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- Andersson, Evelyn, et al.
(author)
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Genetic Polymorphisms in Monoamine Systems and Outcome of Cognitive Behavior Therapy for Social Anxiety Disorder
- 2013
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11
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Journal article (peer-reviewed)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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4. |
- Andersson, Gerhard, et al.
(author)
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Internet-Delivered Treatments for Social Anxiety Disorder
- 2014
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In: The Wiley Blackwell Handbook of Social Anxiety Disorder. - Chichester, UK : John Wiley & Sons. - 9781119968603 - 9781118653920 ; , s. 579-587
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Book chapter (peer-reviewed)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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5. |
- Andersson, Gerhard, et al.
(author)
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Therapeutic alliance in guided internet-delivered cognitive behavioural treatment of depression, generalized anxiety disorder and social anxiety disorder
- 2012
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In: Behaviour Research and Therapy. - : Elsevier. - 0005-7967 .- 1873-622X. ; 50:9, s. 544-550
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Journal article (peer-reviewed)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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6. |
- Andersson, Gerhard, et al.
(author)
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Therapist experience and knowledge acquisition in internet-delivered CBT for social anxiety disorder : a randomized controlled trial
- 2012
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In: PLOS ONE. - : PLoS. - 1932-6203. ; 7:5, s. e37411-
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Journal article (peer-reviewed)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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7. |
- Bergman, Olle, 1978, et al.
(author)
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Association between amygdala reactivity and a dopamine transporter gene polymorphism.
- 2014
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In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 4
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Journal article (peer-reviewed)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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- Buhrman, Monica, 1974-, et al.
(author)
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Guided internet-delivered acceptance and commitment therapy for chronic pain patients: A randomized controlled trial
- 2013
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In: Behaviour Research and Therapy. - : Elsevier. - 0005-7967 .- 1873-622X. ; 51:6, s. 307-315
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Journal article (peer-reviewed)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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10. |
- Dagöö, Jesper, et al.
(author)
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Cognitive behavior therapy versus interpersonal psychotherapy for social anxiety disorder delivered via smartphone and computer: A randomized controlled trial
- 2014
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In: Journal of Anxiety Disorders. - : Elsevier BV. - 1873-7897 .- 0887-6185. ; 28:4, s. 410-417
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Journal article (peer-reviewed)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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11. |
- Danfors, Torsten, et al.
(author)
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Increased neurokinin-1 receptor availability in temporal lobe epilepsy : A positron emission tomography study using [(11)C]GR205171
- 2011
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In: Epilepsy Research. - : Elsevier BV. - 0920-1211 .- 1872-6844. ; 97:1-2, s. 183-189
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Journal article (peer-reviewed)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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- Engman, Jonas, et al.
(author)
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Age, sex and NK1 receptors in the human brain : A positron emission tomography study with [C-11]GR205171
- 2012
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In: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 22:8, s. 562-568
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Journal article (peer-reviewed)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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- Engman, Jonas, et al.
(author)
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Neural Correlates of Anxiety States in Patients with Social Anxiety Disorder
- 2011
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In: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 69, s. 70S-70S
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Journal article (other academic/artistic)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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- Faria, Vanda, et al.
(author)
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Amygdala-frontal couplings characterizing SSRI and placebo response in social anxiety disorder
- 2014
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In: International Journal of Neuropsychopharmacology. - : Oxford University Press. - 1461-1457 .- 1469-5111. ; 17:8, s. 1149-57
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Journal article (peer-reviewed)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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21. |
- Faria, Vanda, et al.
(author)
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Amygdala Subregions Tied to SSRI and Placebo Response in Patients with Social Anxiety Disorder
- 2012
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In: Neuropsychopharmacology. - : Nature Publishing Group. - 0893-133X .- 1740-634X. ; 37:10, s. 2222-2232
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Journal article (peer-reviewed)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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22. |
- Faria, Vanda, et al.
(author)
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Differences in Amygdala Responsivity Between Responders and Nonresponders to SSRIs in Patients with Social Anxiety Disorder
- 2011
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In: Biol. Psychiatry 69, 70S-71S.
