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Sökning: WFRF:(Forsell Erik)

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  • Andersson, Evelyn, et al. (författare)
  • Genetics of response to cognitive behavior therapy in adults with major depression : a preliminary report
  • 2019
  • Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 24:4, s. 484-490
  • Tidskriftsartikel (refereegranskat)abstract
    • Major depressive disorder is heritable and a leading cause of disability. Cognitive behavior therapy is an effective treatment for major depression. By quantifying genetic risk scores based on common genetic variants, the aim of this report was to explore the utility of psychiatric and cognitive trait genetic risk scores, for predicting the response of 894 adults with major depressive disorder to cognitive behavior therapy. The participants were recruited in a psychiatric setting, and the primary outcome score was measured using the Montgomery Asberg Depression Rating Scale-Self Rated. Single-nucleotide polymorphism genotyping arrays were used to calculate the genomic risk scores based on large genetic studies of six phenotypes: major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, intelligence, and educational attainment. Linear mixed-effect models were used to test the relationships between the six genetic risk scores and cognitive behavior therapy outcome. Our analyses yielded one significant interaction effect (B = 0.09, p < 0.001): the autism spectrum disorder genetic risk score correlated with Montgomery Asberg Depression Rating Scale-Self Rated changes during treatment, and the higher the autism spectrum disorder genetic load, the less the depressive symptoms decreased over time. The genetic risk scores for the other psychiatric and cognitive traits were not related to depressive symptom severity or change over time. Our preliminary results indicated, as expected, that the genomics of the response of patients with major depression to cognitive behavior therapy were complex and that future efforts should aim to maximize sample size and limit subject heterogeneity in order to gain a better understanding of the use of genetic risk factors to predict treatment outcome.
  • Dahlström, Märta, et al. (författare)
  • Development of a fluorescent intensity assay amenable for high-throughput screening for determining 15-lipoxygenase activity.
  • 2010
  • Ingår i: Journal of Biomolecular Screening. - 1087-0571 .- 1552-454X. ; 15:6, s. 671-9
  • Tidskriftsartikel (refereegranskat)abstract
    • 15-Lipoxygenase-1 catalyzes the introduction of molecular oxygen into polyunsaturated fatty acids to form a lipid hydroperoxide. The authors have developed an assay for the detection of lipid hydroperoxides formed by human 15-lipoxygenase (15-LO) in enzyme or cellular assays using either a 96-well or a 384-well format. The assays described take advantage of the ability of lipid hydroperoxides to oxidize nonfluorescent diphenyl-1-pyrenylphosphine (DPPP) to a fluorescent phosphine oxide. Oxidation of DPPP yields a fluorescent compound, which is not sensitive to temperature and is stable for more than 2 h. The assay is sensitive toward inhibition and robust with a Z' value of 0.79 and 0.4 in a 96- and 384-well format, respectively, and thus amenable for high-throughput screening. The utility of DPPP as a marker for 15-lipoxygenase activity was demonstrated with both enzyme- and cell-based assays for the identification of hits and to determine potency by IC(50) determinations.
  • Forsell, Erik, et al. (författare)
  • Development of a very brief scale for detecting and measuring panic disorder using two items from the Panic Disorder Severity Scale-Self Report
  • 2019
  • Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 257, s. 615-622
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To minimize the burden in detecting and monitoring Panic Disorder and Agoraphobia by developing a very brief scale with selected items from the Panic Disorder Severity Scale-Self Report (PDSS-SR), and to investigate the proposed scale's psychometric properties in a comorbid sample. Methods: A sample of 5103 patients from the Internet Psychiatry Clinic in Sweden, diagnosed and treated with Internet-based cognitive behavioral therapy for panic disorder (n = 1390), social anxiety disorder (n = 1313) or depression (n = 2400), responded to the PDSS-SR. Six criteria related to factor structure, sensitivity to change and clinical representativeness were used to select items. Psychometric analyses for the selected very brief scale were performed. Results: Items 2 (distress during panic attacks) and 4 (agoraphobic avoidance), were selected to create the very brief PDSS-SR version. Correlations with the full scale were high at screening, pre and post, and for change (0.87-0.93). Categorical Omega was omega(c) = 0.74. With a cut-off of 3 points, the scale could detect panic disorder in a psychiatric sample with a sensitivity of 85% and a specificity of 66%. Limitations: Limitations include lack of healthy controls and lack of blinding on secondary outcome measures. Conclusion: The proposed 2-item PDSS-SR version is a good candidate for a very brief panic disorder questionnaire, both for detecting cases and for measuring change. This is especially useful in clinical settings when measuring more than one condition at a time.
