| 1. |
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| 2. |
- Bas-Hoogendam, Janna Marie, et al.
(författare)
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Voxel-based morphometry multi-center mega-analysis of brain structure in social anxiety disorder
- 2017
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Ingår i: NeuroImage. - : Elsevier BV. - 2213-1582. ; 16, s. 678-688
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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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| 3. |
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| 4. |
- Björkstrand, Johannes, et al.
(författare)
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Disrupting Reconsolidation Attenuates Long-Term Fear Memory in the Human Amygdala and Facilitates Approach Behavior
- 2016
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 26:19, s. 2690-95
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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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| 5. |
- Björkstrand, Johannes, et al.
(författare)
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Disruption of Memory Reconsolidation Erases a Fear Memory Trace in the Human Amygdala : An 18-Month Follow-Up.
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7, s. e0129393-
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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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| 6. |
- Björkstrand, Johannes, et al.
(författare)
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Think twice, it's all right : Long lasting effects of disrupted reconsolidation on brain and behavior in human long-term fear
- 2017
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 324, s. 125-129
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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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| 7. |
- Fagernäs, Simon, et al.
(författare)
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Moderating effects of presence and adherence in internetbased CBT with virtual reality exposure therapy for public speaking anxiety
- 2017
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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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| 8. |
- Faria, Vanda, et al.
(författare)
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Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder : A Randomized Trial
- 2017
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 24, s. 179-188
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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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| 9. |
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| 10. |
- Frick, Andreas, et al.
(författare)
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Anterior cingulate cortex activity as a candidate biomarker for treatment selection in social anxiety disorder
- 2018
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Ingår i: BJPsych Open. - : Royal College of Psychiatrists. - 2056-4724. ; 4:3
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to identify biomarkers to guide the decision to add selective serotonin reuptake inhibitors (SSRI) to psychological treatment for social anxiety disorder (SAD). Forty-eight patients with SAD underwent functional magnetic resonance imaging and collection of clinical and demographic variables before treatment with cognitive-behavioural therapy, combined on a double-blind basis with either escitalopram or placebo for 9 weeks. Pre-treatment neural reactivity to aversive faces in the dorsal anterior cingulate cortex (ACC), but not clinical/demographic variables, moderated clinical outcomes. Cross-validated individual-level predictions accurately identified 81% of responders/non-responders. Dorsal ACC reactivity is thus a potential bio-marker for SAD treatment selection.
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| 11. |
- Frick, Andreas
(författare)
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Imaging Anxiety : Neurochemistry in Anxiety Disorders Assessed by Positron Emission Tomography
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Anxiety disorders, including social anxiety disorder (SAD) and posttraumatic stress disorder (PTSD) are common and disabling conditions. Largely based on animal and pharmacological studies, both the serotonergic and substance P/neurokinin-1 (SP/NK1) systems have been implicated in their underlying pathology. However, only few neuroimaging studies have directly assessed these neurotransmitter systems in human sufferers of anxiety disorders, and none have addressed possible between-systems relationships.The overall aim of this thesis was to study possible neurochemical alterations associated with anxiety disorders. To this end, three studies using positron emission tomography (PET) for in-vivo imaging of the brain serotonergic and SP/NK1 systems in patients with SAD and PTSD were conducted. The radiotracers [11C]5-HTP, [11C]DASB, and [11C]GR205171 were used to index serotonin synthesis rate, serotonin transporter (SERT) availability, and NK1 receptor availability respectively.In Study I, patients with SAD relative to controls exhibited enhanced serotonin synthesis rate and serotonin transporter availability. Serotonin synthesis rate in the amygdala was positively related to social anxiety symptom scores. Study II demonstrated increased NK1 receptor availability in the amygdala in patients with SAD relative to controls. In Study III, patients with PTSD showed elevated NK1 receptor availability in the amygdala as compared to controls. SERT availability in the amygdala was negatively related to PTSD symptom severity, a relationship that was moderated by NK1 receptor levels. The regional overlap between SERT and NK1 receptor expression was altered in patients with PTSD, with reduced overlap linked to more severe symptoms.Collectively, the findings are consistent with the view that serotonin in the amygdala induces rather than reduces anxiety and links exaggerated anxiety to an overactive presynaptic serotonin system. In addition, the involvement of the SP/NK1 system in stress and anxiety, as suggested by animal studies, was demonstrated in two common human anxiety disorders. Finally, PTSD symptomatology is better accounted for by interactions between the serotonergic and SP/NK1 systems in the amygdala than by each system separately. In conclusion, this thesis supports that both the serotonergic and SP/NK1 systems in and of themselves, but also interactively, may be important contributors to anxiety symptomatology.
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| 12. |
- Frick, Andreas, et al.
(författare)
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Increased neurokinin-1 receptor availability in the amygdala in social anxiety disorder : a positron emission tomography study with [11C]GR205171
- 2015
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- The neurokinin-1 (NK1) receptor is abundantly expressed in the fear circuitry of the brain, including the amygdala, where it modulates stress and anxiety. Despite its proposed involvement in psychopathology, only a few studies of NK1 receptor availability in human subjects with anxiety disorders exist. Here, we compared NK1 receptor availability in patients with social anxiety disorder (SAD; n = 17) and healthy controls (n = 17) using positron emission tomography and the radiotracer [11C]GR205171. The Patlak Graphical plot using a cerebellar reference region was used to model the influx parameter, Ki measuring NK1 receptor availability. Voxel-wise statistical parametric mapping analyses revealed increased NK1 receptor availability specifically in the right amygdala in SAD patients relative to controls. Thus, we demonstrate that exaggerated social anxiety is related to enhanced NK1 receptor availability in the amygdala. This finding supports the contribution of NK1 receptors not only in animal models of stress and anxiety but also in humans with anxiety disorders.
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| 13. |
- Frick, Andreas, et al.
(författare)
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Overlapping expression of serotonin transporters and neurokinin-1 receptors in posttraumatic stress disorder : a multi-tracer PET study
- 2016
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 21:10, s. 1400-7
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Tidskriftsartikel (refereegranskat)abstract
- The brain serotonergic system is colocalized and interacts with the neuropeptidergic substance P/neurokinin-1 (SP/NK1) system. Both these neurochemical systems have independently been implicated in stress and anxiety, but interactions between them might be crucial for human anxiety conditions. Here, we examined the serotonin and substance P/neurokinin-1 (SP/NK1) systems individually as well as their overlapping expression in 16 patients with posttraumatic stress disorder (PTSD) and 16 healthy controls. Participants were imaged with the highly selective radiotracers [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB) and [(11)C]GR205171 assessing serotonin transporter (SERT) and NK1 receptor availability, respectively. Voxel-wise analyses in the amygdala, our a priori-defined region of interest, revealed increased number of NK1 receptors, but not SERT in the PTSD group. Symptom severity, as indexed by the Clinician-administered PTSD Scale, was negatively related to SERT availability in the amygdala, and NK1 receptor levels moderated this relationship. Exploratory, voxel-wise whole-brain analyses revealed increased SERT availability in the precentral gyrus and posterior cingulate cortex of PTSD patients. Patients, relative to controls, displayed lower degree of overlapping expression between SERT and NK1 receptors in the putamen, thalamus, insula and lateral orbitofrontal gyrus, lower overlap being associated with higher PTSD symptom severity. Expression overlap also explained more of the symptomatology than did either system individually, underscoring the importance of taking interactions between the neurochemical systems into account. Thus, our results suggest that aberrant serotonergic-SP/NK1 couplings contribute to the pathophysiology of PTSD and, consequently, that normalization of these couplings may be therapeutically important.
