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  • 1. Appel, L
    et al.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Winqvist, I
    Michelgård, Åsa
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Bani, M
    Långström, B
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Enhanced amygdalar NK1-receptor availability in patients with social anxiety disorder.2007In: Biological Psychiatry, 2007, p. 147-Conference paper (Other academic)
  • 2.
    Appel, Lieuwe
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Michelgård, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Linnman, Claes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Fernandez, Manuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Langström, Bengt
    von Knorring, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Altered NK1-receptor availability in patients with post traumatic stress disorder2009In: [Biological Psychiatry 2009, 65(8), Suppl. 1, 118S, no. 394], 2009, p. 118S-Conference paper (Refereed)
    Abstract [en]

    Background: Posttraumatic stress disorder (PTSD) is an anxiety disorder that can develop after one or more traumatic events causing extreme stress or grave physical harm. The neurokinin-1 (NK1) receptor is the primary receptor for substance P (SP); a neuropeptide suggested being involved in anxiety and depression. The present study investigated differences in NK1-receptor availability between PTSD patients and healthy controls, using positron emission tomography (PET). Methods: Eleven male refugee patients (age: 41±10) with DSM-IV defined PTSD and nine healthy male control subjects (age: 33±10) were investigated using the PET-tracer [11C]GR205171, supplied by Uppsala Imanet. GR205171 is a highly selective NK1-receptor antagonist. Scans were performed during 60 minutes in the resting state. Parametric images were generated using the graphical reference Patlak method assuming irreversible binding of [11C]GR205171 from 20-60 minutes and having cerebellum as reference region. Exploratory whole brain analyses were performed using the statistical parametric mapping (SPM2) software. Results: PTSD patients had lower [11C]GR205171 binding compared to controls, in frontal cortical clusters encompassing bilaterally insula and left Brodmann area 11, reflecting lower NK1-receptor availability. No areas were found in which PTSD patients had higher [11C]GR205171 binding. Conclusions: This is the first study reporting differences in NK1-receptor availability in PTSD patients relative to controls. A tentative conclusion is that PTSD patients have a down regulation of the NK1-receptor system, which could be either a risk factor or due to emotional trauma processing.

  • 3.
    Bhatt, Deepak L.
    et al.
    Harvard Med Sch, Brigham & Womens Hosp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA.
    Fox, Kim
    Imperial Coll, Natl Heart & Lung Inst, London, England;Royal Brompton Hosp, London, England.
    Harrington, Robert A.
    Stanford Univ, Dept Med, SCCR, Stanford, CA 94305 USA.
    Leiter, Lawrence A.
    Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada.
    Mehta, Shamir R.
    Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada;McMaster Univ, Hamilton, ON, Canada.
    Simon, Tabassome
    Sorbonne Univ Paris, Hop St Antoine, AP HP, Dept Clin Pharmacol URCEST, Paris, France.
    Andersson, Marielle
    AstraZeneca Gothenburg, Dept Cardiovasc Renal & Metab, Molndal, Sweden.
    Himmelmann, Anders
    AstraZeneca Gothenburg, Dept Cardiovasc Renal & Metab, Molndal, Sweden.
    Ridderstrale, Wilhelm
    AstraZeneca Gothenburg, Dept Cardiovasc Renal & Metab, Molndal, Sweden.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Univ, Uppsala Clin Res Ctr, Dept Med Sci, Cardiol, Uppsala, Sweden.
    Steg, Philippe Gabriel
    Univ Paris Diderot, Hop Bichat, AP HP, Dept Hosp Univ FIRE,F CRIN Network,FACT, Paris, France;Univ Paris Diderot, Hop Bichat, AP HP, Dept Hosp Univ FIRE,INSERM,U 1148, Paris, France;Imperial Coll, Royal Brompton Hosp, NHLI, London, England.
    Steg, Gabriel
    Diaz, Rafael
    Amerena, John
    Huber, Kurt
    Sinnaeve, Peter
    Nicolau, Jose Carlos
    Kerr Saraiva, Jose Francisco
    Petrov, Ivo
    Corbalan, Ramon
    Ge, Junbo
    Zhao, Qiang
    Botero, Rodrigo
    Widimsky, Petr
    Kristensen, Steen Dalby
    Hartikainen, Juha
    Danchin, Nicolas
    Darius, Harald
    Fat, Tse Hung
    Kiss, Robert Gabor
    Pais, Prem
    Lev, Eli
    De Luca, Leonardo
    Goto, Shinya
    Ramos Lopez, Gabriel Arturo
    Cornel, Jan Hein
    Kontny, Frederic
    Medina, Felix
    Babilonia, Noe
    Opolski, Grzegorz
    Vinereanu, Dragos
    Zateyshchikov, Dmitry
    Ruda, Mikhail
    Elamin, Omer
    Kovar, Frantisek
    Dalby, Anthony John
    Jeong, Myung Ho
    Bueno, Hector
    James, Stefan
    Chiang, Chern-En
    Tresukosol, Damras
    Ongen, Zeki
    Ray, Kausik
    Parkhomenko, Alexander
    McGuire, Darren
    Kosiborod, Mikhail
    Nguyen, Tuan Quang
    Wallentin, Lars
    Fox, Keith A. A.
    Eikelboom, John W.
    Tuomilehto, Jaakko
    Lee, Kerry L.
    Al-Khalidi, Hussein R.
    Ellis, Stephen J.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Holmgren, Pernilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Heldestad, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hallberg, Theresa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Renlund Grausne, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alm, Cristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michelgård Palmquist, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svanberg, Camilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Capell, Warren H.
    Nehler, Mark R.
    Hiatt, William R.
    Bonaca, Marc P.
    Houser, Stacey
    Bachler, Susie
    Jaeger, Nicole
    Aunes, Maria
    Brusehed, Asa
    Chen, Jersey
    Dahlof, Bjorn
    Dolezalova, Jitka
    Domzol, Maciej
    Findley, Magdalena
    Holmberg, Niclas
    Jahreskog, Marianne
    Knutsson, Mikael
    Kruszewski, Jakub
    Leonsson-Zachrisson, Maria
    Stark, Maj
    Winder, Elin
    Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study2019In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 42, no 5, p. 498-505Article in journal (Refereed)
    Abstract [en]

