| 1. |
- Ruderfer, Douglas M., et al.
(författare)
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Mosaic copy number variation in schizophrenia
- 2013
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 21:9, s. 1007-1011
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Tidskriftsartikel (refereegranskat)abstract
- Recent reports suggest that somatic structural changes occur in the human genome, but how these genomic alterations might contribute to disease is unknown. Using samples collected as part of the International Schizophrenia Consortium (schizophrenia, n = 3518; control, n = 4238) recruited across multiple university research centers, we assessed single-nucleotide polymorphism genotyping arrays for evidence of chromosomal anomalies. Data from genotyping arrays on each individual were processed using Birdsuite and analyzed with PLINK. We validated potential chromosomal anomalies using custom nanostring probes and quantitative PCR. We estimate chromosomal alterations in the schizophrenia population to be 0.42%, which is not significantly different from controls (0.26%). We identified and validated a set of four extremely large (>10 Mb) chromosomal anomalies in subjects with schizophrenia, including a chromosome 8 trisomy and deletion of the q arm of chromosome 7. These data demonstrate that chromosomal anomalies are present at low frequency in blood cells of both control and schizophrenia subjects.
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| 2. |
- Genovese, Giulio, et al.
(författare)
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Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence.
- 2014
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Ingår i: The New England journal of medicine. - 1533-4406 .- 0028-4793. ; 371:26, s. 2477-87
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Tidskriftsartikel (refereegranskat)abstract
- Cancers arise from multiple acquired mutations, which presumably occur over many years. Early stages in cancer development might be present years before cancers become clinically apparent.
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| 3. |
- Hedelin, M., et al.
(författare)
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Dietary intake of fish, omega-3, omega-6 polyunsaturated fatty acids and vitamin D and the prevalence of psychotic-like symptoms in a cohort of 33 000 women from the general population
- 2010
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Ingår i: BMC Psychiatry. - 1471-244X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low intake of fish, polyunsaturated fatty acids (PUFA) and vitamin D deficiency has been suggested to play a role in the development of schizophrenia. Our aim was to evaluate the association between the intake of different fish species, PUFA and vitamin D and the prevalence of psychotic-like symptoms in a population-based study among Swedish women. Methods: Dietary intake was estimated using a food frequency questionnaire among 33 623 women aged 30-49 years at enrolment (1991/92). Information on psychotic- like symptoms was derived from a follow-up questionnaire in the years 2002/03. Participants were classified into three predefined levels: low, middle and high frequency of symptoms. The association between diet and psychotic- like symptoms was summarized in terms of relative risks (RR) and corresponding 95% confidence intervals and was evaluated by energy-adjusted multinomial logistic regression. Results: 18 411 women were classified as having a low level of psychotic- like symptoms, 14 395 as middle and 817 as having a high level. The risk of high level symptoms was 53% (95% CI, 30-69%) lower among women who ate fish 3-4 times per week compared to women who never ate fish. The risk was also lower for women with a high intake of omega-3 and omega-6 PUFA compared to women with a lower intake of these fatty acids. The effect was most pronounced for omega-6 PUFAs. The RR comparing the highest to the lowest quartile of omega-6 PUFAs intake was 0.78 (95% CI, 0.64-0.97). The associations were J-shaped with the strongest reduced risk for an intermediate intake of fish or PUFA. For fatty fish (herring/mackerel, salmon-type fish), the strongest inverse association was found for an intermediate intake (RR: 0.81, 95% CI, 0.66-0.98), whereas a high intake of fatty fish was associated with an increased risk of psychotic- like symptoms (RR: 1.90, 95% CI, 1.34-2.70). Women in the highest compared with the lowest quartile of vitamin D consumption experienced a 37% (95% CI, 22-50%) lower risk of psychotic- like symptoms. Conclusion: Our findings raise a possibility that adult women with a high intake of fish, omega-3 or omega-6 PUFA and vitamin D have a lower rate of psychotic- like symptoms.
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| 4. |
- Higier, Rachel G, et al.
