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Faria, Vanda
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Publications (10 of 36) Show all publications
Faria, V., Gingnell, M., M. Hoppe, J., Hjorth, O., Alaie, I., Frick, A., . . . Furmark, T. (2017). Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder: A Randomized Trial. EBioMedicine (24), 179-188, Article ID S2352-3964(17)30385-7.
Open this publication in new window or tab >>Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder: A Randomized Trial
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2017 (English)In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, no 24, p. 179-188, article id S2352-3964(17)30385-7Article in journal (Refereed) Published
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).

Keywords
Expectancies, Neuroimaging, Placebo effect, SSRI, Social anxiety disorder, fMRI
National Category
Psychology General Practice
Identifiers
urn:nbn:se:uu:diva-331755 (URN)10.1016/j.ebiom.2017.09.031 (DOI)000414392900030 ()29033138 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2011-1368Swedish Research Council, 421-2013-1366Riksbankens Jubileumsfond, P13-1270:1
Note

Vanda Faria and Malin Gingnell contributed equally

Available from: 2017-10-18 Created: 2017-10-18 Last updated: 2018-02-12Bibliographically approved
Faria, V., Kossowsky, J., Petkov, M. P., Kaptchuk, T. J., Kirsch, I., Lebel, A. & Borsook, D. (2017). Parental Attitudes About Placebo Use in Children. Journal of Pediatric Surgery Case Reports, 181, 272-+
Open this publication in new window or tab >>Parental Attitudes About Placebo Use in Children
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2017 (English)In: Journal of Pediatric Surgery Case Reports, ISSN 0022-3476, E-ISSN 2213-5766, Vol. 181, p. 272-+Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
MOSBY-ELSEVIER, 2017
National Category
Pediatrics
Identifiers
urn:nbn:se:uu:diva-320772 (URN)10.1016/j.jpeds.2016.10.018 (DOI)000396249200043 ()27863847 (PubMedID)
Funder
Swedish Research Council, 437-2014-6767NIH (National Institute of Health), 2k24 AT004095
Available from: 2017-04-25 Created: 2017-04-25 Last updated: 2017-04-25Bibliographically approved
Frick, A., Åhs, F., Appel, L., Jonasson, M., Linnman, C., Faria, V., . . . Furmark, T. (2015). Reduced Serotonin Synthesis after Pharmacological Treatment of Social Anxiety Disorder. Paper presented at 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology, MAY 14-16, 2015, Toronto, CANADA. Biological Psychiatry, 77(9), 90S-90S, Article ID 236.
Open this publication in new window or tab >>Reduced Serotonin Synthesis after Pharmacological Treatment of Social Anxiety Disorder
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2015 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 77, no 9, p. 90S-90S, article id 236Article in journal, Meeting abstract (Other academic) Published
Keywords
Anxiety disorders, Serotonin, SSRI, PET imaging, Treatment study
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-255011 (URN)000352207500229 ()
Conference
70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology, MAY 14-16, 2015, Toronto, CANADA
Available from: 2015-06-15 Created: 2015-06-12 Last updated: 2017-12-04Bibliographically approved
Frick, A., Åhs, F., Engman, J., Jonasson, M., Alaie, I., Björkstrand, J., . . . Furmark, T. (2015). Serotonin Synthesis and Reuptake in Social Anxiety Disorder: A Positron Emission Tomography Study.. JAMA psychiatry, 72(8), 794-802
Open this publication in new window or tab >>Serotonin Synthesis and Reuptake in Social Anxiety Disorder: A Positron Emission Tomography Study.
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2015 (English)In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 72, no 8, p. 794-802Article in journal (Refereed) Published
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.

National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-259730 (URN)10.1001/jamapsychiatry.2015.0125 (DOI)000359200000008 ()26083190 (PubMedID)
Funder
Swedish Research CouncilThe Swedish Brain FoundationRiksbankens JubileumsfondForte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2015-08-11 Created: 2015-08-11 Last updated: 2017-12-04Bibliographically approved
Faria, V., Erpelding, N., Lebel, A., Johnson, A., Wolff, R., Fair, D., . . . Borsook, D. (2015). The migraine brain in transition: girls vs boys. Pain, 156(11), 2212-2221
Open this publication in new window or tab >>The migraine brain in transition: girls vs boys
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2015 (English)In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 156, no 11, p. 2212-2221Article in journal (Refereed) Published
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.

