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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 4. |
- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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| 5. |
- Chang, Zheng, et al.
(författare)
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Association Between Medication Use for Attention-Deficit/Hyperactivity Disorder and Risk of Motor Vehicle Crashes
- 2017
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Ingår i: JAMA psychiatry. - : American Medical Association. - 2168-6238 .- 2168-622X. ; 74:6, s. 597-603
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Motor vehicle crashes (MVCs) are a major public health problem. Research has demonstrated that individuals with attention-deficit/hyperactivity disorder (ADHD) are more likely to experience MVCs, but the effect of ADHD medication treatment on the risk of MVCs remains unclear.OBJECTIVE: To explore associations between ADHD medication use and risk of MVCs in a large cohort of patients with ADHD.DESIGN, SETTING, AND PARTICIPANTS: For this study, a US national cohort of patients with ADHD (n = 2 319 450) was identified from commercial health insurance claims between January 1, 2005, and December 31, 2014, and followed up for emergency department visits for MVCs. The study used within-individual analyses to compare the risk of MVCs during months in which patients received ADHD medication with the risk of MVCs during months in which they did not receive ADHD medication.EXPOSURES: Dispensed prescription of ADHD medications.MAIN OUTCOMES AND MEASURES: Emergency department visits for MVCs.RESULTS: Among 2 319 450 patients identified with ADHD, the mean (SD) age was 32.5 (12.8) years, and 51.7% were female. In the within-individual analyses, male patients with ADHD had a 38%(odds ratio, 0.62; 95% CI, 0.56-0.67) lower risk of MVCs in months when receiving ADHD medication compared with months when not receiving medication, and female patients had a 42%(odds ratio, 0.58; 95% CI, 0.53-0.62) lower risk of MVCs in months when receiving ADHD medication. Similar reductions were found across all age groups, across multiple sensitivity analyses, and when considering the long-term association between ADHD medication use and MVCs. Estimates of the population-attributable fraction suggested that up to 22.1% of the MVCs in patients with ADHD could have been avoided if they had received medication during the entire follow-up.CONCLUSIONS AND RELEVANCE: Among patients with ADHD, rates of MVCs were lower during periods when they received ADHD medication. Considering the high prevalence of ADHD and its association with MVCs, these findings warrant attention to this prevalent and preventable cause of mortality and morbidity.
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| 6. |
- Quinn, Patrick D., et al.
(författare)
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ADHD Medication and Substance-Related Problems
- 2017
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association. - 0002-953X .- 1535-7228. ; 174:9, s. 877-885
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Substance use disorders are major contributors to excess mortality among individuals with attention deficit hyperactivity disorder (ADHD), yet associations between pharmacological ADHD treatment and substance-related problems remain unclear. This study investigated concurrent and tong-term associations between ADHD medication treatment and substance-related events.Method: The authors analyzed 2005-2014 commercial health care claims from 2,993,887 (47,2% female) adolescent and adult ADHD patients. Within-individual analyses compared the risk of substance-related events (i.e., emergency department visits related to substance use disorders) during months in which patients received prescribed stimulant medication or atomoxetine relative to the risk during months in which they did not.Results: In adjusted within-individual comparisons, relative to periods in which patients did not receive ADHD medication, male patients had 35% lower odds of concurrent substance-related events when receiving medication (odds ratio=0.65, 95% CI=0.64-0.67), and female patients had 31% tower odds of concurrent substance-related events (odds ratio=0.69, 95% CI=0.67-0.71). Moreover, male patients had 19% lower odds of substance-related events 2 years after medication periods (odds ratio=0.81, 95% CI=0.78-0.85), and female patients had 14% tower odds of substance-related events 2 years after medication periods (odds ratio = 0.86, 95% CI= 0.82-0.91). Sensitivity analyses supported most findings but were less consistent for long-term associations among women.Conclusions: These results provide evidence that receiving ADHD medication is unlikely to be associated with greater risk of substance-related problems in adolescence or adulthood. Rather, medication was associated with lower concurrent risk of substance-related events and, at least among men, lower long-term risk of future substance-related events.
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| 7. |
- Brikell, Isabell, et al.
