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  • 1.
    Aarnio, Mikko
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fredriksson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wolf, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Måns
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    Peterson, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Linnman, Clas
    Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [(11)C]-D-deprenyl PET/CT.2017In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 17, p. 418-424Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Positron emission tomography (PET) with the radioligand [(11)C]-D-deprenyl has shown increased signal at location of pain in patients with rheumatoid arthritis and chronic whiplash injury. The binding site of [(11)C]-D-deprenyl in peripheral tissues is suggested to be mitochondrial monoamine oxidase in cells engaged in post-traumatic inflammation and tissue repair processes. The association between [(11)C]-D-deprenyl uptake and the transition from acute to chronic pain remain unknown. Further imaging studies of musculoskeletal pain at the molecular level would benefit from establishing a clinical model in a common and well-defined injury in otherwise healthy and drug-naïve subjects. The aim of this study was to investigate if [(11)C]-D-deprenyl uptake would be acutely elevated in unilateral ankle sprain and if tracer uptake would be reduced as a function of healing, and correlated with pain localizations and pain experience.

    METHODS: Eight otherwise healthy patients with unilateral ankle sprain were recruited at the emergency department. All underwent [(11)C]-D-deprenyl PET/CT in the acute phase, at one month and 6-14 months after injury.

    RESULTS: Acute [(11)C]-D-deprenyl uptake at the injury site was a factor of 10.7 (range 2.9-37.3) higher than the intact ankle. During healing, [(11)C]-D-deprenyl uptake decreased, but did not normalize until after 11 months. Patients experiencing persistent pain had prolonged [(11)C]-D-deprenyl uptake in painful locations.

    CONCLUSIONS AND IMPLICATIONS: The data provide further support that [(11)C]-D-deprenyl PET can visualize, quantify and follow processes in peripheral tissue that may relate to soft tissue injuries, inflammation and associated nociceptive signaling. Such an objective correlate would represent a progress in pain research, as well as in clinical pain diagnostics and management.

  • 2.
    Ahs, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Sollers, John J
    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.
    Thayer, Julian F
    High-frequency heart rate variability and cortico-striatal activity in men and women with social phobia2009In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 47, no 3, p. 815-820Article in journal (Refereed)
    Abstract [en]

    Identifying brain systems that regulate or modulate autonomic nervous system functions may identify pathways through which psychosocial factors can influence health and disease. Reduced high-frequency heart rate variability (HF-HRV) characterizes anxiety disordered patients and is predictive of adverse myocardial events. Sex differences in the prevalence of anxiety disorders and cardiac diseases implicate the possibility of sex specific neural regulation of HF-HRV. We investigated the correlation between HF-HRV and regional cerebral blood flow (rCBF) in 28 subjects (15 women) with social phobia undergoing a stressful public speaking task. Regional CBF was measured with [(15)O] water positron emission tomography. Stress induced rCBF correlated positively with HF-HRV in the right supra genual anterior cingulate cortex Brodmann's area (BA) 32, the right head of the caudate nucleus and bilaterally in the medial prefrontal cortex (BA10), extending into the dorsolateral prefrontal cortex (BA46) in the left hemisphere. Men showed larger positive co-variation in the caudate than women. These findings underscore the importance of the emotional division of the anterior cingulate cortex, the prefrontal cortex and the striatum in cardiovagal activity. The study replicates and extends results from published functional neuroimaging studies on cardioregulatory or modulatory areas in healthy subjects to men and women with social phobia. Moreover, caudate functions, possibly related to dopaminergic neurotransmission, have sexually dimorphic effects on vagal modulation of the heart.

  • 3.
    Alaie, Iman
    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.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Björkstrand, Johannes
    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.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Wallenquist, Ulrika
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Wahlstedt, Kurt
    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.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Symptom Improvement in Social Anxiety Disorder is Associated with Reduced Amygdala Reactivity to Emotional Faces2013In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 73, no 9, p. 79S-79SArticle in journal (Other academic)
  • 4.
    Alaie, Iman
    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.
    Marteinsdottir, I
    Hartvig, P
    Tillfors, M
    Eriksson, E
    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.
    Serotonin Synthesis Rate and the Tryptophan Hydroxylase-2 G-703T Polymorphism in Social Anxiety Disorder2014Conference paper (Refereed)
  • 5.
    Alaie, Iman
    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.
    Marteinsdottir, Ina
    Hartvig, Per
    Tillfors, Maria
    Eriksson, Elias
    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.
    Serotonin Synthesis Rate and the Tryptophan Hydroxylase-2 G-703T Polymorphism in Social Anxiety Disorder2014In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 75, no 9, p. 357S-357SArticle in journal (Other academic)
  • 6.
    Andersson, G. E. T.
    et al.
    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.
    Hirvelä, C
    Fredriksson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Changes in cerebral blood flow during cognitive distraction in tinnitus patients2002Conference paper (Refereed)
  • 7. Andersson, G
    et al.
    Fredriksson, M
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Furmark, T
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Hirvelä, C
    Lyttkens, L
    Tillfors, M
    Funktionell neuroanatomi vid tinnitus1999In: Svenska läkaresällskapets riksstämma, 1999, p. 283-Conference paper (Other (popular scientific, debate etc.))
  • 8. Andersson, G
    et al.
    Furmark, T
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Hirvelä, C
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Lyttkens, L
    Tillfors, M
    Fredriksson, M
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Tinnitus: Funktionell neuroanatomi2000In: Svensk ÖHN-tidskrift, 2000, p. 21-Conference paper (Other scientific)
  • 9.
    Andersson, G
    et al.
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Lyttkens, L
    Hirvelä, C
    Furmark, T
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Tillfors, M
    Fredrikson, M
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Regional cerebral blood flow during tinnitus: a PET case study with lidocaine and auditory stimulation.2000In: Acta Otolaryngol, ISSN 0001-6489, Vol. 120, no 8, p. 967-72Article in journal (Refereed)
    Abstract [en]

    Brain imaging of tinnitus has suggested central correlates of tinnitus perception. This study presents positron emission tomographic (PET) measurements of regional cerebral blood flow (rCBF) in a female tinnitus patient with bilateral left dominant tinnitus. Lidocaine infusion (75 mg during 5 min (0.2 mg/kg/min)) resulted in a 75% reduction of tinnitus and a temporary abolition of the dominant tinnitus in her left ear. Regional CBF was measured in four conditions: i) at rest while concentrating on tinnitus, ii) following maximum effect of lidocaine, iii) during sound stimulation, and iv) the following day at rest while concentrating on tinnitus. Subtraction analyses showed that tinnitus was associated with increased rCBF in the left parieto-temporal auditory cortex, including the primary and secondary auditory cortex with a focus in the parietal cortex (Brodmann areas 39, 41, 42, 21, 22). Activations were also found in right frontal paralimbic areas (Brodmann areas 47, 49 and 15). Sound stimulation resulted in bilateral activation of auditory areas. It is suggested that tinnitus is processed in primary, secondary and integrative auditory cortical areas. Tinnitus perception may involve areas related to auditory attention, while emotional processing relates to temporofrontal paralimbic areas.

