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| 2. |
- Carmona-Gutierrez, D., et al.
(författare)
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Guidelines and recommendations on yeast cell death nomenclature
- 2018
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Ingår i: Microbial Cell. - : Shared Science Publishers OG. - 2311-2638. ; 5:1, s. 4-31
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Forskningsöversikt (refereegranskat)abstract
- Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the authors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the progress of this vibrant field of research.
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| 3. |
- Forstner, A. J., et al.
(författare)
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Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 4179-4190
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Tidskriftsartikel (refereegranskat)abstract
- Panic disorder (PD) has a lifetime prevalence of 2–4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0–34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10−4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10−7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.
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| 4. |
- Rayner, C, et al.
(författare)
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A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders
- 2019
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 150-
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Tidskriftsartikel (refereegranskat)abstract
- Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h2SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h2SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.
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| 5. |
- Clements, C. C., et al.
(författare)
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Genome-wide association study of patients with a severe major depressive episode treated with electroconvulsive therapy
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26:10
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Tidskriftsartikel (refereegranskat)abstract
- Although large genome-wide association studies (GWAS) of major depressive disorder (MDD) have identified many significant loci, the SNP-based heritability remains notably low, which might be due to etiological heterogeneity in existing samples. Here, we test the utility of targeting the severe end of the MDD spectrum through genome-wide SNP genotyping of 2725 cases who received electroconvulsive therapy (ECT) for a major depressive episode (MDE) and 4035 controls. A subset of cases (n = 1796) met a narrow case definition (MDE occurring in the context of MDD). Standard GWAS quality control procedures and imputation were conducted. SNP heritability and genetic correlations with other traits were estimated using linkage disequilibrium score regression. Results were compared with MDD cases of mild-moderate severity receiving internet-based cognitive behavioral therapy (iCBT) and summary results from the Psychiatric Genomics Consortium (PGC). The SNP-based heritability was estimated at 29-34% (SE: 6%) for the narrow case definition, considerably higher than the 6.5-8.0% estimate in the most recent PGC MDD study. Our severe MDE cases had smaller genetic correlations with neurodevelopmental disorders and neuroticism than PGC MDD cases but higher genetic risk scores for bipolar disorder than iCBT MDD cases. One genome-wide significant locus was identified (rs114583506, P = 5e-8) in an intron of HLA-B in the major histocompatibility locus on chr6. These results indicate that individuals receiving ECT for an MDE have higher burden of common variant risk loci than individuals with mild-moderate MDD. Furthermore, severe MDE shows stronger relations with other severe adult-onset psychiatric disorders but weaker relations with personality and stress-related traits than mild-moderate MDD. These findings suggest a different genetic architecture at the severest end of the spectrum, and support further study of the severest MDD cases as an extreme phenotype approach to understand the etiology of MDD.
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| 16. |
- Cervenka, Simon, et al.
(författare)
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Changes in dopamine D2-receptor binding are associated to symptom reduction after psychotherapy in social anxiety disorder
- 2012
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- The dopamine system has been suggested to play a role in social anxiety disorder (SAD), partly based on molecular imaging studies showing reduced levels of striatal dopaminergic markers in patients compared with control subjects. However, the dopamine system has not been examined in frontal and limbic brain regions proposed to be central in the pathophysiology of SAD. In the present study, we hypothesized that extrastriatal dopamine D2-receptor (D2-R) levels measured using positron emission tomography (PET) would predict symptom reduction after cognitive behavior therapy (behavior). Nine SAD patients were examined using high-resolution PET and the high-affinity D2-R antagonist radioligand [C-11]FLB 457, before and after 15 weeks of CBT. Symptom levels were assessed using the anxiety subscale of Liebowitz Social Anxiety Scale (LSAS(anx)). At posttreatment, there was a statistically significant reduction of social anxiety symptoms (Po0.005). Using a repeated measures analysis of covariance, significant effects for time and time x LSAS(anx) change on D2-R-binding potential (BPND) were shown (P<0.05). In a subsequent region-by-region analysis, negative correlations between change in D2-R BPND and LSAS(anx) change were found for medial prefrontal cortex and hippocampus (P<0.05). This is the first study to report a direct relationship between symptom change after psychological treatment and a marker of brain P<0.05. Using an intra-individual comparison design, the study supports a role for the dopamine system in cortical and limbic brain regions in the pathophysiology of SAD. Translational Psychiatry (2012) 2, e120; doi:10.1038/tp.2012.40; published online 22 May 2012
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| 18. |
- Gentile, AJ, et al.