(författare)
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Enhanced neurocognitive functioning and positive temperament in twins discordant for bipolar disorder
- 2014
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 171:11, s. 1191-1198
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Based on evidence linking creativity and bipolar disorder, a model has been proposed whereby factors influencing liability to bipolar disorder confer certain traits with positive effects on reproductive fitness. The authors tested this model by examining key traits known to be associated with evolutionary fitness, namely, temperament and neurocognition, in individuals carrying liability for bipolar disorder. Schizophrenia probands and their co-twins were included as psychiatric controls.METHOD: Twin pairs discordant for bipolar disorder and schizophrenia and control pairs were identified through the Swedish Twin Registry. The authors administered a neuropsychological test battery and temperament questionnaires to samples of bipolar probands, bipolar co-twins, schizophrenia probands, schizophrenia co-twins, and controls. Multivariate mixed-model analyses of variance were conducted to compare groups on temperament and neurocognitive scores.RESULTS: Bipolar co-twins showed elevated scores on a "positivity" temperament scale compared with controls and bipolar probands, while bipolar probands scored higher on a "negativity" scale compared with their co-twins and controls, who did not differ. Additionally, bipolar co-twins showed superior performance compared with controls on tests of verbal learning and fluency, while bipolar probands showed performance decrements across all neurocognitive domains. In contrast, schizophrenia co-twins showed attenuated impairments in positivity and overall neurocognitive functioning relative to their ill proband counterparts.CONCLUSIONS: These findings suggest that supra-normal levels of sociability and verbal functioning may be associated with liability for bipolar disorder. These effects were specific to liability for bipolar disorder and did not apply to schizophrenia. Such benefits may provide a partial explanation for the persistence of bipolar illness in the population.
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| 5. |
- Humphreys, Keith, et al.
(författare)
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The Genetic Structure of the Swedish Population
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:8, s. e22547-
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Tidskriftsartikel (refereegranskat)abstract
- Patterns of genetic diversity have previously been shown to mirror geography on a global scale and within continents and individual countries. Using genome-wide SNP data on 5174 Swedes with extensive geographical coverage, we analyzed the genetic structure of the Swedish population. We observed strong differences between the far northern counties and the remaining counties. The population of Dalarna county, in north middle Sweden, which borders southern Norway, also appears to differ markedly from other counties, possibly due to this county having more individuals with remote Finnish or Norwegian ancestry than other counties. An analysis of genetic differentiation (based on pairwise F(st)) indicated that the population of Sweden's southernmost counties are genetically closer to the HapMap CEU samples of Northern European ancestry than to the populations of Sweden's northernmost counties. In a comparison of extended homozygous segments, we detected a clear divide between southern and northern Sweden with small differences between the southern counties and considerably more segments in northern Sweden. Both the increased degree of homozygosity in the north and the large genetic differences between the south and the north may have arisen due to a small population in the north and the vast geographical distances between towns and villages in the north, in contrast to the more densely settled southern parts of Sweden. Our findings have implications for future genome-wide association studies (GWAS) with respect to the matching of cases and controls and the need for within-county matching. We have shown that genetic differences within a single country may be substantial, even when viewed on a European scale. Thus, population stratification needs to be accounted for, even within a country like Sweden, which is often perceived to be relatively homogenous and a favourable resource for genetic mapping, otherwise inferences based on genetic data may lead to false conclusions.
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| 6. |
- Lundström, Sebastian, et al.
(författare)
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Trajectories leading to autism spectrum disorders are affected by paternal age: findings from two nationally representative twin studies.
- 2010
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Ingår i: Journal of Child Psychology and Psychiatry, and Allied Disciplines. - : Wiley. - 0021-9630 .- 1469-7610. ; 51:7, s. 850-856
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite extensive efforts, the causes of autism remain unknown. Advancing paternal age has been associated with various neurodevelopmental disorders. We aim to investigate three unresolved questions: (a) What is the association between paternal age and autism spectrum disorders (ASD)?; (b) Does paternal age moderate the genetic and environmental etiological factors for ASD? (c) Does paternal age affect normal variation in autistic-like traits? Methods: Two nationally representative twin studies from Sweden (n = 11, 122, assessed at age 9 or 12) and the UK (n = 13, 524, assessed at age 9) were used. Categorical and continuous measures of ASD, autistic-like traits and autistic similarity were calculated and compared over paternal age categories. Results: Both cohorts showed a strong association between paternal age and the risk for ASD. A U-shaped risk association could be discerned since the offspring of both the youngest and oldest fathers showed an elevation in the risk for ASD. Autistic similarity increased with advancing paternal age in both monozygotic and dizygotic twins. Both cohorts showed significantly higher autistic-like traits in the offspring of the youngest and oldest fathers. Conclusions: Phenomena associated with paternal age are clearly involved in the trajectories leading to autistic-like traits and ASD. Mechanisms influencing the trajectories might differ between older and younger fathers. Molecular genetic studies are now needed in order to further understand the association between paternal age and ASD, as well as normal variation in social, language, and repetitive behaviors in the general population.
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| 7. |
- Tjärnlund-Wolf, Anna, 1974, et al.
(författare)
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Allelic imbalance of tissue-type plasminogen activator (t-PA) gene expression in human brain tissue.