  • 10. Andersson, Gerhard
    et al.
    Jüris, Linda
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Classon, Elisabeth
    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.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Consequences of suppressing thoughts about tinnitus and the effects of cognitive distraction on brain activity in tinnitus patients2006In: Audiology & neuro-otology, ISSN 1420-3030, E-ISSN 1421-9700, Vol. 11, no 5, p. 301-309Article in journal (Refereed)
    Abstract [en]

    Tinnitus is the perception of sound in the absence of any appropriate external stimulus. Based on the clinical observation that tinnitus patients may distract themselves from their sounds, we performed an experimental test on the effects of suppressing thoughts about tinnitus with 45 tinnitus patients, to systematically evaluate the immediate consequences of suppressing thought vs. attending to tinnitus. Suppression instructions tended to lead to a subsequent decrease in tinnitus-related thoughts, whereas attention to tinnitus resulted in an increase in such thoughts. No effects were seen in a control group who neither suppressed nor attended to their tinnitus. In an independent positron emission tomography study of cerebral blood flow with 8 patients we found that silent backward counting ('serial sevens test') led to a decrease in neural activity in auditory cortex, as well as perceived decrease of tinnitus loudness and annoyance. Thus, distraction that altered the tinnitus experience seemed to attenuate auditory cortex activity.

  • 11.
    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.

  • 12. Baldwin, David S
    et al.
    Allgulander, Christer
    Altamura, Alfredo Carlo
    Angst, Jules
    Bandelow, Borwin
    den Boer, Johan
    Boyer, Patrice
    Davies, Simon
    Dell'osso, Bernardo
    Eriksson, Elias
    Fineberg, Naomi
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Herran, Andres
    Maron, Eduard
    Metspalu, Andres
    Nutt, David
    van der Wee, Nic
    Vázquez-Barquero, Jose Luis
    Zohar, Joseph
    Manifesto for a European anxiety disorders research network2010In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 20, no 6, p. 426-32Article in journal (Refereed)
    Abstract [en]

    Despite the size, burden and costs of anxiety disorders, many patients remain unrecognised, and the effectiveness of evidence-based interventions in routine clinical practice can be disappointing. The European College of Neuropsychopharmacology (ECNP) has established the ECNP Network Initiative (ECNP-NI) to help meet the goal of extending current understanding of the causes of central nervous system disorders, thereby contributing to improvements in clinical outcomes and reducing the associated societal burden. The Anxiety Disorders Research Network (ADRN) has been adopted within the ECNP-NI: this consensus statement summarises its overall aims and objectives.

  • 13.
    Bas-Hoogendam, Janna Marie
    et al.
    Leiden Univ, Leiden, Netherlands..
    van Steenbergen, Henk
    Leiden Univ, Leiden, Netherlands..
    Pannekoek, J. Nienke
    Imperial Coll London, London, England..
    Fouche, Jean-Paul
    Univ Cape Town, Rondebosch, South Africa..
    Lochner, Christine
    Stellenbosch Univ, Stellenbosch, South Africa..
    Hattingh, Coenraad J.
    Univ Cape Town, Rondebosch, South Africa..
    Cremers, Henk R.
    Univ Amsterdam, Amsterdam, Netherlands..
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Månsson, Kristoffer N. T.
    Linkoping Univ, Linkoping, Sweden..
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Boraxbekk, Carl-Johan
    Umea Univ, Umea, Sweden..
    Carlbring, Per
    Stockholm Univ, Stockholm, Sweden..
    Andersson, Gerhard
    Linkoping Univ, Linkoping, Sweden..
    Fredriksson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Straube, Thomas
    Univ Munster, Munster, Germany..
    Peterburs, Jutta
    Univ Munster, Munster, Germany..
    Klumpp, Heide
    Univ Illinois, Chicago, IL USA..
    Phan, K. Luan
    Univ Illinois, Chicago, IL USA..
    Roelofs, Karin
    Radboud Univ Nijmegen, Nijmegen, Netherlands..
    Stein, Dan J.
    Univ Cape Town, Rondebosch, South Africa..
    van der Wee, Nic. J. A.
    Leiden Univ, Med Ctr, Leiden, Netherlands..
    Sample Size Matters: A Voxel-Based Morphometry Multi-Center Mega-Analysis of Gray Matter Volume in Social Anxiety Disorder2017In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 81, no 10, p. S7-S8Article in journal (Other academic)
  • 14.
    Bas-Hoogendam, Janna Marie
    et al.
    Leiden Univ, Inst Psychol, Wassenaarseweg 52, NL-2333 AK Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands.;Leiden Inst Brain & Cognit, Leiden, Netherlands..
    van Steenbergen, Henk
    Leiden Univ, Inst Psychol, Wassenaarseweg 52, NL-2333 AK Leiden, Netherlands.;Leiden Inst Brain & Cognit, Leiden, Netherlands..
    Pannekoek, J. Nienke
    Imperial Coll London, Div Brain Sci, Ctr Psychiat, Neuropsychopharmacol Unit, London, England..
    Fouche, Jean-Paul
    Univ Cape Town, Dept Psychiat & Mental Hlth, Cape Town, South Africa..
    Lochner, Christine
    UCT MRC Unit Anxiety & Stress Disorders, Cape Town, South Africa.;Univ Stellenbosch, Dept Psychiat, Tygerberg, South Africa..
    Hattingh, Coenraad J.
    Univ Cape Town, Dept Psychiat & Mental Hlth, Cape Town, South Africa..
    Cremers, Henk R.
    Univ Amsterdam, Dept Clin Psychol, Amsterdam, Netherlands..
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Månsson, Kristoffer N.T.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Stockholm Univ, Dept Psychol, Stockholm, Sweden.;Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden..
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden..
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Boraxbekk, Carl-Johan
    Umea Univ, Umea Ctr Funct Brain Imaging UFBI, Umea, Sweden.;Copenhagen Univ Hosp Hvidovre, Ctr Funct & Diagnost Imaging & Res, DRCMR, Hvidovre, Denmark..
    Carlbring, Per
    Stockholm Univ, Dept Psychol, Stockholm, Sweden..
    Andersson, Gerhard
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Linkoping Univ, Dept Behav Sci & Learning Psychol, Linkoping, Sweden..
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden..
    Straube, Thomas
    Univ Munster, Inst Med Psychol & Syst Neurosci, Munster, Germany..
    Peterburs, Jutta
    Univ Munster, Inst Med Psychol & Syst Neurosci, Munster, Germany..
    Klumpp, Heide
    Univ Illinois, Dept Psychiat, Chicago, IL USA.;Univ Illinois, Dept Psychol, Chicago, IL USA..
    Phanp, K. Luan
    Univ Illinois, Dept Psychiat, Chicago, IL USA.;Univ Illinois, Dept Psychol, Chicago, IL USA..
    Roelofs, Karin
    Radboud Univ Nijmegen, Behav Sci Inst, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Veltman, Dick J.
    Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Neurosci Campus Amsterdam, Amsterdam, Netherlands..
    van Tol, Marie-Jose
    Univ Groningen, Univ Med Ctr Groningen, Dept Neurosci, Groningen, Netherlands..
    Stein, Dan J.
    Univ Cape Town, Dept Psychiat & Mental Hlth, Cape Town, South Africa.;UCT MRC Unit Anxiety & Stress Disorders, Cape Town, South Africa..
    van der Wee, Nic J. A.
    Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands.;Leiden Inst Brain & Cognit, Leiden, Netherlands..
    Voxel-based morphometry multi-center mega-analysis of brain structure in social anxiety disorder2017In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 16, p. 678-688Article in journal (Refereed)
    Abstract [en]

