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2.
  • Bas-Hoogendam, Janna Marie, et al. (författare)
  • Voxel-based morphometry multi-center mega-analysis of brain structure in social anxiety disorder
  • 2017
  • Ingår i: NeuroImage. - : Elsevier BV. - 2213-1582. ; 16, s. 678-688
  • Tidskriftsartikel (refereegranskat)abstract
    • Social anxiety disorder (SAD) is a prevalent and disabling mental disorder, associated with significant psychiatric co-morbidity. Previous research on structural brain alterations associated with SAD has yielded inconsistent results concerning the direction of the changes in gray matter (GM) in various brain regions, as well as on the relationship between brain structure and SAD-symptomatology. These heterogeneous findings are possibly due to limited sample sizes. Multi-site imaging offers new opportunities to investigate SAD-related alterations in brain structure in larger samples.An international multi-center mega-analysis on the largest database of SAD structural T1-weighted 3T MRI scans to date was performed to compare GM volume of SAD-patients (n = 174) and healthy control (HC)-participants (n = 213) using voxel-based morphometry. A hypothesis-driven region of interest (ROI) approach was used, focusing on the basal ganglia, the amygdala-hippocampal complex, the prefrontal cortex, and the parietal cortex. SAD-patients had larger GM volume in the dorsal striatum when compared to HC-participants. This increase correlated positively with the severity of self-reported social anxiety symptoms. No SAD-related differences in GM volume were present in the other ROIs. Thereby, the results of this mega-analysis suggest a role for the dorsal striatum in SAD, but previously reported SAD-related changes in GM in the amygdala, hippocampus, precuneus, prefrontal cortex and parietal regions were not replicated. Our findings emphasize the importance of large sample imaging studies and the need for meta-analyses like those performed by the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium.
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3.
  • Brännström, Jonas, et al. (författare)
  • The initial evaluation of an Internet-based support system for audiologists and first-time hearing aid clients
  • 2016
  • Ingår i: Internet Interventions. - : Elsevier BV. - 2214-7829. ; 4, s. 82-91
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Audiologists provide professional contact and support between appointments to clients with hearing impairment using telephone and e-mail, but more advanced and flexible technological platforms are also possible. The present study aimed to evaluate the clinical application of an Internet-based support system for audiologists and their first-time hearing aid clients. Design: An Internet-based support system developed by Månsson et al. (2013) for psychologists and their clients was adapted for audiologic purposes. Three audiologic clinics in Sweden tested the support system with their clients. Study sample: Twenty-three clients managed by four audiologists used and evaluated the support system. In addition, five of the clients and all four audiologists were interviewed and their responses were analyzed using content analysis. Results: The clients and the audiologists reported positive experiences and overall satisfaction but audiologists reported that the support system did not address the needs of all clients. More positive experiences and greater satisfaction with the support system were associated with reductions on self-reported consequences of hearing loss and positive hearing aids outcomes. Conclusions: An Internet-based support system can be used in audiologic rehabilitation. Both audiologists and clients recognized the system's potential value to offer an online support to the provision of audiologic services.
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  • Brännström, Jonas, et al. (författare)
  • The Process of Developing an Internet-Based Support System for Audiologists and First-Time Hearing Aid Clients
  • 2015
  • Ingår i: American Journal of Audiology. - : American Speech-Language-Hearing Association. - 1059-0889 .- 1558-9137. ; 24:3, s. 320-324
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In audiologic practice, complementary information sources and access to the clinician between appointments improve information retention and facilitate adjustment behaviors. An Internet-based support system is a novel way to support information sharing and clinician access. Purpose: This research forum article describes the process of developing an Internet-based support system for audiologists and their first-time hearing aid clients. Method: The iterative development process, including revisions by 4 research audiologists and 4 clinical audiologists, is described. The final system is exemplified. Conclusion: An Internet-based support system was successfully developed for audiologic practice.
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6.
