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1.
  • Ahs, Fredrik, et al. (författare)
  • High-frequency heart rate variability and cortico-striatal activity in men and women with social phobia
  • 2009
  • Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 47:3, s. 815-820
  • Tidskriftsartikel (refereegranskat)abstract
    • Identifying brain systems that regulate or modulate autonomic nervous system functions may identify pathways through which psychosocial factors can influence health and disease. Reduced high-frequency heart rate variability (HF-HRV) characterizes anxiety disordered patients and is predictive of adverse myocardial events. Sex differences in the prevalence of anxiety disorders and cardiac diseases implicate the possibility of sex specific neural regulation of HF-HRV. We investigated the correlation between HF-HRV and regional cerebral blood flow (rCBF) in 28 subjects (15 women) with social phobia undergoing a stressful public speaking task. Regional CBF was measured with [(15)O] water positron emission tomography. Stress induced rCBF correlated positively with HF-HRV in the right supra genual anterior cingulate cortex Brodmann's area (BA) 32, the right head of the caudate nucleus and bilaterally in the medial prefrontal cortex (BA10), extending into the dorsolateral prefrontal cortex (BA46) in the left hemisphere. Men showed larger positive co-variation in the caudate than women. These findings underscore the importance of the emotional division of the anterior cingulate cortex, the prefrontal cortex and the striatum in cardiovagal activity. The study replicates and extends results from published functional neuroimaging studies on cardioregulatory or modulatory areas in healthy subjects to men and women with social phobia. Moreover, caudate functions, possibly related to dopaminergic neurotransmission, have sexually dimorphic effects on vagal modulation of the heart.
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4.
  • Andersson, Evelyn, et al. (författare)
  • Genetic Polymorphisms in Monoamine Systems and Outcome of Cognitive Behavior Therapy for Social Anxiety Disorder
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveThe role of genetics for predicting the response to cognitive behavior therapy (CBT) for social anxiety disorder (SAD) has only been studied in one previous investigation. The serotonin transporter (5-HTTLPR), the catechol-o-methyltransferase (COMT) val158met, and the tryptophan hydroxylase-2 (TPH2) G-703Tpolymorphisms are implicated in the regulation of amygdala reactivity and fear extinction and therefore might be of relevance for CBT outcome. The aim of the present study was to investigate if these three gene variants predicted response to CBT in a large sample of SAD patients.MethodParticipants were recruited from two separate randomized controlled CBT trials (trial 1: n = 112, trial 2: n = 202). Genotyping were performed on DNA extracted from blood or saliva samples. Effects were analyzed at follow-up (6 or 12 months after treatment) for both groups and for each group separately at post-treatment. The main outcome measure was the Liebowitz Social Anxiety Scale Self-Report.ResultsAt long-term follow-up, there was no effect of any genotype, or gene × gene interactions, on treatment response. In the subsamples, there was time by genotype interaction effects indicating an influence of the TPH2 G-703T-polymorphism on CBT short-term response, however the direction of the effect was not consistent across trials.ConclusionsNone of the three gene variants, 5-HTTLPR, COMTval158met and TPH2 G-703T, was associated with long-term response to CBT for SAD.
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5.
  • Andersson, Gerhard, 1966-, et al. (författare)
  • Consequences of suppressing thoughts about tinnitus and the effects of cognitive distraction on brain activity in tinnitus patients
  • 2006
  • Ingår i: Audiology & neuro-otology. - : S. Karger AG. - 1420-3030 .- 1421-9700. ; 11:5, s. 301-309
  • Tidskriftsartikel (refereegranskat)abstract
    • Tinnitus is the perception of sound in the absence of any appropriate external stimulus. Based on the clinical observation that tinnitus patients may distract themselves from their sounds, we performed an experimental test on the effects of suppressing thoughts about tinnitus with 45 tinnitus patients, to systematically evaluate the immediate consequences of suppressing thought vs. attending to tinnitus. Suppression instructions tended to lead to a subsequent decrease in tinnitus-related thoughts, whereas attention to tinnitus resulted in an increase in such thoughts. No effects were seen in a control group who neither suppressed nor attended to their tinnitus. In an independent positron emission tomography study of cerebral blood flow with 8 patients we found that silent backward counting ('serial sevens test') led to a decrease in neural activity in auditory cortex, as well as perceived decrease of tinnitus loudness and annoyance. Thus, distraction that altered the tinnitus experience seemed to attenuate auditory cortex activity.
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7.