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| 14. |
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| 15. |
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| 16. |
- Frick, Andreas, et al.
(författare)
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Reduced serotonin synthesis and regional cerebral blood flow after anxiolytic treatment of social anxiety disorder
- 2016
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Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 26:11, s. 1775-1783
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Social anxiety disorder (SAD) is associated with increased fear-related neural activity in the amygdala and we recently found enhanced serotonin synthesis rate in the same region. Anxiolytic agents like selective serotonin re-uptake inhibitors (SSRIs) and neurokinin-1 receptor (NK1R) antagonists reduce amygdala activity and may attenuate serotonin formation according to animal studies. Here, we examined the effects of SSRI pharmacotherapy, NK1R antagonism, and placebo on serotonin synthesis rate in relation to neural activity, measured as regional cerebral blood flow (rCBF), and symptom improvement in SAD. Eighteen SAD patients were randomized to receive daily double-blind treatment for six weeks either with the SSRI citalopram (n=6; 40 mg), the NK1R antagonist GR205171 (n=6; 5 mg; 4 weeks following 2 weeks of placebo), or placebo (n=6). Serotonin synthesis rate at rest and rCBF during stressful public speaking were assessed, before and after treatment, using positron emission tomography with the tracers [11C]5-hydroxytryptophan and [15O]water respectively. The Liebowitz Social Anxiety Scale (LSAS-SR) indexed symptom severity. All groups exhibited attenuated amygdala serotonin synthesis rate after treatment, which was associated with reduced amygdala rCBF during public speaking and accompanied by symptom improvement. These results are consistent with the notion that serotonin in the amygdala exerts an anxiogenic influence and, conversely, that anxiolysis is achieved through decreased serotonin formation in the amygdala.
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| 17. |
- Frick, Andreas, et al.
(författare)
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Serotonin Synthesis and Reuptake in Social Anxiety Disorder : A Positron Emission Tomography Study.
- 2015
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Ingår i: JAMA psychiatry. - : American Medical Association. - 2168-6238 .- 2168-622X. ; 72:8, s. 794-802
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Serotonin is involved in negative affect, but whether anxiety syndromes, such as social anxiety disorder (SAD), are characterized by an overactive or underactive serotonin system has not been established. Serotonin 1A autoreceptors, which inhibit serotonin synthesis and release, are downregulated in SAD, and serotonin transporter availability might be increased; however, presynaptic serotonin activity has not been evaluated extensively.OBJECTIVE: To examine the serotonin synthesis rate and serotonin transporter availability in patients with SAD and healthy control individuals using positron emission tomography (PET) with the radioligands 5-hydroxytryptophan labeled with carbon 11 ([11C]5-HTP) and 11C-labeled 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile [11C]DASB.DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional study at an academic clinical research center. Eighteen patients with SAD (9 men and 9 women; mean [SD] age, 32.6 [8.2] years) and 18 sex- and age-matched healthy controls (9 men and 9 women; mean [SD] age, 34.7 [9.2] years) underwent [11C]5-HTP PET imaging. We acquired [11C]DASB PET images for 26 additional patients with SAD (14 men and 12 women; mean [SD] age, 35.2 [10.7] years) and the same 18 sex- and age-matched healthy controls. Participants were recruited through newspaper advertisements. Data were acquired from March 12, 2002, through March 5, 2012, and analyzed from March 28, 2013, through August 29, 2014.MAIN OUTCOMES AND MEASURES: The influx rate of [11C]5-HTP as a measure of serotonin synthesis rate capacity and [11C]DASB binding potential as an index of serotonin transporter availability were acquired during rest. We used the Liebowitz Social Anxiety Scale to measure severity of social anxiety symptoms.RESULTS: The PET data were not available for analysis in 1 control for each scan. Increased [11C]5-HTP influx rate was observed in the amygdala, raphe nuclei region, caudate nucleus, putamen, hippocampus, and anterior cingulate cortex of patients with SAD compared with healthy controls (P < .05 corrected), supporting an enhanced serotonin synthesis rate. Increased serotonin transporter availability in the patients with SAD relative to healthy controls was reflected by elevated [11C]DASB binding potential in the raphe nuclei region, caudate nucleus, putamen, thalamus, and insula cortex (P < .05 corrected).CONCLUSIONS AND RELEVANCE: Neurotransmission in SAD is characterized by an overactive presynaptic serotonin system, with increased serotonin synthesis and transporter availability. Our findings could provide important new insights into the etiology of anxiety disorders.
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| 18. |
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| 19. |
- Furmark, Tomas, et al.
(författare)
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Serotonin synthesis rate and the tryptophan hydroxylase-2: G-703T polymorphism in social anxiety disorder
- 2016
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Ingår i: Journal of Psychopharmacology. - London, United Kingdom : SAGE Publications. - 0269-8811 .- 1461-7285. ; 30:10, s. 1028-1035
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Tidskriftsartikel (refereegranskat)abstract
- It is disputed whether anxiety disorders, like social anxiety disorder, are characterized by serotonin over- or underactivity. Here, we evaluated whether our recent finding of elevated neural serotonin synthesis rate in patients with social anxiety disorder could be reproduced in a separate cohort, and whether allelic variation in the tryptophan hydroxylase-2 (TPH2) G-703T polymorphism relates to differences in serotonin synthesis assessed with positron emission tomography. Eighteen social anxiety disorder patients and six healthy controls were scanned during 60 minutes in a resting state using positron emission tomography and 5-hydroxy-L-[ -C-11]tryptophan, [C-11]5-HTP, a substrate of the second enzymatic step in serotonin synthesis. Parametric images were generated, using the reference Patlak method, and analysed using Statistical Parametric Mapping (SPM8). Blood samples for genotyping of the TPH2 G-703T polymorphism were obtained from 16 social anxiety disorder patients (T carriers: n=5, GG carriers: n=11). A significantly elevated [C-11]5-HTP accumulation rate, indicative of enhanced decarboxylase activity and thereby serotonin synthesis capacity, was detected in social anxiety disorder patients compared with controls in the hippocampus and basal ganglia nuclei and, at a more lenient (uncorrected) statistical threshold, in the amygdala and anterior cingulate cortex. In patients, the serotonin synthesis rate in the amygdala and anterior cingulate cortex was significantly elevated in TPH2 T carriers in comparison with GG homozygotes. Our results support that social anxiety disorder entails an overactive presynaptic serotonergic system that, in turn, seems functionally influenced by the TPH2 G-703T polymorphism in emotionally relevant brain regions.
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| 20. |
- Furmark, Tomas, et al.
(författare)
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Social fobi - social ångest : effektiv hjälp med KBT
- 2019. - 3
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Social fobi (social ångest) är en stark rädsla för situationer där man känner sig värderad eller granskad av andra. Bokens självhjälpsprogram baseras på KBT och är vetenskapligt utprövat med mycket goda resultat. Programmet omfattar nio steg med både teoretisk kunskap och praktiska övningar.Den tredje omarbetade upplagan innehåller flera nyheter: Ett kunskapstest - Testa dig själv - har lagts till efter varje kapitel (med facit på Libers webbplats). Flera avsnitt har utvidgats och uppdaterats, bland annat med ett nytt avsnitt om forskningsläget kring självhjälpsbehandling där hjärnavbildningsstudier styrker behandlingens effekt.Boken vänder sig till personer som lider av social fobi och deras anhöriga. Den vänder sig också till psykologer, psykiater, psykoterapeuter och andra professionella som arbetar med problematiken, samt till studerande på psykolog- och psykoterapiutbildningar.
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| 21. |
- Gingnell, Malin, et al.