  • Cortes, Diana S., et al. (författare)
  • Increased dorsomedial prefrontal cortex activity to negative emotion displays in men but not in women
  • 2019
  • Ingår i: Program.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • The neuropeptide oxytocin plays a prominentrole in social and emotional cognition. Findings suggest that exogenous intranasal oxytocin administration facilitates emotion recognition in humans, but individual and contextual differences may have moderating effects. A major caveat in this line of work is that it is predominantly based on young males, which limits current knowledge and potential for generalizability across gender. To uncover potential gender effects, the present study included younger and older men and women. Utilizing a randomized, double-blind, placebo-controlled, within-subjects study design, we investigated the effects of a single-dose of 40 IUs intranasal oxytocin administration on emotion recognition of dynamic positive and negative stimuli in 32 men (mean age 45.78, sd. 22.87) and 39 women (mean 47.87, sd. 47.87), 40 minutes prior to MRI scanning. Preliminary analyses show that oxytocin induced brain activity reductions during exposure to negative (relative to positive) stimuli in women, while increasing brain activity in dorsomedial prefrontal cortex in men. We speculate that the effects of oxytocin on emotion recognition may possibly be related to emotion regulation and mentalization processes, and that oxytocin is related to potential sex-differences in these processes. The results also raise concern that previous oxytocin literature on emotion recognition may be biased as there appears to be gender-differential effects of oxytocin on brain activity across adulthood that have been underestimated. In the next stage of the present study, we will investigate the interaction effects among treatment, sex, age, and presentation modality.
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7.
  • Döllinger, Lillian, et al. (författare)
  • Effectively training emotion recognition accuracy : The evaluation of two systematic training programs
  • 2019
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • This study presents findings about the effectiveness of two computerized training-programs for emotion recognition accuracy that were evaluated in a double-blind randomized controlled study with repeated measures design. Both trainings are effective in training emotion recognition accuracy. The trainings and results are presented in detail and practical implications are discussed.
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8.
  • Faria, Vanda, et al. (författare)
  • Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder : A Randomized Trial
  • 2017
  • Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 24, s. 179-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression and anxiety, but their efficacy relative to placebo has been questioned. We aimed to test how manipulation of verbally induced expectancies, central for placebo, influences SSRI treatment outcome and brain activity in patients with social anxiety disorder (SAD).Methods: We did a randomized clinical trial, within an academic medical center (Uppsala, Sweden), of individuals fulfilling the DSM-IV criteria for SAD, recruited through media advertising. Participants were 18 years or older and randomized in blocks, through a computer-generated sequence by an independent party, to nine weeks of overt or covert treatment with escitalopram(20 mg daily). The overt group received correct treatment information whereas the covert group was treated deceptively with the SSRI described, by the psychiatrist, as active placebo. The treating psychiatrist was necessarily unmasked while the research staff was masked from intervention assignment. Treatment efficacy was assessed primarily with the self-rated Liebowitz Social Anxiety Scale (LSAS-SR), administered at week 0, 1, 3, 6 and 9, also yielding a dichotomous estimate of responder status (clinically significant improvement). Before and at the last week of treatment, brain activity during an emotional face-matching task was assessed with functional magnetic resonance imaging (fMRI) and during fMRI sessions, anticipatory speech anxiety was also assessed with the Spielberger State-Trait Anxiety Inventory - State version (STAI-S). Analyses included all randomized patients with outcome data at posttreatment. This study is registered at ISRCTN, number 98890605.Findings: Between March 17th 2014 and May 22nd 2015, 47 patients were recruited. One patient in the covert group dropped out after a few days of treatment and did not provide fMRI data, leaving 46 patients with complete outcome data. After nine weeks of treatment, overt (n = 24) as compared to covert (n = 22) SSRI administration yielded significantly better outcome on the LSAS-SR (adjusted difference 21.17, 95% CI 10.69–31.65, p < 0.0001) with more than three times higher response rate (50% vs. 14%; χ2(1) = 6.91, p = 0.009) and twice the effect size (d = 2.24 vs. d = 1.13) from pre-to posttreatment. There was no significant between-group difference on anticipatory speech anxiety (STAI-S), both groups improving with treatment. No serious adverse reactions were recorded. On fMRI outcomes, there was suggestive evidence for a differential neural response to treatment between groups in the posterior cingulate, superior temporal and inferior frontal gyri (all z thresholds exceeding 3.68, p ≤ 0.001). Reduced social anxiety with treatment correlated significantly with enhanced posterior cingulate (z threshold 3.24, p = 0.0006) and attenuated amygdala (z threshold 2.70, p = 0.003) activity.Interpretation: The clinical and neural effects of escitalopram were markedly influenced by verbal suggestions. This points to a pronounced placebo component in SSRI-treatment of SAD and favors a biopsychosocial over a biomedical explanatory model for SSRI efficacy.