  • Andersson, Gerhard, 1966-, et al. (författare)
  • Internet-based self-help with therapist feedback and in vivo group exposure for social phobia : A randomized controlled trial
  • 2006
  • Ingår i: Journal of Consulting and Clinical Psychology. - 0022-006X .- 1939-2117. ; 74:4, s. 677-686
  • Tidskriftsartikel (refereegranskat)abstract
    • Sixty-four individuals with social phobia (social anxiety disorder) were assigned to a multimodal cognitive-behavioral treatment package or to a waiting list control group. Treatment consisted of a 9-week, Internet-delivered, self-help program that was combined with 2 group exposure sessions in real life and minimal therapist contact via e-mail. Results were analyzed on an intention-to-treat basis, including all randomized participants. From pre- to posttest, treated participants in contrast to controls showed significant improvement on most measured dimensions (social anxiety scales, general anxiety and depression levels, quality of life). The overall within- and between-groups effect sizes were Cohen's d = 0.87 and 0.70, respectively. Treatment gains were maintained at 1-year follow-up. The results from this study support the continued use and development of Internet-distributed, self-help programs for people diagnosed with social phobia.
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8.
  • Andersson, Gerhard, et al. (författare)
  • Internet-Delivered Treatments for Social Anxiety Disorder
  • 2014
  • Ingår i: The Wiley Blackwell Handbook of Social Anxiety Disorder. - Chichester, UK : John Wiley & Sons. - 9781119968603 - 9781118653920 ; , s. 579-587
  • Bokkapitel (refereegranskat)abstract
    • In this chapter we review the literature on internet-delivered treatment for social anxiety disorder (SAD). There are several different treatment programs that have been tested in randomized controlled trials and evidence now suggests that guided internet-based cognitive behavior therapy (ICBT) can be as effective as face-to-face therapy, that therapists may need less training than in face-to-face treatment, and that ICBT works in representative clinical settings, thereby supporting effectiveness. Moreover, there are studies to suggest that ICBT has enduring effects up to five years after treatment and that it is cost-effective. Since there are advantages with internet treatments, this treatment option should be considered as a complement or alternative to face-to-face treatments for SAD. Treatment mechanisms, including moderators and mediators of outcome, remain to be investigated.
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9.
  • Andersson, Gerhard, et al. (författare)
  • Therapeutic alliance in guided internet-delivered cognitive behavioural treatment of depression, generalized anxiety disorder and social anxiety disorder
  • 2012
  • Ingår i: Behaviour Research and Therapy. - : Elsevier. - 0005-7967 .- 1873-622X. ; 50:9, s. 544-550
  • Tidskriftsartikel (refereegranskat)abstract
    • Guided internet-delivered cognitive behaviour therapy (ICBT) has been found to be effective in several controlled trials, but the mechanisms of change are largely unknown. Therapeutic alliance is a factor that has been studied in many psychotherapy trials, but the role of therapeutic alliance in ICBT is less well known. The present study investigated early alliance ratings in three separate samples. Participants from one sample of depressed individuals (N = 49), one sample of individuals with generalized anxiety disorder (N = 35), and one sample with social anxiety disorder (N = 90) completed the Working Alliance Inventory (WAI) modified for ICBT early in the treatment (weeks 3-4) when they took part in guided ICBT for their conditions. Results showed that alliance ratings were high in all three samples and that the WAI including the subscales of Task, Goal and Bond had high internal consistencies. Overall, correlations between the WAI and residualized change scores on the primary outcome measures were small and not statistically significant. We conclude that even if alliance ratings are in line with face-to-face studies, therapeutic alliance as measured by the WAI is probably less important in ICBT than in regular face-to-face psychotherapy.
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10.