(författare)
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Combining escitalopram and cognitive–behavioural therapy for social anxiety disorder : randomised controlled fMRI trial
- 2016
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Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 209:3, s. 229-235
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSelective serotonin reuptake inhibitors (SSRIs) and cognitive–behavioural therapy (CBT) are often used concomitantly to treat social anxiety disorder (SAD), but few studies have examined the effect of this combination.AimsTo evaluate whether adding escitalopram to internet-delivered CBT (ICBT) improves clinical outcome and alters brain reactivity and connectivity in SAD.MethodDouble-blind, randomised, placebo-controlled neuroimaging trial of ICBT combined either with escitalopram (n = 24) or placebo (n = 24), including a 15-month clinical follow-up (trial registration: ISRCTN24929928).ResultsEscitalopram+ICBT, relative to placebo+ICBT, resulted in significantly more clinical responders, larger reductions in anticipatory speech state anxiety at post-treatment and larger reductions in social anxiety symptom severity at 15-month follow-up and at a trend-level (P = 0.09) at post-treatment. Right amygdala reactivity to emotional faces also decreased more in the escitalopram+ICBT combination relative to placebo+ICBT, and in treatment responders relative to non-responders.ConclusionsAdding escitalopram improves the outcome of ICBT for SAD and decreased amygdala reactivity is important for anxiolytic treatment response.
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| 22. |
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| 23. |
- Hassler Hallstedt, Martin, 1973-
(författare)
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Closing the Gap : How an Adaptive Behavioral Based Program on a Tablet Can Help Low Performing Children Catch Up in Math: a Randomized Placebo Controlled Study
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Early mathematic skills have a substantial impact on later school achievement. Children with poor school achievement are at risk for adverse consequences later in life. Math competencies also have consequences for the economy at large because societies are becoming increasingly dependent on skill sets including mathematics. Proficiency with basic arithmetic, also known as math fact (i.e., 3+8, 12-3), is considered to be a critical early math skill. Intervention research in mathematics have demonstrated that math fact deficits among students with low math performance can be improved with additional targeted, non- technological interventions (i.e., small-group tutoring).The aim of the present thesis was to investigate the effect, using a randomized placebo controlled design, of addititional adaptive, behavioral based, math training on a tablet on low performing second graders. The first study (study I), investigated if arithmetic skills could be assessed in a reliable and valid way on tablet. The examination showed that arithmetic scales could be transferred from paper-based tests to tablet with comparable psychometric properties, although not for a pictorial scale, and that separate norms are needed for tablet. Study II demonstrated that training on a tablet, for on average 19 hours across 20 weeks, improved basic arithmetic skills after training in the math conditions compared to control/ placebo conditions. The effects were medium sized at post assessment. There was a fadeout of effects at 6 months follow-up, where small effects were shown, and the effects decreased further at 12 months follow-up. Children with lower non-verbal IQ seemed to gain significantly more at follow- ups than children with higher non-verbal IQ. The study found no additional effects of combining working memory training and math training. Study III, using a machine learning analysis, found that children demonstrating a positive response at 6 months follow-up were characterized by having completed 90 % or more of the math program at the default level, in combination with having a fairly favorable socioeconomic background.In summation, this work demonstrates how an adaptive behavioral based program on a tablet can help low performing children improve critical early math skills.
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| 24. |
- Jonasson, My, et al.
(författare)
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Development of a clinically feasible [11C]PE2I PET method for differential diagnosis of parkinsonism using reduced scan duration and automated reference region extraction.
- 2017
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Ingår i: American Journal of Nuclear Medicine and Molecular Imaging. - 2160-8407. ; 7:6, s. 263-274
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Tidskriftsartikel (refereegranskat)abstract
- [11C]PE2I is a highly selective dopamine transporter PET ligand. Parametric images based on dynamic [11C]PE2I scans, showing dopamine transporter availability (BPND) and relative cerebral blood flow (R1), can be used in differential diagnosis of parkinsonism. This work aimed to investigate a shortened scan duration and automated generation of parametric images which are two prerequisites for routine clinical application. Twelve subjects with parkinsonism and seventeen healthy controls underwent 80 min dynamic [11C]PE2I PET scans. BPND and R1 images were generated using cerebellum reference region defined on a co-registered MRI, as well as a supervised cluster analysis (SVCA)-based reference. Initial 20, 30 and 40 min of the scans were extracted and images of standardized uptake value ratio (SUVR) and R1 were computed using MRI- and SVCA-based reference. Correlation was high between striatal 80 min MRI-based BPND and 40 min SVCA-based SUVR-1 (R2=0.95). High correlation was also found between R1 values in striatal and limbic regions (R2≥0.91) whereas correlation was moderate for cortical regions (R2=0.71). The results indicate that dynamic [11C]PE2I scans can be restricted to 40 min and that SVCA can be used for automatic extraction of a reference region. These outcomes will support routine applications of [11C]PE2I PET in clinical settings.
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| 25. |
- Kraus, Jakub, et al.
(författare)
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Amygdala reactivity and connectivity during social and non-social aversive stimulation in social anxiety disorder
- 2018
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Ingår i: Psychiatry Research. - : Elsevier BV. - 0925-4927 .- 1872-7506. ; 280, s. 56-61
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Tidskriftsartikel (refereegranskat)abstract
- Social anxiety disorder (SAD) is characterized by exaggerated amygdala reactivity in response to symptom provocation, but it is unclear if such hyper-reactivity is elicited by disorder-specific challenges only or characterizes reactions to aversive stimuli in general. Here, using functional magnetic resonance imaging in 14 patients with SAD, as compared to 12 healthy controls, we found that amygdala hyper-reactivity is confined to disorder-relevant social stimulation. SAD patients displayed increased amygdala reactivity to fearful as compared to neutral facial pictures, but not in response to generally aversive but mainly non-social stimulation when compared to neutral pictorial stimuli taken from the International Affective Picture System. The increased amygdala reactivity was not mediated by an altered prefrontal inhibition among SAD patients as compared to controls, suggesting increased bottom-up processes rather than attenuated top-down control. In conclusion, the enhanced amygdala reactivity in SAD seems specific to socially relevant stimuli rather than aversive stimuli in general.
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| 26. |
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| 27. |
- Lindner, Philip, et al.
(författare)
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Differential impact of performance and interaction related types of social anxiety symptoms on different quality of life domains
- 2016
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Ingår i: EABCT 2016 Abstract Book. ; , s. 748-748
-
Konferensbidrag (refereegranskat)abstract
- Social anxiety disorder (SAD) is a common disorder associated with impaired quality of life (QoL), that indexes anxious distress and avoidance related to social situations. The DSM-5 features a specifier to delineate those with only performance-related social anxiety, yet little is known whether performance- and interaction-related anxieties have a differential impact on total QoL and on different QoL domains. To investigate this, we pooled screening data from eight intervention studies for SAD (n = 2017). Total sample mean age was 35.28 (SD = 12.26) and 69% were female. SAD symptoms were measured using the self-rated Liebowitz Social Anxiety Scale with items classified as measuring either performance or interaction anxiety. QoL, both total and across four domains, was measured using the Quality of Life Inventory. Data was analyzed using multiple regression models featuring the two anxiety scores as predictors, and by simulating the Performance-only specifier through 2˙2 median-split subgrouping and standard ANOVAs. Both interaction and performance anxieties were independently associated with lower QoL in general and across domains. Interaction anxiety had a larger negative impact on Personal Growth- and Achievement-related QoL than performance anxiety. The High-Performance/Low-Interaction-group rated higher Achievement-related QoL compared to the Low-Performance/High-Interaction-group (p = .012), yet groups were matched on total QoL and on other domains. Other group differences were in the expected direction.QoL impairments in SAD is primarily driven by number of feared social situations, and only secondarily by types of fear social situations, with interaction anxiety having a larger, negative impact on some QoL domains.
