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Sökning: WFRF:(Landen M) > (2015-2019) > (2015)

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1.
  • O'Dushlaine, C, et al. (författare)
  • Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
  • 2015
  • Ingår i: Nature neuroscience. - 1546-1726. ; 18:2, s. 199-209
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.
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2.
  • Cederlöf, M., et al. (författare)
  • Intellectual disability and cognitive ability in Darier disease: Swedish nation-wide study
  • 2015
  • Ingår i: British Journal of Dermatology. - 0007-0963. ; 173:1, s. 155-158
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Darier disease is an autosomal dominant skin disorder caused by mutations in the ATP2A2 gene. Anecdotal reports suggest a relationship between Darier disease and intellectual disabilities, but these reports are based on small clinical samples and limited by absence of control populations.Objectives: To examine the risk of intellectual disability and subclinical impairments in cognitive ability in Darier disease.Methods: We conducted a matched cohort study based on Swedish Population-, Patient- and Conscript Registers. The risk of being diagnosed with intellectual disability was estimated in 770 individuals with Darier disease, compared with matched comparison individuals without Darier disease. Associations were examined with risk ratios from conditional logistic regressions. In addition, we analysed test-based cognitive ability data (i.e. IQ data) from the Swedish conscript examination, for a subset of patients without diagnosed intellectual disability.Results: Individuals with Darier disease had a sixfold increased risk of being diagnosed with intellectual disability (risk ratio 6.2, 95% confidence interval 3.1-12.4). For conscripted individuals with Darier disease but no diagnosed intellectual disability, mean cognitive ability scores were about half a standard deviation lower than for comparison subjects.Conclusions: Darier disease is associated with intellectual disability and subclinical impairments in cognitive ability. The Darier-causing mutations merit further attention in molecular genetic research on intellectual disability and cognitive ability.
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3.
  • Maier, R., et al. (författare)
  • Joint Analysis of Psychiatric Disorders Increases Accuracy of Risk Prediction for Schizophrenia, Bipolar Disorder, and Major Depressive Disorder
  • 2015
  • Ingår i: American Journal of Human Genetics. - 0002-9297. ; 96:2, s. 283-294
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic risk prediction has several potential applications in medical research and clinical practice and could be used, for example, to stratify a heterogeneous population of patients by their predicted genetic risk. However, for polygenic traits, such as psychiatric disorders, the accuracy of risk prediction is low. Here we use a multivariate linear mixed model and apply multi-trait genomic best linear unbiased prediction for genetic risk prediction. This method exploits correlations between disorders and simultaneously evaluates individual risk for each disorder. We show that the multivariate approach significantly increases the prediction accuracy for schizophrenia, bipolar disorder, and major depressive disorder in the discovery as well as in independent validation datasets. By grouping SNPs based on genome annotation and fitting multiple random effects, we show that the prediction accuracy could be further improved. The gain in prediction accuracy of the multivariate approach is equivalent to an increase in sample size of 34% for schizophrenia, 68% for bipolar disorder, and 76% for major depressive disorders using single trait models. Because our approach can be readily applied to any number of GWAS datasets of correlated traits, it is a flexible and powerful tool to maximize prediction accuracy. With current sample size, risk predictors are not useful in a clinical setting but already are a valuable research tool, for example in experimental designs comparing cases with high and low polygenic risk.
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4.
  • Cederlöf, Martin, et al. (författare)
  • Acute intermittent porphyria : comorbidity and shared familial risks with schizophrenia and bipolar disorder in Sweden
  • 2015
  • Ingår i: British Journal of Psychiatry. - London, United Kingdom : Royal College of Psychiatrists. - 0007-1250. ; 207:6, s. 556-557
  • Tidskriftsartikel (refereegranskat)abstract
    • Acute intermittent porphyria (AIP) has been associated with schizophrenia in some studies, but prior research is limited by the absence of comparison populations. Here, we linked Swedish registers to examine the risk of schizophrenia and bipolar disorder in 717 individuals diagnosed with AIP and their first-degree relatives, compared with matched individuals without AIP and their first-degree relatives. Individuals with AIP had a fourfold increased risk of schizophrenia or bipolar disorder. Similarly, relatives of individuals with AIP had double the risk of schizophrenia or bipolar disorder, suggesting that these associations may be as a result of common genetic influences.
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5.
