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Frick, A., Engman, J., Alaie, I., Björkstrand, J., Gingnell, M., Larsson, E.-M., . . . Furmark, T. (2020). Neuroimaging, genetic, clinical, and demographic predictors of treatment response in patients with social anxiety disorder. Journal of Affective Disorders, 261, 230-237
Open this publication in new window or tab >>Neuroimaging, genetic, clinical, and demographic predictors of treatment response in patients with social anxiety disorder
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2020 (English)In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 261, p. 230-237Article in journal (Refereed) Published
Abstract [en]

Background: Correct prediction of treatment response is a central goal of precision psychiatry. Here, we tested the predictive accuracy of a variety of pre-treatment patient characteristics, including clinical, demographic, molecular genetic, and neuroimaging markers, for treatment response in patients with social anxiety disorder (SAD).

Methods: Forty-seven SAD patients (mean +/- SD age 33.9 +/- 9.4 years, 24 women) were randomized and commenced 9 weeks' Internet-delivered cognitive behavior therapy (CBT) combined either with the selective serotonin reuptake inhibitor (SSRI) escitalopram (20 mg daily [10 mg first week], SSRI+CBT, n= 24) or placebo (placebo+CBT, n= 23). Treatment responders were defined from the Clinical Global Impression-Improvement scale (CGI- I <= 2). Before treatment, patients underwent functional magnetic resonance imaging and the Multi-Source Interference Task taxing cognitive interference. Support vector machines (SVMs) were trained to separate responders from nonresponders based on pre-treatment neural reactivity in the dorsal anterior cingulate cortex (dACC), amygdala, and occipital cortex, as well as molecular genetic, demographic, and clinical data. SVM models were tested using leave-one-subject-out cross-validation.

Results: The best model separated treatment responders (n= 24) from nonresponders based on pre-treatment dACC reactivity (83% accuracy, P= 0.001). Responders had greater pre-treatment dACC reactivity than nonresponders especially in the SSRI+CBT group. No other variable was associated with clinical response or added predictive accuracy to the dACC SVM model.

Limitations: Small sample size, especially for genetic analyses. No replication or validation samples were available.

Conclusions: The findings demonstrate that treatment outcome predictions based on neural cingulate activity, at the individual level, outperform genetic, demographic, and clinical variables for medication-assisted Internet-delivered CBT, supporting the use of neuroimaging in precision psychiatry.

Keywords
Social phobia, SSRI, CBT, Personalized medicine, SVM, Pattern recognition
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-402003 (URN)10.1016/j.jad.2019.10.027 (DOI)000499616400031 ()31655378 (PubMedID)
Funder
Swedish Research CouncilRiksbankens JubileumsfondForte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2020-01-20 Created: 2020-01-20 Last updated: 2020-01-20Bibliographically approved
Månsson, K. N. .., Lindqvist, D., Yang, L. L., Svanborg, C., Isung, J., Nilsonne, G., . . . Furmark, T. (2019). Improvement in indices of cellular protection after psychological treatment for social anxiety disorder. Translational Psychiatry, 9(1), Article ID 340.
Open this publication in new window or tab >>Improvement in indices of cellular protection after psychological treatment for social anxiety disorder
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2019 (English)In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 9, no 1, article id 340Article in journal (Refereed) Published
Abstract [en]