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| 28. |
- Lindner, Philip, et al.
(författare)
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Therapist-led and at-home one-session Virtual Reality exposure therapy for public speaking anxiety using consumer hardware and software, with online maintenance : A randomized controlled trial
- 2017
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Konferensbidrag (refereegranskat)abstract
- Introduction: Exposure therapy is an effective treatment of public speaking anxiety (PSA), yet inherent logistic challenges prevent widespread dissemination. Previous research has revealed that Virtual Reality (VR) may be effectively used for realistic stimuli presentation, but past generations of VR hardware have been inaccessible and expensive. We reasoned that VR stimuli, delivered using modern consumer hardware and software, would enable one-session treatment of PSA, both in the form of traditional therapist-led treatment and as an internet intervention.Methods: N=50 adult participants from the general public with clinically significant PSA were recruited and randomized to either therapist-led one-session treatment followed by online maintenance promoting in-vivo exposure, or waiting-list. The three-hour exposure session included psychoeducation and had participants conducting 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 selfreported PSA, assessed using a validated instrument, measured before and after the treatment session, weekly during the four-week maintenance period, and at the end. After the first phase of the study, the waiting-list group received a simple VR headset by post and were given access to an online version of the same treatment (including the maintenance program), conducted their own one-session treatment followed by the same maintenance program, and reported PSA using the same intervals as before. Data were analyzed using mixed effects modeling.Results: A significant time*group effect was found such that the treatment group reported a 6.92-point larger decrease in PSA symptoms per treatment step than the waiting-list, corresponding to a between-group d=0.84 after the one-session treatment, growing to d=1.56 after the maintenance period. Piece-wise modeling of the waiting-list group’s PSA scores before and after they received their at-home equivalent treatment revealed a 6.39-point difference in decrease (per step) after receiving treatment compared to before, corresponding to a within-group d=1.22 after the at-home one-session treatment, growing to d=1.78 after the maintenance period.Conclusions: This trial demonstrates that simple, consumer VR hardware and software can be used to treat PSA using a one-session format, with large effect sizes. To our knowledge, this is the first study to evaluate the potential of internet-administered, at-home VR treatment, the results of which are promising.
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| 29. |
- Lindner, Philip, et al.
(författare)
-
Therapist-led and self-led one-session Virtual Reality exposure therapy for public speaking anxiety with consumer hardware and software : A randomized controlled trial
- 2018
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Public speaking anxiety (PSA) is a common condition which can be treated effectively with exposure therapy. However, inherent difficulties in stimuli presentation and control limits dissemination and the therapeutic potential. Virtual Reality (VR) technology has the potential to resolve these issues and provide a scalable platform for self-help interventions. No previous study has examined whether this can be achieved using the first generation of consumer VR hardware and software. In the current trial, n=25+25 participants were randomized to either one-session VR exposure therapy for PSA followed by a four-week internet-administered VR to in-vivo transition program, or a waiting-list. Linear mixed effects modeling revealed significant, large (within Cohen’s d=1.67) decreases in self-reported PSA. The waiting-list was then given access to an internet-administered, self-led version of the same VR exposure therapy to be conducted at home, followed by the same transition program. Dual-slope mixed effects modeling revealed significant, large (d=1.35) decreases in self-reported PSA. Results were maintained or improved at the six-month follow-up. We show for the first time that low-cost, off-the-shelf consumer VR hardware and software can be used to conduct exposure therapy for PSA, both in the traditional, previously unpractical one-session format, and in a novel self-led, at-home format.
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| 30. |
- Lindner, Philip, et al.
(författare)
-
Therapist-led and self-led one-session virtual reality exposure therapy for public speaking anxiety with consumer hardware and software : A randomized controlled trial
- 2019
-
Ingår i: Journal of Anxiety Disorders. - : Elsevier BV. - 0887-6185 .- 1873-7897. ; 61, s. 45-54
-
Tidskriftsartikel (refereegranskat)abstract
- Public speaking anxiety (PSA) is a common condition which can be treated effectively with exposure therapy. However, inherent difficulties in stimuli presentation and control limits dissemination and the therapeutic potential. Virtual Reality (VR) technology has the potential to resolve these issues and provide a scalable platform for self-help interventions. No previous study has examined whether this can be achieved using the first generation of consumer VR hardware and software. In the current trial, n = 25 + 25 participants were randomized to either one-session therapist-led VR exposure therapy for PSA followed by a four-week internet-administered VR to in-vivo transition program, or a waiting-list. Linear mixed effects modeling revealed significant, large (within Cohen’s d = 1.67) decreases in self-reported PSA. The waiting-list was then given access to an internet-administered, self-led version of the same VR exposure therapy to be conducted at home, followed by the same transition program. Dual-slope mixed effects modeling revealed significant, large (d = 1.35) decreases in self-reported PSA. Results were maintained or improved at six- and twelve-month follow-ups. We show for the first time that low-cost, off-the-shelf consumer VR hardware and software can be used to conduct exposure therapy for PSA, both in the traditional, previously impractical one-session format, and in a novel self-led, at-home format.
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| 31. |
- Linnman, Clas, et al.
(författare)
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Decreased Brain Neurokinin-1 Receptor Availability in Chronic Tennis Elbow
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Substance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1) receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions between central and peripheral tissue alterations. Ten subjects with chronic tennis elbow (lateral epicondylosis) were selected out of a larger (n = 120) randomized controlled trial evaluating graded exercise as a treatment for chronic tennis elbow (lateral epicondylosis). These ten subjects were examined by positron emission tomography (PET) with the NK1-specific radioligand 11C-GR205171 before, and eight patients were followed up after treatment with graded exercise. Brain binding in the ten patients before treatment, reflecting NK1-receptor availability (NK1-RA), was compared to that of 18 healthy subjects and, longitudinally, to the eight of the original ten patients that agreed to a second PET examination after treatment. Before treatment, patients had significantly lower NK1-RA in the insula, vmPFC, postcentral gyrus, anterior cingulate, caudate, putamen, amygdala and the midbrain but not the thalamus and cerebellum, with the largest difference in the insula contralateral to the injured elbow. No significant correlations between brain NK1-RA and pain, functional severity, or peripheral NK1-RA in the affected limb were observed. In the eight patients examined after treatment, pain ratings decreased in everyone, but there were no significant changes in NK1-RA. These findings indicate a role for the substance P (SP) / NK1 receptor system in musculoskeletal pain and tissue healing. As neither clinical parameters nor successful treatment response was reflected in brain NK1-RA after treatment, this may reflect the diverse function of the SP/NK1 system in CNS and peripheral tissue, or a change too small or slow to capture over the three-month treatment.
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| 32. |
- Ma, Lichen, et al.