    Social anxiety disorder (SAD) is a prevalent and disabling mental disorder, associated with significant psychiatric comorbidity. Previous research on structural brain alterations associated with SAD has yielded inconsistent results concerning the direction of the changes in graymatter (GM) in various brain regions, as well as on the relationship between brain structure and SAD-symptomatology. These heterogeneous findings are possibly due to limited sample sizes. Multisite imaging offers new opportunities to investigate SAD-related alterations in brain structure in larger samples. An international multi-center mega-analysis on the largest database of SAD structural T1-weighted 3T MRI scans to date was performed to compare GM volume of SAD-patients (n = 174) and healthy control (HC)-participants (n = 213) using voxel-based morphometry. A hypothesis-driven region of interest (ROI) approach was used, focusing on the basal ganglia, the amygdala-hippocampal complex, the prefrontal cortex, and the parietal cortex. SAD-patients had larger GM volume in the dorsal striatum when compared to HC-participants. This increase correlated positively with the severity of self-reported social anxiety symptoms. No SAD-related differences in GM volume were present in the other ROIs. Thereby, the results of this mega-analysis suggest a role for the dorsal striatum in SAD, but previously reported SAD-related changes in GM in the amygdala, hippocampus, precuneus, prefrontal cortex and parietal regions were not replicated. Our findings emphasize the importance of large sample imaging studies and the need for meta-analyses like those performed by the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium.

  • 15. Bergman, O
    et al.
    Åhs, Fredrik
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Appel, L
    Linnman, Claes
    Faria, Vanda
    Henningsson, S
    Hariri, A
    Bani, M
    Bettica, P
    Merlo Pich, E
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Eriksson, E
    Westberg, L
    Amygdala blood flow is associated with dopamine transporter gene pslymorphism in patients with social anxiety disorder and healthy controls.Article in journal (Other academic)
  • 16. Bergman, O.
    et al.
    Åhs, Fredrik
    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.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Linnman, Claes
    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.
    Bani, M.
    Pich, E. M.
    Bettica, P.
    Henningsson, S.
    Manuck, S. B.
    Ferrell, R. E.
    Nikolova, Y. S.
    Hariri, A. R.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Westberg, L.
    Eriksson, E.
    Association between amygdala reactivity and a dopamine transporter gene polymorphism2014In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 4, p. e420-Article in journal (Refereed)
    Abstract [en]

    Essential for detection of relevant external stimuli and for fear processing, the amygdala is under modulatory influence of dopamine (DA). The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA. This study examined if a common functional variable number tandem repeat polymorphism in the 3' untranslated region of the DAT gene (SLC6A3) influences amygdala function during the processing of aversive emotional stimuli. Amygdala reactivity was examined by comparing regional cerebral blood flow, measured with positron emission tomography and [O-15] water, during exposure to angry and neutral faces, respectively, in a Swedish sample comprising 32 patients with social anxiety disorder and 17 healthy volunteers. In a separate US sample, comprising 85 healthy volunteers studied with blood oxygen level-dependent functional magnetic resonance imaging, amygdala reactivity was assessed by comparing the activity during exposure to threatening faces and neutral geometric shapes, respectively. In both the Swedish and the US sample, 9-repeat carriers displayed higher amygdala reactivity than 10-repeat homozygotes. The results suggest that this polymorphism contributes to individual variability in amygdala reactivity.

  • 17.
    Björkstrand, Johannes
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Ågren, Thomas
    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.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    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.
    Disruption of Memory Reconsolidation Erases a Fear Memory Trace in the Human Amygdala: An 18-Month Follow-Up.2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 7, p. e0129393-Article in journal (Refereed)
    Abstract [en]

    Fear memories can be attenuated by reactivation followed by disrupted reconsolidation. Using functional magnetic resonance imaging we recently showed that reactivation and reconsolidation of a conditioned fear memory trace in the basolateral amygdala predicts subsequent fear expression over two days, while reactivation followed by disrupted reconsolidation abolishes the memory trace and suppresses fear. In this follow-up study we demonstrate that the behavioral effect persists over 18 months reflected in superior reacquisition after undisrupted, as compared to disrupted reconsolidation, and that neural activity in the basolateral amygdala representing the initial fear memory predicts return of fear. We conclude that disrupting reconsolidation have long lasting behavioral effects and may permanently erase the fear component of an amygdala-dependent memory.