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Conference paper (other academic/artistic)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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23. |
- Faria, Vanda
(author)
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Mind really does matter : The Neurobiology of Placebo-induced Anxiety Relief in Social Anxiety Disorder
- 2012
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Doctoral thesis (other academic/artistic)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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- Fredrikson, Mats, et al.
(author)
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Meta-Analytical Evidence for Segregating and Integrating Brain Activation to Symptom Provocation in Social Anxiety Disorder, Specific Phobia and Post Traumatic Stress Disorder
- 2011
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Conference paper (other academic/artistic)abstract
- Background: In PTSD increased amygdala activity is found in parallel to decreased anterior cingulate activity and this imbalance relate to symptomatology. Consistently, in healthy controls enhanced vmPFC activity suppress fear conditioning and enhance extinction similar to reappraisal studies where dPFC activation supports emotional down regulation through amygdala attenuation. It is not established if phobic disorders display a similar pattern and if treatment induced changes affect “top-down” and/or “bottom-up” mechanisms. Methods: Using a meta-analytical approach, we review brain-imaging studies using symptom provocation in patients with specific or social phobia as well as PTSD to evaluate reactivity in the ACC and the amygdala and its correlation to symptomatology. Further, amygdala ACC connectivity and the effect of CBT will be covered. Results: Functional brain imaging studies reveal increased amygdala reactivity that is correlated with symptomatology across the anxiety disorders. In phobic patients enhanced ACC responsivity is observed. The correlation between symptomatology and prefrontal brain activity is consistently negative and ACC related in PTSD while in phobic patients the relation is positive and encompass prefrontal areas outside the ACC, particularly in SAD. Connectivity patterns suggest couplings between amygdala and PFC, limited to ACC in PTSD but not in phobic disorders. Finally, CBT-treatment is associated both with increased and decreased activity in the ACC and other prefrontal areas. Conclusions: A tentative conclusion is that, even though the pattern of activity and connectivity both segregate and integrate different anxiety disorders, the ACC has a prominent role in coding and controlling affect.
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28. |
- Fredrikson, Mats, et al.
(author)
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Neurotransmission : A review of PET and SPECT studies in anxiety disorders
- 2014
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In: PET and SPECT in Psychiatry. - Berlin : Springer Berlin/Heidelberg. - 9783642403842 - 9783642403835 ; , s. 349-370
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Book chapter (peer-reviewed)abstract
- Neuroimaging studies using PET and SPECT to evaluate neurofunctional differences in the brain between patients with anxiety disorders and healthy controls were reviewed. At rest patients with social anxiety disorder display a reduced dopamine-D2 receptor binding potential. Post-traumatic stress disorder is associated with a compromised benzodiazepine receptor function. In panic disorder, both benzodiazepine receptors and serotonergic (5-hydroxytryptamine 1A; 5HT 1A) receptors are downregulated. Across the anxiety disorders there is downregulation of both benzodiazepine and 5HT 1A receptors. Symptom provocation studies, where regional cerebral blood fl ow is measured, support that activity in the brain’s fear circuit is altered with increased reactivity in the amygdala, the midbrain and possibly also the insula cortex, whereas activity in emotionregulating areas in the prefrontal cortex such as the subgenual anterior cingulate cortex and the orbitofrontal cortex is compromised in the symptomatic state, predominantly in phobic disorders. Some studies demonstrate a coupling between individual differences in neurotransmission and fear network activity. Treatment studies suggest that reductions of neural activity in the amygdala may be a fi nal common pathway for successful therapeutic interventions, thereby linking neurotransmission to plasticity in the core fear network of the brain.
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29. |
- Frick, Andreas, et al.