  • Andersson, Gerhard, et al. (författare)
  • Therapist experience and knowledge acquisition in internet-delivered CBT for social anxiety disorder : a randomized controlled trial
  • 2012
  • Ingår i: PLOS ONE. - : PLoS. - 1932-6203. ; 7:5, s. e37411-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Guided internet-delivered cognitive behavior therapy (ICBT) has been tested in several trials on social anxiety disorder (SAD) with moderate to large effects. The aims of this study were threefold. First, to compare the effects of ICBT including online discussion forum with a moderated online discussion forum only. Second, to investigate if knowledge about SAD increased following treatment and third to compare the effects of inexperienced versus experienced therapists on patient outcomes. Methods: A total of 204 participants with a primary diagnosis of SAD were included and randomized to either guided ICBT or the control condition. ICBT consisted of a 9-week treatment program which was guided by either psychology students at MSc level (n = 6) or by licensed psychologists with previous experience of ICBT (n = 7). A knowledge test dealing with social anxiety was administered before and after treatment. Measures of social anxiety and secondary outcomes dealing with general anxiety, depression, and quality of life were administered before and after treatment. In addition, a 1-year follow-up was conducted on the treated individuals. Results: Immediately following treatment, the ICBT group showed superior outcome on the Liebowitz Social Anxiety Scale self-report version with a between group posttreatment Hedges geffect size ofg = 0.75. In addition, significant differences on all the secondary outcomes were observed. Gains were well maintained one year later. Knowledge, as assessed by the knowledge test, increased following treatment with little gain in the control group. Therapist experience did not result in different outcomes, but experienced therapists logged in less frequently compared to the inexperienced therapists, suggesting that they needed less time to support patients. Discussion: We conclude that guided ICBT reduce symptoms of SAD, increase knowledge about SAD and that therapist experience does not make a difference apart from the finding that experienced therapist may require less time to guide patients. Trial Registration: UMIN.ac.jp UMIN000001383
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  • Appel, Lieuwe, et al. (författare)
  • Altered NK1-receptor availability in patients with post traumatic stress disorder
  • 2009
  • Ingår i: [Biological Psychiatry 2009, 65(8), Suppl. 1, 118S, no. 394]. - : Elsevier BV. ; , s. 118S-
  • Konferensbidrag (refereegranskat)abstract
    • Background: Posttraumatic stress disorder (PTSD) is an anxiety disorder that can develop after one or more traumatic events causing extreme stress or grave physical harm. The neurokinin-1 (NK1) receptor is the primary receptor for substance P (SP); a neuropeptide suggested being involved in anxiety and depression. The present study investigated differences in NK1-receptor availability between PTSD patients and healthy controls, using positron emission tomography (PET). Methods: Eleven male refugee patients (age: 41±10) with DSM-IV defined PTSD and nine healthy male control subjects (age: 33±10) were investigated using the PET-tracer [11C]GR205171, supplied by Uppsala Imanet. GR205171 is a highly selective NK1-receptor antagonist. Scans were performed during 60 minutes in the resting state. Parametric images were generated using the graphical reference Patlak method assuming irreversible binding of [11C]GR205171 from 20-60 minutes and having cerebellum as reference region. Exploratory whole brain analyses were performed using the statistical parametric mapping (SPM2) software. Results: PTSD patients had lower [11C]GR205171 binding compared to controls, in frontal cortical clusters encompassing bilaterally insula and left Brodmann area 11, reflecting lower NK1-receptor availability. No areas were found in which PTSD patients had higher [11C]GR205171 binding. Conclusions: This is the first study reporting differences in NK1-receptor availability in PTSD patients relative to controls. A tentative conclusion is that PTSD patients have a down regulation of the NK1-receptor system, which could be either a risk factor or due to emotional trauma processing.
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15.
  • Bas-Hoogendam, Janna Marie, et al. (författare)
  • Voxel-based morphometry multi-center mega-analysis of brain structure in social anxiety disorder
  • 2017
  • Ingår i: NeuroImage. - : Elsevier BV. - 2213-1582. ; 16, s. 678-688
  • Tidskriftsartikel (refereegranskat)abstract
    • Social anxiety disorder (SAD) is a prevalent and disabling mental disorder, associated with significant psychiatric co-morbidity. Previous research on structural brain alterations associated with SAD has yielded inconsistent results concerning the direction of the changes in gray matter (GM) in various brain regions, as well as on the relationship between brain structure and SAD-symptomatology. These heterogeneous findings are possibly due to limited sample sizes. Multi-site imaging offers new opportunities to investigate SAD-related alterations in brain structure in larger samples.An international multi-center mega-analysis on the largest database of SAD structural T1-weighted 3T MRI scans to date was performed to compare GM volume of SAD-patients (n = 174) and healthy control (HC)-participants (n = 213) using voxel-based morphometry. A hypothesis-driven region of interest (ROI) approach was used, focusing on the basal ganglia, the amygdala-hippocampal complex, the prefrontal cortex, and the parietal cortex. SAD-patients had larger GM volume in the dorsal striatum when compared to HC-participants. This increase correlated positively with the severity of self-reported social anxiety symptoms. No SAD-related differences in GM volume were present in the other ROIs. Thereby, the results of this mega-analysis suggest a role for the dorsal striatum in SAD, but previously reported SAD-related changes in GM in the amygdala, hippocampus, precuneus, prefrontal cortex and parietal regions were not replicated. Our findings emphasize the importance of large sample imaging studies and the need for meta-analyses like those performed by the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium.
