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  • 1.
    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)
  • 2. 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.

  • 3.
    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)
  • 4.
    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.

  • 5.
    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)
  • 6.
    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)
  • 7.
    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)
  • 8.
    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)
  • 9.
    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)
  • 10.
    Faria, Vanda
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Mind really does matter: The Neurobiology of Placebo-induced Anxiety Relief in Social Anxiety Disorder2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The placebo effect, a beneficial effect attributable to a treatment containing no specific properties for the condition being treated, has been demonstrated in a variety of medical conditions. This thesis includes four studies aimed at increasing our knowledge on the neurobiology of placebo. Study I, a review of the placebo neuroimaging literature, suggested that the anterior cingulate cortex (ACC) may be a common site of action for placebo responses. However, because placebo neuroimaging studies in clinical disorders are largely lacking, the clinical relevance of this needs further clarification. The subsequent three empirical studies were thus designed from a clinical perspective. Using positron emission tomography (PET) these studies investigated the underlying neurobiology of sustained placebo responses in patients with social anxiety disorder (SAD), a disabling psychiatric condition that nonetheless may be mitigated by placebo interventions. Study II demonstrated that serotonergic gene polymorphisms affect anxiety-induced neural activity and the resultant placebo phenotype. In particular, anxiety reduction resulting from placebo treatment was tied to the attenuating effects of the TPH2 G-703T polymorphism on amygdala activity. Study III further compared the neural response profile of placebo with selective serotonin reuptake inhibitors (SSRIs), i.e the first-line pharmacological treatment for SAD. A similar anxiety reduction was noted in responders of both treatments. PET-data further revealed that placebo and SSRI responders had similar decreases of the neural response in amygdala subregions including the left basomedial/basolateral (BM/BLA) and the right ventrolateral (VLA) sections. To clarify whether successful placebo and SSRI treatments operate via similar or distinct neuromodulatory pathways, study IV focused on the connectivity patterns between the amygdala and prefrontal cortex that may be crucial for normal emotion regulation. In responders of both treatment modalities, the left amygdala (BM/BLA) exhibited negative coupling with the dorsolateral prefrontal cortex and the rostral ACC as well as a shared positive coupling with the dorsal ACC. This may represent shared treatment mechanisms involving improved emotion regulation and decreased rumination. This thesis constitutes a first step towards better understanding of the neurobiology of placebo in the treatment of anxiety, including the neural mechanisms that unite and segregate placebo and SSRI treatment.

    List of papers
    1. Imaging the placebo response: a neurofunctional review
    Open this publication in new window or tab >>Imaging the placebo response: a neurofunctional review
    2008 (English)In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 18, no 7, p. 473-485Article, review/survey (Refereed) Published
    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.

    Keywords
    Functional magnetic resonance imaging, Neuroimaging, Placebo effect, Positron emission tomography, Review
    National Category
    Psychology
    Identifiers
    urn:nbn:se:uu:diva-125736 (URN)10.1016/j.euroneuro.2008.03.002 (DOI)000257347500001 ()18495442 (PubMedID)
    Available from: 2010-05-27 Created: 2010-05-27 Last updated: 2017-12-12Bibliographically approved
    2. A link between serotonin-related gene polymorphisms, amygdala activity, and placebo-induced relief from social anxiety
    Open this publication in new window or tab >>A link between serotonin-related gene polymorphisms, amygdala activity, and placebo-induced relief from social anxiety
    Show others...
    2008 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 28, no 49, p. 13066-74Article in journal (Refereed) Published
    Abstract [en]