(författare)
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Medication treatment for attention-deficit/hyperactivity disorder and the risk of acute seizures in individuals with epilepsy
- 2019
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Ingår i: Epilepsia. - : Wiley-Blackwell. - 0013-9580 .- 1528-1167. ; 60:2, s. 284-293
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) affects 10%-30% of individuals with epilepsy, yet concerns remain regarding the safety of ADHD medication in this group. The objective of this study was to examine the risk of acute seizures associated with ADHD medication in individuals with epilepsy.METHODS: A total of 21 557 individuals with a seizure history born between 1987 and 2003 were identified from Swedish population registers. Within this study population, we also identified 6773 youth (<19 years of age) who meet criteria for epilepsy, and 1605 youth with continuous antiepileptic drug (AED) treatment. ADHD medication initiation and repeated medication periods were identified from the Swedish Prescribed Drug Register between January 1, 2006 and December 31, 2013. Acute seizures were identified via unplanned visits to hospital or specialist care with a primary seizure discharge diagnosis in the Swedish National Patient Register during the same period. Conditional Poisson regression was used to compare the seizure rate during the 24 weeks before and after initiation of ADHD medication with the rate during the same 48 weeks in the previous year. Cox regression was used to compare the seizure rate during ADHD medication periods with the rate during nonmedication periods. Comparisons were made within-individual to adjust for unmeasured, time?constant confounding.RESULTS: Among 995 individuals who initiated ADHD medication during follow-up, within-individual analyses showed no statistically significant difference in the rate of seizures during the 24 weeks before and after medication initiation, compared to the same period in the previous year. In the full study population 11 754 seizure events occurred during 136 846 person-years and 1855 individuals had at least one ADHD medication period. ADHD medication periods were associated with a reduced rate of acute seizures (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.57-0.94), compared to nonmedication periods within the same individual. Similar associations were found in youth with epilepsy and continuous AED treatment, when adjusting for AEDs, and across sex, age, and comorbid neurodevelopmental disorders.SIGNIFICANCE: We found no evidence for an overall increased rate of acute seizures associated with ADHD medication treatment among individuals with epilepsy. These results suggest that epilepsy should not automatically preclude patients from receiving ADHD medications.
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| 8. |
- Chang, Zheng, et al.
(författare)
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Medication for Attention-Deficit/Hyperactivity Disorder and Risk for Depression : A Nationwide Longitudinal Cohort Study
- 2016
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Ingår i: Biological Psychiatry. - New York : Elsevier. - 0006-3223 .- 1873-2402. ; 80:12, s. 916-922
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Tidskriftsartikel (refereegranskat)abstract
- Background: Attention-deficit/hyperactivity disorder (ADHD) is associated with high rates of psychiatric comorbidity, including depression. However, it is unclear whether ADHD medication increases or decreases the risk for depression.Methods: We studied all individuals with a diagnosis of ADHD born between 1960 and 1998 in Sweden (N = 38,752). We obtained data for prescription of ADHD medication, diagnosis of depression and other psychiatric disorders, and sociodemographic factors from population-based registers. The association between ADHD medication and depression was estimated with Cox proportional hazards regression.Results: After adjustment for sociodemographic and clinical confounders, ADHD medication was associated with a reduced long-term risk (i.e., 3 years later) for depression (hazard ratio = 0.58; 95% confidence interval, 0.51-0.67). The risk was lower for longer duration of ADHD medication. Also, ADHD medication was associated with reduced rates of concurrent depression; within-individual analysis suggested that occurrence of depression was 20% less common during periods when patients received ADHD medication compared with periods when they did not (hazard ratio = 0.80; 95% confidence interval, 0.70-0.92).Conclusions Our study suggests that ADHD medication does not increase the risk of later depression; rather, medication was associated with a reduced risk for subsequent and concurrent depression.
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| 9. |
- Chang, Zheng, et al.