Telomere attrition is a hallmark of cellular aging and shorter telomeres have been reported in mood and anxiety disorders. Telomere shortening is counteracted by the enzyme telomerase and cellular protection is also provided by the antioxidant enzyme glutathione peroxidase (GPx). Here, telomerase, GPx, and telomeres were investigated in 46 social anxiety disorder (SAD) patients in a within-subject design with repeated measures before and after cognitive behavioral therapy. Treatment outcome was assessed by the Liebowitz Social Anxiety Scale (self-report), administered three times before treatment to control for time and regression artifacts, and posttreatment. Venipunctures were performed twice before treatment, separated by 9 weeks, and once posttreatment. Telomerase activity and telomere length were measured in peripheral blood mononuclear cells and GPx activity in plasma. All patients contributed with complete data. Results showed that social anxiety symptom severity was significantly reduced from pretreatment to posttreatment (Cohen’s d = 1.46). There were no significant alterations in telomeres or cellular protection markers before treatment onset. Telomere length and telomerase activity did not change significantly after treatment, but an increase in telomerase over treatment was associated with reduced social anxiety. Also, lower pretreatment telomerase activity predicted subsequent symptom improvement. GPx activity increased significantly during treatment, and increases were significantly associated with symptom improvement. The relationships between symptom improvement and putative protective enzymes remained significant also after controlling for body mass index, sex, duration of SAD, smoking, concurrent psychotropic medication, and the proportion of lymphocytes to monocytes. Thus, indices of cellular protection may be involved in the therapeutic mechanisms of psychological treatment for anxiety.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Psychology Psychiatry
Identifiers
urn:nbn:se:uu:diva-400466 (URN)10.1038/s41398-019-0668-2 (DOI)000518228100001 ()31852887 (PubMedID)
Funder
The Swedish Brain Foundation, FO2016-0106The Swedish Brain Foundation, FO2018-0255Riksbankens Jubileumsfond, 2017-0639:1Swedish Society of MedicineStiftelsen Söderström - Königska sjukhemmetEkhaga FoundationThe Swedish Brain FoundationSwedish Research Council, 2014-10171
Available from: 2019-12-20 Created: 2019-12-20 Last updated: 2020-03-30Bibliographically approved
Rozental, A., Kottorp, A., Forsstrom, D., Månsson, K. N. .., Boettcher, J., Andersson, G., . . . Carlbring, P. (2019). The Negative Effects Questionnaire: psychometric properties of an instrument for assessing negative effects in psychological treatments. Behavioural and Cognitive Psychotherapy, 47(5), 559-572
Open this publication in new window or tab >>The Negative Effects Questionnaire: psychometric properties of an instrument for assessing negative effects in psychological treatments
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2019 (English)In: Behavioural and Cognitive Psychotherapy, ISSN 1352-4658, E-ISSN 1469-1833, Vol. 47, no 5, p. 559-572Article in journal (Refereed) Published
Abstract [en]

Background: Psychological treatments provide many benefits for patients with psychiatric disorders, but research also suggests that negative effects might occur from the interventions involved. The Negative Effects Questionnaire (NEQ) has previously been developed as a way of determining the occurrence and characteristics of such incidents, consisting of 32 items and six factors. However, the NEQ has yet to be examined using modern test theory, which could help to improve the understanding of how well the instrument works psychometrically.

Aims: The current study investigated the reliability and validity of the NEQ from both a person and item perspective, establishing goodness-of-fit, item bias, and scale precision.

Method: The NEQ was distributed to 564 patients in five clinical trials at post-treatment. Data were analysed using Rasch analysis, i.e. a modern test theory application.

Results: (1) the NEQ exhibits fairness in testing across sociodemographics, (2) shows comparable validity for a final and condensed scale of 20 instead of 32 items, (3) uses a rating scale that advances monotonically in steps of 0 to 4, and (4) is suitable for monitoring negative effects on an item-level.

Conclusions: The NEQ is proposed as a useful instrument for investigating negative effects in psychological treatments, and its newer shorter format could facilitate its use in clinical and research settings. However, further research is needed to explore the relationship between negative effects and treatment outcome, as well as to test it in more diverse patient populations.