  • Forsell, Erik, et al. (författare)
  • Internet delivered cognitive behavior therapy for antenatal depression : A randomised controlled trial
  • 2017
  • Ingår i: Journal of Affective Disorders. - Amsterdam, Netherlands : Elsevier. - 0165-0327 .- 1573-2517. ; 221, s. 56-64
  • Tidskriftsartikel (refereegranskat)abstract
    • Major depression occurs in 5-10% of pregnancies and is associated with many negative effects for mother and child, yet treatment options are scarce. To our knowledge, this is the first published randomised controlled trial on Internet delivered Cognitive Behavior Therapy (ICBT) for this group.Objective: To test the efficacy of a pregnancy adapted version of an existing 10-week ICBT-program for depression as well as assessing acceptability and adherence.Design: Randomised controlled trial.Setting: Online and telephone.Population or sample: Self-referred pregnant women (gestational week 10-28 at intake) currently suffering from major depressive disorder.Methods: 42 pregnant women (gestational week 12-28) with major depression were randomised to either treatment as usual (TAU) provided at their antenatal clinic or to ICBT as an add-on to usual care.Main outcome measures: The primary outcome was depressive symptoms measured with the Montgomery-Asberg depression rating scale-self report (MADRS-S). The Edinburgh Postnatal Depression Scale and measures of anxiety and sleep were used. Credibility, satisfaction, adherence and utilization were also assessed.Results: The ICBT group had significantly lower levels of depressive symptoms post treatment (p < 0.001, Hedges g = 1.21) and were more likely to be responders (i.e. achieve a statistically reliable improvement) (RR = 0.36; p = 0.004). Measures of treatment credibility, satisfaction, utilization, and adherence were comparable to implemented ICBT for depression.Limitations: Small sample size and no long-term evaluation.Conclusion: Pregnancy adapted ICBT for antenatal depression is feasible, acceptable and efficacious. These results need to be replicated in larger trials to validate these promising findings.
  • Forsell, Erik, et al. (författare)
  • Predicting Treatment Failure in Regular Care Internet-Delivered Cognitive Behavior Therapy for Depression and Anxiety Using Only Weekly Symptom Measures
  • 2020
  • Ingår i: Journal of Consulting and Clinical Psychology. - : American Psychological Association (APA). - 0022-006X .- 1939-2117. ; 88:4, s. 311-321
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Therapist guided Internet-Delivered Cognitive Behavior Therapy (ICBT) is effective, but as in traditional CBT, not all patients improve, and clinicians generally fail to identify them early enough. We predict treatment failure in 12-week regular care ICBT for Depression, Panic disorder and Social anxiety disorder, using only patients' weekly symptom ratings to identify when the accuracy of predictions exceed 2 benchmarks: (a) chance, and (b) empirically derived clinician preferences for actionable predictions. Method: Screening, pretreatment and weekly symptom ratings from 4310 regular care ICBT-patients from the Internet Psychiatry Clinic in Stockholm, Sweden was analyzed in a series of regression models each adding 1 more week of data. Final score was predicted in a holdout test sample, which was then categorized into Success or Failure (failure defined as the absence of both remitter and responder status). Classification analyses with Balanced Accuracy and 95% Confidence intervals was then compared to predefined benchmarks. Results: Benchmark 1 (better than chance) was reached 1 week into all treatments. Social anxiety disorder reached Benchmark 2 (>65%) at week 5, whereas Depression and Panic Disorder reached it at week 6. Conclusions: For depression, social anxiety and panic disorder, prediction with only patient-rated symptom scores can detect treatment failure 6 weeks into ICBT, with enough accuracy for a clinician to take action. Early identification of failing treatment attempts may be a viable way to increase the overall success rate of existing psychological treatments by providing extra clinical resources to at-risk patients, within a so-called Adaptive Treatment Strategy.