Keywords
Children, MRI, Migraine, Development, Puberty, Sex differences
National Category
Neurosciences Radiology, Nuclear Medicine and Medical Imaging Psychology
Identifiers
urn:nbn:se:uu:diva-269986 (URN)10.1097/j.pain.0000000000000292 (DOI)000364110700015 ()26172552 (PubMedID)
Funder
NIH (National Institute of Health), K24NS064050NIH (National Institute of Health), R01NS0750182NIH (National Institute of Health), R37 NS079678
Available from: 2015-12-19 Created: 2015-12-19 Last updated: 2018-01-10Bibliographically approved
Engman, J., Frick, A., Alaie, I., Björkstrand, J., Ågren, T., Faria, V., . . . Furmark, T. (2014). Amygdala and Default Mode Network Resting-State Functional Connectivity in Social Anxiety Disorder. In: : . Paper presented at 20th Annual Meeting of the Organization for Human Brain Mapping, Hamburg, Germany, 8-12 juni 2014.
Open this publication in new window or tab >>Amygdala and Default Mode Network Resting-State Functional Connectivity in Social Anxiety Disorder
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2014 (English)Conference paper, Oral presentation only (Refereed)
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-247730 (URN)
Conference
20th Annual Meeting of the Organization for Human Brain Mapping, Hamburg, Germany, 8-12 juni 2014
Available from: 2015-03-23 Created: 2015-03-23 Last updated: 2015-03-23
Faria, V., Åhs, F., Appel, L., Linnman, C., Bani, M., Bettica, P., . . . Furmark, T. (2014). Amygdala-frontal couplings characterizing SSRI and placebo response in social anxiety disorder. International Journal of Neuropsychopharmacology, 17(8), 1149-1157
Open this publication in new window or tab >>Amygdala-frontal couplings characterizing SSRI and placebo response in social anxiety disorder
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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
Bergman, O., Åhs, F., Furmark, T., Appel, L., Linnman, C., Faria, V., . . . Eriksson, E. (2014). Association between amygdala reactivity and a dopamine transporter gene polymorphism. Translational Psychiatry, 4, e420
Open this publication in new window or tab >>Association between amygdala reactivity and a dopamine transporter gene polymorphism
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2014 (English)In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 4, p. e420-Article in journal (Refereed) Published
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.

National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-239606 (URN)10.1038/tp.2014.50 (DOI)000344826900001 ()25093598 (PubMedID)
Available from: 2014-12-29 Created: 2014-12-29 Last updated: 2017-12-05Bibliographically approved
Frick, A., Engman, J., Alaie, I., Björkstrand, J., Faria, V., Gingnell, M., . . . Furmark, T. (2014). Enlargement of visual processing regions in social anxiety disorder is related to symptom severity. Neuroscience Letters, 583, 114-119
Open this publication in new window or tab >>Enlargement of visual processing regions in social anxiety disorder is related to symptom severity
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2014 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 583, p. 114-119Article in journal (Refereed) Published
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.

National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-236363 (URN)10.1016/j.neulet.2014.09.033 (DOI)000345604300022 ()25258347 (PubMedID)
Available from: 2014-11-18 Created: 2014-11-18 Last updated: 2018-01-11Bibliographically approved
Faria, V., Linnman, C., Lebel, A. & Borsook, D. (2014). Harnessing the Placebo Effect in Pediatric Migraine Clinic. Journal of Pediatrics, 165(4), 659-665
Open this publication in new window or tab >>Harnessing the Placebo Effect in Pediatric Migraine Clinic
2014 (English)In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 165, no 4, p. 659-665Article in journal, Editorial material (Other academic) Published
National Category
Pediatrics
Identifiers
urn:nbn:se:uu:diva-235854 (URN)10.1016/j.jpeds.2014.06.040 (DOI)000342694200006 ()25063720 (PubMedID)
Available from: 2014-11-12 Created: 2014-11-11 Last updated: 2017-12-05Bibliographically approved
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