Keywords
negative effects, Negative Effects Questionnaire, psychological treatments, Rasch analysis
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-394254 (URN)10.1017/S1352465819000018 (DOI)000483716500006 ()30871650 (PubMedID)
Available from: 2019-10-11 Created: 2019-10-11 Last updated: 2019-10-11Bibliographically approved
Lindner, P., Miloff, A., Fagernäs, S., Andersen, J., Sigeman, M., Andersson, G., . . . Carlbring, P. (2019). Therapist-led and self-led one-session virtual reality exposure therapy for public speaking anxiety with consumer hardware and software: A randomized controlled trial. Journal of Anxiety Disorders, 61, 45-54
Open this publication in new window or tab >>Therapist-led and self-led one-session virtual reality exposure therapy for public speaking anxiety with consumer hardware and software: A randomized controlled trial
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2019 (English)In: Journal of Anxiety Disorders, ISSN 0887-6185, E-ISSN 1873-7897, Vol. 61, p. 45-54Article in journal (Refereed) Published
Abstract [en]

Public speaking anxiety (PSA) is a common condition which can be treated effectively with exposure therapy. However, inherent difficulties in stimuli presentation and control limits dissemination and the therapeutic potential. Virtual Reality (VR) technology has the potential to resolve these issues and provide a scalable platform for self-help interventions. No previous study has examined whether this can be achieved using the first generation of consumer VR hardware and software. In the current trial, n = 25 + 25 participants were randomized to either one-session therapist-led VR exposure therapy for PSA followed by a four-week internet-administered VR to in-vivo transition program, or a waiting-list. Linear mixed effects modeling revealed significant, large (within Cohen’s d = 1.67) decreases in self-reported PSA. The waiting-list was then given access to an internet-administered, self-led version of the same VR exposure therapy to be conducted at home, followed by the same transition program. Dual-slope mixed effects modeling revealed significant, large (d = 1.35) decreases in self-reported PSA. Results were maintained or improved at six- and twelve-month follow-ups. We show for the first time that low-cost, off-the-shelf consumer VR hardware and software can be used to conduct exposure therapy for PSA, both in the traditional, previously impractical one-session format, and in a novel self-led, at-home format.

Keywords
Virtual reality, Exposure therapy, Internet interventions, Social anxiety disorder, Public speaking anxiety, In-vivo
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-358454 (URN)10.1016/j.janxdis.2018.07.003 (DOI)000456898000006 ()30054173 (PubMedID)
Note

Correction in: JOURNAL OF ANXIETY DISORDERS, Volume: 64, Pages: 90-90, DOI: 10.1016/j.janxdis.2019.04.002

Available from: 2018-08-29 Created: 2018-08-29 Last updated: 2019-06-19Bibliographically approved
Månsson, K., Garrett, D., Manzouri, A., Wiegert, S., Furmark, T. & Fischer, H. (2018). Affective Brain Signal Variability Separates Social Anxiety Disorder Patients From Healthy Individuals. Paper presented at 73rd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), MAY 10-12, 2017, New York, NY. Biological Psychiatry, 83(9), S249-S250
Open this publication in new window or tab >>Affective Brain Signal Variability Separates Social Anxiety Disorder Patients From Healthy Individuals
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2018 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 83, no 9, p. S249-S250Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Social Anxiety Disorder, BOLD fMRI, Variability
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-359379 (URN)10.1016/j.biopsych.2018.02.644 (DOI)000433001900042 ()
Conference
73rd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), MAY 10-12, 2017, New York, NY
Available from: 2018-09-17 Created: 2018-09-17 Last updated: 2018-09-17Bibliographically approved
Kraus, J., Frick, A., Fischer, H., Howner, K., Fredriksson, M. & Furmark, T. (2018). Amygdala reactivity and connectivity during social and non-social aversive stimulation in social anxiety disorder. Psychiatry Research: Neuroimaging, 280, 56-61
Open this publication in new window or tab >>Amygdala reactivity and connectivity during social and non-social aversive stimulation in social anxiety disorder
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2018 (English)In: Psychiatry Research: Neuroimaging, ISSN 0925-4927, E-ISSN 1872-7506, Vol. 280, p. 56-61Article in journal (Refereed) Published
Abstract [en]

