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Sökning: WFRF:(Viktorin Alexander)

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  • de Jong, Simone, et al. (författare)
  • Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
  • 2018
  • Ingår i: Communications Biology. - Nature Publishing Group. - 2399-3642. ; 1
  • Tidskriftsartikel (refereegranskat)abstract
    • Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
  • Ripke, Stephan, et al. (författare)
  • A mega-analysis of genome-wide association studies for major depressive disorder
  • 2013
  • Ingår i: Molecular psychiatry. - 1476-5578. ; 18:4, s. 497-511
  • Tidskriftsartikel (refereegranskat)abstract
    • Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 × 10(-8)), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083-53 822 102, minimum P=5.9 × 10(-9) at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.
  • Brew, Bronwyn K., et al. (författare)
  • Longitudinal depression or anxiety in mothers and offspring asthma a Swedish population-based study
  • 2018
  • Ingår i: International Journal of Epidemiology. - Oxford University Press. - 0300-5771. ; 47:1, s. 166-174
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Previous research has found that maternal stress during pregnancy increases the risk of offspring asthma. However, whether this association is consistent with a causal interpretation has never been tested. The objective is to determine whether there is a critical exposure period for maternal depression or anxiety on offspring asthma or whether cumulative exposure is most important, and to investigate evidence of confounding.Methods: The study population included all children born in Sweden from July 2006 to December 2009 (n = 360 526). Information about childhood asthma, maternal depression or anxiety (diagnosis or medication) and covariates was obtained from the Swedish national health registers. The associations between exposure periods (pre-conception, pregnancy, postnatal or current) and childhood asthma were estimated using structured life course approach hypothesis testing. Paternal and cousin analyses were used to test for evidence of confounding from shared genes and environment.Results: For childhood asthma, cumulative exposure best described the effect of exposure to maternal depression or anxiety up to a maximum of any two exposure periods [adjusted odds ratio 1.44, 95% confidence interval (CI) 1.38, 1.52]. The hypotheses of a critical period were not supported. The paternal and cousin analyses indicated minimal influence from familial confounding.Conclusions: These findings support an association between cumulative exposure to maternal depression or anxiety and asthma development in offspring. This association is unique for maternal depression or anxiety and not due to familial confounding. The clinical implication is that effective psychological management of women with chronic distress may reduce offspring asthma risk.
  • Cesta, Carolyn E, et al. (författare)
  • Depression, anxiety, and antidepressant treatment in women: association with in vitro fertilization outcome
  • 2016
  • Ingår i: Fertility and Sterility. - 0015-0282. ; 105:6, s. 1594-U285
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To investigate associations between depression, anxiety, and antidepressants before in vitro fertilization (IVF) and IVF cycle outcomes, including pregnancy, live birth, and miscarriage.DESIGN: Nationwide register-based cohort study.SETTING: Not applicable.PATIENT(S): Nulliparous women undergoing their first IVF cycle recorded in the Swedish Quality Register of Assisted Reproduction, January 2007 to December 2012 (n = 23,557).INTERVENTION(S): Not applicable.MAIN OUTCOME MEASURE(S): Associations between diagnoses of depression/anxiety, antidepressants, and IVF cycle outcome evaluated using logistic regression to produce adjusted odds ratios (AOR) and 95% confidence intervals (CI).RESULT(S): In total, 4.4% of women had been diagnosed with depression/anxiety and/or dispensed antidepressants before their IVF first cycle. The odds for pregnancy and live birth were decreased (n = 1,044; AOR = 0.86; 95% CI, 0.75-0.98; and AOR = 0.83; 95% CI, 0.72-0.96, respectively). For women with a prescription for a selective serotonin reuptake inhibitor (SSRI) only (n = 829), no statistically significant associations were found. Women with non-SSRI antidepressants (n = 52) were at reduced odds of pregnancy (AOR = 0.41; 95% CI, 0.21-0.80) and live birth (AOR = 0.27; 95% CI, 0.11-0.68). Women with a depression/anxiety diagnosis with no antidepressant (n = 164) also had reduced odds of pregnancy (AOR = 0.58; 95% CI, 0.41-0.82) and live birth (AOR = 0.60; 95% CI, 0.41-0.89). Among the women who became pregnant (39.7%), there were no statistically significant associations between exposure and miscarriage except for the women taking non-SSRI antidepressants (AOR = 3.56; 95% CI, 1.06-11.9).CONCLUSION(S): A diagnosis of depression/anxiety and/or treatment with antidepressants before IVF was slightly associated with reduced odds of pregnancy and live birth. Women with the presence of depression/anxiety without antidepressants had a more pronounced reduction in odds, implying that the underlying disorder is important for the observed association.