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17.
  • Bergman, Olle, 1978, et al. (författare)
  • Association between amygdala reactivity and a dopamine transporter gene polymorphism.
  • 2014
  • Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • 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 [(15)O]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.
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19.
  • Björkstrand, Johannes, et al. (författare)
  • Decrease in amygdala activity during repeated exposure to spider images predicts avoidance behavior in spider fearful individuals.
  • 2020
  • Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Spider phobia is characterized by exaggerated fear of situations where spiders could be present, resulting in avoidance of such situations and compromised quality of life. An important component in psychological treatment of spider phobia is exposure to phobic situations that reduces avoidance behaviors. At the neural level, amygdala responses to phobic material are elevated, but normalizes following exposure treatment. To what extent amygdala activity decreases during a session of repeated phobic stimulation, and whether activity decrease is related to subsequent avoidance is not well studied. We hypothesized reduced amygdala activity during the course of repeated exposure to spider pictures, and that the degree of reduction would predict subsequent avoidance of spider pictures. To test our hypothesis, functional magnetic resonance imaging was performed in 45 individuals with spider fear during repeated exposure to spider pictures. Results showed that repeated exposure to spider stimuli attenuated amygdala reactivity and individual differences in activity reductions predicted subsequent avoidance behavior to spider pictures in an incentive-conflict task, with larger attenuations predicting less avoidance. At 6-month follow up, initial reductions in amygdala activation still predicted avoidance. This result demonstrates that reduction in amygdala responses is related to clinically meaningful outcomes in human anxiety, and suggests that within-session reductions in amygdala responses could be an important mechanism explaining the clinical effects of exposure therapy.
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20.
  • Björkstrand, Johannes, et al. (författare)
  • Disrupting Reconsolidation Attenuates Long-Term Fear Memory in the Human Amygdala and Facilitates Approach Behavior
  • 2016
  • Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 26:19, s. 2690-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Memories become labile and malleable to modification when recalled [1]. Fear-conditioning experiments in both rodents and humans indicate that amygdala-localized short-term fear memories can be attenuated by disruption of their reconsolidation with extinction training soon after memory activation [2-7]. However, this may not be true for natural long-term fears. Studies in rodents indicate that although it is possible to disrupt the reconsolidation of older memories [8-11], they appear to be more resistant [1, 3, 9, 12, 13]. In humans, 1-week-old conditioned fear memories have been attenuated by behaviorally induced disruption of reconsolidation [14], but it remains to be seen whether this is possible for naturally occurring long-term fears and whether the underlying neural mechanisms are similar to those found in experimental fear-conditioning paradigms. Using functional brain imaging in individuals with a lifelong fear of spiders, we show that fear memory activation followed by repeated exposure to feared cues after 10 min, which disrupts reconsolidation, attenuates activity in the basolateral amygdala at re-exposure 24 hr later. In contrast, repeated exposure 6 hr after fear memory activation, which allows for reconsolidation, did not attenuate amygdala activity. Disrupted, but not undisrupted, reconsolidation facilitated approach behavior to feared cues, and approach behavior was inversely related to amygdala activity during re-exposure. We conclude that memory activation immediately preceding exposure attenuates the neural and behavioral expression of decades-old fear memories and that, similar to experimentally induced fear memories, the basolateral amygdala is crucially involved in this process.
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22.
  • Björkstrand, Johannes, et al. (författare)
  • Disruption of Memory Reconsolidation Erases a Fear Memory Trace in the Human Amygdala : An 18-Month Follow-Up.
  • 2015
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7, s. e0129393-
  • Tidskriftsartikel (refereegranskat)abstract
    • Fear memories can be attenuated by reactivation followed by disrupted reconsolidation. Using functional magnetic resonance imaging we recently showed that reactivation and reconsolidation of a conditioned fear memory trace in the basolateral amygdala predicts subsequent fear expression over two days, while reactivation followed by disrupted reconsolidation abolishes the memory trace and suppresses fear. In this follow-up study we demonstrate that the behavioral effect persists over 18 months reflected in superior reacquisition after undisrupted, as compared to disrupted reconsolidation, and that neural activity in the basolateral amygdala representing the initial fear memory predicts return of fear. We conclude that disrupting reconsolidation have long lasting behavioral effects and may permanently erase the fear component of an amygdala-dependent memory.
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23.