(författare)
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Risks and Benefits of Attention-Deficit/Hyperactivity Disorder Medication on Behavioral and Neuropsychiatric Outcomes : A Qualitative Review of Pharmacoepidemiology Studies Using Linked Prescription Databases
- 2019
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 86:5, s. 335-343
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Forskningsöversikt (refereegranskat)abstract
- Attention-deficit/hyperactivity disorder (ADHD) medication is one of the most commonly prescribed medication classes in child and adolescent psychiatry, and its use is increasing rapidly in adult psychiatry. However, major questions and concerns remain regarding the benefits and risks of ADHD medication, especially in real-world settings. We conducted a qualitative systematic review of studies that investigated the effects of ADHD medication on behavioral and neuropsychiatric outcomes using linked prescription databases from the last 10 years and identified 40 studies from Europe, North America, and Asia. Among them, 18 used within-individual designs to account for confounding by indication. These studies suggested short-term beneficial effects of ADHD medication on several behavioral or neuropsychiatric outcomes (i.e., injuries, motor vehicle accidents, education, substance use disorder), with estimates suggesting relative risk reduction of 9% to 58% for these outcomes. The within-individual studies found no evidence of increased risks for suicidality and seizures. Replication studies are needed for several other important outcomes (i.e., criminality, depression, mania, psychosis). The available evidence from pharmacoepidemiology studies on long-term effects of ADHD medication was less clear. We discuss time-varying confounding and other limitations that should be considered when interpreting results from pharmacoepidemiology studies. Furthermore, we highlight several knowledge gaps to be addressed in future research and implications for research on mechanisms of outcomes of ADHD medications.
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| 10. |
- De Palma, Adriana, et al.
(författare)
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Predicting bee community responses to land-use changes : effects of geographic and taxonomic biases
- 2016
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Land-use change and intensification threaten bee populations worldwide, imperilling pollination services. Global models are needed to better characterise, project, and mitigate bees' responses to these human impacts. The available data are, however, geographically and taxonomically unrepresentative; most data are from North America and Western Europe, overrepresenting bumblebees and raising concerns that model results may not be generalizable to other regions and taxa. To assess whether the geographic and taxonomic biases of data could undermine effectiveness of models for conservation policy, we have collated from the published literature a global dataset of bee diversity at sites facing land-use change and intensification, and assess whether bee responses to these pressures vary across 11 regions (Western, Northern, Eastern and Southern Europe; North, Central and South America; Australia and New Zealand; South East Asia; Middle and Southern Africa) and between bumblebees and other bees. Our analyses highlight strong regionally-based responses of total abundance, species richness and Simpson's diversity to land use, caused by variation in the sensitivity of species and potentially in the nature of threats. These results suggest that global extrapolation of models based on geographically and taxonomically restricted data may underestimate the true uncertainty, increasing the risk of ecological surprises.
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| 11. |
- Hollis, Chris, et al.
(författare)
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Methylphenidate and the risk of psychosis in adolescents and young adults : a population-based cohort study
- 2019
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Ingår i: Lancet psychiatry. - : Elsevier. - 2215-0374 .- 2215-0366. ; 6:8, s. 651-658
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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.
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| 12. |
- Kennedy, Daniel P., et al.
(författare)
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Genetic Influence on Eye Movements to Complex Scenes at Short Timescales
- 2017
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Ingår i: Current Biology. - : Elsevier. - 0960-9822 .- 1879-0445. ; 27:22, s. 3554-3560
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Tidskriftsartikel (refereegranskat)abstract
- Where one looks within their environment constrains one?s visual experiences, directly affects cognitive, emotional, and social processing [1?4], influences learning opportunities [5], and ultimately shapes one?s developmental path. While there is a high degree of similarity across individuals with regard to which features of a scene are fixated [6?8], large individual differences are also present, especially in disorders of development [9?13], and clarifying the origins of these differences is essential to understand the processes by which individuals develop within the complex environments in which they exist and interact. Toward this end, a recent paper [14] found that ?social visual engagement??namely, gaze to eyes and mouths of faces?is strongly influenced by genetic factors. However, whether genetic factors influence gaze to complex visual scenes more broadly, impacting how both social and non-social scene content are fixated, as well as general visual exploration strategies, has yet to be determined. Using a behavioral genetic approach and eye tracking data from a large sample of 11-year-old human twins (233 same-sex twin pairs; 51% monozygotic, 49% dizygotic), we demonstrate that genetic factors do indeed contribute strongly to eye movement patterns, influencing both one?s general tendency for visual exploration of scene content, as well as the precise moment-to-moment spatiotemporal pattern of fixations during viewing of complex social and non-social scenes alike. This study adds to a now growing set of results that together illustrate how genetics may broadly influence the process by which individuals actively shape and create their own visual experiences.
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| 13. |
- Quinn, Patrick D., et al.
