Overlapping expression of serotonin transporters and neurokinin-1 receptors in posttraumatic stress disorder: a multi-tracer pet study

ABSTRACT 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 [11C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB) and [11C]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

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21 October 2021 SEROTONIN TRANSPORTER BINDING IN MAJOR DEPRESSIVE DISORDER: IMPACT OF SEROTONIN SYSTEM ANATOMY Article 29 April 2022 ASSOCIATION BETWEEN BRAIN SEROTONIN 4 RECEPTOR BINDING

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Swedish Brain Foundation; Riksbankens Jubileumsfond—the Swedish Foundation for Humanities and Social Sciences; and the Swedish Research Council for Health, Working Life and Welfare. We would

like to express our gratitude to all study participants, and to the staff of the Uppsala PET center for their assistance in data collection. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS *

Department of Psychology, Uppsala University, Uppsala, Sweden A Frick, F Åhs, Å M Palmquist, A Pissiota, U Wallenquist, Ö Frans, T Furmark & M Fredrikson * Department of Clinical

Neuroscience, Karolinska Institutet, Stockholm, Sweden F Åhs & M Fredrikson * Department of Neuroscience, Uppsala University, Uppsala, Sweden M Fernandez & L von Knorring *

Department of Nuclear Medicine and PET, Uppsala University, Uppsala, Sweden M Jonasson, L Appel & M Lubberink Authors * A Frick View author publications You can also search for this

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ARTICLE CITE THIS ARTICLE Frick, A., Åhs, F., Palmquist, Å. _et al._ Overlapping expression of serotonin transporters and neurokinin-1 receptors in posttraumatic stress disorder: a

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