  • Björkstrand, Johannes, et al. (författare)
  • Think twice, it's all right : Long lasting effects of disrupted reconsolidation on brain and behavior in human long-term fear
  • 2017
  • Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 324, s. 125-129
  • Tidskriftsartikel (refereegranskat)abstract
    • Memories can be modified when recalled. Experimental fear conditioning studies support that amygdala-localized fear memories are attenuated when reconsolidation is disrupted through extinction training immediately following memory activation. Recently, using functional brain imaging in individuals with lifelong spider fears, we demonstrated that fear memory activation followed by repeated exposure to feared cues after 10 min, thereby disrupting reconsolidation, attenuated activity in the amygdala during later re-exposure, and also facilitated approach behavior to feared cues. In contrast, repeated exposure 6 h after fear memory activation, allowing for reconsolidation, did not attenuate amygdala activity and resulted in less approach behavior as compared to the group that received disrupted reconsolidation. We here evaluated if these effects are stable after 6 months and found that amygdala activity was further reduced in both groups, with a tendency towards greater reductions in the 10 min than the 6 h group. Hence, disrupted reconsolidation results in long lasting attenuation of amygdala activity. The behavioral effect, with more approach towards previously feared cues, in the 10 min than the 6 h group also persisted. Thus, the brain effect of disrupted reconsolidation is stable over 6 months and the behavioral effect also remained. We therefore conclude that disrupted reconsolidation result in a long-lasting diminished fear memory representation in the amygdala which may have clinical importance.
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24.
  • Buhrman, Monica, 1974-, et al. (författare)
  • Guided internet-delivered acceptance and commitment therapy for chronic pain patients: A randomized controlled trial
  • 2013
  • Ingår i: Behaviour Research and Therapy. - : Elsevier. - 0005-7967 .- 1873-622X. ; 51:6, s. 307-315
  • Tidskriftsartikel (refereegranskat)abstract
    • Acceptance and commitment therapy (ACT) interventions for persons with chronic pain have recently received empirical support. ACT focuses on reducing the disabling influences of pain through targeting ineffective control strategies and teaches people to stay in contact with unpleasant emotions, sensations, and thoughts. The aim of the present study was to investigate the effect of a guided internet-delivered ACT intervention for persons with chronic pain. A total of 76 patients with chronic pain were included in the study and randomized to either treatment for 7 weeks or to a control group that participated in a moderated online discussion forum. Intent-to-treat analyses showed significant increases regarding activity engagement and pain willingness. Measurements were provided with the primary outcome variable Chronic Pain Acceptance Questionnaire which was in favour of the treatment group. Reductions were found on other measures of pain-related distress, anxiety and depressive symptoms. A six month follow-up showed maintenance of improvements. We conclude that an acceptance based internet-delivered treatment can be effective for persons with chronic pain.
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25.
  • Carlbring, Per, 1972-, et al. (författare)
  • An open study of Internet-based bibliotherapy with minimal therapist contact via e-mail for social phobia
  • 2006
  • Ingår i: Clinical Psychologist. - 1328-4207 .- 1742-9552. ; 10, s. 30-38
  • Tidskriftsartikel (refereegranskat)abstract
    • This study evaluated a nine-week Internet-based self-help program for people suffering from social phobia. After confirming the diagnosis with a structured clinical interview for the DSM-IV (SCID) by telephone, 26 participants were treated with a multimodal treatment package based on cognitive behavioral therapy plus weekly therapist contact via e-mail. Results were analyzed on a basis of intention-to-treat. There were no differences between the two pre-treatment assessment points. However, from pre- to post-test, treated participants improved signi?cantly on all measured dimensions (social anxiety, general anxiety, depression levels, and quality of life). The overall within-group effect size measured with Cohen-s d was d=0.88. Treatment gains were maintained or improved at the 6-month follow-up (Cohen-s d=1.31). The results of this study support the continued use and development of Internet-distributed self-help programs for people diagnosed with social phobia. 
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26.
  • Carlbring, Per, 1972-, et al. (författare)
  • Internet treatment for social phobia
  • 2005
  • Ingår i: 5th international congress of cognitive psychotherapy,2005. ; , s. 56-
  • Konferensbidrag (refereegranskat)
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27.
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28.
  • Carlbring, Per, et al. (författare)
  • Long-term outcome of Internet-delivered cognitive-behavioural therapy for social phobia : a 30-month follow-up
  • 2009
  • Ingår i: Behaviour Research and Therapy. - : Elsevier BV. - 0005-7967 .- 1873-622X. ; 47:10, s. 848-850
  • Tidskriftsartikel (refereegranskat)abstract
    • Internet-delivered guided cognitive behaviour therapy for social anxiety disorder has been found to generate promising short-term results, up to one year posttreatment. No study has however documented longer follow-up periods. In this 30-month follow-up we contacted 57 participants from the original study of which 77.2% (44/57) responded to the Internet-administered outcome measures and 66.7% (38/57) completed a telephone interview. Results showed large pretreatment to follow-up within-group effect sizes for the primary outcome measures (Cohen's d 1.10-1.71), and a majority (68.4%; 26/38) reported improvements in the interview. The findings suggest that the long-term effects seen in previous live treatment CBT trials can occur in Internet-delivered treatment as well.
