SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Schalling M) "

Sökning: WFRF:(Schalling M)

  • Resultat 11-20 av 308
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
11.
  • Reinbold, C. S., et al. (författare)
  • Analysis of the Influence of microRNAs in Lithium Response in Bipolar Disorder
  • 2018
  • Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable Evidence suggests that some of this variability has a genetic basis. This is supported by the largest genome-wide association study (GWAS) of lithium response to date conducted by the International Consortium on Lithium Genetics (ConLiGen) Recently, we performed the first genome-wide analysis of the involvement of miRNAs in BD and identified nine BD associated miRNAs However, it is unknown whether these miRNAs are also associated with lithium response in BD. In the present study, we therefore tested whether common variants at these nine candidate miRNAs contribute to the variance in lithium response in BD. Furthermore, we systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium. For this purpose, we performed gene-based tests for all known miRNA coding genes in the ConLiGen GWAS dataset (n = 2,563 patients) using a set-based testing approach adapted from the versatile gene based test for GWAS (VEGAS2). In the candidate approach, miR-499a showed a nominally significant association with lithium response, providing some evidence for involvement in both development and treatment of BD. In the genome-wide miRNA analysis, 71 miRNAs showed nominally significant associations with the dichotomous phenotype and 106 with the continuous trait for treatment response. A total of 15 miRNAs revealed nominal significance in both phenotypes with miR-633 showing the strongest association with the continuous trait (p = 9.80E-04) and miR-607 with the dichotomous phenotype (p = 5.79E-04). No association between miRNAs and treatment response to lithium in BD in either of the tested conditions withstood multiple testing correction. Given the limited power of our study, the investigation of miRNAs in larger GWAS samples of BD and lithium response is warranted.
  •  
12.
  • Schubert, K. O., et al. (författare)
  • Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients
  • 2021
  • Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium's therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi(+)Gen; ). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD.
  •  
13.
  •  
14.
  •  
15.
  •  
16.
  •  
17.
  • Sellgren, C. M., et al. (författare)
  • GRK3 deficiency elicits brain immune activation and psychosis
  • 2021
  • Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26
  • Tidskriftsartikel (refereegranskat)abstract
    • The G protein-coupled receptor kinase (GRK) family member protein GRK3 has been linked to the pathophysiology of schizophrenia and bipolar disorder. Expression, as well as protein levels, of GRK3 are reduced in post-mortem prefrontal cortex of schizophrenia subjects. Here, we investigate functional behavior and neurotransmission related to immune activation and psychosis using mice lacking functional Grk3 and utilizing a variety of methods, including behavioral, biochemical, electrophysiological, molecular, and imaging methods. Compared to wildtype controls, the Grk3(-/-) mice show a number of aberrations linked to psychosis, including elevated brain levels of IL-1 beta, increased turnover of kynurenic acid (KYNA), hyper-responsiveness to D-amphetamine, elevated spontaneous firing of midbrain dopamine neurons, and disruption in prepulse inhibition. Analyzing human genetic data, we observe a link between psychotic features in bipolar disorder, decreased GRK expression, and increased concentration of CSF KYNA. Taken together, our data suggest that Grk3(-/-) mice show face and construct validity relating to the psychosis phenotype with glial activation and would be suitable for translational studies of novel immunomodulatory agents in psychotic disorders.
  •  
18.
  • Stone, W, et al. (författare)
  • Prediction of lithium response using genomic data
  • 2021
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 1155-
  • Tidskriftsartikel (refereegranskat)abstract
    • Predicting lithium response prior to treatment could both expedite therapy and avoid exposure to side effects. Since lithium responsiveness may be heritable, its predictability based on genomic data is of interest. We thus evaluate the degree to which lithium response can be predicted with a machine learning (ML) approach using genomic data. Using the largest existing genomic dataset in the lithium response literature (n = 2210 across 14 international sites; 29% responders), we evaluated the degree to which lithium response could be predicted based on 47,465 genotyped single nucleotide polymorphisms using a supervised ML approach. Under appropriate cross-validation procedures, lithium response could be predicted to above-chance levels in two constituent sites (Halifax, Cohen’s kappa 0.15, 95% confidence interval, CI [0.07, 0.24]; and Würzburg, kappa 0.2 [0.1, 0.3]). Variants with shared importance in these models showed over-representation of postsynaptic membrane related genes. Lithium response was not predictable in the pooled dataset (kappa 0.02 [− 0.01, 0.04]), although non-trivial performance was achieved within a restricted dataset including only those patients followed prospectively (kappa 0.09 [0.04, 0.14]). Genomic classification of lithium response remains a promising but difficult task. Classification performance could potentially be improved by further harmonization of data collection procedures.
  •  
19.
  • Amare, Azmeraw T, et al. (författare)
  • Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
  • 2023
  • Ingår i: Molecular psychiatry. - 1476-5578.
  • Tidskriftsartikel (refereegranskat)abstract
    • Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P = 9.8 × 10-12, R2 = 1.9%) and continuous (P = 6.4 × 10-9, R2 = 2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10-4, R2 = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
  •  
20.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 11-20 av 308
Typ av publikation
tidskriftsartikel (245)
konferensbidrag (61)
annan publikation (1)
forskningsöversikt (1)
Typ av innehåll
refereegranskat (233)
övrigt vetenskapligt/konstnärligt (75)
Författare/redaktör
Schalling, M (275)
Lavebratt, C (70)
Stenvinkel, P (41)
Lindholm, B (38)
Landén, Mikael, 1966 (35)
Backlund, L (35)
visa fler...
Heimburger, O (29)
OSBY, U (28)
Barany, P (25)
Frisen, L. (22)
Adolfsson, R. (21)
Qureshi, AR (21)
Millischer, V (21)
Schalling, Martin (21)
Reif, A. (20)
Rietschel, M (19)
Martinsson, L. (19)
Axelsson, J (18)
Bellivier, F. (18)
Cichon, S (17)
Hokfelt, T (17)
Bauer, M (17)
Etain, B. (17)
Jamain, S. (17)
Degenhardt, F (15)
Herms, S. (15)
Leboyer, M. (15)
Mattheisen, M (14)
Grigoroiu-Serbanescu ... (14)
Kittel-Schneider, S. (14)
Johansson, C. (13)
Hauser, J. (13)
Pfennig, A. (13)
Pedersen, NL (12)
Hoffmann, P (12)
Lonnqvist, F (12)
Vieta, E (12)
Heilbronner, U. (12)
Cervantes, P. (12)
Cruceanu, C. (12)
McMahon, FJ (11)
Schulze, TG (11)
Werge, T (10)
Ardau, R. (10)
Chillotti, C. (10)
Del Zompo, M. (10)
Manchia, M. (10)
Monteleone, P. (10)
O'Donovan, C. (10)
Severino, G. (10)
visa färre...
Lärosäte
Karolinska Institutet (294)
Göteborgs universitet (38)
Uppsala universitet (15)
Umeå universitet (5)
Linköpings universitet (5)
Lunds universitet (5)
visa fler...
Kungliga Tekniska Högskolan (3)
RISE (3)
Stockholms universitet (2)
Chalmers tekniska högskola (2)
Örebro universitet (1)
Jönköping University (1)
visa färre...
Språk
Engelska (308)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (57)
Naturvetenskap (4)
Samhällsvetenskap (2)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy