title: 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 [(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.
authors.affiliation: Department of Psychology, Uppsala University, Uppsala, Sweden.
authors.forename: A
authors.identifier: 0000-0003-2516-9075
authors.initials: A
authors.lastname: Frick
authors.affiliation: Department of Psychology, Uppsala University, Uppsala, Sweden.|Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: F
authors.initials: F
authors.lastname: Åhs
authors.affiliation: Department of Psychology, Uppsala University, Uppsala, Sweden.
authors.forename: Å M
authors.initials: ÅM
authors.lastname: Palmquist
authors.affiliation: Department of Psychology, Uppsala University, Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Pissiota
authors.affiliation: Department of Psychology, Uppsala University, Uppsala, Sweden.
authors.forename: U
authors.initials: U
authors.lastname: Wallenquist
authors.affiliation: Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Fernandez
authors.affiliation: Department of Nuclear Medicine and PET, Uppsala University, Uppsala, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Jonasson
authors.affiliation: Department of Nuclear Medicine and PET, Uppsala University, Uppsala, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Appel
authors.affiliation: Department of Psychology, Uppsala University, Uppsala, Sweden.
authors.forename: Ö
authors.initials: Ö
authors.lastname: Frans
authors.affiliation: Department of Nuclear Medicine and PET, Uppsala University, Uppsala, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Lubberink
authors.affiliation: Department of Psychology, Uppsala University, Uppsala, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Furmark
authors.affiliation: Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: von Knorring
authors.affiliation: Department of Psychology, Uppsala University, Uppsala, Sweden.|Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Fredrikson
mesh_terms: D000328:Adult; D000679:Amygdala / Q000378:metabolism; D000814:Aniline Compounds; D001008:Anxiety Disorders / Q000503:physiopathology; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D010880:Piperidines; D049268:Positron-Emission Tomography / Q000379:methods / Q000523:psychology; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D013373:Substance P / Q000235:genetics / Q000378:metabolism; D013440:Sulfides; D013777:Tetrazoles; D059467:Transcriptome
chemical_list: C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides; D013777:Tetrazoles; D012701:Serotonin; D013373:Substance P; C103207:vofopitant