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29.
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30.
  • Carlbring, Per, et al. (författare)
  • Treatment of social phobia : Randomised trial of internet-delivered cognitive-behavioural therapy with telephone support
  • 2007
  • Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 190, s. 123-128
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Although effective therapies for social phobia exist, many individuals refrain from seeking treatment owing to the embarrassment associated with help-seeking. Internet-based cognitive-behavioural self-help can be an alternative, but adherence is a problem. Aims: To evaluate a 9-week programme of internet-based therapy designed to increase treatment adherence by the addition of short weekly telephone calls, nine in all, with a total duration of 95 min. Method: In a randomised controlled trial the effects of internet-based cognitive-behavioural therapy in the treatment group (n=29) were compared with a waiting-list control group (n=28). Results: Compared with the control group the treated participants experienced greater reductions on measures of general and social anxiety, avoidance and depression. Adherence to treatment was high, with 93% finishing the complete treatment package. One year later all improvements were maintained. Conclusions: This study provides evidence to support the use of internet-based treatment supplemented by short, weekly telephone calls.
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31.
  • Costache, Madalina Elena, et al. (författare)
  • Higher- and lower-order personality traits and cluster subtypes in social anxiety disorder
  • 2020
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 15:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Social anxiety disorder (SAD) can come in different forms, presenting problems for diagnostic classification. Here, we examined personality traits in a large sample of patients (N = 265) diagnosed with SAD in comparison to healthy controls (N = 164) by use of the Revised NEO Personality Inventory (NEO-PI-R) and Karolinska Scales of Personality (KSP). In addition, we identified subtypes of SAD based on cluster analysis of the NEO-PI-R Big Five personality dimensions. Significant group differences in personality traits between patients and controls were noted on all Big Five dimensions except agreeableness. Group differences were further noted on most lower-order facets of NEO-PI-R, and nearly all KSP variables. A logistic regression analysis showed, however, that only neuroticism and extraversion remained significant independent predictors of patient/control group when controlling for the effects of the other Big Five dimensions. Also, only neuroticism and extraversion yielded large effect sizes when SAD patients were compared to Swedish normative data for the NEO-PI-R. A two-step cluster analysis resulted in three separate clusters labelled Prototypical (33%), Introvert-Conscientious (29%), and Instable-Open (38%) SAD. Individuals in the Prototypical cluster deviated most on the Big Five dimensions and they were at the most severe end in profile analyses of social anxiety, self-rated fear during public speaking, trait anxiety, and anxiety-related KSP variables. While additional studies are needed to determine if personality subtypes in SAD differ in etiological and treatment-related factors, the present results demonstrate considerable personality heterogeneity in socially anxious individuals, further underscoring that SAD is a multidimensional disorder.
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32.
  • Dagöö, Jesper, et al. (författare)
  • Cognitive behavior therapy versus interpersonal psychotherapy for social anxiety disorder delivered via smartphone and computer: A randomized controlled trial
  • 2014
  • Ingår i: Journal of Anxiety Disorders. - : Elsevier BV. - 1873-7897 .- 0887-6185. ; 28:4, s. 410-417
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, a previously evaluated guided Internet-based cognitive behavior therapy for social anxiety disorder (SAD) was adapted for mobile phone administration (mCBT). The treatment was compared with a guided self-help treatment based on interpersonal psychotherapy (mIPT). The treatment platform could be accessed through smartphones, tablet computers, and standard computers. A total of 52 participants were diagnosed with SAD and randomized to either mCBT (n = 27) or mIPT (n = 25). Measures were collected at pre-treatment, during the treatment, post-treatment and 3-month follow-up. On the primary outcome measure, the Liebowitz Social Anxiety Scale - self-rated, both groups showed statistically significant improvements. However, mCBT performed significantly better than mIPT (between group Cohen's d = 0.64 in favor of mCBT). A larger proportion of the mCBT group was classified as responders at post-treatment (55.6% versus 8.0% in the mIPT group). We conclude that CBT for SAD can be delivered using modern information technology. IPT delivered as a guided self-help treatment may be less effective in this format. (c) 2014 Elsevier Ltd. All rights reserved.