  • Hollis, Chris, et al. (författare)
  • Methylphenidate and the risk of psychosis in adolescents and young adults a population-based cohort study
  • 2019
  • Ingår i: Lancet psychiatry. - Elsevier. - 2215-0374. ; 6:8, s. 651-658
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is a clinical concern that prescribing methylphenidate, the most common pharmacological treatment for attention-deficit hyperactivity disorder (ADHD), might increase the risk of psychotic events, particularly in young people with a history of psychosis. We aimed to determine whether the risk of psychotic events increases immediately after initiation of methylphenidate treatment or, in the longer term, 1 year after treatment initiation in adolescents and young adults with and without a previously diagnosed psychotic disorder.Methods: In this cohort study, we used population-based observational data from the Swedish Prescribed Drug Register, the National Patient Register, and the Total Population Register, three population-based registers containing data on all individuals in Sweden, to attain data on sex, birth, death, migration, medication use, and psychotic events for all eligible participants. We screened individuals on these registers to identify those receiving methylphenidate treatment, and who were aged 12-30 years at the start of treatment, for their inclusion in the study. We used a within-individual design to compare the incidence of psychotic events in these individuals during the 12-week periods immediately before and after methylphenidate initiation. Longer term risk was assessed by comparing the incidence of psychotic events 12 weeks before methylphenidate initiation and during a 12-week period one calendar year before the initiation of methylphenidate with the incidence of these events during the 12-week period one calendar year after methylphenidate initiation. We estimated the incidence rate ratios (IRR) and 95% CIs of psychotic events after the initation of methylphenidate treatment, relative to the events before treatment, which were defined as any hospital visit (inpatient admission or outpatient attendance, based on data from the National Patient Register) because of psychosis, using the International Classification of Diseases version 10 definition. Analyses were stratified by whether the individual had a history of psychosis.Findings: We searched the Swedish Prescribed Drug Register to find eligible individuals who had received methylphenidate between Jan 1, 2007 and June 30, 2012. 61 814 individuals were screened, of whom 23 898 (38.7%) individuals were assessed and 37 916 (61.3%) were excluded from the study because they were outside of the age criteria at the start of treatment, they had immigrated, emigrated, or died during the study period, or because they were administered other ADHD medications. The median age at methylphenidate initiation was 17 years, and a history of psychosis was reported in 479 (2.0%) participants. The IRR of psychotic events in the 12-week period after initiation of methylphenidate treatment relative to that in the 12-week period before treatment start was 1.04 (95% CI 0.80-1.34) in adolescents and young adults without a history of psychosis and 0.95 (0.69-1.30) among those with a history of psychosis.Interpretation: Contrary to clinical concerns, we found no evidence that initiation of methylphenidate treatment increases the risk of psychotic events in adolescents and young adults, including in those individuals with a history of psychosis. Our study should reassure clinicians considering initiating methylphenidate treatment for ADHD in adolescents and young adults, and it challenges the widely held view in clinical practice that methylphenidate should be avoided, or its use restricted, in individuals with a history of psychosis.
  • Landén, Mikael, 1966-, et al. (författare)
  • Response to Ostacher et al.