    In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients >= 50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of >= 50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention.

  • 4.
    Faria, Vanda
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Linnman, Clas
    Pissiota, Anna
    Palmqvist Michelgård, Åsa
    Zancan, S
    Bani, M
    Pich, E
    Appel, L
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Pretreatment Anterior Cingulate Activity Predicts Amygdala Attenuation in Social Phobic Placebo Responders2010In: Biol. Psychiatry 67, 34S-34S, 2010, p. 34S-34S 109Conference paper (Refereed)
  • 5.
    Furmark, T
    et al.
    Uppsala University.
    Åhs, F
    Uppsala University.
    Linnman, C
    Uppsala University.
    Pissiota, A
    Michelgård, Å
    Uppsala University.
    Hellquist, A
    Hernefalk, S
    Flykt, K
    Appel, L
    Bani, M
    Merlo Pich, E
    Zancan, S
    Fredriksson, M
    Uppsala University.
    Amygdalar activity during emotional perception and experience in subjects with social phobia2005Conference paper (Other scientific)
  • 6.
    Furmark, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Appel, L
    Winqvist, I
    Michelgård, Åsa
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Bani, M
    Pich, E M
    Långström, B
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Elevated uptake of [C-11] 5-hydroxy-tryptophan in the amygdala in patients with social anxiety disorder: a PET study2009In: Biol. Psychiatry 65, 126S-127S, 2009, p. 421-Conference paper (Other academic)
    Abstract [en]

    Background: Social anxiety disorder (SAD) is associated with amygdala hyperresponsivity and imbalances in serotonergic neurotransmission. We have previously noted altered uptake of carbon-11 labelled 5-hydroxytryptophan (5-HTP) in a small sample of patients with SAD, suggesting deficiencies in presynaptic serotonin synthesis. In the present study, positron emission tomography (PET) was used to assess uptake of [11C]5-HTP in a larger sample of patients with SAD compared with age and sex-matched healthy controls. Methods: PET-data were available for 17 patients (8 females, age 33±8 years) diagnosed with SAD and for 17 healthy controls (9 females, age 35±10 years). Accumulation of the [11C]5-HTP tracer was assessed at Uppsala Imanet during 60 minutes in the resting state. Parametric images were generated using the graphical reference Patlak method assuming irreversible trapping of [11C]5-HTP from 11-60 minutes. Cerebellum was selected as reference region after correction for the decarboxylation rate of [11C]5-HTP. Exploratory and amygdala focused analyses were performed using statistical parametric mapping (SPM2). Results: Patients with SAD had significantly higher [11C]5-HTP uptake than controls in several regions including the superior, medial and inferior frontal gyrus, anterior cingulate cortex, hippocampus and lentiform nucleus, all in the left hemisphere. Region of interest analyses also revealed significantly higher uptake (SAD > controls) in the left (x-28 y-4 z-12; T=3.16) and right (x24 y1 z-15; T=2.82) amygdala (p<0.05 corrected). Conclusions: Higher [11C]5-HTP uptake, suggesting an elevated serotonin synthesis rate, was noted in patients with SAD compared to healthy controls predominantly in frontal and temporal regions including the amygdala.