  • 18.
    Björkstrand, Johannes
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Ågren, Thomas
    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.
    Eriksson, Elias
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Disruption of Fear Reconsolidation by Extinction and the G-703T Gene Polymorphism2013In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 73, no 9, p. 67S-67SArticle in journal (Other academic)
  • 19.
    Björkstrand, Johannes
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Ågren, Thomas
    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. Department of Clinical Neuroscience, Karolinska Institutet, Tomtebodavägen 18A, 171 77, Stockholm, Sweden.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Department of Clinical Neuroscience, Karolinska Institutet, Tomtebodavägen 18A, 171 77, Stockholm, Sweden.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hjorth, Olof
    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.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Department of Clinical Neuroscience, Karolinska Institutet, Tomtebodavägen 18A, 171 77, Stockholm, Sweden.
    Think twice, it's all right: Long lasting effects of disrupted reconsolidation on brain and behavior in human long-term fear2017In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 324, p. 125-129Article in journal (Refereed)
    Abstract [en]

    Memories can be modified when recalled. Experimental fear conditioning studies support that amygdala-localized fear memories are attenuated when reconsolidation is disrupted through extinction training immediately following memory activation. Recently, using functional brain imaging in individuals with lifelong spider fears, we demonstrated that fear memory activation followed by repeated exposure to feared cues after 10 min, thereby disrupting reconsolidation, attenuated activity in the amygdala during later re-exposure, and also facilitated approach behavior to feared cues. In contrast, repeated exposure 6 h after fear memory activation, allowing for reconsolidation, did not attenuate amygdala activity and resulted in less approach behavior as compared to the group that received disrupted reconsolidation. We here evaluated if these effects are stable after 6 months and found that amygdala activity was further reduced in both groups, with a tendency towards greater reductions in the 10 min than the 6 h group. Hence, disrupted reconsolidation results in long lasting attenuation of amygdala activity. The behavioral effect, with more approach towards previously feared cues, in the 10 min than the 6 h group also persisted. Thus, the brain effect of disrupted reconsolidation is stable over 6 months and the behavioral effect also remained. We therefore conclude that disrupted reconsolidation result in a long-lasting diminished fear memory representation in the amygdala which may have clinical importance.

  • 20.
    Bothelius, Kristoffer
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Jernelöv, Susanna
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    McCracken, Lance
    Kaldo, Viktor
    Measuring Acceptance of Sleep Difficulties: The Development of the Sleep Problem Acceptance Questionnaire2015In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 38, no 11, p. 1815-1822Article in journal (Refereed)
    Abstract [en]

    Study Objectives: Acceptance may be an important therapeutic process in sleep medicine, but valid psychometric instruments measuring acceptance related to sleep difficulties are lacking. The purpose of this study was to develop a measure of acceptance in insomnia, and to examine its factor structure as well as construct validity. Design: In a cross-sectional design, a principal component analysis for item reduction was conducted on a first sample (A) and a confirmatory factor analysis on a second sample (B). Construct validity was tested on a combined sample (C). Setting: Questionnaire items were derived from a measure of acceptance in chronic pain, and data were gathered through screening or available from pretreatment assessments in four insomnia treatment trials, administered online, via bibliotherapy and in primary care. Participants: Adults with insomnia: 372 in sample A and 215 in sample B. Sample C (n = 820) included sample A and B with another 233 participants added. Measures: Construct validity was assessed through relations with established acceptance and sleep scales. Results: The principal component analysis presented a two-factor solution with eight items, explaining 65.9% of the total variance. The confirmatory factor analysis supported the solution. Acceptance of sleep problems was more closely related to subjective symptoms and consequences of insomnia than to diary description of sleep, or to acceptance of general private events. Conclusions: The Sleep Problem Acceptance Questionnaire (SPAQ), containing the subscales "Activity Engagement" and "Willingness", is a valid tool to assess acceptance of insomnia.

  • 21.
    Bothelius, Kristoffer
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Kyhle, Kicki
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Broman, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Initial Sleep Time Predicts Success in Manual-Guided Cognitive Behavioral Therapy for Insomnia2016In: Behavioural Sleep Medicine, ISSN 1540-2002, E-ISSN 1540-2010, Vol. 14, no 4, p. 378-388Article in journal (Refereed)
    Abstract [en]

    Cognitive behavioral therapy produces significant and long-lasting improvement for individuals with insomnia, but treatment resources are scarce. A "stepped care" approach has therefore been proposed, but knowledge is limited on how to best allocate patients to different treatment steps. In this study, 66 primary-care patients with insomnia attended a low-end treatment step: manual-guided cognitive behavioral therapy (CBT) for insomnia delivered by ordinary primary-care personnel. Based on clinically significant treatment effects, subjects were grouped into treatment responders or nonresponders. Baseline data were analyzed to identify predictors for treatment success. Long total sleep time at baseline assessment was the only statistically significant predictor for becoming a responder, and sleep time may thus be important to consider before enrolling patients in low-end treatments.

  • 22.
    Danfors, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Linnman, Clas
    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.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Increased neurokinin-1 receptor availability in temporal lobe epilepsy: A positron emission tomography study using [(11)C]GR2051712011In: Epilepsy Research, ISSN 0920-1211, E-ISSN 1872-6844, Vol. 97, no 1-2, p. 183-189Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Activation of the neurokinin-1 (NK1) receptor by neuropeptide substance P (SP) induces and maintains epileptic activity in various experimental models of epilepsy. The primary objective of this study was to investigate whether neurobiological changes linked to NK1-SP receptor system are associated with hyperexcitability in patients with temporal lobe epilepsy (TLE). A secondary objective was to investigate the relationship between seizure frequency and NK1 receptor availability.

