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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/4ff3750a789143c085c8eb3199b79a99
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spelling	oai:doaj.org-article:4ff3750a789143c085c8eb3199b79a992021-11-07T12:17:36ZExpectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder: a randomized clinical trial10.1038/s41398-021-01682-32158-3188https://doaj.org/article/4ff3750a789143c085c8eb3199b79a992021-11-01T00:00:00Zhttps://doi.org/10.1038/s41398-021-01682-3https://doaj.org/toc/2158-3188Abstract 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.Olof R. HjorthAndreas FrickMalin GingnellJohanna M. HoppeVanda FariaSara HultbergIman AlaieKristoffer N. T. MånssonJörgen RosénMargareta ReisKurt WahlstedtMy JonassonMark LubberinkGunnar AntoniMats FredriksonTomas FurmarkNature Publishing GrouparticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENTranslational Psychiatry, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 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
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.
format	article
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
title	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_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_sort	expectancy effects on serotonin and dopamine transporters during ssri treatment of social anxiety disorder: a randomized clinical trial
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/4ff3750a789143c085c8eb3199b79a99
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Expectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder: a randomized clinical trial

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