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33.
  • Danfors, Torsten, et al. (författare)
  • Increased neurokinin-1 receptor availability in temporal lobe epilepsy : A positron emission tomography study using [(11)C]GR205171
  • 2011
  • Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211 .- 1872-6844. ; 97:1-2, s. 183-189
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Activation of the neurokinin-1 (NK1) receptor by neuropeptide substance P (SP) induces and maintains epileptic activity in various experimental models of epilepsy. The primary objective of this study was to investigate whether neurobiological changes linked to NK1-SP receptor system are associated with hyperexcitability in patients with temporal lobe epilepsy (TLE). A secondary objective was to investigate the relationship between seizure frequency and NK1 receptor availability. METHODS: A positron emission tomography study was conducted with the selective NK1 receptor antagonist [(11)C]GR205171 in nine patients with TLE and 18 healthy control participants. Parametric PET images were generated using the Patlak graphical method, with cerebellum as reference region. Data analyses including group comparisons were performed using statistical parametric mapping. RESULTS: Patients with TLE showed increased NK1 receptor availability in both hemispheres with the most pronounced increase in anterior cingulate gyrus ipsilateral to seizure onset. A positive correlation between NK1 receptor availability and seizure frequency was observed in the medial temporal lobe and in the lentiform nucleus ipsilateral to the seizure onset. CONCLUSION: Our results suggest that there is an intrinsic network using the NK1-SP receptor system for synaptic transmission and epileptiform activity in TLE.
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34.
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35.
  • Engman, Jonas, et al. (författare)
  • Age, sex and NK1 receptors in the human brain : A positron emission tomography study with [C-11]GR205171
  • 2012
  • Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 22:8, s. 562-568
  • Tidskriftsartikel (refereegranskat)abstract
    • The substance P/neurokinin 1 (SP/NK1) system has been implicated in the processing of negative affect. Its role seems complex and findings from animal studies have not been easily translated to humans. Brain imaging studies on NK1 receptor distribution in humans have revealed an abundance of receptors in cortical, striatal and subcortical areas, including the amygdala. A reduction in NK1 receptors with increasing age has been reported in frontal, temporal, and parietal cortices, as well as in hippocampal areas. Also, a previous study suggests sex differences in cortical and subcortical areas, with women displaying fewer NK1 receptors. The present PET study explored NK1 receptor availability in men (n = 9) and women (n = 9) matched for age varying between 20 and 50 years using the highly specific NK1 receptor antagonist [11C]GR205171 and a reference tissue model with cerebellum as the reference region. Age by sex interactions in the amygdala and the temporal cortex reflected a lower NK1 receptor availability with increasing age in men, but not in women. A general age-related decline in NK1 receptor availability was evident in the frontal, temporal, and occipital cortices, as well as in the brainstem, caudate nucleus, and thalamus. Women had lower NK1 receptor availability in the thalamus. The observed pattern of NK1 receptor distribution in the brain might have functional significance for brain-related disorders showing age- and sex-related differences in prevalence.
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36.
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37.
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38.
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39.
  • Engman, Jonas, et al. (författare)
  • Neural Correlates of Anxiety States in Patients with Social Anxiety Disorder
  • 2011
  • Ingår i: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 69, s. 70S-70S
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • 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.
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40.
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41.
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42.
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43.
