| 1. |
- Kurilshikov, Alexander, et al.
(författare)
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Large-scale association analyses identify host factors influencing human gut microbiome composition
- 2021
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 53:2, s. 156-165
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Tidskriftsartikel (refereegranskat)abstract
- To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) < P < 5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
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| 2. |
- Lindqvist, Karin, et al.
(författare)
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Affect-Focused Psychodynamic Internet-Based Therapy for Adolescent Depression : Randomized Controlled Trial
- 2020
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Ingår i: Journal of Medical Internet Research. - Toronto, ON, Canada : JMIR Publications Inc.. - 1438-8871. ; 22:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adolescent depression is one of the largest health issues in the world and there is a pressing need for effective and accessible treatments.Objective: This trial examines whether affect-focused internet-based psychodynamic therapy (IPDT) with therapist support is more effective than an internet-based supportive control condition on reducing depression in adolescents.Methods: The trial included 76 adolescents (61/76, 80% female; mean age 16.6 years), self-referred via an open access website and fulfilling criteria for major depressive disorder. Adolescents were randomized to 8 weeks of IPDT (38/76, 50%) or supportive control (38/76, 50%). The primary outcome was self-reported depressive symptoms, measured with the Quick Inventory of Depressive Symptomatology for Adolescents (QIDS-A17-SR). Secondary outcomes were anxiety severity, emotion regulation, self-compassion, and an additional depression measure. Assessments were made at baseline, postassessment, and at 6 months follow-up, in addition to weekly assessments of the primary outcome measure as well as emotion regulation during treatment.Results: IPDT was significantly more effective than the control condition in reducing depression (d=0.82, P=.01), the result of which was corroborated by the second depression measure (d=0.80, P<.001). IPDT was also significantly more effective in reducing anxiety (d=0.78, P<.001) and increasing emotion regulation (d=0.97, P<.001) and self-compassion (d=0.65, P=.003). Significantly more patients in the IPDT group compared to the control group met criteria for response (56% vs 21%, respectively) and remission (35% vs 8%, respectively). Results on depression and anxiety symptoms were stable at 6 months follow-up. On average, participants completed 5.8 (SD 2.4) of the 8 modules.Conclusions: IPDT may be an effective intervention to reduce adolescent depression. Further research is needed, including comparisons with other treatments.Trial Registration: International Standard Randomised Controlled Trial Number (ISRCTN) 16206254; http://www.isrctn.com/ISRCTN16206254
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| 3. |
- Mechler, Jakob, et al.
(författare)
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Internet-based psychodynamic versus cognitive behaviour therapy for adolescents with depression : study protocol for a non-inferiority randomized controlled trial (the ERiCA study)
- 2020
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adolescent depression is a common mental health problem and there is an urgent need for effective and accessible treatments. Internet-based interventions solve many obstacles for seeking and receiving treatment, thus increasing access to effective treatments. Internet-based cognitive behavioural therapy (ICBT) for adolescent depression has demonstrated efficacy in previous trials. In order to broaden the range of evidence-based treatments for young people, we evaluated a newly developed affect-focused Internet-based psychodynamic treatment (IPDT) in a previous study with promising results. The purpose of the planned study is to evaluate the efficacy of IPDT for adolescent depression in a non-inferiority trial, comparing it to ICBT.Methods: The study will employ a parallel randomized non-inferiority design (ratio 1:1; n = 270). Eligible participants are adolescents 15–19 years suffering from depression. The primary hypothesis is that IPDT will be non-inferior to ICBT in reducing depressive symptoms from pre-treatment to end of treatment. Secondary research questions include comparing outcomes of IPDT and ICBT regarding anxiety symptoms, emotion regulation and self-compassion. Additional data will be collected to evaluate cost-effectiveness as well as investigating predictors, moderators and mediators of outcome. In addition, we will examine long-term outcome up to 1 year after end of treatment. Diagnostic interviews with MINI 7.0 will be used to establish primary diagnosis of depression as well as ruling out any exclusion criteria. Both treatments consist of eight modules over 10 weeks, complemented with therapist support through text messages and weekly chat sessions. Primary outcome measure is the Quick Inventory of Depressive Symptomatology in Adolescents Self-Rated (QIDS-A17-SR). Primary outcome will be analysed using data from all participants entering the study using a multilevel growth curve strategy based on the weekly measurements of QIDS-A17-SR. The non-inferiority margin is defined as d = 0.30.Discussion: This trial will demonstrate whether IPDT is non-inferior to ICBT in the treatment of adolescent depression. The study might therefore broaden the range of evidence-based treatment alternatives for young people struggling with depression. Further analyses of data from this trial may increase our knowledge about “what works for whom” and the pathways of change for two distinct types of interventions.Trial registration: ISRCTN12552584, Registered on 13 August 2019.
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| 4. |
- Mechler, Jakob, et al.