  • 7.
    Furmark, Tomas
    et al.
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Pissiota, Anna
    Frans, Örjan
    Michelgård, Åsa
    Linnander, Caroline
    Lewenhaupt, Susanne
    Appel, Lieuwe
    Långström, Bengt
    Fredrikson, Mats
    Decreased regional cerebral blood flow in the prefrontal cortex during fear provocation: A PET study of specific phobia [CD-ROM]2002In: Neuroimage, Abstract from: Eight International Conference on Functional Mapping of the Human Brain, June 2-6, 2002 Sendai, Japan, 2002Conference paper (Other (popular scientific, debate etc.))
  • 8.
    Laukka, Petri
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Linnman, Clas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Pissiota, Anna
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Frans, Örjan
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Faria, Vanda
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Michelgård, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    In a nervous voice: Acoustic analysis and perception of anxiety in social phobics' speech2008In: Journal of nonverbal behavior, ISSN 0191-5886, E-ISSN 1573-3653, Vol. 32, no 4, p. 195-214Article in journal (Refereed)
    Abstract [en]

    This study investigated the effects of anxiety on nonverbal aspects of speech using data collected in the framework of a large study of social phobia treatment. The speech of social phobics (N = 71) was recorded during an anxiogenic public speaking task both before and after treatment. The speech samples were analyzed with respect to various acoustic parameters related to pitch, loudness, voice quality, and temporal apsects of speech. The samples were further content-masked by low-pass filtering (which obscures the linguistic content of the speech but preserves nonverbal affective cues) and subjected to listening tests. Results showed that a decrease in experienced state anxiety after treatment was accompanied by corresponding decreases in a) several acoustic parameters (i.e., mean and maximum voice pitch, high-frequency components in the energy spectrum, and proportion of silent pauses), and b) listeners' perceived level of nervousness. Both speakers' self-ratings of state anxiety and listeners' ratings of perceived nervousness were further correlated with similar acoustic parameters. The results complement earlier studies on vocal affect expression which have been conducted on posed, rather than authentic, emotional speech.

  • 9. Linnman, Claes
    et al.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Faria, Vanda
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Michelgård, Åsa
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Appel, L
    Bani, M
    Merlo Pich, E
    Wolf, O T
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    A differential cortisol response to stress after treatment of social phobia with a neurokinin-1 receptor antagonist o SSRIs.2008In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, p. 553-Article in journal (Other academic)
  • 10.
    Linnman, Clas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Michelgård, Åsa
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Fredrikson, Mats
    Furmark, Tomas
    State Anxiety and Social Phobia: A PET Study2004In: Biological Psychiatry, 55, Suppl. 8 (Biol. Psychiatry 55, 57S-57S), 2004, p. 57S-Conference paper (Refereed)
  • 11.
    Michelgård Palmquist, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Positron Emission Tomography (PET) Studies in Anxiety Disorders2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Anxiety disorders are very common and the primary feature is abnormal or inappropriate anxiety. Fear and anxiety is often mediated by the amygdala, a brain structure rich in substance P (SP) and neurokinin 1 (NK1) receptors.

    To learn more about how the human amygdala is modulated by fear and anxiety in event-triggered anxiety disorders and to investigate if the SP/NK1 receptor system is affected, regional cerebral blood flow (rCBF) ([15O]-water; Study I and II) and the SP/NK1 receptor system ([11C]GR205171; Study III and IV) were studied with positron emission tomography (PET).

    In Study I we investigated the neural correlates of affective startle modulation in persons with specific phobia by measuring rCBF during exposure to fearful and non-fearful pictures, paired and unpaired with acoustic startle stimuli. Fear-potentiated startle was associated with activation of the affective part of the anterior cingulate cortex and the left amygdaloid–hippocampal area.

    In Study II short-term drug treatment effects on rCBF in patients diagnosed with social phobia was evaluated, comparing the NK1 receptor antagonist GR205171 to the selective serotonin reuptake inhibitor citalopram and placebo. Social anxiety and neural activity in the medial temporal lobe including the amygdala was significantly reduced by both drugs but not placebo.

    In Study III we investigated if activity in the SP/NK1 receptor system in the amygdala would be affected by fear provocation in individuals with specific snake or spider phobia. Fear provocation was associated with a decreased uptake of the NK1 antagonist [11C]GR205171 in the amygdala, possibly explained by an increase in endogenous SP release occupying the NK1 receptors.

