Reduced serotonin synthesis and regional cerebral blood flow after anxiolytic treatment of social anxiety disorder
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; 40mg), the NK1R antagonist GR205171 (n=6; 5mg; 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 [11 C]5-hydroxytryptophan and [15 O]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.
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Our results do not rule out other serotonergic mechanisms with SSRIs, such as altered synthesis rate or indirect influence on serotonin signaling.
“Our results do not rule out other serotonergic mechanisms with SSRIs, such as altered synthesis rate (Frick et al., 2016) or the possibility that effective treatment of social anxiety may influence serotonin signaling indirectly, through pathways beyond transporter blockade.”
From Revisiting the SSRI vs. placebo debate in the treatment of social anxiety disorder: the role of expectancy effects, neural responsivity, and monoamine transporters (2025) · cites this paper as Frick et al., 2016
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- Authors
- Frick, A., Åhs, F., Appel, L., Jonasson, M., Wahlstedt, K., Bani, M., Merlo Pich, E., Bettica, P., Långström, B., Lubberink, M., Fredrikson, M., & Furmark, T.
- Affiliations
- Uppsala University (SE)
- GlaxoSmithKline (Italy) (IT)
- Corresponding author
- Frick, Andreas
- ORCID
- Venue
- European Neuropsychopharmacology
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 26
- Issue
- 11
- Pages
- 1775-1783
- ISSN
- 0924-977X (ISSN-L)
- OpenAlex
- W2432104123
- Cited by
- 22
- References
- 56
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 1
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Uppsala Universitet
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- social anxiety disorder, amygdala, regional cerebral blood flow, citalopram, selective serotonin reuptake inhibitors, NK1 receptor antagonists, public speaking stress, anxiolysis, 15O-water
- MeSH terms
- Phobia, Social, Adult, Amygdala, Cerebrovascular Circulation, Double-Blind Method, Female, Humans, Kinetics, Male, Piperidines, Psychiatric Status Rating Scales, Serotonin, Social Environment, Stress, Psychological, Tetrazoles, Anti-Anxiety Agents, Citalopram, Selective Serotonin Reuptake Inhibitors, Positron-Emission Tomography, Neurokinin-1 Receptor Antagonists
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