(författare)
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Therapist-guided internet-based psychodynamic therapy versus cognitive behavioural therapy for adolescent depression in Sweden : a randomised, clinical, non-inferiority trial
- 2022
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Ingår i: The Lancet Digital Health. - : Elsevier. - 2589-7500. ; 4:8, s. E594-E603
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Tidskriftsartikel (refereegranskat)abstract
- Background Adolescent major depressive disorder (MDD) is highly prevalent and associated with lifelong adversity. Evidence-based treatments exist, but accessible treatment alternatives are needed. We aimed to compare internet-based psychodynamic therapy (IPDT) with an established evidence-based treatment (internet-based cognitive behavioural therapy [ICBT]) for the treatment of adolescents with depression. Methods In this randomised, clinical trial, we tested whether IPDT was non-inferior to ICBT in the treatment of adolescent MDD. Eligible participants were 15-19 years old, presenting with a primary diagnosis of MDD according to DSM-5. Participants were recruited nationwide in Sweden through advertisements on social media, as well as contacts with junior and senior high schools, youth associations, social workers, and health-care providers. Adolescents who scored 9 or higher on the Quick Inventory of Depressive Symptomatology for Adolescents (QIDS-A17-SR) in an initial online screening were contacted by telephone for a diagnostic assessment using the Mini International Neuropsychiatric Interview. Participants were randomly assigned to ICBT or IPDT. Both interventions comprised eight self-help modules delivered over 10 weeks on a secure online platform. The primary outcome was change in depression severity measured weekly by the QIDS-A17-SR. Primary analyses were based on an intention -to-treat sample including all participants randomly assigned. A non-inferiority margin of Cohen's d=0.30 was predefined. The study is registered at ISRCTN, ISRCTN12552584. Findings Between Aug 19, 2019, and Oct 7, 2020, 996 young people completed screening; 516 (52%) were contacted for a diagnostic interview. 272 participants were eligible and randomly assigned to ICBT (n=136) or IPDT (n=136). In the ICBT group, 51 (38%) of 136 participants were classified as remitted, and 54 (40%) of 136 participants were classified as remitted in the IPDT group. Within-group effects were large (ICBT: within-group d=1.75, 95% CI 1.49 to 2.01; IPDT: within-group d=1.93, 1.67 to 2.20; both p<0.0001). No statistically significant treatment difference was found in the intention-to-treat analysis. Non-inferiority for IPDT was shown for the estimated change in depression during treatment (d=-0.18, 90% CI -0.49 to 0.13; p=0.34). All secondary outcomes showed non-significant between-group differences. Interpretation IPDT was non-inferior to ICBT in terms of change in depression for the treatment of adolescents with MDD. This finding increases the range of accessible and effective treatment alternatives for adolescents with depression. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 5. |
- Wallgren, Jakob, 1987-, et al.
(författare)
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Structure elucidation of urinary metabolites of fentanyl and five fentanyl analogues using LC-QTOF-MS, hepatocyte incubations and synthesized reference standards
- 2020
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Ingår i: Journal of Analytical Toxicology. - : Oxford University Press. - 0146-4760 .- 1945-2403. ; 44:9
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Tidskriftsartikel (refereegranskat)abstract
- Fentanyl analogues constitute a particularly dangerous group of new psychoactive compounds responsible for many deaths around the world. Little is known about their metabolism and studies utilizing LC-QTOF-MS analysis of hepatocyte incubations and/or authentic urine samples does not allow for determination of the exact metabolite structures, especially when it comes to hydroxylated metabolites. In this study seven motifs (2-, 3-, 4- and β-OH as well as 3,4-diOH, 4-OH-3-OMe and 3-OH-4-OMe) of fentanyl and five fentanyl analogues, acetylfentanyl, acrylfentanyl, cyclopropylfentanyl, isobutyrylfentanyl and 4F-isobutyrylfentanyl were synthesized. The reference standards were analyzed by LC-QTOF-MS, which enabled identification of the major metabolites formed in hepatocyte incubations of the studied fentanyls. By comparison with our previous data sets, major urinary metabolites could tentatively be identified. For all analogues, β-OH, 4-OH and 4-OH-3-OMe were identified after hepatocyte incubation. β-OH was the major hydroxylated metabolite for all studied fentanyls, except for acetylfentanyl where 4-OH was more abundant. However, the ratio 4-OH/β-OH was higher in urine samples than in hepatocyte incubations for all studied fentanyls. Also, 3-OH-4-OMe was not detected in any hepatocyte samples, indicating a clear preference for the 4-OH-3-OMe, which was also found to be more abundant in urine compared to hepatocytes. The patterns appear to be consistent across all studied fentanyls and could serve as a starting point in the development of methods and synthesis of reference standards of novel fentanyl analogues where nothing is known about the metabolism.
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