Social anxiety disorder (SAD) is characterized by exaggerated amygdala reactivity in response to symptom provocation, but it is unclear if such hyper-reactivity is elicited by disorder-specific challenges only or characterizes reactions to aversive stimuli in general. Here, using functional magnetic resonance imaging in 14 patients with SAD, as compared to 12 healthy controls, we found that amygdala hyper-reactivity is confined to disorder-relevant social stimulation. SAD patients displayed increased amygdala reactivity to fearful as compared to neutral facial pictures, but not in response to generally aversive but mainly non-social stimulation when compared to neutral pictorial stimuli taken from the International Affective Picture System. The increased amygdala reactivity was not mediated by an altered prefrontal inhibition among SAD patients as compared to controls, suggesting increased bottom-up processes rather than attenuated top-down control. In conclusion, the enhanced amygdala reactivity in SAD seems specific to socially relevant stimuli rather than aversive stimuli in general.

Keywords
Social phobia, Emotional faces, International Affective Picture System, IAPS, fMRI, Fear
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-364125 (URN)10.1016/j.pscychresns.2018.08.012 (DOI)000443824900008 ()30165271 (PubMedID)
Funder
Swedish Research CouncilRiksbankens JubileumsfondRiksbankens JubileumsfondThe Swedish Brain Foundation
Available from: 2018-11-05 Created: 2018-11-05 Last updated: 2018-11-05Bibliographically approved
Frick, A., Engman, J., Wahlstedt, K., Gingnell, M., Fredrikson, M. & Furmark, T. (2018). Anterior cingulate cortex activity as a candidate biomarker for treatment selection in social anxiety disorder. BJPsych bulletin, 4(3)
Open this publication in new window or tab >>Anterior cingulate cortex activity as a candidate biomarker for treatment selection in social anxiety disorder
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2018 (English)In: BJPsych bulletin, ISSN 2056-4694, E-ISSN 2056-4708, Vol. 4, no 3Article in journal (Refereed) Published
Abstract [en]

We aimed to identify biomarkers to guide the decision to add selective serotonin reuptake inhibitors (SSRI) to psychological treatment for social anxiety disorder (SAD). Forty-eight patients with SAD underwent functional magnetic resonance imaging and collection of clinical and demographic variables before treatment with cognitive–behavioural therapy, combined on a double-blind basis with either escitalopram or placebo for 9 weeks. Pre-treatment neural reactivity to aversive faces in the dorsal anterior cingulate cortex (ACC), but not clinical/demographic variables, moderated clinical outcomes. Cross-validated individual-level predictions accurately identified 81% of responders/non-responders. Dorsal ACC reactivity is thus a potential biomarker for SAD treatment selection.

Place, publisher, year, edition, pages
Cambridges Institutes Press, 2018
Keywords
Functional magnetic resonance imaging, anxiety, prediction, selective serotonin reuptake inhibitors, cognitive–behavioural therapy, social phobia
National Category
Psychology Psychiatry
Identifiers
urn:nbn:se:uu:diva-353596 (URN)10.1192/bjo.2018.15 (DOI)000436933400012 ()29922481 (PubMedID)
Funder
Swedish Research CouncilRiksbankens JubileumsfondThe Swedish Brain FoundationForte, Swedish Research Council for Health, Working Life and WelfareSwedish Society for Medical Research (SSMF)
Available from: 2018-06-14 Created: 2018-06-14 Last updated: 2018-09-26Bibliographically approved
Motilla Hoppe, J., Frick, A., Åhs, F., Linnman, C., Appel, L., Jonasson, M., . . . Furmark, T. (2018). Association between amygdala neurokinin-1 receptor availability and anxiety-related personality traits. Translational Psychiatry, 8(1), 168
Open this publication in new window or tab >>Association between amygdala neurokinin-1 receptor availability and anxiety-related personality traits
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2018 (English)In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 8, no 1, p. 168-Article in journal (Refereed) Published
Abstract [en]

