methods Here we present a case-control study using a clinical population from two psychiatric clinics and matched controls. An initial inclusion criterion was established through the M.I.NI interview. Subsequently, the ESV questionnaire and event assessment was applied. The rs6265 variant was genotyped using real time PCR with Taqman probes from Applied Biosystems 7500/7500. Results This study was approved by the ethics committee of all the participant institutions. We did not find any association or gene x environment interaction between the rs6265 variant and MDD. Early stress events and recent stressful live events are significant risk factors for MDD. Discussion When analyzing the response to these events we found that the experimental group had a significant increase in negative affectivity, frequency of stressful events and the level of stress the event provoked. In conclusion, the assessment given to each individual stress event are determinant for the phenotypic expression on MDD and should be analyzed together with other known genetic variants involved in MDD.

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