A large-scale multimodal investigation of the interplay between the serotonergic system and emotion processing
Abstract Considering the complexity of serotonergic influence on emotions, we conducted a comprehensive investigation of the interplay between emotion processing and the serotonergic system using simultaneous functional and molecular neuroimaging during pharmacological challenge while disentangling...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-06-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-025-03407-2 |
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| author | Manfred Klöbl Matej Murgaš Murray Bruce Reed Leo Robert Silberbauer Annette M. Hartmann Godber Mathis Godbersen Gregor Gryglewski Lukas Nics Andreas Hahn Dan Rujescu Marcus Hacker Rupert Lanzenberger |
| author_facet | Manfred Klöbl Matej Murgaš Murray Bruce Reed Leo Robert Silberbauer Annette M. Hartmann Godber Mathis Godbersen Gregor Gryglewski Lukas Nics Andreas Hahn Dan Rujescu Marcus Hacker Rupert Lanzenberger |
| author_sort | Manfred Klöbl |
| collection | DOAJ |
| description | Abstract Considering the complexity of serotonergic influence on emotions, we conducted a comprehensive investigation of the interplay between emotion processing and the serotonergic system using simultaneous functional and molecular neuroimaging during pharmacological challenge while disentangling the effects of serotonin transporter (SERT) binding, genotype, and diagnosis of major depressive disorder (MDD). Herein, 153 subjects (44 with MDD) performed a facial emotion processing task during functional magnetic resonance imaging (fMRI) before and after an acute intravenous application of 8 mg citalopram or placebo. Patients with MDD were assessed again after at least three months of antidepressant treatment. Citalopram administration resulted in a reduced fMRI activation in regions involved in fear processing, including the anterior cingulate cortex (ACC), when viewing fearful faces contrasted against happy or neutral faces. ACC activation correlated negatively with striatal/thalamic SERT availability across drug conditions as measured by [11 C]DASB positron emission tomography. Across groups, citalopram-induced changes in ACC activation correlated with emotional attribution, indicating stronger reductions for subjects with higher self- versus other- attribution. Moreover, striatal SERT availability mediated the influence of the number of 5-HTTLPR/rs25531 LA alleles on ACC activation under placebo. Patients with MDD exhibited increased activations in the intraparietal and superior frontal sulcus in response to fearful versus happy faces at baseline, and along the parieto-occipital/calcarine fissure after treatment. We interpret our findings on multiple levels of the serotonergic-emotional interaction within the context of enhanced passive coping and acute anxiolytic effects of citalopram following potential changes in serotonin or SERT availability. |
| format | Article |
| id | doaj-art-b355c8766bde4b84ba503f58f25de202 |
| institution | Kabale University |
| issn | 2158-3188 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj-art-b355c8766bde4b84ba503f58f25de2022025-08-20T03:45:32ZengNature Publishing GroupTranslational Psychiatry2158-31882025-06-0115111010.1038/s41398-025-03407-2A large-scale multimodal investigation of the interplay between the serotonergic system and emotion processingManfred Klöbl0Matej Murgaš1Murray Bruce Reed2Leo Robert Silberbauer3Annette M. Hartmann4Godber Mathis Godbersen5Gregor Gryglewski6Lukas Nics7Andreas Hahn8Dan Rujescu9Marcus Hacker10Rupert Lanzenberger11Department of Psychiatry and Psychotherapy, Medical University of ViennaDepartment of Psychiatry and Psychotherapy, Medical University of ViennaDepartment of Psychiatry and Psychotherapy, Medical University of ViennaDepartment of Psychiatry and Psychotherapy, Medical University of ViennaDepartment of Psychiatry and Psychotherapy, Medical University of ViennaDepartment of Psychiatry and Psychotherapy, Medical University of ViennaDepartment of Psychiatry and Psychotherapy, Medical University of ViennaDepartment of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of ViennaDepartment of Psychiatry and Psychotherapy, Medical University of ViennaDepartment of Psychiatry and Psychotherapy, Medical University of ViennaDepartment of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of ViennaDepartment of Psychiatry and Psychotherapy, Medical University of ViennaAbstract Considering the complexity of serotonergic influence on emotions, we conducted a comprehensive investigation of the interplay between emotion processing and the serotonergic system using simultaneous functional and molecular neuroimaging during pharmacological challenge while disentangling the effects of serotonin transporter (SERT) binding, genotype, and diagnosis of major depressive disorder (MDD). Herein, 153 subjects (44 with MDD) performed a facial emotion processing task during functional magnetic resonance imaging (fMRI) before and after an acute intravenous application of 8 mg citalopram or placebo. Patients with MDD were assessed again after at least three months of antidepressant treatment. Citalopram administration resulted in a reduced fMRI activation in regions involved in fear processing, including the anterior cingulate cortex (ACC), when viewing fearful faces contrasted against happy or neutral faces. ACC activation correlated negatively with striatal/thalamic SERT availability across drug conditions as measured by [11 C]DASB positron emission tomography. Across groups, citalopram-induced changes in ACC activation correlated with emotional attribution, indicating stronger reductions for subjects with higher self- versus other- attribution. Moreover, striatal SERT availability mediated the influence of the number of 5-HTTLPR/rs25531 LA alleles on ACC activation under placebo. Patients with MDD exhibited increased activations in the intraparietal and superior frontal sulcus in response to fearful versus happy faces at baseline, and along the parieto-occipital/calcarine fissure after treatment. We interpret our findings on multiple levels of the serotonergic-emotional interaction within the context of enhanced passive coping and acute anxiolytic effects of citalopram following potential changes in serotonin or SERT availability.https://doi.org/10.1038/s41398-025-03407-2 |
| spellingShingle | Manfred Klöbl Matej Murgaš Murray Bruce Reed Leo Robert Silberbauer Annette M. Hartmann Godber Mathis Godbersen Gregor Gryglewski Lukas Nics Andreas Hahn Dan Rujescu Marcus Hacker Rupert Lanzenberger A large-scale multimodal investigation of the interplay between the serotonergic system and emotion processing Translational Psychiatry |
| title | A large-scale multimodal investigation of the interplay between the serotonergic system and emotion processing |
| title_full | A large-scale multimodal investigation of the interplay between the serotonergic system and emotion processing |
| title_fullStr | A large-scale multimodal investigation of the interplay between the serotonergic system and emotion processing |
| title_full_unstemmed | A large-scale multimodal investigation of the interplay between the serotonergic system and emotion processing |
| title_short | A large-scale multimodal investigation of the interplay between the serotonergic system and emotion processing |
| title_sort | large scale multimodal investigation of the interplay between the serotonergic system and emotion processing |
| url | https://doi.org/10.1038/s41398-025-03407-2 |
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