| 1. |
- Brew, Bronwyn K., et al.
(författare)
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Paediatric asthma and non-allergic comorbidities : A review of current risk and proposed mechanisms
- 2022
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Ingår i: Clinical and Experimental Allergy. - Stockholm : Wiley-Blackwell Publishing Inc.. - 0954-7894 .- 1365-2222. ; 15:9, s. 1035-1047
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Forskningsöversikt (refereegranskat)abstract
- It is increasingly recognized that children with asthma are at a higher risk of other non-allergic concurrent diseases than the non-asthma population. A plethora of recent research has reported on these comorbidities and progress has been made in understanding the mechanisms for comorbidity. The goal of this review was to assess the most recent evidence (2016-2021) on the extent of common comorbidities (obesity, depression and anxiety, neurodevelopmental disorders, sleep disorders and autoimmune diseases) and the latest mechanistic research, highlighting knowledge gaps requiring further investigation. We found that the majority of recent studies from around the world demonstrate that children with asthma are at an increased risk of having at least one of the studied comorbidities. A range of potential mechanisms were identified including common early life risk factors, common genetic factors, causal relationships, asthma medication and embryologic origins. Studies varied in their selection of population, asthma definition and outcome definitions. Next, steps in future studies should include using objective measures of asthma, such as lung function and immunological data, as well as investigating asthma phenotypes and endotypes. Larger complex genetic analyses are needed, including genome-wide association studies, gene expression-functional as well as pathway analyses or Mendelian randomization techniques; and identification of gene-environment interactions, such as epi-genetic studies or twin analyses, including omics and early life exposure data. Importantly, research should have relevance to clinical and public health translation including clinical practice, asthma management guidelines and intervention studies aimed at reducing comorbidities.
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| 2. |
- Viktorin, Alexander, et al.
(författare)
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Selective serotonin re-uptake inhibitor use during pregnancy : association with offspring birth size and gestational age
- 2016
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Ingår i: International Journal of Epidemiology. - Oxford, United Kingdom : Oxford University Press. - 0300-5771 .- 1464-3685. ; 45:1, s. 170-177
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Tidskriftsartikel (refereegranskat)abstract
- Background: Depression around the time of pregnancy affects at least 1 in 8 women and treatment with selective serotonin re-uptake inhibitors (SSRIs) in pregnant women has been increasing, but research on adverse effects on the fetus have so far commonly used designs unable to account for confounding. We aimed to examine the effects of prenatal SSRI exposure on offspring size outcomes and gestational age, and disentangle whether associations observed were due to the medication or other factors.Methods: We used a Swedish population-based cohort of 392,029 children and national registers to estimate the associations between prenatal exposure to SSRIs and depression on the outcomes birthweight, birth length, birth head circumference, gestational age at birth and preterm birth. A sub-sample of 1007 children was analysed in a within-family design that accounts for unmeasured parental genetic and environmental confounders.Results: Crude analyses revealed associations between prenatal SSRI exposure, and offspring birth size and gestational age. However, in the within-family analyses, only the association between SSRI exposure and reduced gestational age (-2.3 days; 95% confidence interval -3.8 to -0.8) was observed.Conclusions: This study indicates that prenatal SSRI exposure may not be causally related to offspring birth size. Rather, our analyses suggest that the association could be caused by other underlying differences instead of the medication per se. A small reduction of gestational age was associated with SSRI exposure in the within-family analysis and could be due to either the exposure, or other factors changing between pregnancies.
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| 3. |
- Wang, Chen, et al.
(författare)
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Long-term Follow-up of Psychiatric Disorders in Children and Adolescents Conceived by Assisted Reproductive Techniques in Sweden.
