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| 2. |
- Bas-Hoogendam, Janna Marie, et al.
(author)
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Voxel-based morphometry multi-center mega-analysis of brain structure in social anxiety disorder
- 2017
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In: NeuroImage. - : Elsevier BV. - 2213-1582. ; 16, s. 678-688
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Journal article (peer-reviewed)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. |
- Månsson, Kristoffer N T, et al.
(author)
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Altered neural correlates of affective processing after internet-delivered cognitive behavior therapy for social anxiety disorder
- 2013
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In: Psychiatry Research. - : Elsevier BV. - 0925-4927 .- 1872-7506 .- 0165-1781 .- 1872-7123. ; 214:3, s. 229-237
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Journal article (peer-reviewed)abstract
- Randomized controlled trials have yielded promising results for internet-delivered cognitive behavior therapy (iCBT) for patients with social anxiety disorder (SAD). The present study investigated anxiety-related neural changes after iCBT for SAD. The amygdala is a critical hub in the neural fear network, receptive to change using emotion regulation strategies and a putative target for iCBT. Twenty-two subjects were included in pre- and post-treatment functional magnetic resonance imaging at 3T assessing neural changes during an affective face processing task. Treatment outcome was assessed using social anxiety self-reports and the Clinical Global Impression-Improvement (CGI-I) scale. ICBT yielded better outcome than ABM (66% vs. 25% CGI-I responders). A significant differential activation of the left amygdala was found with relatively decreased reactivity after iCBT. Changes in the amygdala were related to a behavioral measure of social anxiety. Functional connectivity analysis in the iCBT group showed that the amygdala attenuation was associated with increased activity in the medial orbitofrontal cortex and decreased activity in the right ventrolateral and dorsolateral (dlPFC) cortices. Treatment-induced neural changes with iCBT were consistent with previously reported studies on regular CBT and emotion regulation in general.
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| 5. |
- Månsson, Kristoffer N. T., et al.
(author)
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Improvement in indices of cellular protection after psychological treatment for social anxiety disorder
- 2019
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In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1
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Journal article (peer-reviewed)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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| 6. |
- Månsson, Kristoffer N.T., et al.
(author)
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Multi-voxel Patterns in Fear Network Regions Predict Clinical Outcome One-year after Cognitive Behavior Therapy for Social Anxiety Disorder : A Support Vector Machine fMRI Study
- 2014
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In: Biological Psychiatry. - : Elsevier. ; , s. 83S-84S
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Conference paper (peer-reviewed)abstract
- Background: Cognitive behavioral therapy (CBT) has yielded robust treatment effects for social anxiety disorder (SAD) but still many patients do not respond fully to treatment, and a substantial proportion relapse after treatment has ended. Identification of robust predictors of sustained treatment responses could be of high clinical importance. Methods: We used functional magnetic resonance imaging (fMRI; 3T General Electric) to assess 26 patients (85% women, mean age 32.3 years) with SAD. Blood-oxygen-level dependent (BOLD) responses to self-referential criticism, i.e. reading sentences such as “Nobody likes you” were compared to criticism referring to other individuals. Responses in the fear network, i.e. the amygdala, hippocampus, anterior cingulate cortex (ACC), and insula, were evaluated in a Support Vector Machine (SVM) approach to predict treatment outcome one-year after Internet-delivered CBT. We applied leave-one-out cross-validation to increase the generalizability of the data. Results: At one-year follow-up, three patients had dropped out. Twelve (52%) of the assessed patients met the response criteria, i.e. very much or much improved according to the Clinical Global Impression-Improvement scale (CGI-I). SVM on initial BOLD response, accurately classified patients according to responder status, based on multi-voxel patterns in the ACC (balanced accuracy of 91.7%, p=.001, Figure 1), and the ACC together with the amygdala (83.0%, p=.004) as well as the hippocampus (73.9%, p=.032). Conclusions: We demonstrate that initial multi-voxel BOLD response patterns to self-referential criticism in the ACC, amygdala, and hippocampus are highly predictive of long-term improvement of CBT in patients with SAD.
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| 7. |
- Månsson, Kristoffer N T, et al.
(author)
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Neuroplasticity in response to cognitive behavior therapy for social anxiety disorder
- 2016
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In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 6
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Journal article (peer-reviewed)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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| 8. |
- Månsson, Kristoffer N T, et al.
(author)
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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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In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 5
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Journal article (peer-reviewed)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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| 9. |
- Månsson, Kristoffer N.T., et al.
(author)
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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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In: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 318, s. 45-51
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Journal article (peer-reviewed)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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