| Date |
Jul 10, 2018 |
| Speaker |
Peter Petschneru,
Associate Research fellow,
MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Department of Pharmacodynamics, Semmelweis University, Hungary
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| Title |
Complexity of environment-dependent genetic effects in major depression through the scope of 5-HTTLPR
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| Abstract |
Major depression represents currently the largest burden of diseases in developed countries. From the etiological perspective genetic and environmental factors both play key roles in the development of the disease. A seminal paper of 2003 characterized an interaction between a polymorphism in the serotonin transporter gene (5-HTTLPR) and recent negative life events as an important environment-dependent genetic effect behind depression. Further results, however, proved contradictory and both pro and contra evidences emerged with a harmonized, thorough meta-analysis on more than 38000 participants refuting the idea of a generalizable effect. At the same time, examination of our smaller, but deep-phenotyped data also revealed that recent stress-dependent effect of the polymorphism on depression is, at least partially, mediated by anxiety and is probably more relevant in young participants exposed to maltreatment in their childhood than in the general population. Interestingly, there may even be particular types of stress that interact with the polymorphism, like financial difficulties. At the same time, serotonin transporter polymorphism is certainly not the only, and not the most relevant polymorphism behind depression. Other polymorphisms, like that of GALR2, BDNF and P2RX7 were demonstrated to be more important contributors in function of the amount of recent stress than the variant in the serotonin transporter. Nevertheless, 5-HTTLPR may interact with them further complicating its role. Such fine dependence of 5-HTTLPR genetic effects on phenotype selection, stress type and inclusion of other genetic factors highlights complexity of gene-environment interactions in the background of the disease and underlines the importance of detailed sample collection and analysis in depression.
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