  • Forsell, Erik, et al. (författare)
  • Proof of Concept for an Adaptive Treatment Strategy to Prevent Failures in Internet-Delivered CBT : A Single-Blind Randomized Clinical Trial With Insomnia Patients
  • 2019
  • Ingår i: American Journal of Psychiatry. - : American Psychiatric Publishing. - 0002-953X .- 1535-7228. ; 176:4, s. 315-323
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: This study aimed to demonstrate proof of concept for an adaptive treatment strategy in Internet-delivered cognitive-behavioral therapy (ICBT), where risk of treatment failure is assessed early in treatment and treatment for at-risk patients is adapted to prevent treatment failure. Methods: A semiautomated algorithm assessed risk of treatment failure early in treatment in 251 patients undergoing ICBT for insomnia with therapist guidance. At-risk patients were randomly assigned to continue standard ICBT or to receive adapted ICBT. The primary outcome was self-rated insomnia symptoms using the Insomnia Severity Index in a linear mixed-effects model. The main secondary outcome was treatment failure (having neither responded nor remitted at the posttreatment assessment). Results: A total of 102 patients were classified as at risk and randomly assigned to receive adapted ICBT (N=51) or standard ICBT (N=51); 149 patients were classified as not at risk. Patients not at risk had significantly greater score reductions on the Insomnia Severity Index than at-risk patients given standard ICBT. Adapted ICBT for at-risk patients was significantly more successful in reducing symptoms compared with standard ICBT, and it decreased the risk of failing treatment (odds ratio= 0.33). At-risk patients receiving adapted ICBT were not more likely to experience treatment failure than those not at risk (odds ratio= 0.51), though they were less likely to experience remission. Adapted treatment required, on average, 14 more minutes of therapist-patient time per remaining week. Conclusions: An adaptive treatment strategy can increase treatment effects for at-risk patients and reduce the number of failed treatments. Future studies should improve accuracy in classification algorithms and identify key factors that boost the effect of adapted treatments.
  • Furukawa, Toshi A, et al. (författare)
  • Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression : a systematic review and component network meta-analysis using individual participant data
  • 2021
  • Ingår i: Lancet psychiatry. - London, United Kingdom : The Lancet Publishing Group. - 2215-0374 .- 2215-0366. ; 8:6, s. 500-511
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Internet cognitive behavioural therapy (iCBT) is a viable delivery format of CBT for depression. However, iCBT programmes include training in a wide array of cognitive and behavioural skills via different delivery methods, and it remains unclear which of these components are more efficacious and for whom.METHODS: We did a systematic review and individual participant data component network meta-analysis (cNMA) of iCBT trials for depression. We searched PubMed, PsycINFO, Embase, and the Cochrane Library for randomised controlled trials (RCTs) published from database inception to Jan 1, 2019, that compared any form of iCBT against another or a control condition in the acute treatment of adults (aged ≥18 years) with depression. Studies with inpatients or patients with bipolar depression were excluded. We sought individual participant data from the original authors. When these data were unavailable, we used aggregate data. Two independent researchers identified the included components. The primary outcome was depression severity, expressed as incremental mean difference (iMD) in the Patient Health Questionnaire-9 (PHQ-9) scores when a component is added to a treatment. We developed a web app that estimates relative efficacies between any two combinations of components, given baseline patient characteristics. This study is registered in PROSPERO, CRD42018104683.FINDINGS: We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42·0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD -1·83 [95% credible interval (CrI) -2·90 to -0·80]) and that relaxation might be harmful (1·20 [95% CrI 0·17 to 2·27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0·32 [95% CrI 0·13 to 0·93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components.INTERPRETATION: The individual patient data cNMA revealed potentially helpful, less helpful, or harmful components and delivery formats for iCBT packages. iCBT packages aiming to be effective and efficient might choose to include beneficial components and exclude ones that are potentially detrimental. Our web app can facilitate shared decision making by therapist and patient in choosing their preferred iCBT package.FUNDING: Japan Society for the Promotion of Science.