(författare)
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Association Between Maternal Smoking During Pregnancy and Severe Mental Illness in Offspring
- 2017
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Ingår i: JAMA psychiatry. - : American Medical Association. - 2168-6238 .- 2168-622X. ; 74:6, s. 589-596
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Several recent population-based studies have linked exposure to maternal smoking during pregnancy to increased risk of severe mental illness in offspring (eg, bipolar disorder, schizophrenia). It is not yet clear, however, whether this association results from causal teratogenic effects or from confounding influences shared by smoking and severe mental illness.OBJECTIVE: To examine the association between smoking during pregnancy and severe mental illness in offspring, adjusting for measured covariates and unmeasured confounding using family-based designs.DESIGN, SETTING, AND PARTICIPANTS: This study analyzed population register data through December 31, 2013, for a cohort of 1 680 219 individuals born in Sweden from January 1, 1983, to December 31, 2001. Associations between smoking during pregnancy and severe mental illness in offspring were estimated with adjustment for measured covariates. Cousins and siblings who were discordant on smoking during pregnancy and severe mental illness were then compared, which helped to account for unmeasured genetic and environmental confounding by design.EXPOSURES: Maternal self-reported smoking during pregnancy, obtained from antenatal visits.MAIN OUTCOMES AND MEASURES: Severe mental illness, with clinical diagnosis obtained from inpatient and outpatient visits and defined using International Classification of Diseases codes for bipolar disorder and schizophrenia spectrum disorders.RESULTS: Of the 1 680 219 offspring included in the analysis, 816 775 (48.61%) were female. At the population level, offspring exposed to moderate and high levels of smoking during pregnancy had greater severe mental illness rates than did unexposed offspring (moderate smoking during pregnancy: hazard ratio [HR], 1.25; 95% CI, 1.19-1.30; high smoking during pregnancy: HR, 1.51; 95% CI, 1.44-1.59). These associations decreased in strength with increasing statistical and methodologic controls for familial confounding. In sibling comparisons with within-family covariates, associations were substantially weaker and nonsignificant (moderate smoking during pregnancy: HR, 1.09; 95% CI, 0.94-1.26; high smoking during pregnancy: HR, 1.14; 95% CI, 0.96-1.35). The pattern of associations was consistent across subsets of severe mental illness disorders and was supported by further sensitivity analyses.CONCLUSIONS AND RELEVANCE: This population-and family-based study failed to find support for a causal effect of smoking during pregnancy on risk of severe mental illness in offspring. Rather, these results suggest that much of the observed population-level association can be explained by measured and unmeasured factors shared by siblings.
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| 14. |
- Quinn, Patrick D., et al.
(författare)
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Associations of mental health and family background with opioid analgesic therapy : a nationwide Swedish register-based study
- 2019
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Ingår i: Pain. - : Elsevier. - 0304-3959 .- 1872-6623. ; 160:11, s. 2464-2472
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Tidskriftsartikel (refereegranskat)abstract
- There is evidence of greater opioid prescription to individuals in the United States with mental health conditions. Whether these associations generalize beyond the US prescription environment and to familial mental health and socioeconomic status (SES) has not been examined comprehensively. This study estimated associations of diverse preexisting mental health diagnoses, parental mental health history, and SES in childhood with opioid analgesic prescription patterns nationwide in Sweden. Using register-based data, we identified 5,071,193 (48.4% female) adolescents and adults who were naive to prescription opioid analgesics and followed them from 2007 to 2014. The cumulative incidence of any dispensed opioid analgesic within 3 years was 11.4% (95% CI, 11.3%-11.4%). Individuals with preexisting self-injurious behavior, as well as opioid and other substance use, attention-deficit/hyperactivity, depressive, anxiety, and bipolar disorders had greater opioid therapy initiation rates than did individuals without the respective conditions (hazard ratios from 1.24 [1.20-1.27] for bipolar disorder to 2.12 [2.04-2.21] for opioid use disorder). Among 1,298,083 opioid recipients, the cumulative incidence of long-term opioid therapy (LTOT) was 7.6% (7.6%-7.7%) within 3 years of initiation. All mental health conditions were associated with greater LTOT rates (hazard ratios from 1.66 [1.56-1.77] for bipolar disorder to 3.82 [3.51-4.15] for opioid use disorder) and were similarly associated with concurrent benzodiazepine-opioid therapy. Among 1,482,462 adolescents and young adults, initiation and LTOT rates were greater for those with parental mental health history or lower childhood SES. Efforts to understand and ameliorate potential adverse effects of opioid analgesics must account for these patterns.
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| 15. |
- Quinn, Patrick D., et al.