(författare)
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Attentional bias modification in virtual reality
- 2017
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Konferensbidrag (refereegranskat)abstract
- Introduction: It has been theorised that attentional biases (sensitivity and hypervigilance towards threat-related information) may play a causal role in the aetiology and maintenance of dysfunctional anxiety. Attentional bias modification (ABM) aims to directly modify the underlying attentional biases implicated in anxiety disorders, and consequently reduce anxiety symptoms.We conducted two studies that examined the effectiveness of ABM training programs in reducing attentional bias and anxiety. Both programs were delivered via virtual reality (VR) technology. Study 1 utilised a traditional dot-probe ABM, and Study 2 utilised a Person Identity Match (PIM) ABM. In addition to the comparison of two different ABM programs, the studies also investigated whether the use of 3 dimensional stimuli has an impact on the outcome of the ABM training.Methods:Study 1One hundred participants with elevated anxiety scores (LSAS > 30) were randomly assigned to 4 groups:1. ABM with 2D stimuli (n = 25)2. Mock-ABM with 2D stimuli (n = 25)3. ABM with 3D stimuli (n = 25)4. Mock-ABM with 3D stimuli (n = 25)The participants first completed questionnaires that measured their anxiety and other factors of interest. After which the participants completed 100 trials of a dot-probe task to measure their pre-training attentional bias. The participants then completed 360 trials of ABM training. Following ABM, the participants carried out post-training bias measurement and anxiety measurement. Finally, the participants answered follow-up questionnaires 1 week and 3months after the ABM training.Study 2Study 2 shares the exact same design as Study 1, but utilised a different version of ABMtraining.Results: Data analysis is currently ongoing and results are pending. The change in attentional bias and anxiety are the primary outcome measures. Both within-group comparisons (pre-training vs. post-training) and between-group comparisons (ABM vs. mock; 2D vs 3D; Dot-probe vs. PIM) will be carried out. Some preliminary results will be presented at the conference.Conclusions: Pending
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| 33. |
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| 34. |
- Motilla Hoppe, Johanna, et al.
(författare)
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Association between amygdala neurokinin-1 receptor availability and anxiety-related personality traits
- 2018
-
Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Animal studies indicate that substance P (SP) and its preferred neurokinin-1 (NK1) receptor modulate stress and anxiety-related behavior. Alterations in the SP-NK1 system have also been observed in human anxiety disorders, yet little is known about the relation between this system and individual differences in personality traits associated with anxiety propensity and approach-avoidance behavior, including trait anxiety, neuroticism, and extraversion. Exploring this relation could provide important insights into the neurobiological underpinnings of human anxiety and the etiology of anxiety disorders, as anxious traits are associated with increased susceptibility to develop psychopathological conditions. Here we examined the relationship between central NK1 receptor availability and selfrated measures of trait anxiety, neuroticism, and extraversion. The amygdala was chosen as the primary region of interest since this structure has been suggested to mediate the effect of the SP-NK1 system on anxiety. Anxious traits and NK1 receptor availability, determined with positron emission tomography and the radiotracer [C-11]GR205171, were measured in 17 healthy individuals. Voxel-wise analyses showed a significant positive correlation between bilateral amygdala NK1 receptor availability and trait anxiety, and a trend in similar direction was observed for neuroticism. Conversely, extraversion was found to be negatively associated with amygdala NK1 receptor availability. Extraversion also correlated negatively with the NK1 measure in the cuneus/precuneus and fusiform gyrus according to exploratory whole-brain analyses. In conclusion, our findings indicate that amygdala NK1 receptor availability is associated with anxiety-related personality traits in healthy subjects, consistent with a modulatory role for the SP-NK1 system in human anxiety.
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| 35. |
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| 36. |
- Månsson, Kristoffer, et al.
(författare)
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Affective Brain Signal Variability Separates Social Anxiety Disorder Patients From Healthy Individuals
- 2018
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 83:9, s. S249-S250
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Amygdala hyper-responsiveness to negative socio-affective stimuli have typically been demonstrated in patients with social anxiety disorder (SAD). Relative to conventional methods, there is emerging evidence that brain signal variability could be a better predictor of behavior than mean neural response.Methods: We recruited 46 patients with SAD (mean age 31, 63% females) and 40 matched healthy controls (HC) to undergo 3 Tesla functional magnetic resonance imaging (fMRI) at 2 time-points, totaling 172 MRIsessions. Blood-oxygen level-dependent (BOLD-fMRI) was performed while viewing happy and fearful faces in blocks of 80 seconds. BOLD-fMRI data was reviewed by manually classifying signal from noise. Variability was calculated as each voxel’s standard deviation on signal across scanning-time. Multivariate partial least squares (PLS) estimated patterns of variability that separates patient from controls.Results: PLS found one significant latent variable with cross-block covariance on 64%, permutated (x 1000) P<0.001, bootstrapped 95% confidence intervals on each condition, demonstrating less signal variability to happy faces in patients, relative to controls. This pattern of response was spatially located in several regions across the whole-brain, with large clusters appearing in bilateral amygdala, medial prefrontal cortex and posterior cingulate cortex/precuneus.Conclusions: We found that neural response variability to positive socio-affective stimuli accurately separated patients from controls. It is likely that less signal variability highlights a deficit in effective emotion processing. We add to the growing literature on healthy individuals suggesting that task-specific brain signal variability contains useful information. The brain signal variability approach opens new avenues to evaluate and better understand brain function in common psychopathology.
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| 37. |
- Månsson, Kristoffer, et al.
(författare)
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Brain Before Behavior : Temporal Dynamics in the Treatment of Social Anxiety - Neural Changes Occur Early and Precede Clinical Improvement
- 2018
-
Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 83:9, s. S130-S131
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: The brain rapidly responds to affective processing and neural responsivity can separate anxiety disorder patients from healthy individuals. Psychiatric treatment also alters brain responsiveness however, the brain’s temporal dynamics during treatment remain unknown. Here, patients with social anxiety disorder (SAD) were treated with cognitive-behavioral therapy (CBT) and functional magnetic resonance imaging (fMRI) assessments were performed before, during and after intervention.Methods: Forty-six SAD patients received a 9-week Internet-delivered CBTand symptoms were assessed weekly using the Liebowitz social anxiety scale (LSAS-SR). MRI was acquired at 4 time-points (2 baselines, mid- and post-treatment). Blood-oxygen level-dependent(BOLD-fMRI) was performed while patients viewed negative facial expressions. BOLD-fMRI data was reviewed manually by classifying signal from noise, all subjects contributing with complete data.Results: Patients improved slightly from baseline to mid-treatment (P<.001, Cohen’s d=0.34) on the LSAS-SR, but more so from mid- to post-treatment (P<.001, d=1.46). Whole-brain neural responsivity decreased from baseline to post-treatment (False Discovery Rate, FDR P<.005) in the medial prefrontal cortex, precuneus and amygdala/parahippocampus. However, no changes (FDR P>.05) from mid- to post-treatment were found, suggesting that the early alterations accounted for the effect. Furthermore, early response reductions were positively associated with symptom improvement from pre-post treatment (Pearson’s r=.50, P<.001).Conclusions: This is, to our knowledge, the first study assessing early and late psychiatric treatment changes in the brain. Interestingly, altered neural responsivity in limbic and default-mode network regions preceded self-reported alleviation of social anxiety. Understanding the brain’s temporal dynamics and subsequent modification of behavior may be highly important for future clinical neuroimaging research.
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| 38. |
- Månsson, Kristoffer, et al.
