The effect of 5-HTTLPR and a serotonergic multi-marker score on amygdala,prefrontal and anterior cingulate cortex reactivity and habituation in a large,healthy fMRI cohort |
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Authors: | J.H. Piel T.A. Lett C. Wackerhagen M.M. Plichta S. Mohnke O. Grimm N. Romanczuk-Seiferth F. Degenhardt H. Tost S. Witt M. Nöthen M. Rietschel A. Heinz A. Meyer-Lindenberg H. Walter S. Erk |
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Affiliation: | 1. Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany;2. Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany;3. Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany;4. Institute of Human Genetics, University of Bonn, Bonn, Germany;5. Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany;6. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany;g. Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe-University, Frankfurt, Germany |
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Abstract: | Major depressive disorder (MDD) is characterized by low mood for at least two weeks. Impaired emotion regulation has been suggested to be the consequence of dysfunctional serotonergic regulation of limbic and prefrontal regions, especially the amygdala, the anterior cingulate cortex (ACC) and the prefrontal cortex (PFC). The impact of genetic variation on brain function can be investigated with intermediate phenotypes. A suggested intermediate phenotype of MDD is emotion recognition: The 5-HTTLPR polymorphism of SLC6A4 as well as other serotonergic genes have been associated with amygdala and prefrontal function during emotion recognition. Previously, it has been suggested that habituation is a more reliable index of emotion recognition than functional activation. We examined the relationship of genes involved in serotonergic signaling with amygdala as well as prefrontal functional activation and habituation during an emotion recognition task in 171 healthy subjects. While effects of 5-HTTLPR and of a serotonergic multi-marker score (5-HTTLPR, TPH1(rs1800532), TPH2(rs4570625), HTR1A(rs6295) and HTR2A(rs6311)) on amygdala activation did not withstand correction for multiple regions of interest, we observed a strong correlation of the multi-marker score and habituation in the amygdala, DLPFC, and ACC. We replicated a well-studied intermediate phenotype for association with 5-HTTLPR and provided additional evidence for polygenic involvement. Furthermore, we showed that task habituation may be influenced by genetic variation in serotonergic signaling, particularly by a serotonergic multi-marker score. We provided preliminary evidence that PFC activation is an important intermediate phenotype of MDD. Future studies are needed to corroborate the results in larger samples. |
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Keywords: | Amygdala Functional magnetic resonance imaging Intermediate phenotype Genetics 5-HTTLPR Polygenic Serotonin Habituation |
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