    METHODS: A positron emission tomography study was conducted with the selective NK1 receptor antagonist [(11)C]GR205171 in nine patients with TLE and 18 healthy control participants. Parametric PET images were generated using the Patlak graphical method, with cerebellum as reference region. Data analyses including group comparisons were performed using statistical parametric mapping.

    RESULTS: Patients with TLE showed increased NK1 receptor availability in both hemispheres with the most pronounced increase in anterior cingulate gyrus ipsilateral to seizure onset. A positive correlation between NK1 receptor availability and seizure frequency was observed in the medial temporal lobe and in the lentiform nucleus ipsilateral to the seizure onset.

    CONCLUSION: Our results suggest that there is an intrinsic network using the NK1-SP receptor system for synaptic transmission and epileptiform activity in TLE.

  • 23.
    Engman, Jonas
    et al.
    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.
    Appel, L
    Åhs, Fredrik
    Linnman, Clas
    Bani, M
    Wahlstedt, Kurt
    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.
    Amygdala response to SSRIs in social anxiety disorder2012In: International Journal of Neuropsychopharmacology, ISSN 1461-1457, E-ISSN 1469-5111, Vol. 15, no S1, p. 230-230Article in journal (Other academic)
  • 24.
    Engman, Jonas
    et al.
    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.
    Appel, Lieuwe
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Linnman, Clas
    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.
    Bani, Massimo
    Bettica, Paolo
    Pich, Emilio Merlo
    Jacobsson, Eva
    Wahlstedt, Kurt
    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.
    Neural Correlates of Anxiety States in Patients with Social Anxiety Disorder2011In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 69, p. 70S-70SArticle in journal (Other academic)
    Abstract [en]

    Background: In social anxiety disorder (SAD), the fear of being negatively evaluated by others can restrict individual everyday life, due to the anxiety caused by social interactions. How this anxiety is processed in the brain is only partly understood. We aimed to examine the correlations between subjective anxiety states and brain activity in a large sample of SAD patients, during an anxiety-provoking task.

    Methods: Data were merged from three randomized clinical PET-trials investigating regional cerebral blood flow (rCBF) during a public speaking task pre- and post treatment (SSRI n = 35, placebo n = 37). All participants met diagnostical criteria for SAD. rCBF was assessed with [15O]-labeled water and state anxiety was measured using the Spielberger state anxiety scale (STAI-S). These measures where then correlated using a covariate of interest approach in Statistical Parametric Mapping (SPM2).

    Results: rCBF and STAI-S scores correlated positively in the left parahippocampal gyrus and amygdala, as well as in the right premotor cortex (area 6). Negative correlations were observed in the left superior frontal gyrus, thalamus, and the right parahippocampal gyrus. Negative correlations were also found bilaterally in the cerebellum.

    Conclusions: The correlations between clinical anxiety states and brain activity were noted in areas previously demonstrated to be involved in emotional regulation and motor preparedness.

  • 25.
    Engman, Jonas
    et al.
    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.
    Fredrikson, Mats
    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.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Ågren, Thomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Wallenquist, U
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Neural processing of emotional faces in social anxiety disorder2012Conference paper (Other academic)
  • 26.
    Engman, Jonas
    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.
    Alaie, Iman
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Björkstrand, Johannes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Ågren, Thomas
    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.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Wallenquist, U.
    Wahlstedt, K.
    Larsson, E.-M.
    Morell, A.
    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.
    Amygdala and Default Mode Network Resting-State Functional Connectivity in Social Anxiety Disorder2014Conference paper (Refereed)
  • 27.
    Engman, Jonas
    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.
    Alaie, Iman
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Björkstrand, Johannes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Ågren, Thomas
    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.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Wallenquist, Ulrika
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Wahlstedt, Kurt
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Morell, Arvid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    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.
    Altered Amygdala but not Default Mode Network Functional Connectivity in Social Anxiety Disorder2013In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 73, no 9, p. 79S-79SArticle in journal (Other academic)
  • 28.
    Engman, Jonas
    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.
    Wallenquist, Ulrika
    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.
    Ågren, Thomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Larsson, E-M.
    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.
    Neural processing of emotionalfaces in social anxiety disorder2012Conference paper (Refereed)
  • 29.
    Engman, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Moby, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fredriksson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Gingnell, Malin
    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 Women's and Children's Health.
    Hormonal Cycle and Contraceptive Effects on Amygdala and Salience Resting-State Networks in Women with Previous Affective Side Effects on the Pill.2018In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 43, no 3, p. 555-563Article in journal (Refereed)
    Abstract [en]

    The mechanisms linking ovarian hormones to negative affect are poorly characterized, but important clues may come from the examination of the brain's intrinsic organization. Here, we studied the effects of both the menstrual cycle and oral contraceptives (OCs) on amygdala and salience network resting-state functional connectivity using a double-blind, randomized, and placebo-controlled design. Hormone levels, depressive symptoms, and resting-state functional connectivity were measured in 35 healthy women (24.9±4.2 years) who had previously experienced OC-related negative affect. All participants were examined in the follicular phase of a baseline cycle and in the third week of the subsequent cycle during treatment with either a combined OC (30 μg ethinyl estradiol/0.15 mg levonorgestrel) or placebo. The latter time point targeted the midluteal phase in placebo users and steady-state ethinyl estradiol and levonorgestrel concentrations in OC users. Amygdala and salience network connectivity generally increased with both higher endogenous and synthetic hormone levels, although amygdala-parietal cortical connectivity decreased in OC users. When in the luteal phase, the naturally cycling placebo users demonstrated higher connectivity in both networks compared with the women receiving OCs. Our results support a causal link between the exogenous administration of synthetic hormones and amygdala and salience network connectivity. Furthermore, they suggest a similar, potentially stronger, association between the natural hormonal variations across the menstrual cycle and intrinsic network connectivity.