  • Fagernäs, Simon, et al. (författare)
  • Moderating effects of presence and adherence in internetbased CBT with virtual reality exposure therapy for public speaking anxiety
  • 2017
  • Konferensbidrag (refereegranskat)abstract
    • Introduction: Previous research has revealed that Virtual Reality Exposure Therapy (VRET) is an effective method for reducing symptoms of public speaking anxiety (PSA). Research about presence in the virtual environment indicates a moderating effect on physiological arousal, but more ambiguous effect on treatment effects where some research indicates a small effect while other indicate no effect. Furthermore, previous research has found adherence to home work assignments to moderate treatment outcome. In this treatment study which aimed for treating public speaking anxiety with VRET and a internetbased CBT-program, we investigated whether presence in the virtual environment and adherence to home work moderated treatment effects.Methods: N=25 adult participants from the general public with clinically significant PSA were recruited to a wait-list to another study. After five weeks on waitlist, they started the treatment with a self-guided in virtuo exposure session followed by a four week online maintenance promoting in-vivo exposure. Participants got a simple VR headset by post. The three-hour exposure session included psychoeducation in text, and the participants conducted speech exercises, framed as behavioral experiments targeting idiosyncratic catastrophic beliefs, in front of virtual audiences, and listening to audio recording afterwards. Primary outcome measure was self-reported PSA. To measure moderating effects of presence on the primary outcome measure a self-reported validated scale with subscales for presence (iGroup Presence Questionnaire, IPQ) were used, and for adherence a score were manually calculated based on the number of completed home-work assignments in both a linear model and a binary model dividing participants in two groups: one with at least one completed home work assignment and one with no completed home work assignment. The analysis on presence included both the effects of the VRET-session alone and in combination with the internetbased CBT-program. Data were analyzed using mixed effects modeling.Results: No significant results were found in moderating effects of presence with its subscales on the primary outcome measure for either the VRET-session (p = .375-.616) nor in combination with the internetbased CBT-program (p = .454 - .877). Moderating effects of adherence on primary outcome measure neither revealed no significant results in the linear model (p = .368) nor the binary model (p = .113).Conclusions: The findings of this study indicate, in line with some previous research, that presence in the virtual environment has no significant moderating effect on treatment outcome. Furthermore, in contrast to previous research, this study found no significant moderating effect on adherence to home work assignments on primary treatment outcome. Internal- and external validity and other potential explanations are discussed in detail in the poster.
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44.
  • Faria, Vanda, et al. (författare)
  • Amygdala-frontal couplings characterizing SSRI and placebo response in social anxiety disorder
  • 2014
  • Ingår i: International Journal of Neuropsychopharmacology. - : Oxford University Press. - 1461-1457 .- 1469-5111. ; 17:8, s. 1149-57
  • Tidskriftsartikel (refereegranskat)abstract
    • UNLABELLED: In patients with social anxiety disorder (SAD) it has been reported that selective serotonin reuptake inhibitors (SSRIs) and placebo induce anxiolytic effects by attenuating neural activity in overlapping amygdala subregions, i.e. left basolateral and right ventrolateral amygdala. However, it is not known whether these treatments inhibit amygdala subregions via similar or distinct brain pathways. As anxiolytic treatments may alter amygdala-frontal couplings we investigated differences and similarities in amygdala-frontal functional co-activation patterns between responders and nonresponders to SSRIs and placebo in patients with SAD. Positron emission tomography (PET) with oxygen-15-labeled water was used to measure anxiety-related regional cerebral blood flow in 72 patients with SAD before and after 6-8 wk of treatment under double-blind conditions. Functional couplings were evaluated with a seed region approach using voxel values from the left basolateral and right ventrolateral amygdala. Responders and nonresponders to SSRIs and placebo showed different treatment-induced co-activations between the left amygdala and the dorsolateral prefrontal cortex (dlPFC) as well as the rostral anterior cingulate cortex (ACC). Conjunction analysis suggested shared anxiolysis-dependent inverse co-activations in SSRI and placebo responders between the left amygdala-dlPFC and left amygdala-rostral ACC, and a shared positive co-activation between left amygdala-dorsal ACC. We demonstrate that amygdala-frontal co-activation patterns differentiate effective from ineffective anxiolytic treatments and that SSRI and placebo responders share overlapping neuromodulatory paths that may underlie improved emotion regulation and reduced expression of anxiety.TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00343707.
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45.
  • Faria, Vanda, et al. (författare)
  • Amygdala Subregions Tied to SSRI and Placebo Response in Patients with Social Anxiety Disorder
  • 2012
  • Ingår i: Neuropsychopharmacology. - : Nature Publishing Group. - 0893-133X .- 1740-634X. ; 37:10, s. 2222-2232
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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46.
  • Faria, Vanda, et al. (författare)
  • Differences in Amygdala Responsivity Between Responders and Nonresponders to SSRIs in Patients with Social Anxiety Disorder
  • 2011
  • Ingår i: Biol. Psychiatry 69, 70S-71S.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • 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.
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47.
  • Faria, Vanda, et al. (författare)
  • Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder : A Randomized Trial
  • 2017
  • Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 24, s. 179-188
  • Tidskriftsartikel (refereegranskat)abstract
    • 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 18 years 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(20 mg 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%; χ2(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.
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48.
  • Faria, Vanda, et al. (författare)
  • Imaging the placebo response : a neurofunctional review
  • 2008
  • Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 18:7, s. 473-485
  • Forskningsöversikt (refereegranskat)abstract
    • 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.
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49.
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50.
  • Faria, Vanda (författare)
  • Mind really does matter : The Neurobiology of Placebo-induced Anxiety Relief in Social Anxiety Disorder
  • 2012
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • 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.
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