Interacción del polimorfismo de la región promotora del gen del transportador de serotonina y factores ambientales para predecir síntomas depresivos : mas allá del modelo de vulnerabilidad

Abstract

Introduction: Research on the potential role of gene-environment interactions (GxE) in explaining vulnerability to psychopathology in humans has witnessed a shift from a diathesis-stress approach to differential susceptibility approaches. This project critically reviews that body of research. Depression has been associated with alterations in the response systems to environmental stress. The serotonergic system is widely related to the stress response system, through the hypothalamic-pituitary-adrenal axis. Variations in this system—especially being a carrier of short allele (S) of the polymorphism of the serotonin transporter (5HTTLPR) —has been associated with an increased vulnerability to depression when exposed to adverse environments. However, few studies—and none in Chile—have analyzed the interaction between this polymorphism and the environmental factors from the differential susceptibility approaches. Methodology: Databases were screened for studies of GxE in the prediction of personality traits, behavior, and mental health disorders in humans, published between January 2002 and January 2015. In total, 315 papers were included. The project is a quasi-experimental study: mixed (through analysis between groups and within subjects), unifactorial, quantitative and transversal. The interaction between the 5HTTLPR polymorphism and the following variables in predicting depressive symptoms were evaluated: (1) childhood trauma; (2) recent life events (positive and negative); (3) social support; (4) attachment style, and; (5) personality style (anaclitic/introjective). Furthermore, an experimental task was performed, and salivary cortisol was measured to determine whether these interactions were related to changes in the neurobiological response to stress. The sample consisted of 151 adult subjects. Results: Independent of the type of environment studied (early or recent life events, positive or negative environments), about 66.9-83.3% of the articles reported GxE interaction, which is consistent with the social susceptibility model. However, methodological considerations limit the ability to draw definite conclusions, especially since almost 90% (n=283/315) of the papers are based on samples from North America and Europe, and many studies (219/315) are based on overlapped samples. Methodological improvements in this area are shown by a significant increase in longitudinal and experimental studies as well as improved minimum genotyping. In our study, S allele carriers showed fewer depressive symptoms when they presented high social support and low anxious attachment, compared to S allele carriers with low social support and high anxious attachment. In turn, L allele carriers did not show these differences. Moreover, SS subjects with mixed personality configuration obtained significantly higher depressive scores. Furthermore, we found a GxE interaction between the 5HTTLPR polymorphism and social support and the depressive experience type for the average area under the curve (AUC) of cortisol during the experiment. Conclusions: The systematic review showed no differences on the GxE between different environment types to predict changes in human conduct, so it is possible that the model behind the interaction is one of differentiated sensitivity to the environment and not just vulnerability to psychopathology. Moreover, we observed that the short allele of the 5HTTLPR polymorphism confers a vulnerability to depressive symptoms in the presence of a mixed personality organization (high self-criticism and high dependence). But concerning attachment style and social support, it could provide a differentiated sensitivity to environmental stimuli, predicting lower depressive symptoms when interacting with positive environments and a worse outcome when interacting with more adverse environments. And, finally, the release of cortisol during the experiment depends on the interaction between the 5HTTLPR polymorphism and social support and the type of depressive experience.