  • Cederlöf, Martin, et al. (författare)
  • Obsessive-Compulsive Disorder, Psychosis, and Bipolarity A Longitudinal Cohort and Multigenerational Family Study
  • 2015
  • Ingår i: Schizophrenia Bulletin. - Oxford, United Kingdom : Oxford University Press. - 0586-7614. ; 41:5, s. 1076-1083
  • Tidskriftsartikel (refereegranskat)abstract
    • Obsessive-compulsive disorder (OCD) often co-occurs with psychotic and bipolar disorders; this comorbidity complicates the clinical management of these conditions. In this population-based longitudinal and multigenerational family study, we examined the patterns of comorbidity, longitudinal risks, and shared familial risks between these disorders. Participants were individuals with a diagnosis of OCD (n = 19,814), schizophrenia (n = 58,336), bipolar disorder (n = 48,180), and schizoaffective disorder (n = 14,904) included in the Swedish Patient Register between January 1969 and December 2009; their first-, second-, and third-degree relatives; and population-matched (1:10 ratio) unaffected comparison individuals and their relatives. The Swedish Prescribed Drug Register was used to control for the potential effect of medication in the longitudinal analyses. Individuals with OCD had a 12-fold increased risk of having a comorbid diagnosis of schizophrenia and a 13-fold increased risk of bipolar disorder and schizoaffective disorder. Longitudinal analyses showed that individuals first diagnosed with OCD had an increased risk for later diagnosis of all other disorders, and vice versa. The risk of bipolar disorder was reduced, but not eliminated, when the use of selective serotonin reuptake inhibitors was adjusted for. OCD-unaffected first-, second-, and third-degree relatives of probands with OCD had a significantly increased risk for all 3 disorders; the magnitude of this risk decreased as the genetic distance increased. We conclude that OCD is etiologically related to both schizophrenia spectrum and bipolar disorders. The results have implications for current gene-searching efforts and for clinical practice.
6.
  • Cederlöf, Martin, et al. (författare)
  • The association between Darier disease, bipolar disorder, and schizophrenia revisited: a population-based family study.
  • 2015
  • Ingår i: Bipolar disorders. - 1399-5618. ; 17:3, s. 340-4
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Darier disease is an autosomal dominant skin disorder caused by mutations in the ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 (ATP2A2) gene and previously reported to cosegregate with bipolar disorder and schizophrenia in occasional pedigrees. It is, however, unknown whether these associations exist also in the general population, and the objective of this study was to examine this question.Methods: We compared a national sample of individuals with Darier disease and their first-degree relatives with matched unexposed individuals from the general population and their first-degree relatives, respectively. To examine risks for bipolar disorder and schizophrenia, risk ratios and 95% confidence intervals (CIs) were estimated using conditional logistic regressions.Results: Individuals with Darier disease had a 4.3 times higher risk of being diagnosed with bipolar disorder (95% CI: 2.6-7.3) and a 2.3 times higher risk of being diagnosed with schizophrenia (95% CI: 1.1-5.2) than matched individuals from the general population. Relatives of individuals with Darier disease had a 1.6 times higher risk of having bipolar disorder (95% CI: 1.1-2.5) than relatives of matched individuals from the general population, but no increased risk of schizophrenia (risk ratio = 0.8, 95% CI: 0.4-1.8).Conclusions: The association between Darier disease and bipolar disorder is manifest also in the population, and our data suggest that genetic variability within the ATP2A2 gene that causes Darier disease also confers susceptibility for bipolar disorder. The Darier-causing mutations merit additional attention in molecular genetic research on bipolar disorder.
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7.
  • Isgren, Anniella, et al. (författare)
  • Increased cerebrospinal fluid interleukin-8 in bipolar disorder patients associated with lithium and antipsychotic treatment.
  • 2015
  • Ingår i: Brain, behavior, and immunity. - 1090-2139. ; 43
  • Tidskriftsartikel (refereegranskat)abstract
    • Inflammation has been linked to the pathophysiology of bipolar disorder based on studies of inflammation markers, such as cytokine concentrations, in plasma and serum samples from cases and controls. However, peripheral measurements of cytokines do not readily translate to immunological activity in the brain. The aim of the present study was to study brain immune and inflammatory activity. To this end, we analyzed cytokines in cerebrospinal fluid from 121 euthymic bipolar disorder patients and 71 age and sex matched control subjects. Concentrations of 11 different cytokines were determined using immunoassays. Cerebrospinal fluid IL-8 concentrations were significantly higher in patients as compared to controls. The other cytokines measured were only detectable in part of the sample. IL-8 concentrations were positively associated to lithium- and antipsychotic treatment. The findings might reflect immune aberrations in bipolar disorder, or be due to the effects of medication.
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8.