- 2011
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Ingår i: Thrombosis and haemostasis. - 0340-6245. ; 105:6, s. 945-53
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Tidskriftsartikel (refereegranskat)abstract
- We have identified a single-nucleotide polymorphism (SNP) in the t-PA enhancer (-7351C>T), which is associated with endothelial t-PA release in vivo. In vitro studies demonstrated that this SNP is functional at the level of transcription. In the brain, t-PA has been implicated in both physiologic and pathophysiologic processes. The aim of the present study was to examine the effect of the t-PA -7351C>T SNP on t-PA gene expression in human brain tissue. Allelic mRNA expression was measured in heterozygous post-mortem brain tissues using quantitative TaqMan genotyping assay. Protein-DNA interactions were assessed using electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). Significantly higher levels of t-PA mRNA were generated from chromosomes that harboured the wild-type -7351C allele, as compared to those generated from the mutant T allele (for the hippocampus, C to T allelic ratio of ~1.3, p=0.010, n=12; and for the cortex, C to T allelic ratio of ~1.2, p=0.017, n=12). EMSA showed reduced neuronal and astrocytic nuclear protein binding affinity to the T allele, and identified Sp1 and Sp3 as the major transcription factors that bound to the -7351 site. ChIP analyses confirmed that Sp1 recognises this site in intact cells. In conclusion, the t-PA -7351C>T SNP affects t-PA gene expression in human brain tissue. This finding might have clinical implications for neurological conditions associated with enhanced t-PA levels, such as in the acute phase of cerebral ischaemia, and also for stroke recovery.
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| 8. |
- Arnberg, Filip K, 1981-, et al.
(författare)
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Fifteen years after a ferry disaster : Clinical interviews and survivors’ self-assessment of their experience
- 2013
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Ingår i: European Journal of Psychotraumatology. - : Informa UK Limited. - 2000-8198 .- 2000-8066. ; 4, s. 20650-
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Tidskriftsartikel (refereegranskat)abstract
- Background:Disasters yield increased rates of psychological disorders decades later. Other consequences, however, have received little attention in the past.Objective:We aimed to examine diagnostic status and survivors’ views on disaster-related consequences and social support.Methods:A mixed-methods approach was used with 22 survivors (of 49 eligible) 15 years after a ferry disaster. Data collection included audiotaped interviews with open-ended questions and diagnostic assessment of Axis-I disorders.Results:The post-disaster incidence was 54% (12/22) for Axis-I disorders, and 45% (10/22) for full or subsyndromal posttraumatic stress disorder. Thematic analysis revealed that survivor perception of the longterm consequences included positive (character change) and negative aspects (being ascribed a survivor identity). Participants’ sought social support for several years, yet many felt hindered by experiential dissimilarity and distress of significant others.Conclusions:Axis-I disorders were prevalent, but not salient to survivors’ perceptions in the long-term. Postdisaster interventions need to attend to common barriers to support.
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| 9. |
- Arnberg, Filip K, 1981-, et al.
(författare)
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Prospective longitudinal long-term studies 14-20 years after three disasters
- 2011
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Ingår i: European Journal of Psychotraumatology. ; , s. 72-72
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Konferensbidrag (refereegranskat)abstract
- Although clinical experience and past research have shown that posttraumatic stress (PTS) can last for decades after a disaster, long-term follow-ups are scarce and little is known about predictors of chronic PTS. In this presentation, long-term consequences of disasters will be described by a summary of the findings from three surveys of man-made/technological disasters with 2-4 assessments during the first 34-4 years and with a long-term assessment of PTSD and general mental health after 14-20 years (Ns = 33-57). Similarities and dissimilarities in the course of PTS between the disasters will be presented. The influence of traumatic bereavement, psychological or pharmacological treatment, and additional negative life events on long-term PTS will be discussed, and experiences form conducting long-term studies will be communicated.
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| 10. |
- Arnberg, Filip K, 1981-, et al.
(författare)
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Social support moderates posttraumatic stress and general distress after disaster
- 2012
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Ingår i: Journal of Traumatic Stress. - : Wiley. - 0894-9867 .- 1573-6598. ; 25:6, s. 721-727
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Tidskriftsartikel (refereegranskat)abstract
- Social support buffers the negative impact of stressful events. Less, however, is known about the characteristics of this association in the context of disaster and findings have been discrepant regarding direct and buffering effects. This study tested whether the protective effects of social support differed across levels of exposure severity (i.e., buffered distress) and assessed whether the buffering effect differed between event-specific and general distress. Participants were 4,600 adult Swedish tourists (44% of invited; 55% women) repatriated within 3 weeks after the 2004 Indian Ocean tsunami. A survey 14 months after the disaster included the Crisis Support Scale, the Impact of Event Scale-Revised (IES-R), and the General Health Questionnaire (GHQ-12). Social support buffered the negative impact of exposure on both outcomes. The support and distress association ranged from very small in participants with low exposure to moderate in those with high exposure (ηp2 = .004 to .053). The buffering effect was not found to differ between the IES-R and GHQ-12, F(2, 4589) = 0.87, p = .42. The findings suggest that social support moderates the stressor-distress relationship after disasters. This study might help explain discrepant findings and point to refinements of postdisaster interventions.
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