  • 30.
    Engman, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Sundström-Poromaa, Inger
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Amygdala Resting State Functional Connectivity is Affected by Oral Contraceptives and Menstrual Cycle Phase2015In: Magnetic Resonance Materials in Physics, Biology and Medicine, ISSN 0968-5243, E-ISSN 1352-8661, Vol. 28, no 1S, p. S70-S70Article in journal (Other academic)
  • 31.
    Engman, Jonas
    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.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Linnman, Clas
    Pissiota, Anna
    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 Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Frans, Örjan
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Age, sex and NK1 receptors in the human brain: A positron emission tomography study with [C-11]GR2051712012In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 22, no 8, p. 562-568Article in journal (Refereed)
    Abstract [en]

    The substance P/neurokinin 1 (SP/NK1) system has been implicated in the processing of negative affect. Its role seems complex and findings from animal studies have not been easily translated to humans. Brain imaging studies on NK1 receptor distribution in humans have revealed an abundance of receptors in cortical, striatal and subcortical areas, including the amygdala. A reduction in NK1 receptors with increasing age has been reported in frontal, temporal, and parietal cortices, as well as in hippocampal areas. Also, a previous study suggests sex differences in cortical and subcortical areas, with women displaying fewer NK1 receptors. The present PET study explored NK1 receptor availability in men (n = 9) and women (n = 9) matched for age varying between 20 and 50 years using the highly specific NK1 receptor antagonist [11C]GR205171 and a reference tissue model with cerebellum as the reference region. Age by sex interactions in the amygdala and the temporal cortex reflected a lower NK1 receptor availability with increasing age in men, but not in women. A general age-related decline in NK1 receptor availability was evident in the frontal, temporal, and occipital cortices, as well as in the brainstem, caudate nucleus, and thalamus. Women had lower NK1 receptor availability in the thalamus. The observed pattern of NK1 receptor distribution in the brain might have functional significance for brain-related disorders showing age- and sex-related differences in prevalence.

  • 32.
    Engman, Jonas
    et al.
    Department of psychology.
    Åhs, Fredrik
    Linnman, Clas
    Palmquist Michelgård, Åsa
    Department of Neuroscience, Psychiatry, University Hospital.
    Bani, M
    Appel, L
    Fredrikson, Mats
    Furmark, Tomas
    Department of Psychology.
    Age and Sex Differences in NK1 Receptor Availability Assessed with [11C]GR2051712010In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 67, no 9, p. 206S-206SArticle in journal (Other academic)
  • 33.
    Faria, V
    et al.
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Rosman, J B
    Henningson, S
    Marschner, A
    Åhs, F
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Linnman, C
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Pissiota, A
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Appel, L
    Eriksson, E
    Fredriksson, M
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Furmark, T
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Serotonin-1A receptor allelic variation and brain endophenotypes: A PET study of social phobia2006Conference paper (Refereed)
  • 34.
    Faria, Vanda
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.
    Linnman, Clas
    P.A.I.N. Group, Department of Anesthesia, Children's Hospital, Boston, MA, USA.
    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.
    Bani, Massimo
    GlaxoSmithKline, Medicine Centre, Verona, Italy.
    Bettica, Paolo
    GlaxoSmithKline, Medicine Centre, Verona, Italy.
    M Pich, Emilio
    GlaxoSmithKline, Medicine Centre, Verona, Italy.
    Jacobsson, Eva
    Uppsala University Hospital and Quintiles AB Phase I Services, Uppsala, Sweden.
    Wahlsted, Kurt
    Uppsala University Hospital and Quintiles AB Phase I Services, Uppsala, Sweden.
    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.
    Amygdala Subregions Tied to SSRI and Placebo Response in Patients with Social Anxiety Disorder2012In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 37, no 10, p. 2222-2232Article in journal (Refereed)
    Abstract [en]

    The amygdala is a key structure in the pathophysiology of anxiety disorders, and a putative target for anxiolytic treatments, Selective serotonin reuptake inhibitors (SSRIs) and placebo seem to induce anxiolytic effects by attenuating amygdala responsiveness. However, conflicting amygdala findings have also been reported. Moreover, the neural profile of responders and nonresponders is insufficiently characterized and it remains unknown whether SSRIs and placebo engage common or distinct amygdala subregions or different modulatory cortical areas. We examined similarities and differences in the neural response to SSRIs and placebo in patients with social anxiety disorder (SAD). Positron emission tomography (PET) with oxygen-15-labeled water was used to assess regional cerebral blood flow (rCBF) in 72 patients with SAD during an anxiogenic public speaking task, before and after 6-8 weeks of treatment under double-blind conditions. Response rate was determined by the Clinical Global Impression-Improvement scale. Conjunction analysis revealed a common rCBF-attenuation from pre- to post-treatment in responders to SSRIs and placebo in the left basomedial/basolateral and right ventrolateral amygdala. This rCBF pattern con-elated with behavioral measures of reduced anxiety and differentiated responders from nonresponders. However, nonanxiolytic treatment effects were also observed in the amygdala. All subgroups, including nonresponders, showed deactivation of the left lateral part of the amygdala. No rCBF differences were found between SSRI responders and placebo responders. This study provides new insights into the brain dynamics underlying anxiety relief by demonstrating common amygdala targets for pharmacologically and psychologically induced anxiety reduction, and by showing that the amygdala is functionally heterogeneous in anxiolysis.

  • 35.
    Faria, Vanda
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Appel, Lieuwe
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Linnman, Clas
    Pissiota, Anna
    Frans, Örjan
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Bani, Massimo
    Bettica, Paolo
    Pich, Emilio Merlo
    Jacobsson, Eva
    Wahlstedt, Kurt
    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.
    Differences in Amygdala Responsivity Between Responders and Nonresponders to SSRIs in Patients with Social Anxiety Disorder2011In: Biol. Psychiatry 69, 70S-71S, 2011, Vol. 69Conference paper (Other academic)
    Abstract [en]

    Background: Selective serotonin reuptake inhibitors (SSRIs) are commonly accepted as the first line pharmacological therapy for anxiety disorders and depression. However, there is a high percentage of patients that fail to achieve satisfactory response with SSRI treatments. The neural mechanisms underlying effective and ineffective outcome with SSRIs are not well characterized. The amygdala has dense serotonergic innervation, and studies have suggested the amygdala to be a crucial brain target for SSRI treatment. This study aimed at investigating differences in amygdala responsivity between responders and nonresponders to SSRI treatments in patients with social anxiety disorder (SAD).

    Methods: Stress-related regional cerebral blood flow (rCBF) was measured in SAD patients (n=35) with 15O-water positron emission tomography (PET) during public speaking before and after 6-8 weeks of treatment with citalopram or paroxetine. Response rate was determined by the Clinical Global Impression-Improvement scale.