    Placebo may yield beneficial effects that are indistinguishable from those of active medication, but the factors underlying proneness to respond to placebo are widely unknown. Here, we used functional neuroimaging to examine neural correlates of anxiety reduction resulting from sustained placebo treatment under randomized double-blind conditions, in patients with social anxiety disorder. Brain activity was assessed during a stressful public speaking task by means of positron emission tomography before and after an 8 week treatment period. Patients were genotyped with respect to the serotonin transporter-linked polymorphic region (5-HTTLPR) and the G-703T polymorphism in the tryptophan hydroxylase-2 (TPH2) gene promoter. Results showed that placebo response was accompanied by reduced stress-related activity in the amygdala, a brain region crucial for emotional processing. However, attenuated amygdala activity was demonstrable only in subjects who were homozygous for the long allele of the 5-HTTLPR or the G variant of the TPH2 G-703T polymorphism, and not in carriers of short or T alleles. Moreover, the TPH2 polymorphism was a significant predictor of clinical placebo response, homozygosity for the G allele being associated with greater improvement in anxiety symptoms. Path analysis supported that the genetic effect on symptomatic improvement with placebo is mediated by its effect on amygdala activity. Hence, our study shows, for the first time, evidence of a link between genetically controlled serotonergic modulation of amygdala activity and placebo-induced anxiety relief.

    Keywords
    placebo, genes, phobia, serotonin, brain, functional neuroimaging
    National Category
    Pharmaceutical Sciences
    Identifiers
    urn:nbn:se:uu:diva-102680 (URN)10.1523/JNEUROSCI.2534-08.2008 (DOI)000261378100005 ()19052197 (PubMedID)
    Available from: 2009-05-11 Created: 2009-05-11 Last updated: 2018-01-13Bibliographically approved
    3. Amygdala Subregions Tied to SSRI and Placebo Response in Patients with Social Anxiety Disorder
    Open this publication in new window or tab >>Amygdala Subregions Tied to SSRI and Placebo Response in Patients with Social Anxiety Disorder
    Show others...
    2012 (English)In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 37, no 10, p. 2222-2232Article in journal (Refereed) Published
    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.

    Place, publisher, year, edition, pages
    Nature Publishing Group, 2012
    Keywords
    amygdala, SSRIs, placebo, SAD, subregions, PET
    National Category
    Medical and Health Sciences
    Research subject
    Neuroscience
    Identifiers
    urn:nbn:se:uu:diva-181544 (URN)10.1038/npp.2012.72 (DOI)000307796600005 ()
    Available from: 2012-09-25 Created: 2012-09-25 Last updated: 2017-12-07Bibliographically approved
    4. Amygdala-frontal couplings characterizing SSRI and placebo response in social anxiety disorder
    Open this publication in new window or tab >>Amygdala-frontal couplings characterizing SSRI and placebo response in social anxiety disorder
    Show others...
    2014 (English)In: International Journal of Neuropsychopharmacology, ISSN 1461-1457, E-ISSN 1469-5111, Vol. 17, no 8, p. 1149-1157Article in journal (Refereed) Published
    National Category
    Neurosciences
    Research subject
    Neuroscience
    Identifiers
    urn:nbn:se:uu:diva-181547 (URN)10.1017/S1461145714000352 (DOI)000338098500004 ()
    Note

    Correction in: International Journal of Neuropsychopharmacology, vol. 17, issue 8, page 1353.

    Available from: 2012-09-25 Created: 2012-09-25 Last updated: 2018-01-12Bibliographically approved
  • 11.
    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.

  • 12.
    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.

  • 13.
    Faria, Vanda
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Harvard Univ, Sch Med, Boston Childrens Hosp, Ctr Pain & Brain,Dept Anesthesiol Perioperat & Pa, Boston, MA USA..
    Erpelding, Nathalie
    Harvard Univ, Sch Med, Boston Childrens Hosp, Ctr Pain & Brain,Dept Anesthesiol Perioperat & Pa, Boston, MA USA..
    Lebel, Alyssa
    Harvard Univ, Sch Med, Boston Childrens Hosp, Ctr Pain & Brain,Dept Anesthesiol Perioperat & Pa, Boston, MA USA.;Harvard Univ, Sch Med, Boston Childrens Hosp, Chron Headache Program, Boston, MA USA..
    Johnson, Adriana
    Harvard Univ, Sch Med, Boston Childrens Hosp, Ctr Pain & Brain,Dept Anesthesiol Perioperat & Pa, Boston, MA USA..
    Wolff, Robert
    Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Neurol, Boston, MA USA..
    Fair, Damien
    Oregon Hlth & Sci Univ, Sch Med, Dept Behav Neurosci, Portland, OR 97201 USA.;Oregon Hlth & Sci Univ, Sch Med, Dept Psychiat, Portland, OR 97201 USA..
    Burstein, Rami
    Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02215 USA..
    Becerra, Lino
    Harvard Univ, Sch Med, Boston Childrens Hosp, Ctr Pain & Brain,Dept Anesthesiol Perioperat & Pa, Boston, MA USA..
    Borsook, David
    Harvard Univ, Sch Med, Boston Childrens Hosp, Ctr Pain & Brain,Dept Anesthesiol Perioperat & Pa, Boston, MA USA.;Harvard Univ, Sch Med, Boston Childrens Hosp, Chron Headache Program, Boston, MA USA..
    The migraine brain in transition: girls vs boys2015In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 156, no 11, p. 2212-2221Article in journal (Refereed)
    Abstract [en]