  • 2015
  • Ingår i: The American journal of psychiatry. - 1535-7228. ; 172:6, s. 586-7
  • Tidskriftsartikel (övrigt vetenskapligt)
  • Li, Lin, 1989-, et al. (författare)
  • Associations of Prescribed ADHD Medication in Pregnancy with Pregnancy-Related and Offspring Outcomes : A Systematic Review
  • 2020
  • Ingår i: CNS Drugs. - Adis International. - 1172-7047 .- 1179-1934.
  • Forskningsöversikt (refereegranskat)abstract
    • BACKGROUND: Increasing numbers of reproductive-aged women are using attention-deficit/hyperactivity disorder (ADHD) medications. Findings from studies exploring the safety of these medications during pregnancy are mixed, and it is unclear whether associations reflect causal effects or could be partially or fully explained by other factors that differ between exposed and unexposed offspring.OBJECTIVES: The aim of this systematic review was to evaluate the adverse pregnancy-related and offspring outcomes associated with exposure to prescribed ADHD medication during pregnancy with a focus on how studies to date have handled the influence of confounding.METHODS: We searched PubMed, Embase, PsycINFO, and Web of Science up to 1 July 2019 without any restrictions on language or date of publication. We included all observational studies (e.g., cohort studies, case-control studies, case-crossover studies, cross-sectional studies, and registry-based studies) with pregnant women of any age or from any setting who were prescribed ADHD medications and evaluated any outcome, including both short- and long-term maternal and offspring outcomes. Two independent authors then used the Newcastle-Ottawa Scale to rate the quality of the included studies.RESULTS: Eight cohort studies that estimated adverse pregnancy-related and offspring outcomes associated with exposure to ADHD medication during pregnancy were included in the qualitative review. The included studies had substantial methodological differences in data sources, type of medications examined, definitions of studied pregnancy-related and offspring outcomes, types of control groups, and confounding adjustment. There was no convincing evidence for teratogenic effects according to the relative risk of pregnancy-related and offspring outcomes, and the observed differences in absolute risks were overall small in magnitude. Adjustment for confounding was inadequate in most studies, and none of the included studies adjusted for ADHD severity in the mothers.CONCLUSION: The current evidence does not suggest that the use of ADHD medication during pregnancy results in significant adverse consequences for mother or offspring. However, the data are too limited to make an unequivocal recommendation. Therefore, physicians should consider whether the advantages of using ADHD medication outweigh the potential risks for the developing fetus according to each woman's specific circumstances. Future research should attempt to triangulate research findings based on a combination of different designs that differ in their underlying strengths and limitations and should investigate specific confounding factors, the potential impact of timing of exposure, and potential long-term outcomes in the offspring.
  • Magnusson, Patrik K E, et al. (författare)
  • The Swedish Twin Registry establishment of a biobank and other recent developments
  • 2013
  • Ingår i: Twin Research and Human Genetics. - Cambridge, United Kingdom : Cambridge University Press. - 1832-4274. ; 16:1, s. 317-329
  • Tidskriftsartikel (refereegranskat)abstract
    • The Swedish Twin Registry (STR) today contains more than 194,000 twins and more than 75,000 pairs have zygosity determined by an intra-pair similarity algorithm, DNA, or by being of opposite sex. Of these, approximately 20,000, 25,000, and 30,000 pairs are monozygotic, same-sex dizygotic, and opposite-sex dizygotic pairs, respectively. Since its establishment in the late 1950s, the STR has been an important epidemiological resource for the study of genetic and environmental influences on a multitude of traits, behaviors, and diseases. Following large investments in the collection of biological specimens in the past 10 years we have now established a Swedish twin biobank with DNA from 45,000 twins and blood serum from 15,000 twins, which effectively has also transformed the registry into a powerful resource for molecular studies. We here describe the main projects within which the new collections of both biological samples as well as phenotypic measures have been collected. Coverage by year of birth, zygosity determination, ethnic heterogeneity, and influences of in vitro fertilization are also described.
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