    Results: Within-group comparisons revealed reduced rCBF response bilaterally in the amygdala in responders (n=20) as well as in nonresponders (n=15). Between-group contrasts revealed a greater amygdala attenuation in responders (>nonresponders) in the left basolateral/basomedial (x-16, y-6, z-14, Z=1.66, Puncorr=0.024) and right ventrolateral subregions (x26, y-4, z-26, Z=2.12, Puncorr=0.009). However, greater rCBF attenuation in nonresponders (> responders) was observed in the left lateral amygdala (x-28, y-6, z-14, Z=2.38, Puncorr=0.005).

    Conclusions: Lowered amygdala responsivity does not seem to be exclusively related to clinical improvement in anxiety patients. In accordance with animal literature, our data suggest that amygdala subregions are functionally heterogeneous with regards to anxiolysis.

  • 36.
    Faria, Vanda
    et al.
    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.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Imaging the placebo response: a neurofunctional review2008In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 18, no 7, p. 473-485Article, review/survey (Refereed)
    Abstract [en]

    An emerging literature has started to document the neuronal changes associated with the placebo phenomenon. This has altered placebo from being considered a nuisance factor in clinical research to a target of scientific investigation per se. This paper reviews the neuroimaging literature on the placebo effect, and illustrates how imaging tools can improve current understanding of brain mechanisms underlying the placebo response. Imaging studies provide evidence of specific, predictable and replicable patterns of neural changes associated with placebo administration. In general, placebo responses seem mediated by "top-down" processes dependent on frontal cortical areas that generate and maintain cognitive expectancies. Dopaminergic reward pathways may underlie these expectancies. Placebo-induced clinical benefits also involve disorder-specific neuronal responses, yielding neurofunctional or neurochemical alterations similar to those produced by pharmacological treatments.

  • 37.
    Faria, Vanda
    et al.
    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.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Revealing the biological underpinnings of tha placebo response2010In: Advances in Psychology Research / [ed] A. M. Columbus, New York: Nova Science Publishers , 2010, 69, p. 85-104Chapter in book (Other academic)
  • 38.
    Faria, Vanda
    et al.
    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.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Subregional Amygdala Responsivity in Responders and Nonresponders to SSRIs in Patients with Social Anxiety Disorder2012Conference paper (Other academic)
  • 39.
    Faria, Vanda
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    M. Hoppe, Johanna
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Hjorth, Olof
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Alaie, Iman
    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 Neuroscience, Child and Adolescent Psychiatry.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hultberg, Sara
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Wahlstedt, Kurt
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Månsson, Kristoffer N.T.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.; Department of Psychology, Stockholm University, Stockholm, Sweden.
    Carlbring, Per
    Department of Psychology, Stockholm University, Stockholm, Sweden.
    Andersson, Gerhard
    Department of Behavioural Sciences and Learning, Linköping University, Linköping, Sweden.
    Reis, Margareta
    Department of Medical and Health Sciences, Division of Drug Research, Linköping University, Linköping, Sweden.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder: A Randomized Trial2017In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, no 24, p. 179-188, article id S2352-3964(17)30385-7Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression and anxiety, but their efficacy relative to placebo has been questioned. We aimed to test how manipulation of verbally induced expectancies, central for placebo, influences SSRI treatment outcome and brain activity in patients with social anxiety disorder (SAD).

    METHODS: We did a randomized clinical trial, within an academic medical center (Uppsala, Sweden), of individuals fulfilling the DSM-IV criteria for SAD, recruited through media advertising. Participants were 18years or older and randomized in blocks, through a computer-generated sequence by an independent party, to nine weeks of overt or covert treatment with escitalopram (20mg daily). The overt group received correct treatment information whereas the covert group was treated deceptively with the SSRI described, by the psychiatrist, as active placebo. The treating psychiatrist was necessarily unmasked while the research staff was masked from intervention assignment. Treatment efficacy was assessed primarily with the self-rated Liebowitz Social Anxiety Scale (LSAS-SR), administered at week 0, 1, 3, 6 and 9, also yielding a dichotomous estimate of responder status (clinically significant improvement). Before and at the last week of treatment, brain activity during an emotional face-matching task was assessed with functional magnetic resonance imaging (fMRI) and during fMRI sessions, anticipatory speech anxiety was also assessed with the Spielberger State-Trait Anxiety Inventory - State version (STAI-S). Analyses included all randomized patients with outcome data at posttreatment. This study is registered at ISRCTN, number 98890605.

    FINDINGS: Between March 17th 2014 and May 22nd 2015, 47 patients were recruited. One patient in the covert group dropped out after a few days of treatment and did not provide fMRI data, leaving 46 patients with complete outcome data. After nine weeks of treatment, overt (n=24) as compared to covert (n=22) SSRI administration yielded significantly better outcome on the LSAS-SR (adjusted difference 21.17, 95% CI 10.69-31.65, p<0.0001) with more than three times higher response rate (50% vs. 14%; χ(2)(1)=6.91, p=0.009) and twice the effect size (d=2.24 vs. d=1.13) from pre-to posttreatment. There was no significant between-group difference on anticipatory speech anxiety (STAI-S), both groups improving with treatment. No serious adverse reactions were recorded. On fMRI outcomes, there was suggestive evidence for a differential neural response to treatment between groups in the posterior cingulate, superior temporal and inferior frontal gyri (all z thresholds exceeding 3.68, p≤0.001). Reduced social anxiety with treatment correlated significantly with enhanced posterior cingulate (z threshold 3.24, p=0.0006) and attenuated amygdala (z threshold 2.70, p=0.003) activity.

    INTERPRETATION: The clinical and neural effects of escitalopram were markedly influenced by verbal suggestions. This points to a pronounced placebo component in SSRI-treatment of SAD and favors a biopsychosocial over a biomedical explanatory model for SSRI efficacy.

    FUNDING RESOURCES: The Swedish Research Council for Working Life and Social Research (grant 2011-1368), the Swedish Research Council (grant 421-2013-1366), Riksbankens Jubileumsfond - the Swedish Foundation for Humanities and Social Sciences (grant P13-1270:1).