(författare)
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Childhood attention-deficit/hyperactivity disorder symptoms and the development of adolescent alcohol problems : A prospective, population-based study of Swedish twins
- 2016
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Ingår i: American Journal of Medical Genetics Part B. - Hoboken, USA : John Wiley & Sons. - 1552-4841 .- 1552-485X. ; 171:7, s. 958-970
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Tidskriftsartikel (refereegranskat)abstract
- Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of problematic alcohol and other substance use in adolescence. This study used data from an ongoing, prospective, population-based twin study of Swedish children and adolescents to evaluate the extent to which the association between ADHD symptoms and alcohol problems reflects a unique source of genetic or environmental risk related to ADHD versus a broader predisposition to youth externalizing behavior. We used all available data from same-sex monozygotic (MZ) and dizygotic (DZ) twins on ADHD symptoms in childhood (age 9/12; N = 15,549) and alcohol problems in late adolescence (age 18; N = 2,564). Consistent with prior longitudinal studies, the phenotypic association between hyperactive/impulsive ADHD symptoms and alcohol problems was small in magnitude, whereas the association for inattentive symptoms was even weaker. Additive genetic influences explained 99.8% of the association between hyperactive/impulsive symptoms and alcohol problems. Furthermore, we found that the genetic risk specifically associated with hyperactive/impulsive symptoms was attenuated when estimated in the context of externalizing behavior liability during childhood, of which ADHD symptoms were specific expressions. In sensitivity analyses exploring hyperactivity in mid-adolescence, we found a similar pattern of genetic associations. These results are consistent with previous findings of genetically driven overlap in the etiology of ADHD and problematic alcohol use. At least some of this co-occurrence may result from a general predisposition to externalizing behaviors in youth. © 2015 Wiley Periodicals, Inc.
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| 16. |
- Sujan, Ayesha C, et al.
(författare)
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Associations of maternal antidepressant use during the first trimester of pregnancy with preterm birth, small for gestational age, autism spectrum disorder, and attention-deficit/hyperactivity disorder in offspring
- 2017
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Ingår i: JAMA. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0098-7484 .- 1538-3598.
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Prenatal antidepressant exposure has been associated with adverse outcomes. Previous studies, however, may not have adequately accounted for confounding. Objective: To evaluate alternative hypotheses for associations between first-trimester antidepressant exposure and birth and neurodevelopmental problems. Design, Setting, and Participants: This retrospective cohort study included Swedish offspring born between 1996 and 2012 and followed up through 2013 or censored by death or emigration. Analyses controlling for pregnancy, maternal and paternal covariates, as well as sibling comparisons, timing of exposure comparisons, and paternal comparisons, were used to examine the associations. Exposures: Maternal self-reported first-trimester antidepressant use and first-trimester antidepressant dispensations. Main Outcomes and Measures: Preterm birth (<37 gestational weeks), small for gestational age (birth weight <2 SDs below the mean for gestational age), and first inpatient or outpatient clinical diagnosis of autism spectrum disorder and attention-deficit/hyperactivity disorder in offspring. Results: Among 1580629 offspring (mean gestational age, 279 days; 48.6% female; 1.4% [n = 22544] with maternal first-trimester self-reported antidepressant use) born to 943776 mothers (mean age at childbirth, 30 years), 6.98% of exposed vs 4.78% of unexposed offspring were preterm, 2.54% of exposed vs 2.19% of unexposed were small for gestational age, 5.28% of exposed vs 2.14% of unexposed were diagnosed with autism spectrum disorder by age 15 years, and 12.63% of exposed vs 5.46% of unexposed were diagnosed with attention-deficit/hyperactivity disorder by age 15 years. At the population level, first-trimester exposure was associated with all outcomes compared with unexposed offspring (preterm birth odds ratio [OR], 1.47 [95% CI, 1.40-1.55]; small for gestational age OR, 1.15 [95% CI, 1.06-1.25]; autism spectrum disorder hazard ratio [HR], 2.02 [95% CI, 1.80-2.26]; attention-deficit/hyperactivity disorder HR, 2.21 [95% CI, 2.04-2.39]). However, in models that compared siblings while adjusting for pregnancy, maternal, and paternal traits, first-trimester antidepressant exposure was associated with preterm birth (OR, 1.34 [95% CI, 1.18-1.52]) but not with small for gestational age (OR, 1.01 [95% CI, 0.81-1.25]), autism spectrum disorder (HR, 0.83 [95% CI, 0.62-1.13]), or attention-deficit/hyperactivity disorder (HR, 0.99 [95% CI, 0.79-1.25]). Results from analyses assessing associations with maternal dispensations before pregnancy and with paternal first-trimester dispensations were consistent with findings from the sibling comparisons. Conclusions and Relevance: Among offspring born in Sweden, after accounting for confounding factors, first-trimester exposure to antidepressants, compared with no exposure, was associated with a small increased risk of preterm birth but no increased risk of small for gestational age, autism spectrum disorder, or attention-deficit/hyperactivity disorder.