    Study IV was conducted to explore the resting state NK1 receptor availability in PTSD patients as compared to healthy controls. Increased resting state binding of the tracer [11C]GR205171 in the amygdala of patients with PTSD suggested an increased amount of available receptors.

    In summary, fear and fear-potentiated startle modulates the human amygdala, possibly through the SP/NK1 receptor system.

    List of papers
    1.
    The record could not be found. The reason may be that the record is no longer available or you may have typed in a wrong id in the address field.
    2. Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo.
    Open this publication in new window or tab >>Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo.
    Show others...
    2005 (English)In: Biol Psychiatry, ISSN 0006-3223, Vol. 58, no 2, p. 132-42Article in journal (Other scientific) Published
    Abstract [en]

    BACKGROUND: Evidence is accumulating that pharmacological blockade of the substance P preferring neurokinin-1 (NK1) receptor reduces anxiety. This study compared the effects of an NK1 receptor antagonist, citalopram, and placebo on brain activity and anxiety symptoms in social phobia. METHODS: Thirty-six patients diagnosed with social phobia were treated for 6 weeks with the NK1 antagonist GR205171 (5 mg), citalopram (40 mg), or matching placebo under randomized double-blind conditions. GR205171 was administered for 4 weeks preceded by 2 weeks of placebo. Before and after treatment, regional cerebral blood flow (rCBF) during a stressful public speaking task was assessed using oxygen-15 positron emission tomography. Response rate was determined by the Clinical Global Impression Improvement Scale. RESULTS: Patients improved to a larger extent with the NK1 antagonist (41.7% responders) and citalopram (50% responders), compared with placebo (8.3% responders). Within- and between-group comparisons showed that symptom improvement was paralleled by a significantly reduced rCBF response to public speaking in the rhinal cortex, amygdala, and parahippocampal-hippocampal regions. The rCBF pattern was corroborated in follow-up analyses of responders and subjects showing large state anxiety reduction. CONCLUSIONS: Short-term administration of GR205171 and citalopram alleviated social anxiety. Neurokinin-1 antagonists may act like serotonin reuptake inhibitors by attenuating neural activity in a medial temporal lobe network.

    Keywords
    Adult, Anxiety/*drug therapy/physiopathology, Cerebrovascular Circulation/*drug effects, Citalopram/*pharmacology/therapeutic use, Comparative Study, Double-Blind Method, Female, Humans, Male, Phobic Disorders/*drug therapy/physiopathology, Piperidines/*pharmacology/therapeutic use, Positron-Emission Tomography, Receptors; Neurokinin-1/antagonists & inhibitors, Research Support; Non-U.S. Gov't, Serotonin Uptake Inhibitors/*pharmacology/therapeutic use, Temporal Lobe/blood supply/radionuclide imaging, Tetrazoles/*pharmacology/therapeutic use
    Identifiers
    urn:nbn:se:uu:diva-19636 (URN)16038684 (PubMedID)
    Available from: 2006-11-30 Created: 2006-11-30 Last updated: 2011-01-12
    3.
    The record could not be found. The reason may be that the record is no longer available or you may have typed in a wrong id in the address field.
    4. Enhanced neurokinin 1 receptor availability in the amygdala in posttraumatic stress disorder
    Open this publication in new window or tab >>Enhanced neurokinin 1 receptor availability in the amygdala in posttraumatic stress disorder
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Posttraumatic stress disorder (PTSD) may result from experiencing severe distress, and is in part amygdala dependent. Animal studies demonstrate that stress and negative affect enhance the amygdala-release of the neuropeptide substance P (SP) which binds to the neurokinin 1 (NK1) receptor. This positron emission tomography (PET) study investigated if NK1 receptor availability in the amygdala of PTSD patients were different from healthy control subjects. Methods: Eleven male patients with DSM-IV defined PTSD and nine healthy male control subjects were PET scanned during 60 min at rest using the NK1 preferring tracer [11C]GR205171. Parametric Patlak images were generated and analyzed using statistical parametric mapping software. The effect of age was co-varied out because the amount of NK1 receptors decline with age. Results: PTSD patients had elevated uptake of [11C]GR205171 in the amygdala as compared to controls, also when anxiety differences were controlled for. Conclusions: We suggest that enhanced NK1 receptor availability could be a risk factor for developing PTSD rather than reflecting trauma induced alterations.

