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Overlapping expression of serotonin transporters and neurokinin-1 receptors in posttraumatic stress disorder: a multi-tracer PET study
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 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.
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2016 (English)In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 21, no 10, 1400-1407 p.Article in journal (Refereed) Published
Abstract [en]

The brain serotonergic system is colocalized and interacts with the neuropeptidergic substance P/neurokinin-1 (SP/NK1) system. Both these neurochemical systems have independently been implicated in stress and anxiety, but interactions between them might be crucial for human anxiety conditions. Here, we examined the serotonin and substance P/neurokinin-1 (SP/NK1) systems individually as well as their overlapping expression in 16 patients with posttraumatic stress disorder (PTSD) and 16 healthy controls. Participants were imaged with the highly selective radiotracers [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB) and [(11)C]GR205171 assessing serotonin transporter (SERT) and NK1 receptor availability, respectively. Voxel-wise analyses in the amygdala, our a priori-defined region of interest, revealed increased number of NK1 receptors, but not SERT in the PTSD group. Symptom severity, as indexed by the Clinician-administered PTSD Scale, was negatively related to SERT availability in the amygdala, and NK1 receptor levels moderated this relationship. Exploratory, voxel-wise whole-brain analyses revealed increased SERT availability in the precentral gyrus and posterior cingulate cortex of PTSD patients. Patients, relative to controls, displayed lower degree of overlapping expression between SERT and NK1 receptors in the putamen, thalamus, insula and lateral orbitofrontal gyrus, lower overlap being associated with higher PTSD symptom severity. Expression overlap also explained more of the symptomatology than did either system individually, underscoring the importance of taking interactions between the neurochemical systems into account. Thus, our results suggest that aberrant serotonergic-SP/NK1 couplings contribute to the pathophysiology of PTSD and, consequently, that normalization of these couplings may be therapeutically important.

Place, publisher, year, edition, pages
2016. Vol. 21, no 10, 1400-1407 p.
National Category
Psychology
Identifiers
URN: urn:nbn:se:uu:diva-268105DOI: 10.1038/mp.2015.180ISI: 000384127000011PubMedID: 26619809OAI: oai:DiVA.org:uu-268105DiVA: diva2:875931
Funder
Swedish Research CouncilThe Swedish Brain FoundationRiksbankens JubileumsfondForte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2015-12-02 Created: 2015-12-02 Last updated: 2017-12-01Bibliographically approved

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Frick, AndreasÅhs, FredrikWallenquist, UlrikaFernandez, ManuelJonasson, MyAppel, LieuweFrans, ÖrjanLubberink, MarkFurmark, Tomasvon Knorring, LarsFredrikson, Mats

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Frick, AndreasÅhs, FredrikWallenquist, UlrikaFernandez, ManuelJonasson, MyAppel, LieuweFrans, ÖrjanLubberink, MarkFurmark, Tomasvon Knorring, LarsFredrikson, Mats
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Department of PsychologyPsychiatry, University HospitalRadiology
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