    The prevalence of migraine has an exponential trajectory that is most obvious in young females between puberty and early adulthood. Adult females are affected twice as much as males. During development, hormonal changes may act on predetermined brain circuits, increasing the probability of migraine. However, little is known about the pediatric migraine brain and migraine evolution. Using magnetic resonance. imaging, we evaluated 28 children with migraine (14 females and 14 males) and 28 sex-matched healthy controls to determine differences in brain structure and function between (1) females and males with migraine and (2) females and males with migraine during earlier (10-11 years) vs later (14-16 years) developmental stages compared with matched healthy controls. Compared with males, females had more gray matter in the primary somatosensory cortex (Si), supplementary motor area, precuneus, basal ganglia, and amygdala, as well as greater precuneus resting state functional connectivity to the thalamus, amygdala, and basal ganglia and greater amygdala resting state functional connectivity to the thalamus, anterior midcingulate cortex, and supplementary motor area. Moreover, older females with migraine had more gray matter in the Si, amygdala, and caudate compared to older males with migraine and matched healthy controls. This is the first study showing sex and developmental differences in pediatric migraineurs in brain regions associated with sensory, motor, and affective functions, providing insight into the neural mechanisms underlying distinct migraine sex phenotypes and their evolution that could result in important clinical implications increasing treatment effectiveness.

  • 14.
    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.

  • 15.
    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)
  • 16.
    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)
  • 17.
    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).

  • 18.
    Faria, Vanda
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Harvard Med Sch, Ctr Pain & Brain, Dept Anesthesiol Perioperat & Pain Med, Boston Childrens Hosp, Boston, MA USA.;Beth Israel Deaconess Med Ctr, Program Placebo Studies, Boston, MA 02215 USA..
    Kossowsky, Joe
    Beth Israel Deaconess Med Ctr, Program Placebo Studies, Boston, MA 02215 USA.;Harvard Med Sch, Dept Anesthesiol Perioperat & Pain Med, Boston Childrens Hosp, Boston, MA USA.;Univ Basel, Dept Clin Psychol & Psychotherapy, Basel, Switzerland..
    Petkov, Mike P.
    Harvard Med Sch, Ctr Pain & Brain, Dept Anesthesiol Perioperat & Pain Med, Boston Childrens Hosp, Boston, MA USA..
    Kaptchuk, Ted J.
    Beth Israel Deaconess Med Ctr, Program Placebo Studies, Boston, MA 02215 USA..
    Kirsch, Irving
    Beth Israel Deaconess Med Ctr, Program Placebo Studies, Boston, MA 02215 USA..
    Lebel, Alyssa
    Harvard Med Sch, Ctr Pain & Brain, Dept Anesthesiol Perioperat & Pain Med, Boston Childrens Hosp, Boston, MA USA..
    Borsook, David
    Harvard Med Sch, Ctr Pain & Brain, Dept Anesthesiol Perioperat & Pain Med, Boston Childrens Hosp, Boston, MA USA..
    Parental Attitudes About Placebo Use in Children2017In: Journal of Pediatric Surgery Case Reports, ISSN 0022-3476, E-ISSN 2213-5766, Vol. 181, p. 272-+Article in journal (Refereed)
    Abstract [en]