  • 40.
    Faria, Vanda
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Ågren, Thomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Bah Rosman, J
    Henningsson, S
    Appel, L
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Linnman, Claes
    Oreland,
    Bani, M
    Pich, E M
    Eriksson, E
    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.
    Influence of the COMT Val158Met polymorphism on amygdala reactivity in social anxiety disorder.2009In: Biol. Psychiatry 65, 126S-126S, 2009, p. 420-Conference paper (Refereed)
  • 41.
    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. Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Linnman, Clas
    P.A.I.N. Group, Department of Anesthesia, Children's Hospital, Boston, MA, USA.
    Bani, Massimo
    GlaxoSmithKline, Medicine Centre, Verona, Italy.
    Bettica, Paolo
    GlaxoSmithKline, Medicine Centre, Verona, Italy.
    M Pich, Emilio
    GlaxoSmithKline, Medicine Centre, Verona, Italy.
    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.
    Amygdala-frontal couplings characterizing SSRI and placebo response in social anxiety disorder2014In: International Journal of Neuropsychopharmacology, ISSN 1461-1457, E-ISSN 1469-5111, Vol. 17, no 8, p. 1149-1157Article in journal (Refereed)
  • 42.
    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)
  • 43.
    Fernandez, Manuel
    et al.
    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.
    Frans, Örjan
    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.
    Fischer, Håkan
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Brain function in a patient with torture related post-traumatic stress disorder before and after fluoxetine treatment: a positron emission tomography provocation study2001In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 297, no 2, p. 101-104Article in journal (Refereed)
    Abstract [en]

    We report positron emission tomographic measurements of regional cerebral blood flow (rCBF) in a male patient with war and torture related post-traumatic stress disorder (PTSD) during symptom provocation. The subject was exposed to war related sounds before and after treatment with a selective serotonin reuptake inhibitor (SSRI; Fluoxetine; Fontex((R))). Therapy reduced PTSD symptoms, provoked anxiety and heart rate. Before treatment trauma reminders resulted in decreased rCBF in the insula, prefrontal, and inferior frontal cortices. Increased activity was evident in the cerebellum, precuneus and supplementary motor cortex. This was normalized after SSRI administration. Prefrontal and cingulate rCBF correlated with heart rate. Hence, the anxiolytic effect of SSRI for PTSD could be mediated by prefrontal and paralimbic cortices. Data suggest that SSRI treatment normalize provocation induced rCBF alterations in areas involved in memory, emotion, attention and motor-control.

  • 44. Fischer, H
    et al.
    Furmark, T
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Wik, G
    Fredrikson, M
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Brain representation of habituation to repeated complex visual stimulation studied with PET.2000In: Neuroreport, ISSN 0959-4965, Vol. 11, no 1, p. 123-6Article in journal (Refereed)
  • 45.
    Fischer, H
    et al.
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Tillfors, M
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Furmark, T
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Fredrikson, M
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Pessimism and amygdala activity: A PET study2001In: NEUROIMAGE, ISSN 1053-8119, Vol. 13, no 6, p. 398-Article in journal (Refereed)
  • 46. Fischer, Hakan
    et al.
    Andersson, Jesper L R
    Furmark, Tomas
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Wik, Gustav
    Fredrikson, Mats
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Right-sided human prefrontal brain activation during acquisition of conditioned fear.2002In: Emotion, ISSN 1528-3542, Vol. 2, no 3, p. 233-41Article in journal (Refereed)
    Abstract [en]

    This H2(15)O positron emission tomography (PET) study reports on relative regional cerebral blood flow (rCBF) alterations during fear conditioning in humans. In the PET scanner, subjects viewed a TV screen with either visual white noise or snake videotapes displayed alone, then with electric shocks, followed by final presentations of white noise and snakes. Autonomic nervous system responses confirmed fear conditioning only to snakes. To reveal neural activation during acquisition, while equating sensory stimulation, scans during snakes with shocks and white noise alone were contrasted against white noise with shocks and snakes alone. During acquisition, rCBF increased in the right medial frontal gyrus, supporting a role for the prefrontal cortex in fear conditioning to unmasked evolutionary fear-relevant stimuli.

  • 47.
    Frans, Örjan
    et al.
    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.
    Fernandez, Manuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Psychiatry, University hospital.
    Fischer, Håkan
    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 Psychiatry, University hospital.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Neurofunctional correlates of post-traumatic stress disorder: A PET case study1999In: NeuroImage / [ed] Rosen, Seitz, Volkmann, Academic Press, 1999, p. 632-Conference paper (Other academic)
  • 48.
    Frans, Örjan
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Rimmö, Per-Arne
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Åberg, Lars
    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.
    Trauma exposure and posttraumatic stress disorder in the general population2005In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 111, no 4, p. 291-299Article in journal (Refereed)
    Abstract [en]

    Objective:  To examine the lifetime prevalence of trauma experiences and post-traumatic stress disorder (PTSD).

    Method:  Questionnaire-assessed PTSD, the type of traumatic event experienced, perceived trauma impact, and trauma frequency in 1824 randomly selected men and women.

    Results:  PTSD lifetime prevalence was estimated at 5.6% with a 1 : 2 male-to-female ratio, in spite of men reporting greater trauma exposure. The highest PTSD risk was associated with sexual and physical assault, robbery and multiple trauma experiences. Controlling for trauma type did not account for gender differences, while controlling for experienced distress did.

    Conclusion:  The conditional probability for PTSD varied as a function of trauma type, frequency and impact of the event, with increased rates associated with prevalent trauma exposure and higher perceived distress. The latter accounted for the gender effect, suggesting that gender differences in PTSD in part represent a generally greater vulnerability to stress in women.

  • 49.
    Fredrikson, M
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Psychophysiological theories on sympathetic nervous system reactivity in the development of essential hypertension1991In: Scandinavian journal of psychology, Vol. 32, p. 254-274Article, review/survey (Other (popular scientific, debate etc.))
  • 50.
    Fredrikson, M
    et al.
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Furmark, T
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Brain imaging studies in social anxiety disorder2004In: Social anxiety disorder, Decker, New York , 2004, p. 215-233Chapter in book (Other scientific)
1234 1 - 50 of 161
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