  • Kyaga, S., et al. (författare)
  • Bipolar disorder and leadership - a total population study
  • 2015
  • Ingår i: Acta Psychiatrica Scandinavica. - 0001-690X. ; 131:2, s. 111-119
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo investigate whether persons with bipolar disorder and their siblings have leadership traits and are overrepresented in executive professions. MethodA nested case-control study based on longitudinal Swedish total population registries. Data from officer suitability interviews (n=1126519), and information on occupations were collected. Bipolar patients (n=68915) and their healthy siblings were compared with controls. ResultsBipolar patients without comorbidity (pure; n=22980) were overrepresented in both the highest and lowest strata of officer suitability; their healthy siblings in the highest strata only. Patients with pure bipolar disorder were underrepresented in executive professions, whereas their siblings were overrepresented in these professions (particularly political professions). Patients with general bipolar disorder (including those with comorbidities) and their healthy siblings were overrepresented only in the lowest strata of officer suitability ratings. General bipolar patients were underrepresented in executive professions, whereas their siblings had similar rates of executive professions as controls. Adjusting results for IQ slightly attenuated point estimates, but resulted in pure bipolar patients and their siblings no longer being significantly overrepresented in superior strata of officer suitability, and siblings no longer being overrepresented in executive professions. ConclusionResults support that traits associated with bipolar disorder are linked to superior leadership qualities.
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9.
  • Abé, Christoph, et al. (författare)
  • Manic episodes are related to changes in frontal cortex: a longitudinal neuroimaging study of bipolar disorder 1.
  • 2015
  • Ingår i: Brain : a journal of neurology. - 1460-2156. ; 138:Pt 11, s. 3440-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Higher numbers of manic episodes in bipolar patients has, in cross-sectional studies, been associated with less grey matter volume in prefrontal brain areas. Longitudinal studies are needed to determine if manic episodes set off progressive cortical changes, or if the association is better explained by premorbid brain conditions that increase risk for mania. We followed patients with bipolar disorder type 1 for 6 years. Structural brain magnetic resonance imaging scans were performed at baseline and follow-up. We compared patients who had at least one manic episode between baseline and follow-up (Mania group, n = 13) with those who had no manic episodes (No-Mania group, n = 18). We used measures of cortical volume, thickness, and area to assess grey matter changes between baseline and follow-up. We found significantly decreased frontal cortical volume (dorsolateral prefrontal and inferior frontal cortex) in the Mania group, but no volume changes in the No-Mania group. Our results indicate that volume decrease in frontal brain regions can be attributed to the incidence of manic episodes.
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10.
  • Butwicka, Agnieszka, et al. (författare)
  • Hypospadias and increased risk for neurodevelopmental disorders.
  • 2015
  • Ingår i: Journal of child psychology and psychiatry, and allied disciplines. - 1469-7610. ; 56:2
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Hypospadias (aberrant opening of the urethra on the underside of the penis) occurs in 1 per 300 newborn boys. It has been previously unknown whether this common malformation is associated with increased psychiatric morbidity later in life. Studies of individuals with hypospadias also provide an opportunity to examine whether difference in androgen signaling is related to neurodevelopmental disorders. To elucidate the mechanisms behind a possible association, we also studied psychiatric outcomes among brothers of the hypospadias patients. METHODS: Registry study within a national cohort of all 9,262 males with hypospadias and their 4,936 healthy brothers born in Sweden between 1973 and 2009. Patients with hypospadias and their brothers were matched with controls by year of birth and county. The following outcomes were evaluated (1) any psychiatric (2) psychotic, (3) mood, (4) anxiety, (5) eating, and (6) personality disorders, (7) substance misuse, (8) attention-deficit hyperactivity disorder (ADHD), (9) autism spectrum disorders (ASD), (10) intellectual disability, and (11) other behavioral/emotional disorders with onset in childhood. RESULTS: Patients with hypospadias were more likely to be diagnosed with intellectual disability (OR 3.2; 95% CI 2.8-3.8), ASD (1.4; 1.2-1.7), ADHD (1.5; 1.3-1.9), and behavioral/emotional disorders (1.4; 1.2-1.6) compared with the controls. Brothers of patients with hypospadias had an increased risk of ASD (1.6; 1.3-2.1) and other behavioral/emotional disorders with onset in childhood (1.2; 0.9-1.5) in comparison to siblings of healthy individuals. A slightly higher, although not statistically significant, risk was found for intellectual disability (1.3; 1.0-1.9). No relation between other psychiatric diagnosis and hypospadias was found. CONCLUSIONS: This is the first study to identify an increased risk for neurodevelopmental disorders in patients with hypospadias, as well as an increased risk for ASD in their brothers, suggesting a common familial (genetic and/or environmental) liability.
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