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9.
  • Fischer, Håkan, et al. (författare)
  • Divergent effects of oxytocin in men and women : Increased dorsomedial prefrontal cortex activity to negative emotion displays in men but not in women
  • 2019
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • The neuropeptide oxytocin plays a prominent role in social and emotional cognition. Findings suggest that intranasal oxytocin administration facilitates emotion recognition in humans, but individual and contextual differences may have moderating effects. A major caveat in this line of work is its predominant focus on young males, which limits current knowledge and generalizability across gender. To uncover potential gender effects, the present study included 32 men (mean age 45.78, sd. 22.87) and 39 women (mean 47.87, sd. 22.59). Utilizing a randomized, double-blind, placebo-controlled, within-subjects design, participants self-administered a single-dose of 40 IUs intranasal oxytocin 40 minutes prior to completion of a dynamic emotion recognition task in the MRI scanning. The task paradigm used positive and negative stimuli from the Geneva Multimodal Emotion Portrayals Core Set. Preliminary analyses show that oxytocin induced dorsomedial prefrontal cortex (dmPFC) activity reductions during exposure to negative (relative to positive) stimuli in women, while dmPCF activity was increased under this condition in men. We observed no effect of sex in the behavioral data, however, the results show a similar trend as in brain data. We speculate that the effects of oxytocin on brain activity during emotion recognition may be related to emotion-regulatory and mentalization processes. The observed gender-differential modulatory role of oxytocin raises concern of a bias in the previous oxytocin literature on emotion recognition and associated brain activity by neglecting women in the examination. Next, we will determine the role of age effects on gender-bytreatment interactions, as well as consider modality of the emotion stimulus presentation.  
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11.
  • Goodwin, Guy M., et al. (författare)
  • From neuroscience to evidence based psychological treatments - The promise and the challenge, ECNP March 2016, Nice, France
  • 2018
  • Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 28:2, s. 317-333
  • Tidskriftsartikel (refereegranskat)abstract
    • This ECNP meeting was designed to build bridges between different constituencies of mental illness treatment researchers from a range of backgrounds with a specific focus on enhancing the development of novel, evidence based, psychological treatments. In particular we wished to explore the potential for basic neuroscience to support the development of more effective psychological treatments, just as this approach is starting to illuminate the actions of drugs. To fulfil this aim, a selection of clinical psychologists, psychiatrists and neuroscientists were invited to sit at the same table. The starting point of the meeting was the proposition that we know certain psychological treatments work, but we have only an approximate understanding of why they work. The first task in developing a coherent mental health science would therefore be to uncover the mechanisms (at all levels of analysis) of effective psychological treatments. Delineating these mechanisms, a task that will require input from both the clinic and the laboratory, will provide a key foundation for the rational optimisation of psychological treatments. As reviewed in this paper, the speakers at the meeting reviewed recent advances in the understanding of clinical and cognitive psychology, neuroscience, experimental psychopathology, and treatment delivery technology focussed primarily on anxiety disorders and depression. We started by asking three rhetorical questions: What has psychology done for treatment? What has technology done for psychology? What has neuroscience done for psychology? We then addressed how research in five broad research areas could inform the future development of better treatments: Attention, Conditioning, Compulsions and addiction, Emotional Memory, and Reward and emotional bias. Research in all these areas (and more) can be harnessed to neuroscience since psychological therapies are a learning process with a biological basis in the brain. Because current treatment approaches are not fully satisfactory, there is an imperative to understand why not. And when psychological therapies do work we need to understand why this is the case, and how we can improve them. We may be able to improve accessibility to treatment without understanding mechanisms. But for treatment innovation and improvement, mechanistic insights may actually help. Applying neuroscience in this way will become an additional mission for ECNP. (C) 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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12.
