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Reduced serotonin synthesis and regional cerebral blood flow after anxiolytic treatment of social anxiety disorder
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.ORCID iD: 0000-0003-2516-9075
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
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2016 (English)In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 26, no 11, 1775-1783 p.Article in journal (Refereed) Published
Abstract [en]

Abstract Social anxiety disorder (SAD) is associated with increased fear-related neural activity in the amygdala and we recently found enhanced serotonin synthesis rate in the same region. Anxiolytic agents like selective serotonin re-uptake inhibitors (SSRIs) and neurokinin-1 receptor (NK1R) antagonists reduce amygdala activity and may attenuate serotonin formation according to animal studies. Here, we examined the effects of SSRI pharmacotherapy, NK1R antagonism, and placebo on serotonin synthesis rate in relation to neural activity, measured as regional cerebral blood flow (rCBF), and symptom improvement in SAD. Eighteen SAD patients were randomized to receive daily double-blind treatment for six weeks either with the SSRI citalopram (n=6; 40 mg), the NK1R antagonist GR205171 (n=6; 5 mg; 4 weeks following 2 weeks of placebo), or placebo (n=6). Serotonin synthesis rate at rest and rCBF during stressful public speaking were assessed, before and after treatment, using positron emission tomography with the tracers [11C]5-hydroxytryptophan and [15O]water respectively. The Liebowitz Social Anxiety Scale (LSAS-SR) indexed symptom severity. All groups exhibited attenuated amygdala serotonin synthesis rate after treatment, which was associated with reduced amygdala rCBF during public speaking and accompanied by symptom improvement. These results are consistent with the notion that serotonin in the amygdala exerts an anxiogenic influence and, conversely, that anxiolysis is achieved through decreased serotonin formation in the amygdala.

Place, publisher, year, edition, pages
2016. Vol. 26, no 11, 1775-1783 p.
Keyword [en]
Social phobia, 5-HT, NK1, Positron emission tomography, SSRI
National Category
Psychology Neurology
Identifiers
URN: urn:nbn:se:uu:diva-306707DOI: 10.1016/j.euroneuro.2016.09.004ISI: 000387523600006PubMedID: 27642077OAI: oai:DiVA.org:uu-306707DiVA: diva2:1044203
Funder
Swedish Research CouncilThe Swedish Brain FoundationForte, Swedish Research Council for Health, Working Life and WelfareGlaxoSmithKline (GSK)
Available from: 2016-11-02 Created: 2016-11-02 Last updated: 2016-12-13Bibliographically approved

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