  • Hansson, Erik, 1983-, et al. (författare)
  • A Quantitative Comparison of PRAM based Emulated Shared Memory Architectures to Current Multicore CPUs and GPUs
  • 2014
  • Ingår i: 27th International Conference on Architecture of Computing Systems (ARCS), 2014, ARCS Workshops: Proc. PASA-2014 11th Workshop on Parallel Systems and Algorithms, Lübeck, Germany. - Lübeck, Germany : VDE Verlag GmbH. - 9783800735792 ; , s. 27-33
  • Konferensbidrag (refereegranskat)abstract
    • The performance of current multicore CPUs and GPUs is limited in computations making frequent use of communication/synchronization between the subtasks executed in parallel. This is because the directory-based cache systems scale weakly and/or the cost of synchronization is high. The Emulated Shared Memory (ESM) architectures relying on multithreading and efficient synchronization mechanisms have been developed to solve these problems affecting both performance and programmability of current machines. In this paper, we compare preliminarily the performance of three hardware implemented ESM architectures with state-of-the-art multicore CPUs and GPUs. The benchmarks are selected to cover different patterns of parallel computation and therefore reveal the performance potential of ESM architectures with respect to current multicores.
  • Heinonen, Essi, et al. (författare)
  • MAGDALENA : study protocol of a randomised, placebo-controlled trial on cognitive development at 2 years of age in children exposed to SSRI in utero
  • 2018
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055 .- 2044-6055. ; 8:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Ten per cent of all pregnant women are depressed. Standard therapy of pregnant women with moderate depression is selective serotonin reuptakeinhibitors (SSRI). Observational studies on neurodevelopment after fetal SSRI exposure show conflicting results. Our primary objective is to compare the cognitive development in children exposed to sertraline and maternal depression with those exposed to maternal depression and placebo in utero. We hypothesise that there is a significant neurodevelopmental difference between the groups. As a secondary objective, we study the add-on effect of sertraline to internet-based cognitive behavioural therapy (ICBT) to treat moderate depression during pregnancy. Methods and analysis MAGDALENA is a randomised, placebo-controlled, double-blinded trial in Stockholm Healthcare Region with 2.3 million inhabitants. The women are recruited in weeks 9-21 of pregnancy either through Antenatal Health Clinics or through social media. They are to be diagnosed with moderate depression without ongoing antidepressive therapy or any serious comorbidity. The women in the intervention arm receive sertraline combined with a 12-week period of ICBT; the control arm is treated with placebo and ICBT. We assess the cognitive development in the offspring at the age of 2 years using Bayley Scales of Infant and Toddler Development, third edition (BSID-III). We aim at recruiting 200 women, 100 women in each treatment arm, to ensure statistical power to detect a clinically relevant difference between the groups. Ethics and dissemination This randomised trial will provide long-sought evidence about the effects of SSRI and maternal depression during pregnancy on the neurodevelopment in the offspring. The study is approved by the Regional Ethical Review Board at Karolinska Institutet in Stockholm and the Swedish Medical Products Agency. It is registered with the European Clinical Trials Database (EudraCT), Number: 2013-004444-31. Results will be disseminated at scientific conferences, published in peer-reviewed journals and made available to the public.
  • Karyotaki, Eirini, et al. (författare)
  • Internet-Based Cognitive Behavioral Therapy for Depression: A Systematic Review and Individual Patient Data Network Meta-analysis
  • 2021
  • Ingår i: JAMA Psychiatry. - 2168-622X .- 2168-6238. ; 78:54, s. 361-371
  • Forskningsöversikt (refereegranskat)abstract
    • Importance: Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions that better suit them. Objective: To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information. Data Sources: We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019. Study Selection: Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization. Data Extraction and Synthesis: We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression. Main Outcomes and Measures: Patient Health Questionnaire-9 (PHQ-9) scores. Results: Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference [MD] in posttreatment PHQ-9 scores, -0.8; 95% CI, -1.4 to -0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (PHQ-9 scores 5-9) were small, while guided iCBT was associated with overall better outcomes in patients with baseline PHQ-9 greater than 9. Conclusions and Relevance: In this network meta-analysis with IPD, guided iCBT was associated with more effectiveness than unguided iCBT for individuals with depression, benefits were more substantial in individuals with moderate to severe depression. Unguided iCBT was associated with similar effectiveness among individuals with symptoms of mild/subthreshold depression. Personalized treatment selection is entirely possible and necessary to ensure the best allocation of treatment resources for depression.
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