  • Han, Laura K. M., et al. (författare)
  • Accelerating research on biological aging and mental health : Current challenges and future directions
  • 2019
  • Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 106, s. 293-311
  • Tidskriftsartikel (refereegranskat)abstract
    • Aging is associated with complex biological changes that can be accelerated, slowed, or even temporarily reversed by biological and non-biological factors. This article focuses on the link between biological aging, psychological stressors, and mental illness. Rather than comprehensively reviewing this rapidly expanding field, we highlight challenges in this area of research and propose potential strategies to accelerate progress in this field. This effort requires the interaction of scientists across disciplines - including biology, psychiatry, psychology, and epidemiology; and across levels of analysis that emphasize different outcome measures - functional capacity, physiological, cellular, and molecular. Dialogues across disciplines and levels of analysis naturally lead to new opportunities for discovery but also to stimulating challenges. Some important challenges consist of 1) establishing the best objective and predictive biological age indicators or combinations of indicators, 2) identifying the basis for inter-individual differences in the rate of biological aging, and 3) examining to what extent interventions can delay, halt or temporarily reverse aging trajectories. Discovering how psychological states influence biological aging, and vice versa, has the potential to create novel and exciting opportunities for healthcare and possibly yield insights into the fundamental mechanisms that drive human aging.
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13.
  • Ivanov, Volen Z., et al. (författare)
  • Enhancing group cognitive-behavioral therapy for hoarding disorder with between-session Internet-based clinician support : A feasibility study
  • 2018
  • Ingår i: Journal of Clinical Psychology. - : Wiley. - 0021-9762 .- 1097-4679. ; 74:7, s. 1092-1105
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Hoarding disorder (HD) is difficult to treat. In an effort to increase efficacy and engagement in cognitive-behavioral therapy (CBT), we developed and evaluated a novel intervention comprising group CBT combined with between-session Internet-based clinician support for people with HD.Method Twenty participants with HD received group CBT combined with an Internet-support system enabling therapist-participant communication between group sessions.Results The treatment was associated with a significant reduction on the Saving InventoryRevised (SI-R) and a large effect size (Cohen's d=1.57) was found at posttreatment. Treatment gains were maintained at the 3-month follow-up. Group attendance was high and no participants dropped out from treatment prematurely. Between-session motivational support from the therapist was most frequently mentioned as the main strength of the system.Conclusion The results of this study support adding Internet-based clinician support to group CBT for HD to increase treatment adherence and, potentially, improve the overall efficacy of CBT.
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14.
  • Laukka, Petri, et al. (författare)
  • Neural correlates of individual differences in emotion recognition ability : an fMRI study
  • 2019
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • The ability to understand how others are feeling is important for social interaction. Studies have reported large inter-individual variability in emotion recognition ability (ERA) in the general population, but the causes for such differences are not well understood. This study investigated neural response during emotion recognition in individuals with high and low ERA. Forty-nine young adults were selected for inclusion based on their performance during previous testing of ERA (e.g., Hovey et al., 2018, Soc Cogn Affect Neurosci, 13, 173-181). Neural response was determined using the blood-oxygen level-dependent (BOLD) signal in a 3-Tesla functional magnetic resonance imaging (fMRI) experiment. The participants were asked to judge which emotions (anger, fear, disgust, happiness, interest, pride, relief, sadness, and neutral expression) were demonstrated in brief clips (i.e. audio-only, video-only, and multimodal audio- video) using a forced-choice response format. Stimuli were taken from the GEMEP emotion portrayal database (Bänziger et al., 2009, Emotion, 9, 691-704). In neural response to emotional stimuli, individuals with high ERA, relative to low ERA, showed higher activation bilaterally in the supplementary motor area, and in the left postcentral gyrus. Results provide initial evidence that the ability to effectively recognize the emotions of others is related to motor and somatosensory neural responses. We speculate that these neural responses in individuals with improved skills in emotion recognition could be related to increased embodiment of emotion expressions during emotion perception.
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15.