(författare)
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Brain Signal Variability and Indices of Cellular Protection Predicts Social Anxiety Disorder Treatment Outcome
- 2019
-
Ingår i: Proceedings of the 9th World Congress of Behavioural & Cognitive Therapies. - Tübingen : dgvt-Verlag. - 9783871598517 ; , s. 158-158
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We are currently lacking clinically useful predictors of treatment response in common psychiatric disorders. Non-invasive and increasingly accessible neuroimaging techniques like functional magnetic resonance imaging (fMRI) could be a useful tool. In contrast to the conventional approach investigating the brain’s average responses, the brain’s signal variability could be a better estimate of the brain’s dynamic operations (Garrett et al., 2010, 2015). In addition, telomere attrition is a hallmark of cellular aging and shorter telomeres have been reported in mood and anxiety disorders. Telomere shortening is counteracted by the enzyme telomerase and cellular protection is also provided by the antioxidant enzyme glutathione peroxidase (GPx). Here, we investigate if baseline BOLD-fMRI signal variability, and indices of cellular protection, predicts social anxiety disorder patient’s response to internet-delivered cognitive behavior therapy. Forty-six patients with social anxiety disorder (SAD) were scanned twice with a 3 Tesla fMRI before initiating CBT. Treatment outcome was assessed the Liebowitz Social Anxiety Scale (self-report). 1) BOLD-fMRI acquisition was performed while passively viewing emotional faces flashing on the screen for 80 seconds. Raw BOLD-fMRI data was implemented in an Independent Component Analysis in order to manually denoise images by carefully remove noise from neural signal. Across time, each voxel’s standard deviation was calculated and used as an index of variability. Multivariate partial least squares regression models were used for second level analysis. 2) Telomerase activity and telomere length were measured in peripheral blood mononuclear cells and GPx activity in plasma. Significant latent level brain scores, and baseline analytes were implemented in linear regressions with LSAS-SR change score as the outcome. Results will be presented and discussed.
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| 39. |
- Månsson, Kristoffer, et al.
(författare)
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Can Psychological Treatment Slow Down Cellular Aging in Social Anxiety Disorder? : An Intervention Study Evaluating Changes in Telomere Length and Telomerase Activity
- 2018
-
Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 83:9, s. S351-S352
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Mental illness, including anxiety disorders, is linked to accelerated cell aging. This is evidenced by shorter leukocyte telomere length. Cells with critically short telomeres may undergo apoptosis. In dividing cells, telomere shortening is counteracted by the telomeraseenzyme. Telomerase is reportedly low following chronic psychological stress. We hypothesized that a psychological treatment may increase telomerase activity, less telomere attritionand greater symptom improvement.Methods: Forty-six patients (91% SSRI naïve) with social anxiety disorder(SAD; mean age 31, 63% females) underwent a 9-week waiting period, and 9 weeks of Internet-delivered cognitive behavior therapy(CBT). During treatment, symptoms were assessed weekly using the Liebowitz Social Anxiety Scale (LSAS-SR). Fasting blood samples were collected twice before treatment, and at post-treatment. Genomic DNA was extracted using DNeasy® Blood & Tissue Kit (Qiagene) to assess leukocyte telomere length. Telomerase activity was detected by real-time telomeric repeat amplification protocol (RT-TRAP).Results: Patients improved significantly on the LSAS-SR (p<.001; Cohen’s d=1.5). Pre-post changes in telomerase and telomere length correlated positively (Pearson’s r=.31, p=.05). Reduced telomerase activity (<33th percentile) was associated with less improvement and increased activity (>66th percentile) with more improvement on the LSAS-SR (Z=-2.4, p=.02).Conclusions: We demonstrate, to our knowledge for the first time, that altered telomerase activity is associated with clinical response to a psychological treatment in a psychiatric population. The observed CBT effect on telomerase in patients with SAD is consistent with results from animal trials and a small previous study of antidepressants in humans. Thus, telomerase activation may play an important role in clinical recovery.
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| 40. |
- Månsson, Kristoffer N. T., et al.
(författare)
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Improvement in indices of cellular protection after psychological treatment for social anxiety disorder
- 2019
-
Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- Telomere attrition is a hallmark of cellular aging and shorter telomeres have been reported in mood and anxiety disorders. Telomere shortening is counteracted by the enzyme telomerase and cellular protection is also provided by the antioxidant enzyme glutathione peroxidase (GPx). Here, telomerase, GPx, and telomeres were investigated in 46 social anxiety disorder (SAD) patients in a within-subject design with repeated measures before and after cognitive behavioral therapy. Treatment outcome was assessed by the Liebowitz Social Anxiety Scale (self-report), administered three times before treatment to control for time and regression artifacts, and posttreatment. Venipunctures were performed twice before treatment, separated by 9 weeks, and once posttreatment. Telomerase activity and telomere length were measured in peripheral blood mononuclear cells and GPx activity in plasma. All patients contributed with complete data. Results showed that social anxiety symptom severity was significantly reduced from pretreatment to posttreatment (Cohen’s d = 1.46). There were no significant alterations in telomeres or cellular protection markers before treatment onset. Telomere length and telomerase activity did not change significantly after treatment, but an increase in telomerase over treatment was associated with reduced social anxiety. Also, lower pretreatment telomerase activity predicted subsequent symptom improvement. GPx activity increased significantly during treatment, and increases were significantly associated with symptom improvement. The relationships between symptom improvement and putative protective enzymes remained significant also after controlling for body mass index, sex, duration of SAD, smoking, concurrent psychotropic medication, and the proportion of lymphocytes to monocytes. Thus, indices of cellular protection may be involved in the therapeutic mechanisms of psychological treatment for anxiety.
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| 41. |
- Månsson, Kristoffer N T, et al.
(författare)
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Neuroplasticity in response to cognitive behavior therapy for social anxiety disorder
- 2016
-
Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with anxiety disorders exhibit excessive neural reactivity in the amygdala, which can be normalized by effective treatment like cognitive behavior therapy (CBT). Mechanisms underlying the brain’s adaptation to anxiolytic treatments are likely related both to structural plasticity and functional response alterations, but multimodal neuroimaging studies addressing structure–function interactions are currently missing. Here, we examined treatment-related changes in brain structure (gray matter (GM) volume) and function (blood–oxygen level dependent, BOLD response to self-referential criticism) in 26 participants with social anxiety disorder randomly assigned either to CBT or an attention bias modification control treatment. Also, 26 matched healthy controls were included. Significant time × treatment interactions were found in the amygdala with decreases both in GM volume (family-wise error (FWE) corrected PFWE=0.02) and BOLD responsivity (PFWE=0.01) after successful CBT. Before treatment, amygdala GM volume correlated positively with anticipatory speech anxiety (PFWE=0.04), and CBT-induced reduction of amygdala GM volume (pre–post) correlated positively with reduced anticipatory anxiety after treatment (PFWE0.05). In addition, we observed greater amygdala neural responsivity to self-referential criticism in socially anxious participants, as compared with controls (PFWE=0.029), before but not after CBT. Further analysis indicated that diminished amygdala GM volume mediated the relationship between decreased neural responsivity and reduced social anxiety after treatment (P=0.007). Thus, our results suggest that improvement-related structural plasticity impacts neural responsiveness within the amygdala, which could be essential for achieving anxiety reduction with CBT.
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| 42. |
- Månsson, Kristoffer N T, et al.
(författare)
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Predicting long-term outcome of Internet-delivered cognitive behavior therapy for social anxiety disorder using fMRI and support vector machine learning
- 2015
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Cognitive behavior therapy (CBT) is an effective treatment for social anxiety disorder (SAD), but many patients do not respond sufficiently and a substantial proportion relapse after treatment has ended. Predicting an individual’s long-term clinical response therefore remains an important challenge. This study aimed at assessing neural predictors of long-term treatment outcome in participants with SAD 1 year after completion of Internet-delivered CBT (iCBT). Twenty-six participants diagnosed with SAD underwent iCBT including attention bias modification for a total of 13 weeks. Support vector machines (SVMs), a supervised pattern recognition method allowing predictions at the individual level, were trained to separate long-term treatment responders from nonresponders based on blood oxygen level-dependent (BOLD) responses to self-referential criticism. The Clinical Global Impression-Improvement scale was the main instrument to determine treatment response at the 1-year follow-up. Results showed that the proportion of long-term responders was 52%(12/23). From multivariate BOLD responses in the dorsal anterior cingulate cortex (dACC) together with the amygdala, we were able to predict long-term response rate of iCBT with an accuracy of 92% (confidence interval 95% 73.2–97.6). This activation pattern was, however, not predictive of improvement in the continuous Liebowitz Social Anxiety Scale—Self-report version. Follow-up psychophysiological interaction analyses revealed that lower dACC–amygdala coupling was associated with better long-term treatment response. Thus, BOLD response patterns in the fear-expressing dACC–amygdala regions were highly predictive of long-term treatment outcome of iCBT, and the initial coupling between these regions differentiated long-term responders from nonresponders. The SVM-neuroimaging approach could be of particular clinical value as it allows for accurate prediction of treatment outcome at the level of the individual.