    Keywords
    PTSD; NK1 receptor; substance P; PET; amygdala; STAI-S
    National Category
    Psychiatry
    Research subject
    Neuroscience
    Identifiers
    urn:nbn:se:uu:diva-130093 (URN)
    Available from: 2010-08-31 Created: 2010-08-31 Last updated: 2011-02-25Bibliographically approved
  • 12.
    Michelgård Palmquist, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Fernandez, Manuel
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    von Knorring, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Pissiota, Anna
    Åhs, Fredrik
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Enhanced neurokinin 1 receptor availability in the amygdala in posttraumatic stress disorderManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Posttraumatic stress disorder (PTSD) may result from experiencing severe distress, and is in part amygdala dependent. Animal studies demonstrate that stress and negative affect enhance the amygdala-release of the neuropeptide substance P (SP) which binds to the neurokinin 1 (NK1) receptor. This positron emission tomography (PET) study investigated if NK1 receptor availability in the amygdala of PTSD patients were different from healthy control subjects. Methods: Eleven male patients with DSM-IV defined PTSD and nine healthy male control subjects were PET scanned during 60 min at rest using the NK1 preferring tracer [11C]GR205171. Parametric Patlak images were generated and analyzed using statistical parametric mapping software. The effect of age was co-varied out because the amount of NK1 receptors decline with age. Results: PTSD patients had elevated uptake of [11C]GR205171 in the amygdala as compared to controls, also when anxiety differences were controlled for. Conclusions: We suggest that enhanced NK1 receptor availability could be a risk factor for developing PTSD rather than reflecting trauma induced alterations.

  • 13.
    Michelgård, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Winqvist, I M
    Fernandez, M
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Långström, B
    von Knorring, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Appel, L
    Altered serotonin transporter function in post traumatic stress disorder2007In: Biological Psychiatry, 2007, p. 98-Conference paper (Other academic)
  • 14.
    Palmquist, Åsa Michelgård
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Fernandez, Manuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    von Knorring, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Serotonin Transporter Binding in Posttraumatic Stress Disorder Measured with [11c]-DASB2014In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 75, no 9, p. 357S-357SArticle in journal (Other academic)
  • 15.
    Åhs, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Michelgård Palmquist, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Pissiota, Anna
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Appel, Lieuwe
    Frans, Örjan
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Liberzon, Israel
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Arousal modulation of memory and amygdala-parahippocampal connectivity: A PET-psychophysiology study in specific phobia2011In: Psychophysiology, ISSN 0048-5772, E-ISSN 1469-8986, Vol. 48, no 11, p. 1463-1469Article in journal (Refereed)
    Abstract [en]

    Phobic fear is accompanied by intense bodily responses modulated by the amygdala. An amygdala moderated psychophysiological measure related to arousal is electrodermal activity. We evaluated the contributions of electrodermal activity to amygdala-parahippocampal regional cerebral blood flow (rCBF) during phobic memory encoding in subjects with spider or snake phobia. Recognition memory was increased for phobia-related slides and covaried with rCBF in the amygdala and the parahippocampal gyrus. The covariation between parahippocampal rCBF and recognition was related to electrodermal activity suggesting that parahippocampal memory processes were associated with sympathetic activity. Electrodermal activity further mediated the amygdala effect on parahippocampal activity. Memory encoding during phobic fear therefore seems contingent on amygdala's influence on arousal and parahippocampal activity.

  • 16.
    Åhs, Fredrik
    et al.
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Michelgård, Åsa
    Fredrikson, Mats
    Wolf, O.T.
    Kirschbaum, C.
    Appel, Lieuwe
    Furmark, Tomas
    Central neural correlates of salivary cortisol during stress in subjects with social phobia2004In: Biological Psychiatry, 55, Suppl. 8, 2004, p. 211S-Conference paper (Refereed)
  • 17.
    Åhs, Fredrik
    et al.
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Michelgård, Åsa
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Fredrikson, Mats
    Wolf, O.T.
    Kirschbaum, C.
    Appel, Lieuwe
    Furmark, Tomas
    Central neural correlates of salivary cortisol in social phobics performing a speech2003In: Psychophysiology, 40, Suppl. 1, 2003, p. S21-Conference paper (Refereed)
  • 18.
    Åhs, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Michelgård, Åsa
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Pissiota, Anna
    Uppsala University.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Appel, Lieuwe
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Bodily arousal gates amygdala-hippocampal interaction in phobic memory encoding2009In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 65, no 8, p. 126S-126SArticle in journal (Other academic)
  • 19.
    Åhs, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Pissiota, Anna
    Uppsala University.
    Michelgård, Åsa
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Appel, Lieuwe
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Functional connectivity of the amygdala in specific phobia2008In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 63, no 7, p. 169S-169SArticle in journal (Other academic)
1 - 19 of 19
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