(author)
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Altered fusiform connectivity during processing of fearful faces in social anxiety disorder
- 2013
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In: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 3, s. e312-
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Journal article (peer-reviewed)abstract
- Social anxiety disorder (SAD) has been associated with hyper-reactivity in limbic brain regions like the amygdala, both during symptom provocation and emotional face processing tasks. In this functional magnetic resonance imaging study we sought to examine brain regions implicated in emotional face processing, and the connectivity between them, in patients with SAD (n=14) compared with healthy controls (n=12). We furthermore aimed to relate brain reactivity and connectivity to self-reported social anxiety symptom severity. SAD patients exhibited hyper-reactivity in the bilateral fusiform gyrus in response to fearful faces, as well as greater connectivity between the fusiform gyrus and amygdala, and decreased connectivity between the fusiform gyrus and ventromedial prefrontal cortex. Within the SAD group, social anxiety severity correlated positively with amygdala reactivity to emotional faces, amygdala-fusiform connectivity and connectivity between the amygdala and superior temporal sulcus (STS). These findings point to a pivotal role for the fusiform gyrus in SAD neuropathology, and further suggest that altered amygdala-fusiform and amygdala-STS connectivity could underlie previous findings of aberrant socio-emotional information processing in this anxiety disorder.
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- Frick, Andreas, et al.
(author)
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Classifying social anxiety disorder using multivoxel pattern analyses of brain function and structure
- 2014
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In: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 75:9, s. 358S-358S
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Journal article (peer-reviewed)abstract
- Functional neuroimaging of social anxiety disorder (SAD) support altered neural activation to threat-provoking stimuli focally in the fear network, while structural differences are distributed over the temporal and frontal cortices as well as limbic structures. Previous neuroimaging studies have investigated the brain at the voxel level using mass-univariate methods which do not enable detection of more complex patterns of activity and structural alterations that may separate SAD from healthy individuals. Support vector machine (SVM) is a supervised machine learning method that capitalizes on brain activation and structural patterns to classify individuals. The aim of this study was to investigate if it is possible to discriminate SAD patients (n = 14) from healthy controls (n = 12) using SVM based on (1) functional magnetic resonance imaging during fearful face processing and (2) regional gray matter volume. Whole brain and region of interest (fear network) SVM analyses were performed for both modalities. For functional scans, significant classifications were obtained both at whole brain level and when restricting the analysis to the fear network while gray matter SVM analyses correctly classified participants only when using the whole brain search volume. These results support that SAD is characterized by aberrant neural activation to affective stimuli in the fear network, while disorder-related alterations in regional gray matter volume are more diffusely distributed over the whole brain. SVM may thus be useful for identifying imaging biomarkers of SAD.
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32. |
- Frick, Andreas, et al.
(author)
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Cortical thickness alterations in social anxiety disorder
- 2013
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In: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 536, s. 52-55
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Journal article (peer-reviewed)abstract
- Social anxiety disorder (SAD) has been associated with aberrant processing of socio-emotional stimuli and failure to adaptively regulate emotion, corroborated by functional neuroimaging studies. However, only a few studies of structural brain abnormalities in SAD have been reported, and among these only one investigated cortical thickness. In the present study we used magnetic resonance imaging (MRI) in conjunction with an automated method to measure cortical thickness in patients with SAD (n=14) and healthy controls (n=12). Results showed significantly increased thickness of the left inferior temporal cortex in SAD patients relative to controls. Within the patient group, a negative association was found between social anxiety symptom severity and thickness of the right rostral anterior cingulate cortex. The observed alterations in brain structure may help explain previous findings of dysfunctional regulation and processing of emotion in SAD.
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33. |
- Frick, Andreas, et al.
(author)
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Enlargement of visual processing regions in social anxiety disorder is related to symptom severity
- 2014
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In: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 583, s. 114-119
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Journal article (peer-reviewed)abstract
- 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.
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41. |
- Furmark, Tomas, et al.
(author)
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Social fobi : ingen vanlig blyghet
- 2011
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In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 108:14, s. 802-805
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Journal article (peer-reviewed)
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42. |
- Furmark, Tomas, et al.
(author)
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Social fobi : ingen vanlig blyghet
- 2011
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In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 108:14, s. 802-805
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Research review (peer-reviewed)abstract
- Social fobi innebär att plågas av ångest iumgänget med andra eller vid framträdanden.Problemet kan vara mycket handikappande,och många drabbade får inteeffektiv behandling.
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43. |
- Hedman, Erik, et al.