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| 17. |
- Sujan, Ayesha C., et al.
(författare)
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Associations of Maternal Antidepressant Use During the First Trimester of Pregnancy With Preterm Birth, Small for Gestational Age, Autism Spectrum Disorder, and Attention-Deficit/Hyperactivity Disorder in Offspring
- 2017
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Ingår i: Obstetrical and Gynecological Survey. - : Lippincott Williams & Wilkins. - 0029-7828 .- 1533-9866. ; 72:9, s. 523-524
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Tidskriftsartikel (refereegranskat)abstract
- While antidepressant use during pregnancy has been associated with adverse birth and neurodevelopmental outcomes, these associations may be attributed to confounding factors, such as genetic influences, maternal stress, or poor health practices during pregnancy. This study used 4 observational designs to investigate these associations, including sibling and paternal information.The study used multiple national Swedish registries. First-trimester exposures, defined as at least 1 dispensation between 90 days before estimated conceptions and 90 days after estimated conception, to any antidepressants and selective serotonin reuptake inhibitors, reported through either maternal self-report or dispensation records, were the main exposures evaluated. The main outcomes were small for gestational age, defined as birth weight less than 2 SDs below the mean for gestational age; preterm birth, defined as less than 37 gestational weeks; and diagnosis of autism spectrum disorder or attention-deficit/hyperactivity disorder (ADHD). Maternal and paternal covariates included age of childbearing, highest level of completed education, history of criminal conviction, history of psychiatric illnesses, history of suicide attempts, and country of origin (Sweden or outside Sweden). Parity and year of birth were pregnancy covariates. Population-wide baseline models were assessed adjusting only for pregnancy covariates. Then, population-wide associations were adjusted for maternal and paternal covariates as well. A third model compared exposure-and outcome-discordant offspring within families.After exclusion of multiple births, missing father identifiers, or other missing information, a final cohort of 1,580,629 offspring born to 943,776 was used. Of these, 26,477 offspring had first-trimester maternal antidepressant dispensations, 22,125 of which were selective serotonin reuptake inhibitor dispensations. Preterm births accounted for 6.98% of exposed and 4.78% of unexposed offspring. In the baseline models, first-trimester exposure was associated with all 4 outcomes (preterm birth odds ratio [OR], 1.47; 95% confidence interval [CI], 1.40-1.55]; small for gestational age OR, 1.15 [95% CI, 1.06-1.25]; ADHD HR, 2.21 [95% CI, 2.04-2.39]). After adjusting for pregnancy and maternal and paternal traits and comparing sibling data, first-trimester antidepressant exposure was associated with only a small increased risk of preterm birth (OR, 1.34 [95% CI, 1.18-1.52]) and was not associated with small for gestational age (OR, 1.01 [95% CI, 0.81-1.25]), ADHD (HR, 0.99 [95% CI, 0.79-1.25]), or autism spectrum disorder (HR, 0.83 [95% CI, 0.62-1.13]).Unexposed and exposed siblings were found to be at equal risk of small for gestational age, ADHD, and autism spectrum disorder as one another, whereas exposed siblings had a slightly increased risk of preterm birth. Both autism spectrum disorder and ADHD were associated with paternal first-trimester antidepressant dispensations, supporting the idea that familial confounding may explain associations between exposure and neurodevelopmental disorders.
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| 18. |
- Sujan, Ayesha C., et al.