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| 43. |
- Månsson, Kristoffer N. T.
(författare)
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Restructuring the socially anxious brain : Using magnetic resonance imaging to advance our understanding of effective cognitive behaviour therapy for social anxiety disorder
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Social anxiety disorder (SAD) is a common psychiatric disorder associated with considerable suffering. Cognitive behaviour therapy (CBT) has been shown to be effective but a significant proportion does not respond or relapses, stressing the need of augmenting treatment. Using neuroimaging could elucidate the psychological and neurobiological interaction and may help to improve current therapeutics. To address this issue, functional and structural magnetic resonance imaging (MRI) were repeatedly conducted on individuals with SAD randomised to receive CBT or an active control condition. MRI was performed pre-, and post-treatment, as well as at one-year follow-up. Matched healthy controls were also scanned to be able to evaluate disorder-specific neural responsivity and structural morphology. This thesis aimed at answering three major questions. I) Does the brain’s fear circuitry (e.g., the amygdala) change, with regard to neural response and structural morphology, immediately after CBT? II) Are the immediate changes in the brain still present at long-term follow-up? III) Can neural responsivity in the fear circuitry predict long-term treatment outcome at the level of the individual? Thus, different analytic methods were performed. Firstly, multimodal neuroimaging addressed questions on concomitant changes in neural response and grey matter volume. Secondly, two different experimental functional MRI tasks captured both neural response to emotional faces and self-referential criticism. Thirdly, support vector machine learning (SVM) was used to evaluate neural predictors at the level of the individual.Amygdala responsivity to self-referential criticism was found to be elevated in individuals with SAD, as compared to matched healthy controls, and the neural response was attenuated after effective CBT. In individuals with SAD, amygdala grey matter volume was positively correlated with symptoms of anticipatory speech anxiety, and CBT-induced symptom reduction was associated with decreased grey matter volume of the amygdala. Also, CBT-induced reduction of amygdala grey matter volume was evident both at short- and long-term follow-up. In contrast, the amygdala neural response was weakened immediately after treatment, but not at one-year follow-up. In extension to treatment effects on the brain, pre-treatment connectivity between the amygdala and the dorsal anterior cingulate cortex (dACC) was stronger in long-term CBT non-responders, as compared to long-term CBT responders. Importantly, by use of an SVM algorithm, pre-treatment neural response to self-referential criticism in the dACC accurately predicted (>90%) the clinical response to CBT.In conclusion, modifying the amygdala is a likely mechanism of action in CBT, underlying the anxiolytic effects of this treatment, and the brain’s neural activity during self-referential criticism may be an accurate and clinically relevant predictor of the long-term response to CBT. Along these lines, neuroimaging is a vital tool in clinical psychiatry that could potentially improve clinical decision-making based on an individual’s neural characteristics.
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| 44. |
- Månsson, Kristoffer N.T., et al.
(författare)
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Structural but not functional neuroplasticity one year after effective cognitive behaviour therapy for social anxiety disorder
- 2017
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 318, s. 45-51
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Tidskriftsartikel (refereegranskat)abstract
- Effective psychiatric treatments ameliorate excessive anxiety and induce neuroplasticity immediately after the intervention, indicating that emotional components in the human brain are rapidly adapTable Still, the interplay between structural and functional neuroplasticity is poorly understood, and studies of treatment-induced long-term neuroplasticity are rare. Functional and structural magnetic resonance imaging (using 3 T MRI) was performed in 13 subjects with social anxiety disorder on 3 occasions over 1 year. All subjects underwent 9 weeks of Internet-delivered cognitive behaviour therapy in a randomized cross-over design and independent assessors used the Clinically Global Impression-Improvement (CGI-I) scale to determine treatment response. Gray matter (GM) volume, assessed with voxel-based morphometry, and functional blood-oxygen level-dependent (BOLD) responsivity to self-referential criticism were compared between treatment responders and non-responders using 2 × 2 (group × time; pretreatment to follow-up) ANOVA. At 1-year follow-up, 7 (54%) subjects were classified as CGI-I responders. Left amygdala GM volume was more reduced in responders relative to non-responders from pretreatment to 1-year follow-up (Z = 3.67, Family-Wise Error corrected p = 0.02). In contrast to previous short-term effects, altered BOLD activations to self-referential criticism did not separate responder groups at follow-up. The structure and function of the amygdala changes immediately after effective psychological treatment of social anxiety disorder, but only reduced amygdala GM volume, and not functional activity, is associated with a clinical response 1 year after CBT.
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| 45. |
- Mörtberg, Ewa, et al.
(författare)
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Factor solutions of the Social Phobia Scale (SPS) and the Social Interaction Anxiety Scale (SIAS) in a Swedish population
- 2017
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Ingår i: Cognitive Behaviour Therapy. - Oxon, United Kingdom : Routledge. - 1650-6073 .- 1651-2316. ; 46:4, s. 300-314
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Tidskriftsartikel (refereegranskat)abstract
- Culturally validated rating scales for social anxiety disorder (SAD) are of significant importance when screening for the disorder, as well as for evaluating treatment efficacy. This study examined construct validity and additional psychometric properties of two commonly used scales, the Social Phobia Scale and the Social Interaction Anxiety Scale, in a clinical SAD population (n = 180) and in a normal population (n = 614) in Sweden. Confirmatory factor analyses of previously reported factor solutions were tested but did not reveal acceptable fit. Exploratory factor analyses (EFA) of the joint structure of the scales in the total population yielded a two-factor model (performance anxiety and social interaction anxiety), whereas EFA in the clinical sample revealed a three-factor solution, a social interaction anxiety factor and two performance anxiety factors. The SPS and SIAS showed good to excellent internal consistency, and discriminated well between patients with SAD and a normal population sample. Both scales showed good convergent validity with an established measure of SAD, whereas the discriminant validity of symptoms of social anxiety and depression could not be confirmed. The optimal cut-off score for SPS and SIAS were 18 and 22 points, respectively. It is concluded that the factor structure and the additional psychometric properties of SPS and SIAS support the use of the scales for assessment in a Swedish population.