  • Lenhard, Fabian, et al. (författare)
  • Prediction of outcome in internet-delivered cognitive behaviour therapy for paediatric obsessive-compulsive disorder : A machine learning approach
  • 2018
  • Ingår i: International Journal of Methods in Psychiatric Research. - : Wiley. - 1049-8931 .- 1557-0657. ; 27:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There are no consistent predictors of treatment outcome in paediatric obsessive–compulsive disorder (OCD). One reason for this might be the use of suboptimal statistical methodology. Machine learning is an approach to efficiently analyse complex data. Machine learning has been widely used within other fields, but has rarely been tested in the prediction of paediatric mental health treatment outcomes.Objective: To test four different machine learning methods in the prediction of treatment response in a sample of paediatric OCD patients who had received Internet-delivered cognitive behaviour therapy (ICBT).Methods: Participants were 61 adolescents (12–17 years) who enrolled in a randomized controlled trial and received ICBT. All clinical baseline variables were used to predict strictly defined treatment response status three months after ICBT. Four machine learning algorithms were implemented. For comparison, we also employed a traditional logistic regression approach.Results: Multivariate logistic regression could not detect any significant predictors. In contrast, all four machine learning algorithms performed well in the prediction of treatment response, with 75 to 83% accuracy.Conclusions: The results suggest that machine learning algorithms can successfully be applied to predict paediatric OCD treatment outcome. Validation studies and studies in other disorders are warranted.
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16.
  • Månsson, Kristoffer N. T., et al. (författare)
  • 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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17.
  • Månsson, Kristoffer N. T., et al. (författare)
  • Neuroplasticity in Response to Cognitive Behavior Therapy for Social Anxiety Disorder
  • 2015
  • Ingår i: Abstracts from the 7th Swedish Congress on internet interventions (SWEsrii). - Linköping : Linköping University Press. ; , s. 13-13
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Functional magnetic resonance imaging studies have consistently showed increased amygdala responsiveness in Social Anxiety Disorder (SAD), which decreases after anxiolytic treatment (e.g., Cognitive Behavior Therapy, CBT). However, less is known about treatment-related structural gray matter (GM) volume changes. Furthermore, the relationship between functional and structural plasticity are largely neglected in the literature. Methods: Functional and structural neuroimaging were used to assess 26 SAD patients. The patients were randomized to receive Internet-delivered CBT (ICBT), or a control condition. The Clinical Global Impression-Improvement scale (CGI-I) determined clinical response. Also, we assessed level of anticipatory speech anxiety. At pre-, and post-treatment, blood-oxygen-level dependent (BOLD) responses to self-referential criticism were recorded, and structural data was examined with voxel-based morphometry (VBM). Results: CGI-I assessment showed that eight (61%) patients were deemed as responders following ICBT, and 3 (23%) in the control group (χ2=3.90, p=0.047). Time ˙ treatment interactions showed decreased amygdala BOLD response (Z=3.28, p=0.015, Family Wise-Error corrected, FWE), and amygdala GM volume (Z=3.30, pFWE=0.024) after ICBT. At baseline, GM amygdala volume was correlated with anticipatory anxiety (Z=2.96, pFWE=0.040), and amygdala GM atrophy following ICBT was correlated with decreased anticipatory anxiety (Z>2.83, pFWE<0.055). Moreover, the amygdala BOLD response change was associated with the local GM atrophy after ICBT (Z>2.45, pFWE<0.029). Conclusions: This is the first randomized study to evaluate multiple imaging modalities and the brain´s plasticity to an anxiolytic treatment. The functional and structural plasticity was highly correlated as indicated by anxiety-related BOLD signal change and GM volume in the amygdala following ICBT.
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18.
  • Månsson, Kristoffer N T, et al. (författare)
  • 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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19.
  • Månsson, Kristoffer N T, et al. (författare)
  • Predicting long-term outcome of Internet-delivered cognitive behavior therapy for social anxiety disorder using fMRI and support vector machine learning
  • 2015
  • 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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20.
  • Månsson, Kristoffer N. T. (författare)
  • Restructuring the socially anxious brain : Using magnetic resonance imaging to advance our understanding of effective cognitive behaviour therapy for social anxiety disorder
  • 2016
  • 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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21.
  • Månsson, Kristoffer N.T., et al. (författare)
  • Structural but not functional neuroplasticity one year after effective cognitive behaviour therapy for social anxiety disorder
  • 2017
  • Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 318, s. 45-51
  • 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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22.
