Expectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder: a randomized clinical trial
Abstract It has been extensively debated whether selective serotonin reuptake inhibitors (SSRIs) are more efficacious than placebo in affective disorders, and it is not fully understood how SSRIs exert their beneficial effects. Along with serotonin transporter blockade, altered dopamine signaling an...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-11-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-021-01682-3 |
| _version_ | 1818985966693515264 |
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| author | Olof R. Hjorth Andreas Frick Malin Gingnell Johanna M. Hoppe Vanda Faria Sara Hultberg Iman Alaie Kristoffer N. T. Månsson Jörgen Rosén Margareta Reis Kurt Wahlstedt My Jonasson Mark Lubberink Gunnar Antoni Mats Fredrikson Tomas Furmark |
| author_facet | Olof R. Hjorth Andreas Frick Malin Gingnell Johanna M. Hoppe Vanda Faria Sara Hultberg Iman Alaie Kristoffer N. T. Månsson Jörgen Rosén Margareta Reis Kurt Wahlstedt My Jonasson Mark Lubberink Gunnar Antoni Mats Fredrikson Tomas Furmark |
| author_sort | Olof R. Hjorth |
| collection | DOAJ |
| description | Abstract It has been extensively debated whether selective serotonin reuptake inhibitors (SSRIs) are more efficacious than placebo in affective disorders, and it is not fully understood how SSRIs exert their beneficial effects. Along with serotonin transporter blockade, altered dopamine signaling and psychological factors may contribute. In this randomized clinical trial of participants with social anxiety disorder (SAD) we investigated how manipulation of verbally-induced expectancies, vital for placebo response, affect brain monoamine transporters and symptom improvement during SSRI treatment. Twenty-seven participants with SAD (17 men, 10 women), were randomized, to 9 weeks of overt or covert treatment with escitalopram 20 mg. The overt group received correct treatment information whereas the covert group was treated deceptively with escitalopram, described as an active placebo in a cover story. Before and after treatment, patients underwent positron emission tomography (PET) assessments with the [11C]DASB and [11C]PE2I radiotracers, probing brain serotonin (SERT) and dopamine (DAT) transporters. SAD symptoms were measured by the Liebowitz Social Anxiety Scale. Overt was superior to covert SSRI treatment, resulting in almost a fourfold higher rate of responders. PET results showed that SERT occupancy after treatment was unrelated to anxiety reduction and equally high in both groups. In contrast, DAT binding decreased in the right putamen, pallidum, and the left thalamus with overt SSRI treatment, and increased with covert treatment, resulting in significant group differences. DAT binding potential changes in these regions correlated negatively with symptom improvement. Findings support that the anxiolytic effects of SSRIs involve psychological factors contingent on dopaminergic neurotransmission while serotonin transporter blockade alone is insufficient for clinical response. |
| first_indexed | 2024-12-20T18:43:18Z |
| format | Article |
| id | doaj.art-4ff3750a789143c085c8eb3199b79a99 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-12-20T18:43:18Z |
| publishDate | 2021-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-4ff3750a789143c085c8eb3199b79a992022-12-21T19:29:45ZengNature Publishing GroupTranslational Psychiatry2158-31882021-11-011111810.1038/s41398-021-01682-3Expectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder: a randomized clinical trialOlof R. Hjorth0Andreas Frick1Malin Gingnell2Johanna M. Hoppe3Vanda Faria4Sara Hultberg5Iman Alaie6Kristoffer N. T. Månsson7Jörgen Rosén8Margareta Reis9Kurt Wahlstedt10My Jonasson11Mark Lubberink12Gunnar Antoni13Mats Fredrikson14Tomas Furmark15Department of Psychology, Uppsala UniversityDepartment of Psychology, Uppsala UniversityDepartment of Psychology, Uppsala UniversityDepartment of Psychology, Uppsala UniversityDepartment of Psychology, Uppsala UniversityDepartment of Psychology, Uppsala UniversityDepartment of Neuroscience, Child and Adolescent Psychiatry, Uppsala UniversityCenter for Psychiatry Research, Department of Clinical Neuroscience, Karolinska InstitutetDepartment of Psychology, Uppsala UniversityDepartment of Biomedical And Clinical Sciences, Linköping UniversityDepartment of Psychology, Uppsala UniversityDepartment of of Surgical Sciences/Nuclear Medicine and PET, Uppsala UniversityDepartment of of Surgical Sciences/Nuclear Medicine and PET, Uppsala UniversityDepartment of Medicinal Chemistry, Uppsala UniversityDepartment of Psychology, Uppsala UniversityDepartment of Psychology, Uppsala UniversityAbstract It has been extensively debated whether selective serotonin reuptake inhibitors (SSRIs) are more efficacious than placebo in affective disorders, and it is not fully understood how SSRIs exert their beneficial effects. Along with serotonin transporter blockade, altered dopamine signaling and psychological factors may contribute. In this randomized clinical trial of participants with social anxiety disorder (SAD) we investigated how manipulation of verbally-induced expectancies, vital for placebo response, affect brain monoamine transporters and symptom improvement during SSRI treatment. Twenty-seven participants with SAD (17 men, 10 women), were randomized, to 9 weeks of overt or covert treatment with escitalopram 20 mg. The overt group received correct treatment information whereas the covert group was treated deceptively with escitalopram, described as an active placebo in a cover story. Before and after treatment, patients underwent positron emission tomography (PET) assessments with the [11C]DASB and [11C]PE2I radiotracers, probing brain serotonin (SERT) and dopamine (DAT) transporters. SAD symptoms were measured by the Liebowitz Social Anxiety Scale. Overt was superior to covert SSRI treatment, resulting in almost a fourfold higher rate of responders. PET results showed that SERT occupancy after treatment was unrelated to anxiety reduction and equally high in both groups. In contrast, DAT binding decreased in the right putamen, pallidum, and the left thalamus with overt SSRI treatment, and increased with covert treatment, resulting in significant group differences. DAT binding potential changes in these regions correlated negatively with symptom improvement. Findings support that the anxiolytic effects of SSRIs involve psychological factors contingent on dopaminergic neurotransmission while serotonin transporter blockade alone is insufficient for clinical response.https://doi.org/10.1038/s41398-021-01682-3 |
| spellingShingle | Olof R. Hjorth Andreas Frick Malin Gingnell Johanna M. Hoppe Vanda Faria Sara Hultberg Iman Alaie Kristoffer N. T. Månsson Jörgen Rosén Margareta Reis Kurt Wahlstedt My Jonasson Mark Lubberink Gunnar Antoni Mats Fredrikson Tomas Furmark Expectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder: a randomized clinical trial Translational Psychiatry |
| title | Expectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder: a randomized clinical trial |
| title_full | Expectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder: a randomized clinical trial |
| title_fullStr | Expectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder: a randomized clinical trial |
| title_full_unstemmed | Expectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder: a randomized clinical trial |
| title_short | Expectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder: a randomized clinical trial |
| title_sort | expectancy effects on serotonin and dopamine transporters during ssri treatment of social anxiety disorder a randomized clinical trial |
| url | https://doi.org/10.1038/s41398-021-01682-3 |
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