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| 46. |
- Olofsdotter, Susanne
(författare)
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Anxiety among Adolescents : Measurement, Clinical Characteristics, and Influences of Parenting and Genetics
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Anxiety is the most commonly reported mental health problem among adolescents. Still, many adolescents in need of treatment are not detected and the clinical characteristics and etiological pathways of adolescent anxiety are under-researched topics. This thesis examined the clinical utility of the Swedish versions of the Spence Children’s Anxiety Scale (SCAS) and the clinical characteristics of multiple anxiety disorders among psychiatrically referred adolescents, and the influence of parenting and oxytocin gene (OXT) variants on anxiety among adolescents in the general population. Studies employed cross-sectional and longitudinal designs and were based on questionnaire, interview, and genotype data.Support for the reliability and validity of both SCAS and SCAS-P was obtained. The overall ability to predict anxiety among referred adolescents ranged from fair to excellent for both scales. Among adolescents psychiatrically referred for any reason, the prevalence of any anxiety disorder was 46%. Homotypic comorbidity was observed in 43%, and heterotypic comorbidity in 91%.Early adolescent anxiety influenced homotypic anxiety in late adolescence independent of parental rejection and control. The mediating role of parenting was small with indirect effect sizes no larger than one-tenth the size of direct effects, irrespective of the informant on parenting behavior.Significant interaction effects with positive and negative parenting were observed for OXT variants rs4813625 and rs2770378 in relation to social anxiety. The nature of the interactions was in line with the differential susceptibility framework for rs4813625, whereas for rs2770378, results indicated a diathesis–stress type of interaction.The findings suggest that psychiatrically referred adolescents with anxiety disorders are best characterized as a highly complex patient group and call attention to the necessity of structured assessment. For this purpose, this thesis provides evidence for the clinical utility of the SCAS; routine utilization of this questionnaire can improve detection of adolescents in need of anxiety treatment. Findings of this theses further suggest that the influence of positive and negative parenting behaviors on anxiety may be of greater importance among some adolescents than others, depending on individual differences in sensitivity to parenting. The etiology of anxiety among adolescents may therefore involve differential susceptibility effects of the interplay between genes and parenting behaviors.
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| 47. |
- Olofsdotter, Susanne, et al.
(författare)
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Anxiety disorders among adolescents referred to general psychiatry for multiple causes : clinical presentation, prevalence, and comorbidity
- 2016
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Ingår i: Scandinavian Journal of Child and Adolescent Psychiatry and Psychology. - : Walter de Gruyter GmbH. - 2245-8875. ; 4:2, s. 55-64
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reports of anxiety disorder characteristics among youth in clinical settings typically include descriptions of patients who have been specifically referred for anxiety treatment. At odds with a large body of evidence which demonstrates these disorders to be most common among young people, prevalence studies in samples referred to general psychiatry for multiple causes are scarce and report highly discrepant estimates.Methods: For this study and regardless of their presenting symptoms, 125 adolescents (57.6% girls) between the ages of 12 and 18 years who were consecutively referred to two child and adolescent general psychiatry clinics in Sweden were assessed for anxiety disorders and comorbidity using the Schedule for Affective Disorders and Schizophrenia for School-Age Children. Self-ratings of anxiety symptoms and difficulties with family, school, friends, sleep, and body aches were also obtained.Results: At least one anxiety disorder was found in 46% of participants. Among anxious adolescents, homotypic comorbidity (concurrent anxiety) was observed in 43%, and heterotypic comorbidity (concurrent non-anxiety psychiatric disorders) was observed in 91%. No comorbidity was observed in 5%. Trauma, ache, and difficulties making friends were more common among anxious adolescents as compared with psychiatrically referred adolescents without anxiety.Conclusions: The finding that only 21% of adolescents diagnosed with anxiety disorders were referred for anxiety further supports the routine use of standardized and structured instruments—irrespective of referral cause—to improve both precision and detection rates in the clinical setting. Comprehensive assessments are of utmost importance to fully address the complexity of the symptoms in this patient group.
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| 48. |
- Olofsdotter, Susanne, et al.
(författare)
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Assessing Adolescent Anxiety in General Psychiatric Care : Diagnostic Accuracy of the Swedish Self-Report and Parent Versions of the Spence Children's Anxiety Scale
- 2016
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Ingår i: Assessment (Odessa, Fla.). - : SAGE Publications. - 1073-1911 .- 1552-3489. ; 23:6, s. 744-757
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Tidskriftsartikel (refereegranskat)abstract
- This study examined the psychometric properties and diagnostic accuracy of the Swedish translations of the Spence Children's Anxiety Scale, self- and parent report versions, in a sample of 104 adolescents presenting at two general psychiatric outpatient units. Results showed high informant agreement and good internal reliability and concurrent and discriminant validity for both versions and demonstrated that this scale can distinguish between adolescents with and without an anxiety disorder in a non-anxiety-specific clinical setting. The relative clinical utility of different cutoff scores was compared by looking at the extent to which dichotomized questionnaire results altered the pretest probability of the presence of a diagnosis as defined by the Schedule for Affective Disorders and Schizophrenia for School-Age Children. Optimized for screening and diagnostic purposes in Sweden, cutoff scores obtained in the current study outperformed a previously identified cutoff score derived from an Australian community sample. The Spence Children's Anxiety Scale is a useful clinical instrument for the assessment of anxiety in adolescents.
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| 49. |
- Olofsdotter, Susanne, et al.
(författare)
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Differential susceptibility effects of oxytocin gene (OXT) polymorphisms and perceived parenting on social anxiety among adolescents
- 2018
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Ingår i: Development and psychopathology (Print). - : CAMBRIDGE UNIV PRESS. - 0954-5794 .- 1469-2198. ; 30:2, s. 449-459
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Tidskriftsartikel (refereegranskat)abstract
- Social anxiety is one of the most commonly reported mental health problems among adolescents, and it has been suggested that parenting style influences an adolescent's level of anxiety. A context-dependent effect of oxytocin on human social behavior has been proposed; however, research on the oxytocin gene (OXT) has mostly been reported without considering contextual factors. This study investigated the interactions between parenting style and polymorphic variations in the OXT gene in association with social anxiety symptoms in a community sample of adolescents (n = 1,359). Two single nucleotide polymorphisms linked to OXT, rs4813625 and rs2770378, were genotyped. Social anxiety and perceived parenting style were assessed by behavioral questionnaires. In interaction models adjusted for sex, significant interaction effects with parenting style were observed for both variants in relation to social anxiety. The nature of the interactions was in line with the differential susceptibility framework for rs4813625, whereas for rs2770378 the results indicated a diathesis–stress type of interaction. The findings may be interpreted from the perspective of the social salience hypothesis of oxytocin, with rs4813625 affecting social anxiety levels along a perceived unsafe–safe social context dimension.
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| 50. |
- Olofsdotter, Susanne, et al.
(författare)
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Interaction between oxytocin gene variants and perceived parenting in relation to social anxiety in adolescents : Evidence for differential susceptibility effects
- 2017
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Ingår i: European psychiatry. - : Cambridge University Press (CUP). - 0924-9338 .- 1778-3585. ; 41, s. S72-S72
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Adolescence is a period of increasing demands in independent social functioning where parenting style may have an impact on social anxiety. A context-dependent effect of oxytocin on human social behavior has been suggested, however research on the gene coding for oxytocin (OXT) has mostly been reported without considering contextual factors.AimThis study investigated interactions between parenting style and polymorphic variations in the OXT gene in association with social anxiety symptoms in a community sample of adolescents.MethodsThe study group consisted of 1359 adolescents. Two single nucleotide polymorphisms located near OXT, rs4813625 and rs2770378, were genotyped. Social anxiety and perceived parenting style were assessed by behavioral questionnaires.ResultsSignificant joint effects in line with the differential susceptibility framework were observed for rs4813625 with parenting style. The levels of social anxiety among C allele carriers were conditional on the level of supportive parenting style whereas homozygote G carriers’ levels of social anxiety were unaffected by supportive parenting style. The nature of the interactions between rs2770378 and parenting style was in line with the diatheses-stress model. However, associations of rs2770378 and parenting style with social anxiety became nonsignificant in nonlinear models.ConclusionsThe study provides preliminary evidence for a modifying effect of supportive parenting style on the relationship between rs4813625 and social anxiety symptoms in adolescents, independent of sex. The findings may be interpreted from the perspective of the social salience hypotheses of oxytocin, with rs4813625 affecting social anxiety levels along a perceived unsafe–safe social context dimension.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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