    Objective To assess parental attitudes regarding placebo use in pediatric randomized controlled trials and clinical care. Study design Parents with children under age 18 years living in the US completed and submitted an online survey between September and November 2014. Results Among all 1300 participants, 1000 (76.9%; 538 mothers and 462 fathers) met the study inclusion criteria. The majority of surveyed parents considered the use of placebos acceptable in some pediatric care situations (86%) and some pediatric trials (91.5%), whereas only 5.7% of parents found the use of placebos in children always unacceptable. The clinical use of placebo was considered acceptable by a majority of parents for only 7 (mostly psychological) of the 17 conditions presented. Respondents' judgment about acceptability was influenced by the doctors' opinions about the therapeutic benefits of placebo treatment, the conditions for pediatric placebo use, transparency, safety, and purity of placebos. Conclusion Most surveyed parents accepted the idea of using placebos in pediatric trials and within the clinic for some conditions without the practice of deception and with the creation of guidelines for ethical and safe use. This study suggests a need to reconsider pediatric trial design and clinical therapy in the light of generally positive parental support of appropriate placebo use.

  • 19.
    Faria, Vanda
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Linnman, Clas
    Lebel, Alyssa
    Borsook, David
    Harnessing the Placebo Effect in Pediatric Migraine Clinic2014In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 165, no 4, p. 659-665Article in journal (Other academic)
  • 20.
    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)
  • 21.
    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)
  • 22.
    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)
  • 23.
    Fredrikson, Mats
    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.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Neurotransmission: A review of PET and SPECT studies in anxiety disorders2014In: PET and SPECT in Psychiatry, Berlin: Springer Berlin/Heidelberg, 2014, p. 349-370Chapter in book (Refereed)
    Abstract [en]

    Neuroimaging studies using PET and SPECT to evaluate neurofunctional differences in the brain between patients with anxiety disorders and healthy controls were reviewed. At rest patients with social anxiety disorder display a reduced dopamine-D2 receptor binding potential. Post-traumatic stress disorder is associated with a compromised benzodiazepine receptor function. In panic disorder, both benzodiazepine receptors and serotonergic (5-hydroxytryptamine 1A; 5HT 1A) receptors are downregulated. Across the anxiety disorders there is downregulation of both benzodiazepine and 5HT 1A receptors. Symptom provocation studies, where regional cerebral blood fl ow is measured, support that activity in the brain’s fear circuit is altered with increased reactivity in the amygdala, the midbrain and possibly also the insula cortex, whereas activity in emotionregulating areas in the prefrontal cortex such as the subgenual anterior cingulate cortex and the orbitofrontal cortex is compromised in the symptomatic state, predominantly in phobic disorders. Some studies demonstrate a coupling between individual differences in neurotransmission and fear network activity. Treatment studies suggest that reductions of neural activity in the amygdala may be a fi nal common pathway for successful therapeutic interventions, thereby linking neurotransmission to plasticity in the core fear network of the brain.

  • 24.
    Fredrikson, Mats
    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.
    Ågren, Thomas
    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.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Meta-Analytical Evidence for Segregating and Integrating Brain Activation to Symptom Provocation in Social Anxiety Disorder, Specific Phobia and Post Traumatic Stress Disorder2011Conference paper (Other academic)
    Abstract [en]

    Background: In PTSD increased amygdala activity is found in parallel to decreased anterior cingulate activity and this imbalance relate to symptomatology. Consistently, in healthy controls enhanced vmPFC activity suppress fear conditioning and enhance extinction similar to reappraisal studies where dPFC activation supports emotional down regulation through amygdala attenuation. It is not established if phobic disorders display a similar pattern and if treatment induced changes affect “top-down” and/or “bottom-up” mechanisms.

    Methods: Using a meta-analytical approach, we review brain-imaging studies using symptom provocation in patients with specific or social phobia as well as PTSD to evaluate reactivity in the ACC and the amygdala and its correlation to symptomatology. Further, amygdala ACC connectivity and the effect of CBT will be covered.

    Results: Functional brain imaging studies reveal increased amygdala reactivity that is correlated with symptomatology across the anxiety disorders. In phobic patients enhanced ACC responsivity is observed. The correlation between symptomatology and prefrontal brain activity is consistently negative and ACC related in PTSD while in phobic patients the relation is positive and encompass prefrontal areas outside the ACC, particularly in SAD. Connectivity patterns suggest couplings between amygdala and PFC, limited to ACC in PTSD but not in phobic disorders. Finally, CBT-treatment is associated both with increased and decreased activity in the ACC and other prefrontal areas.