(författare)
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Internet-based, therapist-guided, cognitive-behavioural therapy for body dysmorphic disorder with global eligibility for inclusion: an uncontrolled pilot study
- 2019
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:3, s. e024693-
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive–behavioural therapy (CBT) has been shown to be an effective treatment for body dysmorphic disorder (BDD), but access to treatment around the world is limited. One way to increase access is to administer CBT remotely via the internet. This study represents the first effort to remotely deliver a therapist-supported, internet-based CBT treatment with no restrictions on enrolment based on geographical location, and it aims to assess whether this treatment can be delivered safely across international borders, with outcomes comparable to previous BDD-NET trials.DesignUncontrolled clinical trial.ParticipantsPatients (n=32) in nine different countries were recruited primarily through internet advertisements.InterventionBDD-NET is a 12-week treatment, consisting of eight treatment modules previously shown to be effective in a Swedish version.SettingTherapists based at a single, secondary care centre in Sweden provided active guidance and feedback throughout the treatment via asynchronous electronic messages.Main outcome measureThe clinician-administered Yale-Brown Obsessive Compulsive Scale for BDD (BDD-YBOCS). Symptom severity was assessed pretreatment, mid-treatment (6 weeks), post-treatment and at the 3-month follow-up.ResultsThere were significant improvements on BDD-YBOCS scores (F(3, 71.63)=31.79, p<0.001), that were maintained at 3-month follow-up. Mean differences from baseline in BDD-YBOCS scores were −8.12 (week 6), –12.63 (post-treatment) and −11.71 (3-month follow-up). 47% and 50% of participants were considered treatment responders at post-treatment and 3-month follow-up, respectively. Additionally, remission rates were 28% at post-treatment and 44% at 3-month follow-up. The treatment was also deemed acceptable by patients.ConclusionsThe results suggest that BDD-NET can be safely and effectively delivered across international borders to a culturally diverse sample. Larger scale randomised controlled trials with more participants from non-Western cultures are warranted to further validate the cross-cultural generalisability of this treatment.Trial registration numberNCT03517384.
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| 24. |
- Hedman, E., et al.
(författare)
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Effectiveness of Internet-based cognitive behaviour therapy for depression in routine psychiatric care
- 2014
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Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 155:1, s. 49-58
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efficacy of guided Internet-based cognitive behaviour therapy (ICBT) for depression has been demonstrated in several randomised controlled trials. Knowledge on the effectiveness of the treatment, i.e. how it works when delivered within routine care, is however scarce. The aim of this study was to investigate the effectiveness of ICBT for depression.Methods: We conducted a cohort study investigating all patients (N =1203) who had received guided ICBT for depression between 2007 and 2013 in a routine care setting at an outpatient psychiatric clinic providing Internet-based treatment The primary outcome measure was the Montgomery Asberg Depression Rating Scale-Self rated (MADRS-S).Results: Patients made large improvements from pre-treatment assessments to post-treatment on the primary outcome (effect size d on the MADRS-S = 1.27, 99% CI, 1.14-1.39). Participants were significantly improved in terms of suicidal ideation and sleep difficulties improvements were sustained at 6-month follow-up.Limitations: Attrition was rather large at 6-month follow-up. However, additional data was collected through telephone interviews with dropouts and advanced statistical models indicated that missing data did not bias the findings.Conclusions: ICBT for depression can be highly effective when delivered within the context of routine psychiatric care. This study suggests that the effect sizes are at least as high when the treatment is delivered in routine psychiatric care by qualified staff as when delivered in a controlled trial setting.
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| 29. |
- Krebs, G., et al.
