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- Cesta, Carolyn E., et al.
(författare)
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Maternal polycystic ovary syndrome and risk of neuropsychiatric disorders in offspring : prenatal androgen exposure or genetic confounding?
- 2020
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 50:4, s. 616-624
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Maternal polycystic ovary syndrome (PCOS) has been proposed as a model for investigating the role of prenatal androgen exposure in the development of neuropsychiatric disorders. However, women with PCOS are at higher risk of developing psychiatric conditions and previous studies are likely confounded by genetic influences.METHODS: A Swedish nationwide register-based cohort study was conducted to disentangle the influence of prenatal androgen exposure from familial confounding in the association between maternal PCOS and offspring attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and Tourette's disorder and chronic tic disorders (TD/CTD). PCOS-exposed offspring (n = 21 280) were compared with unrelated PCOS-unexposed offspring (n = 200 816) and PCOS-unexposed cousins (n = 17 295). Associations were estimated with stratified Cox regression models.RESULTS: PCOS-exposed offspring had increased risk of being diagnosed with ADHD, ASD, and TD/CTD compared with unrelated PCOS-unexposed offspring. Associations were stronger in girls for ADHD and ASD but not TD/CTD [ADHD: adjusted hazard ratio (aHR) = 1.61 (95% confidence interval (CI) 1.31-1.99), ASD: aHR = 2.02 (95% CI 1.45-2.82)] than boys [ADHD: aHR = 1.37 (95% CI 1.19-1.57), ASD: aHR = 1.46 (95% CI 1.21-1.76)]. For ADHD and ASD, aHRs for girls were stronger when compared with PCOS-unexposed cousins, but slightly attenuated for boys.CONCLUSIONS: Estimates were similar when accounting for familial confounding (i.e. genetics and environmental factors shared by cousins) and stronger in girls for ADHD and ASD, potentially indicating a differential influence of prenatal androgen exposure v. genetic factors. These results strengthen evidence for a potential causal influence of prenatal androgen exposure on the development of male-predominant neuropsychiatric disorders in female offspring of women with PCOS.
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| 2. |
- Dimmock, Andrew P., et al.
(författare)
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Modeling the Geomagnetic Response to the September 2017 Space Weather Event Over Fennoscandia Using the Space Weather Modeling Framework : Studying the Impacts of Spatial Resolution
- 2021
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Ingår i: Space Weather. - : American Geophysical Union (AGU). - 1542-7390. ; 19:5
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Tidskriftsartikel (refereegranskat)abstract
- We must be able to predict and mitigate against geomagnetically induced current (GIC) effects to minimize socio-economic impacts. This study employs the space weather modeling framework (SWMF) to model the geomagnetic response over Fennoscandia to the September 7-8, 2017 event. Of key importance to this study is the effects of spatial resolution in terms of regional forecasts and improved GIC modeling results. Therefore, we ran the model at comparatively low, medium, and high spatial resolutions. The virtual magnetometers from each model run are compared with observations from the IMAGE magnetometer network across various latitudes and over regional-scales. The virtual magnetometer data from the SWMF are coupled with a local ground conductivity model which is used to calculate the geoelectric field and estimate GICs in a Finnish natural gas pipeline. This investigation has lead to several important results in which higher resolution yielded: (1) more realistic amplitudes and timings of GICs, (2) higher amplitude geomagnetic disturbances across latitudes, and (3) increased regional variations in terms of differences between stations. Despite this, substorms remain a significant challenge to surface magnetic field prediction from global magnetohydrodynamic modeling. For example, in the presence of multiple large substorms, the associated large-amplitude depressions were not captured, which caused the largest model-data deviations. The results from this work are of key importance to both modelers and space weather operators. Particularly when the goal is to obtain improved regional forecasts of geomagnetic disturbances and/or more realistic estimates of the geoelectric field.
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| 4. |
- Risal, S., et al.
(författare)
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Prenatal androgen exposure causes a sexually dimorphic transgenerational increase in offspring susceptibility to anxiety disorders
- 2021
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- If and how obesity and elevated androgens in women with polycystic ovary syndrome (PCOS) affect their offspring's psychiatric health is unclear. Using data from Swedish population health registers, we showed that daughters of mothers with PCOS have a 78% increased risk of being diagnosed with anxiety disorders. We next generated a PCOS-like mouse (F-0) model induced by androgen exposure during late gestation, with or without diet-induced maternal obesity, and showed that the first generation (F-1) female offspring develop anxiety-like behavior, which is transgenerationally transmitted through the female germline into the third generation of female offspring (F-3) in the androgenized lineage. In contrast, following the male germline, F-3 male offspring (mF(3)) displayed anxiety-like behavior in the androgenized and the obese lineages. Using a targeted approach to search for molecular targets within the amygdala, we identified five differentially expressed genes involved in anxiety-like behavior in F-3 females in the androgenized lineage and eight genes in the obese lineage. In mF(3) male offspring, three genes were dysregulated in the obese lineage but none in the androgenized lineage. Finally, we performed in vitro fertilization (IVF) using a PCOS mouse model of continuous androgen exposure. We showed that the IVF generated F-1 and F-2 offspring in the female germline did not develop anxiety-like behavior, while the F-2 male offspring (mF(2)) in the male germline did. Our findings provide evidence that elevated maternal androgens in PCOS and maternal obesity may underlie the risk of a transgenerational transmission of anxiety disorders in children of women with PCOS.