    Conclusions: A tentative conclusion is that, even though the pattern of activity and connectivity both segregate and integrate different anxiety disorders, the ACC has a prominent role in coding and controlling affect.

  • 25.
    Frick, Andreas
    et al.
    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.
    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.
    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.
    Regional Gray Matter Volume of the Lingual Gyrus is Related to Symptom Severity in Patients with Social Anxiety Disorder2013In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 73, no 9, p. 79S-80SArticle in journal (Other academic)
  • 26.
    Frick, Andreas
    et al.
    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.
    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.
    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.
    Ågren, Thomas
    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.
    Enlargement of visual processing regions in social anxiety disorder is related to symptom severity2014In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 583, p. 114-119Article in journal (Refereed)
    Abstract [en]

    Social anxiety disorder (SAD) is associated with altered brain function and structure, but most structural studies include small samples and findings are mixed. This study compared regional gray matter volume between 48 SAD patients and 29 healthy controls (HC) as well as the relationship between volume and symptom severity. Structural magnetic resonance images from SAD patients and HC were evaluated using standard voxel-based morphometry (VBM) processing in the SPM8 software package. Social anxiety symptom severity was rated in SAD patients by a clinician using the Liebowitz Social Anxiety Scale (LSAS). SAD patients had greater regional gray matter volume in the lingual gyrus and lateral occipital cortex than the controls, and within the SAD group a positive correlation was found between symptom severity and regional gray matter volume in the lingual gyrus and the retrosplenial cortex. These findings replicate and extend earlier reports of enlarged visual processing areas in SAD. Increased gray matter volume in regions involved in visual processing and self-consciousness could underlie, or be the result of, abnormal emotional information processing and self-focused attention previously demonstrated in patients with SAD.

  • 27.
    Frick, Andreas
    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.
    Appel, Lieuwe
    Jonasson, My
    Linnman, Clas
    Faria, Vanda
    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.
    Pich, Emilio Merlo
    Bani, Massimo
    Bettica, Paolo
    Lubberink, Mark
    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.
    Reduced Serotonin Synthesis after Pharmacological Treatment of Social Anxiety Disorder2015In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 77, no 9, p. 90S-90S, article id 236Article in journal (Other academic)
  • 28. Frick, Andreas
    et al.
    Åhs, Fredrik
    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.
    Jonasson, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    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.
    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.
    Linnman, Clas
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wahlstedt, Kurt
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Lubberink, Mark
    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.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Serotonin Synthesis and Reuptake in Social Anxiety Disorder: A Positron Emission Tomography Study.2015In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 72, no 8, p. 794-802Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: Serotonin is involved in negative affect, but whether anxiety syndromes, such as social anxiety disorder (SAD), are characterized by an overactive or underactive serotonin system has not been established. Serotonin 1A autoreceptors, which inhibit serotonin synthesis and release, are downregulated in SAD, and serotonin transporter availability might be increased; however, presynaptic serotonin activity has not been evaluated extensively.

    OBJECTIVE: To examine the serotonin synthesis rate and serotonin transporter availability in patients with SAD and healthy control individuals using positron emission tomography (PET) with the radioligands 5-hydroxytryptophan labeled with carbon 11 ([11C]5-HTP) and 11C-labeled 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile [11C]DASB.

    DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional study at an academic clinical research center. Eighteen patients with SAD (9 men and 9 women; mean [SD] age, 32.6 [8.2] years) and 18 sex- and age-matched healthy controls (9 men and 9 women; mean [SD] age, 34.7 [9.2] years) underwent [11C]5-HTP PET imaging. We acquired [11C]DASB PET images for 26 additional patients with SAD (14 men and 12 women; mean [SD] age, 35.2 [10.7] years) and the same 18 sex- and age-matched healthy controls. Participants were recruited through newspaper advertisements. Data were acquired from March 12, 2002, through March 5, 2012, and analyzed from March 28, 2013, through August 29, 2014.

    MAIN OUTCOMES AND MEASURES: The influx rate of [11C]5-HTP as a measure of serotonin synthesis rate capacity and [11C]DASB binding potential as an index of serotonin transporter availability were acquired during rest. We used the Liebowitz Social Anxiety Scale to measure severity of social anxiety symptoms.