(författare)
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Concurrent and prospective associations of obsessive-compulsive symptoms with suicidality in young adults: A genetically-informative study
- 2021
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 281, s. 422-430
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obsessive-compulsive disorder (OCD) has been linked with elevated risk of suicidality. However, most previous studies have been cross-sectional, and little is known about the aetiology of the association between obsessive-compulsive symptoms (OCS) and suicidality in young adults. Methods: Participants were members of the Child and Adolescent Twin Study in Sweden, at ages 18 (n = 9,162) and 24 (n = 3,466). Twins completed self-report measures, including assessment of OCS, suicidal ideation, and suicidal attempts. Logistic regression models tested concurrent and prospective associations of total OCS and OCS dimensions with suicidality, with and without adjustment for depression and anxiety symptoms. Genetic models tested the extent to which the main phenotypic associations were accounted for by genetic and environmental influences. Results: Total OCS were significantly associated with concurrent reports of suicidality at age 18 and 24, even when controlling for depressive and anxiety symptoms. Taboo obsessions (e.g., sexual and aggressive thoughts) were more robustly associated with suicidality than other OCS dimensions, and prospectively predicted suicidality symptoms over time, even when controlling for baseline suicide attempts. Genetic factors accounted for most of the concurrent and longitudinal covariance between OCS and suicidality, with substantial non-shared environmental influences. Limitations: We relied on self-report measures and did not include diagnostic assessment of OCD. Conclusions: OCS, particularly taboo obsessions, are associated with significantly elevated risk of suicidality in late adolescence and early adulthood. This relationship is explained by a combination of common genetic liability and non-shared environmental effects, suggesting that effective OCS treatment might reduce suicidality risk in this group.
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| 32. |
- Nelke, C, et al.
(författare)
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High-Dimensional Cytometry Dissects Immunological Fingerprints of Idiopathic Inflammatory Myopathies
- 2022
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 11:20
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Tidskriftsartikel (refereegranskat)abstract
- Chronic inflammation of skeletal muscle is the common feature of idiopathic inflammatory myopathies (IIM). Given the rarity of the disease and potential difficulty of routinely obtaining target tissue, i.e., standardized skeletal muscle, our understanding of immune signatures of the IIM spectrum remains incomplete. Further insight into the immune topography of IIM is needed to determine specific treatment targets according to clinical and immunological phenotypes. Thus, we used high-dimensional flow cytometry to investigate the immune phenotypes of anti-synthetase syndrome (ASyS), dermatomyositis (DM) and inclusion-body myositis (IBM) patients as representative entities of the IIM spectrum and compared them to healthy controls. We studied the CD8, CD4 and B cell compartments in the blood aiming to provide a contemporary overview of the immune topography of the IIM spectrum. ASyS was characterized by altered CD4 composition and expanded T follicular helper cells supporting B cell-mediated autoimmunity. For DM, unsupervised clustering identified expansion of distinct B cell subtypes highly expressing immunoglobulin G4 (IgG4) and CD38. Lastly, terminally differentiated, cytotoxic CD8 T cells distinguish IBM from other IIM. Interestingly, these terminally differentiated CD8 T cells highly expressed the integrin CD18 mediating cellular adhesion and infiltration. The distinct immune cell topography of IIM might provide the framework for targeted treatment approaches potentially improving therapeutic outcomes.
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| 33. |
- Pinseel, E., et al.
(författare)
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Strain-specific transcriptional responses overshadow salinity effects in a marine diatom sampled along the Baltic Sea salinity cline
- 2022
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Ingår i: Isme Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370.
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Tidskriftsartikel (refereegranskat)abstract
- The salinity gradient separating marine and freshwater environments represents a major ecological divide for microbiota, yet the mechanisms by which marine microbes have adapted to and ultimately diversified in freshwater environments are poorly understood. Here, we take advantage of a natural evolutionary experiment: the colonization of the brackish Baltic Sea by the ancestrally marine diatom Skeletonema marinoi. To understand how diatoms respond to low salinity, we characterized transcriptomic responses of acclimated S. marinoi grown in a common garden. Our experiment included eight strains from source populations spanning the Baltic Sea salinity cline. Gene expression analysis revealed that low salinities induced changes in the cellular metabolism of S. marinoi, including upregulation of photosynthesis and storage compound biosynthesis, increased nutrient demand, and a complex response to oxidative stress. However, the strain effect overshadowed the salinity effect, as strains differed significantly in their response, both regarding the strength and the strategy (direction of gene expression) of their response. The high degree of intraspecific variation in gene expression observed here highlights an important but often overlooked source of biological variation associated with how diatoms respond to environmental change.
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| 36. |
- Skoglund, Charlotte, et al.