- 2022
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-622X .- 2168-6238. ; 79:2, s. 133-142
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Tidskriftsartikel (refereegranskat)abstract
- Individuals conceived with assisted reproductive techniques (ARTs) could be at elevated risk of psychiatric disorders owing to potential adverse effects of the procedures themselves, or because such traits or their risk factors may be more common in couples with infertility.To investigate the risk of psychiatric disorders in adolescents and young adults conceived with ARTs and to evaluate the role of treatment-related parental characteristics.This prospective follow-up of a nationwide birth cohort used linkage of Swedish population registers with coverage through 2018. All children born in Sweden from January 1, 1994, to December 31, 2006, were included in the analysis. Follow-up was completed on December 31, 2018, when participants were 12 to 25 years of age, and data was analyzed from March 17, 2020, to September 10, 2021.In vitro fertilization with or without intracytoplasmic sperm injection and transfer of fresh or frozen-thawed embryos.Clinical diagnoses of mood disorder, including major depression, anxiety, obsessive-compulsive disorder (OCD), or suicidal behavior, were identified from hospital records and outpatient specialist care. Suicide was additionally identified from death certificates. Antidepressant use was identified from dispensations of prescribed medications.A total of 1 221 812 children (48.6% female, 51.4% male) born between 1994 and 2006 were followed up to a median age of 18 (IQR, 15-21) years. Among these participants, 31 565 (2.6%) were conceived with ART. Compared with all others, adolescents conceived with ART had an elevated risk of OCD (hazard ratio [HR], 1.35 [95% CI, 1.20-1.51]), but the association was attenuated and no longer statistically significant after adjustment for parental characteristics (adjusted HR [aHR], 1.10 [95% CI, 0.98-1.24]) and was no longer present when restricted to individuals born to couples with known infertility (aHR, 1.02 [95% CI, 0.89-1.17]). Adolescents conceived with ARTs were not at elevated risk of depression or suicidal behavior compared with other adolescents (irrespective of parental infertility). Type of fertilization (standard in vitro fertilization or intracytoplasmic sperm injection) had no association with outcomes. Compared with non-ART-conceived children of couples with infertility, fresh, but not frozen, embryo transfer was associated with a lower risk of mood disorders (aHR, 0.90 [95% CI, 0.83-0.97]), making frozen embryo transfer appear less advantageous when directly contrasted with fresh embryo transfer.These findings suggest that adolescents conceived with ARTs around the millennium are not at risk of poor psychiatric health compared with the general population, except for an elevated risk of OCD that may be explained by differences in parental characteristics.
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| 4. |
- Brander, Gustaf, et al.
(författare)
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Association of Perinatal Risk Factors With Obsessive-Compulsive Disorder : A Population-Based Birth Cohort, Sibling Control Study
- 2016
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Ingår i: JAMA psychiatry. - Chicago, USA : American Medical Association. - 2168-6238 .- 2168-622X. ; 73:11, s. 1135-1144
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Perinatal complications may increase the risk of obsessive-compulsive disorder (OCD). Previous reports were based on small, retrospective, specialist clinic-based studies that were unable to rigorously control for unmeasured environmental and genetic confounding.Objective: To prospectively investigate a wide range of potential perinatal risk factors for OCD, controlling for unmeasured factors shared between siblings in the analyses.Design, Setting, and Participants: This population-based birth cohort study included all 2 421 284 children from singleton births in Sweden from January 1, 1973, to December 31, 1996, who were followed up through December 31, 2013. From the 1 403 651 families in the cohort, differentially exposed siblings from the 743 885 families with siblings were evaluated; of these, 11 592 families included clusters of full siblings that were discordant for OCD. Analysis of the data was conducted from January, 26, 2015, to September, 5, 2016.Exposures: Perinatal data were collected from the Swedish Medical Birth Register and included maternal smoking during pregnancy, labor presentation, obstetric delivery, gestational age (for preterm birth), birth weight, birth weight in relation to gestational age, 5-minute Apgar score, and head circumference.Main Outcomes and Measures: Previously validated OCD codes (International Statistical Classification of Diseases and Health Related Problems, Tenth Revision, code F42) in the Swedish National Patient Register.Results: Of 2 421 284 individuals included in the cohort, 17 305 persons were diagnosed with OCD. Of these, 7111 were men (41.1%). The mean (SD) age of individuals at first diagnosis of OCD was 23.4 (6.5) years. An increased risk for OCD remained after controlling for shared familial confounders and measured covariates (including sex, year of birth, maternal and paternal age at birth, and parity), for smoking 10 or more cigarettes per day during pregnancy (hazard ratio [HR], 1.27; 95% CI, 1.02-1.58), breech presentation (HR, 1.35; 95% CI, 1.06-1.71), delivery by cesarean section (HR, 1.17; 95% CI, 1.01-1.34), preterm birth (HR, 1.24; 95% CI, 1.07-1.43), birth weight 1501 to 2500 g (HR, 1.30; 95% CI, 1.05-1.62) and 2501 to 3500 g (HR, 1.08; 95% CI, 1.01-1.16), being large for gestational age (HR, 1.23; 95% CI, 1.05-1.45), and Apgar distress scores at 5 minutes (HR, 1.50; 95% CI, 1.07-2.09). Gestational age and birth weight followed inverse dose-response associations, whereby an increasingly higher risk for OCD was noted in children with a shorter gestational age and lower birth weight. We also observed a dose-response association between the number of perinatal events and increased OCD risk, with HRs ranging from 1.11 (95% CI, 1.07-1.15) for 1 event to 1.51 (95% CI, 1.18-1.94) for 5 or more events.Conclusions and Relevance: A range of perinatal risk factors is associated with a higher risk for OCD independent of shared familial confounders, suggesting that perinatal risk factors may be in the causal pathway to OCD.