Animal studies indicate that substance P (SP) and its preferred neurokinin-1 (NK1) receptor modulate stress and anxiety-related behavior. Alterations in the SP-NK1 system have also been observed in human anxiety disorders, yet little is known about the relation between this system and individual differences in personality traits associated with anxiety propensity and approach-avoidance behavior, including trait anxiety, neuroticism, and extraversion. Exploring this relation could provide important insights into the neurobiological underpinnings of human anxiety and the etiology of anxiety disorders, as anxious traits are associated with increased susceptibility to develop psychopathological conditions. Here we examined the relationship between central NK1 receptor availability and self-rated measures of trait anxiety, neuroticism, and extraversion. The amygdala was chosen as the primary region of interest since this structure has been suggested to mediate the effect of the SP-NK1 system on anxiety. Anxious traits and NK1 receptor availability, determined with positron emission tomography and the radiotracer [11C]GR205171, were measured in 17 healthy individuals. Voxel-wise analyses showed a significant positive correlation between bilateral amygdala NK1 receptor availability and trait anxiety, and a trend in similar direction was observed for neuroticism. Conversely, extraversion was found to be negatively associated with amygdala NK1 receptor availability. Extraversion also correlated negatively with the NK1 measure in the cuneus/precuneus and fusiform gyrus according to exploratory whole-brain analyses. In conclusion, our findings indicate that amygdala NK1 receptor availability is associated with anxiety-related personality traits in healthy subjects, consistent with a modulatory role for the SP-NK1 system in human anxiety.

National Category
Pedagogy
Identifiers
urn:nbn:se:uu:diva-358759 (URN)10.1038/s41398-018-0163-1 (DOI)000443079700001 ()
Available from: 2018-08-31 Created: 2018-08-31 Last updated: 2018-12-10Bibliographically approved
Mansson, K., Wager, T. D., Isacsson, N., Kolbeinsson, O., Andersson, G., Fischer, H. & Furmark, T. (2018). Brain Before Behavior: Temporal Dynamics in the Treatment of Social Anxiety - Neural Changes Occur Early and Precede Clinical Improvement. Paper presented at 73rd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), 2018, New York, NY. Biological Psychiatry, 83(9), S130-S131
Open this publication in new window or tab >>Brain Before Behavior: Temporal Dynamics in the Treatment of Social Anxiety - Neural Changes Occur Early and Precede Clinical Improvement
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2018 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 83, no 9, p. S130-S131Article in journal, Meeting abstract (Other academic) Published
Keywords
Social Anxiety Disorder, BOLD fMRI, Cognitive Behavior Therapy, Temporal Dynamics, Amygdala
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-361430 (URN)000432466300319 ()
Conference
73rd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), 2018, New York, NY
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2018-12-10Bibliographically approved
Månsson, K., Lindqvist, D., Yang, L., Wolkowitz, O., Nilsonne, G., Isung, J., . . . Furmark, T. (2018). Can Psychological Treatment Slow Down Cellular Aging in Social Anxiety Disorder?: An Intervention Study Evaluating Changes in Telomere Length and Telomerase Activity. Paper presented at 73rd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), MAY 10-12, 2017, New York, NY. Biological Psychiatry, 83(9), S351-S352
Open this publication in new window or tab >>Can Psychological Treatment Slow Down Cellular Aging in Social Anxiety Disorder?: An Intervention Study Evaluating Changes in Telomere Length and Telomerase Activity
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2018 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 83, no 9, p. S351-S352Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Telomerase, Telomere, Social Anxiety Disorder, Cognitive Behavior Therapy, Cellular Aging
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-359378 (URN)10.1016/j.biopsych.2018.02.904 (DOI)000433001900299 ()
Conference
73rd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), MAY 10-12, 2017, New York, NY
Note

Meeting Abstract: S13

Available from: 2018-09-17 Created: 2018-09-17 Last updated: 2018-09-17Bibliographically approved
Organisations
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ORCID iD: ORCID iD iconorcid.org/0000-0001-6821-9058

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