(författare)
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Familial risk and heritability of diagnosed borderline personality disorder: a register study of the Swedish population
- 2021
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:3, s. 999-1008
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Tidskriftsartikel (refereegranskat)abstract
- Family and twin studies of Borderline Personality Disorder (BPD) have found familial aggregation and genetic propensity for BPD, but estimates vary widely. Large-scale family studies of clinically diagnosed BPD are lacking. Therefore, we performed a total-population study estimating the familial aggregation and heritability of clinically diagnosed BPD. We followed 1,851,755 individuals born 1973–1993 in linked Swedish national registries. BPD-diagnosis was ascertained between 1997 and 2013, 11,665 received a BPD-diagnosis. We identified relatives and estimated sex and birth year adjusted hazard ratios, i.e., the rate of BPD-diagnoses in relatives to individuals with BPD-diagnosis compared to individuals with unaffected relatives, and used structural equation modeling to estimate heritability. The familial association decreased along with genetic relatedness. The hazard ratio was 11.5 (95% confidence interval (CI) = 1.6–83.8) for monozygotic twins; 7.4 (95% CI = 1.0–55.3) for dizygotic twins; 4.7 (95% CI = 3.9–5.6) for full siblings; 2.1 (95% CI = 1.5–3.0) for maternal half-siblings; 1.3 (95% CI = 0.9–2.1) for paternal half-siblings; 1.7 (95% CI = 1.4–2.0) for cousins whose parents were full siblings; 1.1 (95% CI = 0.7–1.8) for cousins whose parents were maternal half-siblings; and 1.9 (95% CI = 1.2–2.9) for cousins whose parents were paternal half-siblings. Heritability was estimated at 46% (95% CI = 39–53), and the remaining variance was explained by individually unique environmental factors. Our findings pave the way for further research into specific genetic variants, unique environmental factors implicated, and their interplay in risk for BPD.
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| 43. |
- Andersson, E, et al.
(författare)
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Internet-based cognitive behaviour therapy for obsessive-compulsive disorder: a randomized controlled trial
- 2012
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Ingår i: Psychological Medicine. - : Cambridge University Press (CUP). - 0033-2917 .- 1469-8978. ; 42:10, s. 2193-2203
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Tidskriftsartikel (refereegranskat)abstract
- Background. Cognitive behaviour therapy (CBT) is an effective treatment for obsessive-compulsive disorder (OCD) but access to CBT is limited. Internet-based CBT (ICBT) with therapist support is potentially a more accessible treatment. There are no randomized controlled trials testing ICBT for OCD. The aim of this study was to investigate the efficacy of ICBT for OCD in a randomized controlled trial. less thanbrgreater than less thanbrgreater thanMethod. Participants (n=101) diagnosed with OCD were randomized to either 10 weeks of ICBT or to an attention control condition, consisting of online supportive therapy. The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (YBOCS) administered by blinded assessors. less thanbrgreater than less thanbrgreater thanResults. Both treatments lead to significant improvements in OCD symptoms, but ICBT resulted in larger improvements than the control condition on the YBOCS, with a significant between-group effect size (Cohens d) of 1.12 (95% CI 0.69-1.53) at post-treatment. The proportion of participants showing clinically significant improvement was 60% (95% CI 46-72) in the ICBT group compared to 6% (95% CI 1-17) in the control condition. The results were sustained at follow-up. less thanbrgreater than less thanbrgreater thanConclusions. ICBT is an efficacious treatment for OCD that could substantially increase access to CBT for OCD patients. Replication studies are warranted.
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| 48. |
- Bergström, Jan, 1976-, et al.
(författare)
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An open study of the effectiveness of Internet treatment for panic disorder delivered in a psychiatric setting
- 2009
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 63:1, s. 44-50
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Tidskriftsartikel (refereegranskat)abstract
- Panic Disorder with or without or without agoraphobia (PD/A) is common and can be treated effectively with SSRI medication or cognitive behavior therapy (CBT). There is however a great lack of access to CBT services, which has motivated the development of self-help approaches requiring less therapist contact. A novel treatment modality in this field, showing efficacy in several randomised trials but until now not evaluated within the context of regular psychiatric care, is Internet-based treatment. The present study evaluated the effectiveness of Internet-based CBT for 20 consecutively referred PD patients in a psychiatric setting. At post-treatment, 94% of patients no longer met DSM-IV criteria for PD (82% at 6-month follow up). The within-group effect sizes (for the main outcome PDSS; Panic Disorder Severity Scale) were Cohens d=2.5 (pre- to posttreatment) and 2.8 (pre-treatment to follow up) respectively. The proportion of responders on the PDSS was 75% at posttreatment and 70% at 6-month follow up. These results indicate that Internet-based CBT can be both an effective, feasible and potentially cost-effective alternative within regular psychiatric care for patients with PD.
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