  • Månsson, Kristoffer N. T., et al. (författare)
  • Viewing Pictures Triggers Rapid Morphological Enlargement in the Human Visual Cortex
  • 2019
  • Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 30:3, s. 851-857
  • Tidskriftsartikel (refereegranskat)abstract
    • Measuring brain morphology with non-invasive structural magnetic resonance imaging is common practice, and can be used to investigate neuroplasticity. Brain morphology changes have been reported over the course of weeks, days, and hours in both animals and humans. If such short-term changes occur even faster, rapid morphological changes while being scanned could have important implications. In a randomized within-subject study on 47 healthy individuals, two high-resolution T1-weighted anatomical images were acquired (á 263 s) per individual. The images were acquired during passive viewing of pictures or a fixation cross. Two common pipelines for analyzing brain images were used: voxel-based morphometry on gray matter (GM) volume and surface-based cortical thickness. We found that the measures of both GM volume and cortical thickness showed increases in the visual cortex while viewing pictures relative to a fixation cross. The increase was distributed across the two hemispheres and significant at a corrected level. Thus, brain morphology enlargements were detected in less than 263 s. Neuroplasticity is a far more dynamic process than previously shown, suggesting that individuals’ current mental state affects indices of brain morphology. This needs to be taken into account in future morphology studies and in everyday clinical practice.
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23.
  • Nilsonne, Gustav, et al. (författare)
  • A multimodal brain imaging dataset on sleep deprivation in young and old humans
  • 2017
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • The Stockholm Sleepy Brain Study I is a functional brain imaging study of 48 younger (20-30 years) and 36 older (65-75 years) healthy participants, with magnetic resonance imaging after normal sleep and partial sleep deprivation in a crossover design. We performed experiments investigating emotional mimicry, empathy for pain, and cognitive reappraisal, as well as resting state functional magnetic resonance imaging (fMRI). We also acquired T1- and T2-weighted structural images and diffusion tensor images (DTI). On the night before imaging, participants were monitored with ambulatory polysomnography and were instructed to sleep either as usual or only three hours. Participants came to the scanner the following evening. Besides MRI scanning, participants underwent behavioral tests and contributed blood samples, which have been stored in a biobank and used for DNA analyses. Participants also completed a variety of self-report measures. The resulting multimodal dataset may be useful for hypothesis generation or independent validation of effects of sleep deprivation and aging, as well as investigation of cross-sectional associations between the different outcomes. V. 2 of this manuscript published 2017-10-12. Changes: new co-author (Claus Lamm), changed affiliations for Kristoffer Månsson, minor changes in the abstract, and revisions of the main text and figures.
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24.
  • Nilsonne, Gustav, et al. (författare)
  • Leukocyte telomere length and hippocampus volume : a meta-analysis [version 1; referees: 2 approved]
  • 2015
  • Ingår i: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 4
  • Forskningsöversikt (refereegranskat)abstract
    • Leukocyte telomere length has been shown to correlate to hippocampus volume, but effect estimates differ in magnitude and are not uniformly positive. This study aimed primarily to investigate the relationship between leukocyte telomere length and hippocampus gray matter volume by meta-analysis and secondarily to investigate possible effect moderators. Five studies were included with a total of 2107 participants, of which 1960 were contributed by one single influential study. A random-effects meta-analysis estimated the effect to r = 0.12 [95% CI -0.13, 0.37] in the presence of heterogeneity and a subjectively estimated moderate to high risk of bias. There was no evidence that apolipoprotein E (APOE) genotype was an effect moderator, nor that the ratio of leukocyte telomerase activity to telomere length was a better predictor than leukocyte telomere length for hippocampus volume. This meta-analysis, while not proving a positive relationship, also is not able to disprove the earlier finding of a positive correlation in the one large study included in analyses. We propose that a relationship between leukocyte telomere length and hippocamus volume may be mediated by transmigrating monocytes which differentiate into microglia in the brain parenchyma.
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25.
