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Increased neurokinin-1 receptor availability in the amygdala in social anxiety disorder: a positron emission tomography study with [(11)C]GR205171
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
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2015 (English)In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 5, e597Article in journal (Refereed) Published
Abstract [en]

The neurokinin-1 (NK1) receptor is abundantly expressed in the fear circuitry of the brain, including the amygdala, where it modulates stress and anxiety. Despite its proposed involvement in psychopathology, only a few studies of NK1 receptor availability in human subjects with anxiety disorders exist. Here, we compared NK1 receptor availability in patients with social anxiety disorder (SAD; n = 17) and healthy controls (n = 17) using positron emission tomography and the radiotracer [(11)C]GR205171. The Patlak Graphical plot using a cerebellar reference region was used to model the influx parameter, Ki measuring NK1 receptor availability. Voxel-wise statistical parametric mapping analyses revealed increased NK1 receptor availability specifically in the right amygdala in SAD patients relative to controls. Thus, we demonstrate that exaggerated social anxiety is related to enhanced NK1 receptor availability in the amygdala. This finding supports the contribution of NK1 receptors not only in animal models of stress and anxiety but also in humans with anxiety disorders.

Place, publisher, year, edition, pages
2015. Vol. 5, e597
National Category
Psychology
Identifiers
URN: urn:nbn:se:uu:diva-259735DOI: 10.1038/tp.2015.92ISI: 000367660200004PubMedID: 26151925OAI: oai:DiVA.org:uu-259735DiVA: diva2:845248
Funder
Swedish Research CouncilRiksbankens Jubileumsfond
Note

De två sista författarna delar sistaförfattarskapet.

Available from: 2015-08-11 Created: 2015-08-11 Last updated: 2017-12-04Bibliographically approved
In thesis
1. Imaging Anxiety: Neurochemistry in Anxiety Disorders Assessed by Positron Emission Tomography
Open this publication in new window or tab >>Imaging Anxiety: Neurochemistry in Anxiety Disorders Assessed by Positron Emission Tomography
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Anxiety disorders, including social anxiety disorder (SAD) and posttraumatic stress disorder (PTSD) are common and disabling conditions. Largely based on animal and pharmacological studies, both the serotonergic and substance P/neurokinin-1 (SP/NK1) systems have been implicated in their underlying pathology. However, only few neuroimaging studies have directly assessed these neurotransmitter systems in human sufferers of anxiety disorders, and none have addressed possible between-systems relationships.

The overall aim of this thesis was to study possible neurochemical alterations associated with anxiety disorders. To this end, three studies using positron emission tomography (PET) for in-vivo imaging of the brain serotonergic and SP/NK1 systems in patients with SAD and PTSD were conducted. The radiotracers [11C]5-HTP, [11C]DASB, and [11C]GR205171 were used to index serotonin synthesis rate, serotonin transporter (SERT) availability, and NK1 receptor availability respectively.

In Study I, patients with SAD relative to controls exhibited enhanced serotonin synthesis rate and serotonin transporter availability. Serotonin synthesis rate in the amygdala was positively related to social anxiety symptom scores. Study II demonstrated increased NK1 receptor availability in the amygdala in patients with SAD relative to controls. In Study III, patients with PTSD showed elevated NK1 receptor availability in the amygdala as compared to controls. SERT availability in the amygdala was negatively related to PTSD symptom severity, a relationship that was moderated by NK1 receptor levels. The regional overlap between SERT and NK1 receptor expression was altered in patients with PTSD, with reduced overlap linked to more severe symptoms.

Collectively, the findings are consistent with the view that serotonin in the amygdala induces rather than reduces anxiety and links exaggerated anxiety to an overactive presynaptic serotonin system. In addition, the involvement of the SP/NK1 system in stress and anxiety, as suggested by animal studies, was demonstrated in two common human anxiety disorders. Finally, PTSD symptomatology is better accounted for by interactions between the serotonergic and SP/NK1 systems in the amygdala than by each system separately. In conclusion, this thesis supports that both the serotonergic and SP/NK1 systems in and of themselves, but also interactively, may be important contributors to anxiety symptomatology.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 85 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Social Sciences, ISSN 1652-9030 ; 115
Keyword
Fear, Brain, Serotonin, Neurokinin, Substance P
National Category
Psychology
Research subject
Psychology
Identifiers
urn:nbn:se:uu:diva-261983 (URN)978-91-554-9330-1 (ISBN)
Public defence
2015-10-26, Auditorium Minus, Gustavianum, Akademigatan 3, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2015-09-29 Created: 2015-09-07 Last updated: 2015-10-01

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Frick, AndreasÅhs, FredrikJonasson, MyAppel, LieuweLubberink, MarkLångström, BengtFredrikson, MatsFurmark, Tomas

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