(author)
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A 5-year follow-up of internet-based cognitive behavior therapy for Social Anxiety Disorder
- 2011
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In: Journal of Medical Internet Research. - : JMIR Publications Inc.. - 1438-8871. ; 13:2
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Journal article (peer-reviewed)abstract
- Background: Internet-basedcognitive behavior therapy (CBT) has been shown to be a promising method todisseminate cognitive behavior therapy for social anxiety disorder (SAD).Several trials have demonstrated that Internet-based CBT can be effective forSAD in the shorter term. However, the long-term effects of Internet-based CBTfor SAD are less well known. Objective: Our objectivewas to investigate the effect of Internet-based CBT for SAD 5 years aftercompleted treatment. Method: We conducted a 5-yearfollow-up study of 80 persons with SAD who had undergone Internet-based CBT.The assessment comprised a diagnostic interview and self-report questionnaires.The main outcome measure was the Liebowitz Social Anxiety Scale-Self-Report (LSAS-SR). Additional measures of social anxiety were the Social InteractionAnxiety Scale (SIAS) and the Social Phobia Scale (SPS). Attrition rates werelow: 89% (71/80) of the participants completed the diagnostic interview and 80% (64/80) responded to the questionnaires. Results: Mixed-effect models analysisshowed a significant effect of time on the three social anxiety measures,LSAS-SR, SIAS, and SPS (F3,98-102 = 16.05 -29.20, P < .001)indicating improvement. From baseline to 5-year follow-up, participants’ meanscores on the LSAS-SR were reduced from 71.3 (95% confidence interval [CI]66.1-76.5) to 40.3 (95% CI 35.2 - 45.3). The effect sizes of the LSAS-SR were large (Cohen’s d range 1.30 - 1.40, 95% CI 0.77 - 1.90). Improvementsgained at the 1-year follow-up were sustained 5 years after completedtreatment. Conclusions: Internet-basedCBT for SAD is a treatment that can result in large and enduring effects. Trial registration: Clinicaltrials.govNCT01145690; http://clinicaltrials.gov/ct2/show/NCT01145690 (Archived byWebCite athttp://www.webcitation.org/5ygRxDLfK)
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44. |
- Hedman, E., et al.
(author)
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Internet administration of self-report measures commonly used in research on social anxiety disorder : a psychometric evaluation
- 2010
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In: Computers in human behavior. - : Elsevier BV. - 0747-5632 .- 1873-7692. ; 26:4, s. 736-740
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Journal article (peer-reviewed)abstract
- The Internet has become increasingly popular as a way to administer self-report questionnaires, especially in the field of Internet delivered psychological treatments. Collecting questionnaire data over the Internet has advantages, such as ease of administration, and automated scoring. However, psychometric properties cannot be assumed to be identical to the paper-and-pencil versions. The aim of this study was to test the equivalence of paper-and-pencil and Internet administered versions of self-report questionnaires used in social phobia research. We analyzed data from two trials in which samples were recruited in a similar manner. One sample (N = 64) completed the paper-and-pencil version of questionnaires and the second sample (N = 57) completed the same measures online. We included the Liebowitz Social Anxiety Scale-self-assessment (LSAS-SR), the Social Interaction and Anxiety Scale (SIAS), and the Social Phobia Scale (SPS) as measures of social anxiety. Also included were the Montgomery sberg Depression Rating Scale-self-assessment (MADRS-S), the Beck Anxiety Inventory (BAI), and the Quality of Life Inventory (QOLI). Results showed equivalent psychometric properties across administration formats. Cronbach's α ranged between 0.77 and 0.94. There was an indication of a somewhat higher construct validity when participants filled out questionnaires using paper-and-pencil. We conclude that the LSAS-SR, SIAS, and SPS can be administered via the Internet with maintained psychometric properties.
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45. |
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46. |
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47. |
- Jonasson, My, et al.