  • Rozental, Alexander, et al. (författare)
  • Measuring adverse and unwanted events in psychotherapy
  • 2018
  • Konferensbidrag (refereegranskat)abstract
    • Background: Psychotherapy offers many benefits, but research also indicate that negative effects sometimes occur. The Negative Effects Questionnaire (NEQ) was therefore developed to help researchers and clinicians determine the occurrence and characteristics of such incidents. Method: The NEQ was evaluated in two studies, using data from both clinical trials and a survey distributed among individuals in the general population (Ns 653 and 564). Results: The results from an exploratory factor analysis suggest that six factors could be relevant to retain: symptoms, quality, dependency, stigma, hopelessness, and failure, with poor treatment quality and therapeutic relationship having the highest self-rated negative effects. Further, the results from a Rasch analysis, a modern test theory application, suggest that the self-report measure exhibits fairness in testing across sociodemographics and that it is suitable for monitoring items with regard to their frequencies or levels of impact. Overall, 18.8% of the patients experienced more stress, 12.6% reported the resurfacing of unpleasant memories, and 12.2% were more anxious during treatment, implying that adverse and unwanted events are not uncommon in psychotherapy and may have to be monitored. Conclusion: The NEQ could be a useful self-report measure to investigate negative effects in both research and clinical practice.
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26.
  • Rozental, Alexander, et al. (författare)
  • The Negative Effects Questionnaire : Psychometric Properties of an Instrument for Assessing Negative Effects in Psychological Treatments
  • 2019
  • Ingår i: Proceedings of the 9th World Congress of Behavioural &amp; Cognitive Therapies. - Tübingen : dgvt-Verlag. - 9783871598517 ; 47:5, s. 559-572
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Psychological treatments provide many benefits for patients with psychiatric disorders, but research also suggest that negative effects might occur from the interventions involved. The Negative Effects Questionnaire (NEQ) has previously been developed as a way of determining the occurrence and characteristics of such incidents, consisting of 32 items and six factors. However, the NEQ has yet to be examined using modern test theory, which could help to improve the understanding of how well the instrument works psychometrically. Aims: The current study investigated the reliability and validity of the NEQ from both a person and item perspective, establishing goodness-of-fit, item bias, and scale precision. Method: The NEQ was distributed to 564 patients in five clinical trials at post-treatment. Data was analyzed using Rasch analysis, i.e., a modern test theory application. Results: 1) the NEQ exhibits fairness in testing across sociodemographics, 2) shows comparable validity for a final and condensed scale of 20 instead of 32 items, 3) uses a rating scale that advances monotonically in steps of 0-4, and 4) is suitable for monitoring negative effects on an item-level. Conclusion: The NEQ is proposed as a useful instrument for investigating negative effects in psychological treatments, and its newer shorter format could facilitate its use in clinical and research settings. However, further research is needed to explore the relationship between negative effects and treatment outcome, as well as to test it in more diverse patient populations
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27.
  • Tudor Tulbure, Bogdan, et al. (författare)
  • Internet-Delivered Cognitive-Behavioral Therapy for Social Anxiety Disorder in Romania: A Randomized Controlled Trial
  • 2015
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 10:5, s. e0123997-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims Internet-based cognitive-behavioral therapy (iCBT) for social anxiety disorder has been found effective, as attested by independently conducted randomized controlled trials in four languages. The study aim is to test the efficacy of an iCBT program in a culture where it was not tested before (i.e. Romania). Methods Participants (n = 76) were recruited, screened and randomized to either a nine-week guided iCBT or a wait-list control group in April and May 2012. Self-report measures were collected before (April 2012) and after the intervention (July 2012), as well as six months later (January 2013). Although social anxiety was assessed with multiple measures, the Liebowitz Social Anxiety Scale - Self Report version (LSAS-SR) and Social Phobia Inventory (SPIN) were used as the primary outcome measures. Results A significant difference with a large between-group effect size in favor of iCBT was found (Cohens d = 1.19 for LSAS-SR and d = 1.27 for SPIN). Recovery rates show that 36.8% (n = 14) in the treatment group score below the SPIN clinical cut-off compared to only 2.6% (n = 1) in the wait-list control group. Post-intervention clinical interviews also revealed that 34.2% (n = 13) of the treatment group was completely recovered (full remission) while additionally 36.8%(n = 14) retained some social anxiety symptoms (partial remission). However, an important study limitation is that post-intervention interviewers were not blinded to the study conditions. The program also effectively reduced depression and dysfunctional thinking (between-group Cohens d = 0.84 for depression and d = 0.63 for dysfunctional thinking). Moreover, the iCBT intervention appears to have a long-term impact for participants functioning, as the treatment gains were maintained six months later. Conclusions Internet-delivered interventions display a high potential to quickly and widely disseminate effective evidence-based programs around the world. This study provides support for guided iCBT as a promising treatment approach in Romania.
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