    RESULTS: The PET data were not available for analysis in 1 control for each scan. Increased [11C]5-HTP influx rate was observed in the amygdala, raphe nuclei region, caudate nucleus, putamen, hippocampus, and anterior cingulate cortex of patients with SAD compared with healthy controls (P < .05 corrected), supporting an enhanced serotonin synthesis rate. Increased serotonin transporter availability in the patients with SAD relative to healthy controls was reflected by elevated [11C]DASB binding potential in the raphe nuclei region, caudate nucleus, putamen, thalamus, and insula cortex (P < .05 corrected).

    CONCLUSIONS AND RELEVANCE: Neurotransmission in SAD is characterized by an overactive presynaptic serotonin system, with increased serotonin synthesis and transporter availability. Our findings could provide important new insights into the etiology of anxiety disorders.

  • 29.
    Furmark, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Henningsson, S
    Appel, L
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Linnman, Claes
    Pissiota, Anna
    Faria, Vanda
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Oreland, V
    Bani, M
    Merlo Pich, E
    Eriksson, E
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Serotonin-related genotypes but not diagnosis of social anxiety disorder predict amygdala responsiveness to angry faces.2008Conference paper (Other academic)
  • 30.
    Gingnell, Malin
    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.
    Appel, L
    Linnman, Claes
    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.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Habituation of regional cerebral blood flow to repeated symptom provocation in individuals with generalized and non-generalized social phobia.2009In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, p. 124-Article in journal (Other academic)
  • 31.
    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.

  • 32. 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)
  • 33.
    Ågren, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Bjurström, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Signals and Systems Group.
    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
    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.
    Gustafsson, Mats
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Signals and Systems Group.
    Appel, Lieuwe
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Effective brain connectivity in social anxiety disorder: a Bayesian approach2007In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 61, no 8, p. 47S-47SArticle in journal (Other academic)
  • 34.
    Ågren, Thomas
    et al.
    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.
    Engman, Jonas
    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.
    No link between amygdala reactivity to emotional faces and fear conditioning2012Conference paper (Other academic)
  • 35.
    Ågren, Thomas
    et al.
    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.
    Frick, Andreas
    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.
    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.
    No link between amygdalareactivity to emotional faces and fear conditioning2012Conference paper (Refereed)
  • 36.
    Ågren, Thomas
    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.
    Engman, Jonas
    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.
    Gustafsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Effective Connectivity of Fear Circuitry and Emotion Regulation in Specific Phobia2011Conference paper (Other academic)
    Abstract [en]

    Background: The aim of the present study was to characterize effective brain connectivity patterns in patients with specific phobia.

    Methods: Sixteen patients with specific phobia were exposed to phobic and fear-relevant but non-phobic stimuli while regional cerebral blood flow was measured using [15O]-labelled water and positron emission tomography. Self reported state anxiety was also evaluated using the Spielberger State Anxiety Inventory (STAI-S). Different connectivity architectures were built based on five regions of interest (ROIs): the amygdala; subgenual anterior cingulate cortex (sACC) area 25; anterior midcingulate cortex (aMCC) area 24; insular cortex and dorsolateral prefrontal cortex (DLPFC) area 8. The ROIs were chosen based on their role in generating and attenuating fear. Structural equations modelling and Bayesian inference were used to assign probabilities to all possible architectures.

    Results: Top ranking models reveal different connectivity patterns resulting from phobic and non-phobic exposure. When exposed to phobic stimuli sACC appear to be driving the network. In contrast, when exposed to non-phobic stimuli the DLPFC is more active and dampen amygdala activity. This could reflect successful reappraisal processes during non-phobic exposure. The DLPFC correlated negatively (r=-0.49) with STAI-S during non-phobic exposure, but not phobic exposure also suggesting that emotional regulation fails in phobia. No direct correlation between amygdala activity and STAI-S was evident during either phobic or non-phobic conditions.

    Conclusions: These results suggest that emotional control processes operative when exposed to fear-relevant, but non-phobic cues are impaired during exposure to phobic stimuli.

1 - 36 of 36
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