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| 5. |
- Al-Khalili, F, et al.
(författare)
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Clinical and echocardiographic characteristics of individuals aged 75/76 years old with screening-detected elevated NT-proBNP levels
- 2020
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Ingår i: Open heart. - : BMJ. - 2053-3624. ; 7:1, s. e001200-
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Tidskriftsartikel (refereegranskat)abstract
- High plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) indicate increased probability of congestive heart failure (CHF) and atrial fibrillation (AF) and are associated with poor prognosis.ObjectiveWe aimed to describe the clinical and echocardiographic characteristics of a population of individuals aged 75/76 years old with NT-proBNP ≥900 ng/L without previously known CHF or AF.MethodsAll individuals aged 75/76 years in the Stockholm region were randomised to a screening study for AF. Half of them were invited to screening. Of those invited, 49.5% agreed to participate. Individuals with NT-proBNP ≥900 ng/L without known CHF were invited for further clinical evaluation.ResultsAmong 6315 participants without AF who had NT-proBNP sampled, 102 without previously known CHF had ≥900 ng/L. Of these, 93 completed further clinical investigations. In the population that was clinically investigated, 53% were female, and the median NT-proBNP was 1200 ng/L. New AF was found in 28 (30%). The NT-proBNP value in this group was not significantly different from those where AF was not detected (median 1285 vs 1178 ng/L). Patients with newly detected AF had larger left atrial volume and higher pulmonary artery pressure than those without AF. Preserved left ventricular ejection fraction (≥50%) was found in 86% of the participants, mid-range ejection fraction (40%–49%) in 3.2% and reduced ejection fraction (<40%) in 10.8%. Thirteen patients (14%) had other serious cardiac disorders that required medical attention.ConclusionElderly individuals with NT-proBNP levels ≥900 ng/L constitute a population at high cardiovascular risk even in the absence of diagnosed CHF or AF, and therefore merit further investigation.
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| 6. |
- Andersson, Anneli, 1992-, et al.
(författare)
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Attention-deficit/hyperactivity disorder and smoking habits in pregnant women
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 15:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Attention-deficit/hyperactivity disorder (ADHD) has been associated with an increased risk of tobacco smoking, and more difficulties with smoking cessation compared to non-ADHD individuals. Women with ADHD may therefore show elevated rates of smoking during pregnancy.Aims: To examine the association between ADHD and smoking habits among pregnant women in Sweden and Norway.Methods: Women pregnant for the first time were identified in Sweden (n = 622,037), and Norway (n = 293,383), of which 1.2% (n = 7,444), and 1.7% (n = 4,951) were defined as having ADHD, respectively. Data on smoking habits were collected early and late in pregnancy.Results: In Sweden, ADHD was associated with an increased risk of smoking early in pregnancy, adjusted risk ratio (adjRR) 2.69 (95% confidence interval, 2.58-2.81), and late in pregnancy, adjRR 2.95 (2.80-3.10). Similar findings were observed in the Norwegian data, early in pregnancy, adjRR 2.31 (2.21-2.40), and late in pregnancy, adjRR 2.56 (2.42-2.70). Women with ADHD were more likely to continue smoking during pregnancy, compared to women without ADHD, both in Sweden adjRR 1.13 (1.10-1.17), and in Norway, adjRR 1.16 (1.12-1.20). Having a sibling diagnosed with ADHD was associated with an increased risk of smoking early and late in pregnancy, in both Sweden and Norway.Conclusions: Women with ADHD are considerably more likely to smoke early and late in (their first) pregnancy and are less likely to stop smoking between the two time points. Smoking, early and late in pregnancy, co-aggregates in families with ADHD. Smoking prevention and intervention programs should be targeted towards women with ADHD, specifically during their childbearing years, to ensure better mother and child outcomes.
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| 10. |
- Le Ray, Isabelle, et al.
(författare)
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Neonatal jaundice, attention deficit hyperactivity disorder and familial effects : A Swedish register study with sibling analysis
- 2021
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Ingår i: Acta Paediatrica. - : Wiley-Blackwell Publishing Inc.. - 0803-5253 .- 1651-2227. ; 110:2, s. 473-479
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Neonatal jaundice is associated with higher risk of attention deficit hyperactivity disorder (ADHD), but it is unclear if the association is influenced by genetic and other familial factors. In this large population-based study, we investigated the association between neonatal jaundice and ADHD while adjusting for familial factors.METHODS: We linked several Swedish registers to identify all singleton births without congenital malformations between 1992 and 2000 (n = 814 420, including 384 290 full siblings) and followed them up until 2009. We calculated hazard ratios (HRs) for the association between neonatal jaundice and ADHD, adjusting for pregnancy, delivery and neonatal characteristics including prematurity, and parental age and education. We repeated the analyses among siblings to adjust for shared familial factors.RESULTS: At a population level, children treated for neonatal jaundice had an increased risk of ADHD (adjusted HR (aHR): 1.13, 95% CI: 1.05-1.22). In the sibling comparisons, there was no clear association between neonatal jaundice and ADHD (aHR: 1.03, 95% CI: 0.82-1.29).CONCLUSION: We found no evidence of an independent association between neonatal jaundice and ADHD within siblings in this large population-based study, suggesting that the association is probably influenced by shared familial factors, such as parental genetic and/or lifestyle effects.
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