(författare)
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Maternal prescribed opioid analgesic use during pregnancy and associations with adverse birth outcomes : A population-based study
- 2019
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 16:12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Published research on prescribed opioid analgesic (POA) use during pregnancy and birth outcomes is limited in scope and has not adequately adjusted for potential confounding factors. To help address these gaps, we estimated associations between maternal POAs during pregnancy and two adverse birth outcomes using a large population-based dataset, multiple definitions of POA exposure, and several methods to evaluate the influence of both measured and unmeasured confounding factors.METHODS AND FINDINGS: We obtained data by linking information from several Swedish registers and conducted a retrospective cohort study on a population-based sample of 620,458 Swedish births occurring between 2007 and 2013 (48.6% female; 44.4% firstborn). We evaluated associations between prenatal POA exposure and risk for preterm birth (PTB; <37 gestational weeks) and small for gestational age (SGA; birth weight 2 standard deviations below the expected weight for gestational age or lower). We evaluated the influence of confounding by adjusting for a wide range of measured covariates while comparing exposed and unexposed infants. Additionally, we adjusted for unmeasured confounding factors by using several advanced epidemiological designs. Infants exposed to POAs anytime during pregnancy were at increased risk for PTB compared with unexposed infants (6.4% exposed versus 4.4% unexposed; adjusted odds ratio [OR] = 1.38, 95% confidence interval [CI] 1.31-1.45, p < 0.001). This association was attenuated when we compared POA-exposed infants with acetaminophen-exposed infants (OR = 1.18, 95% CI 1.07-1.30, p < 0.001), infants born to women who used POAs before pregnancy only (OR = 1.05, 95% CI 0.96-1.14, p = 0.27), and unexposed siblings (OR = 0.99, 95% CI 0.85-1.14, p = 0.92). We also evaluated associations with short-term versus persistent POA use during pregnancy and observed a similar pattern of results, although the magnitudes of associations with persistent exposure were larger than associations with any use or short-term use. Although short-term use was not associated with SGA (adjusted ORsingle-trimester = 0.95, 95% CI 0.87-1.04, p = 0.29), persistent use was associated with increased risk for SGA (adjusted ORmultiple-trimester = 1.40, 95% CI 1.17-1.67, p < 0.001) compared with unexposed infants. The association with persistent exposure was attenuated when we used alternative comparison groups (e.g., sibling comparison OR = 1.22, 95% CI 0.60-2.48, p = 0.58). Of note, our study had limitations, including potential bias from exposure misclassification, an inability to adjust for all sources of confounding, and uncertainty regarding generalizability to countries outside of Sweden.CONCLUSIONS: Our results suggested that observed associations between POA use during pregnancy and risk of PTB and SGA were largely due to unmeasured confounding factors, although we could not rule out small independent associations, particularly for persistent POA use during pregnancy.
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| 19. |
- Wiggs, Kelsey K., et al.
(författare)
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Attention-deficit/hyperactivity disorder medication and seizures
- 2018
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Ingår i: Neurology. - : AAN Publications. - 0028-3878 .- 1526-632X. ; 90:13, s. e1104-e1110
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Individuals with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of seizures, but there is uncertainty about whether ADHD medication treatment increases risk among patients with and without preexisting seizures.METHODS: We followed a sample of 801,838 patients with ADHD who had prescribed drug claims from the Truven Health MarketScan Commercial Claims and Encounters databases to examine whether ADHD medication increases the likelihood of seizures among ADHD patients with and without a history of seizures. First, we assessed overall risk of seizures among patients with ADHD. Second, within-individual concurrent analyses assessed odds of seizure events during months when a patient with ADHD received ADHD medication compared with when the same individual did not, while adjusting for antiepileptic medications. Third, within-individual long-term analyses examined odds of seizure events in relation to the duration of months over the previous 2 years patients received medication.RESULTS: Patients with ADHD were at higher odds for any seizure compared with non-ADHD controls (odds ratio [OR] = 2.33, 95% confidence interval [CI] = 2.24-2.42 males; OR = 2.31, 95% CI = 2.22-2.42 females). In adjusted within-individual comparisons, ADHD medication was associated with lower odds of seizures among patients with (OR = 0.71, 95% CI = 0.60-0.85) and without (OR = 0.71, 95% CI = 0.62-0.82) prior seizures. Long-term within-individual comparisons suggested no evidence of an association between medication use and seizures among individuals with (OR = 0.87, 95% CI = 0.59-1.30) and without (OR = 1.01, 95% CI = 0.80-1.28) a seizure history.CONCLUSIONS: Results reaffirm that patients with ADHD are at higher risk of seizures. However, ADHD medication was associated with lower risk of seizures within individuals while they were dispensed medication, which is not consistent with the hypothesis that ADHD medication increases risk of seizures.
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