(author)
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Validation of parametric methods for [(11)C]PE2I positron emission tomography
- 2013
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In: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 74, s. 172-178
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Journal article (peer-reviewed)abstract
- OBJECTIVESThe radioligand [(11)C]PE2I is highly selective for dopamine transporter (DAT) and can be used in vivo for investigation of changes in DAT concentration, progression of disease and validation of treatment using positron emission tomography (PET). DAT is an important protein for regulation of central dopamine concentration and DAT deficiency has been associated with several neurodegenerative and neuropsychiatric disorders. Accurate parametric images are a prerequisite for clinical application of [(11)C]PE2I. The purpose of this study was to evaluate different methods for producing [(11)C]PE2I parametric images, showing binding potential (BPND) and relative delivery (R1) at the voxel level, using clinical data as well as simulations.METHODSInvestigations were made in twelve subjects either with social anxiety disorder (n=6) or parkinsonian syndrome (n=6), each receiving an 80min dynamic PET scan. All subjects underwent a T1-weighted MRI scan which was co-registered to the PET images and used for definition of regions of interest using a probabilistic template (PVElab). Two basis function implementations (receptor parametric mapping: RPM, RPM2) of the simplified reference tissue model (SRTM) and three multilinear reference tissue models (MRTMo, MRTM and MRTM2) were used for computation of parametric BPND and R1 images. In addition, reference Logan and standard uptake value ratio (SUVr) were investigated. Evaluations of BPND and R1 images were performed using linear regression to compare the parametric methods to region-based analyses with SRTM and cerebellar gray matter as reference region. Accuracy and precision of each method were assessed by simulations.RESULTSCorrelation and slope of linear regression between parametric and region-based BPND and R1 values in both striatum and extra-striatal regions were optimal for RPM (R(2)=0.99 for both BPND and R1; slopes 0.99 and 0.98 for BPND and R1, respectively, in striatum). In addition, accuracy and precision were best for RPM and RPM2.CONCLUSIONThe basis function methods provided more robust estimations of the parameters compared to the other models and performed best in simulations. RPM, a basis function implementation of SRTM, is the preferred method for voxel level analysis of [(11)C]PE2I PET studies.
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48. |
- Laukka, Petri, et al.
(author)
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Neurofunctional correlates of expressed vocal affect in social phobia
- 2011
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In: Cognitive, Affective, & Behavioral Neuroscience. - : Springer Science and Business Media LLC. - 1530-7026 .- 1531-135X. ; 11:3, s. 413-425
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Journal article (peer-reviewed)abstract
- We investigated the neural correlates of expressed vocal affect in patients with social phobia. A group of 36 patients performed an anxiogenic public-speaking task while regional cerebral blood flow (rCBF) was assessed using oxygen-15 positron emission tomography. The patients’ speech was recorded and content masked using low-pass filtering (which obscures linguistic content but preserves nonverbal affective cues). The content-masked speech samples were then evaluated with regard to their level of vocally expressed nervousness. We hypothesized that activity in prefrontal and subcortical brain areas previously implicated in emotion regulation would be associated with the degree of expressed vocal affect. Regression analyses accordingly revealed significant negative correlations between expressed vocal affect and rCBF in inferior frontal gyrus, putamen, and hippocampus. Further, functional connectivity was revealed between inferior frontal gyrus and (a) anterior cingulate cortex and (b) amygdala and basal ganglia. We suggest that brain areas important for emotion regulation may also form part of a network associated with the modulation of affective prosody in social phobia.
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49. |
- Linnman, Clas, et al.
(author)
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Ventromedial prefrontal neurokinin 1 receptor availability is reduced in chronic pain
- 2010
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In: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 149:1, s. 64-70
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Journal article (peer-reviewed)abstract
- Neurokinin 1 (NK1) receptors are involved in pain and anxiety behaviors in animals, but little is known about central alterations in this receptor system in human pain. With positron emission tomography, using a [11]-Carbon labeled NK1 receptor antagonist, we demonstrate attenuated NK1 receptor availability in frontal, insular and cingulate cortex, as well as the hippocampus, amygdala and the periaqueductal gray area in patients with chronic pain. The reduced availability was most pronounced in the ventromedial prefrontal cortex (vmPFC), where attenuations correlated to measures of fear and avoidance of movement. Further, vmPFC NK1 levels also displayed opposing influences in patients as compared to controls on regional cerebral blood flow in the anterior cingulate. We conclude that the central NK1 receptor system is altered in human chronic pain. The results suggest that NK1 receptors in the vmPFC modulate motor inhibition, and contribute to fear and avoidance of movement.
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50. |
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