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| 5. |
- Brander, Gustaf, et al.
(författare)
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Association of Tourette Syndrome and Chronic Tic Disorder With Metabolic and Cardiovascular Disorders
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 76:4, s. 454-461
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Tidskriftsartikel (refereegranskat)abstract
- Importance: There are limited data concerning the risk of metabolic and cardiovascular disorders among individuals with Tourette syndrome (TS) or chronic tic disorder (CTD).Objective: To investigate the risk of metabolic and cardiovascular disorders among individuals with TS or CTD over a period of 40 years.Design, Settings, and Participants: This longitudinal population-based cohort study included all individuals living in Sweden between January 1, 1973, and December 31, 2013. Families with clusters of full siblings discordant for TS or CTD were further identified. Data analyses were conducted from August 1, 2017, to October 11, 2018.Exposures: Previously validated International Classification of Diseases diagnoses of TS or CTD in the Swedish National Patient Register.Main Outcomes and Measures: Registered diagnoses of obesity, dyslipidemia, hypertension, type 2 diabetes, and cardiovascular diseases (including ischemic heart diseases, arrhythmia, cerebrovascular diseases and transient ischemic attack, and arteriosclerosis).Results: Of the 14 045 026 individuals in the cohort, 7804 individuals (5964 males [76.4%]; median age at first diagnosis, 13.3 years [interquartile range, 9.9-21.3 years]) had a registered diagnosis of TS or CTD in specialist care. Of 2 675 482 families with at least 2 singleton full siblings, 5141 families included siblings who were discordant for these disorders. Individuals with TS or CTD had a higher risk of any metabolic or cardiovascular disorders compared with the general population (hazard ratio adjusted by sex and birth year [aHR], 1.99; 95% CI, 1.90-2.09) and sibling controls (aHR for any disorder, 1.37; 95% CI, 1.24-1.51). Specifically, individuals with TS or CTD had higher risks for obesity (aHR, 2.76; 95% CI, 2.47-3.09), type 2 diabetes (aHR, 1.67; 95% CI, 1.42-1.96), and circulatory system diseases (aHR, 1.76; 95% CI, 1.67-1.86). The risk of any cardiometabolic disorder was significantly greater in males than in females (aHR, 2.13; 95% CI, 2.01-2.26 vs aHR, 1.79; 95% CI, 1.64-1.96), as was the risk of obesity (aHR, 3.24; 95% CI, 2.83-3.70 vs aHR, 1.97; 95% CI, 1.59-2.44). The risks were already evident from childhood (the groups were significantly different by age 8 years) and were significantly reduced with the exclusion of individuals with comorbid attention-deficit/hyperactivity disorder (aHR, 1.52; 95% CI, 1.42-1.62), while excluding other comorbidities did not significantly affect the results. Compared with patients with TS or CTD who were not taking antipsychotics, patients with a longer duration of antipsychotic treatment (>1 year) had significantly lower risks of metabolic and cardiovascular disorders.Conclusions and Relevance: The findings of this study suggest that TS and CTD are associated with a substantial risk of metabolic and cardiovascular disorders. The results highlight the importance of carefully monitoring cardiometabolic health in patients with TS or CTD across the lifespan, particularly in those with comorbid attention-deficit/hyperactivity disorder.
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| 6. |
- Brander, Gustaf, et al.
(författare)
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Perinatal risk factors in Tourette's and chronic tic disorders : a total population sibling comparison study
- 2018
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 23:5, s. 1189-1197
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Tidskriftsartikel (refereegranskat)abstract
- Adverse perinatal events may increase the risk of Tourette's and chronic tic disorders (TD/CTD), but previous studies have been unable to control for unmeasured environmental and genetic confounding. We aimed to prospectively investigate potential perinatal risk factors for TD/CTD, taking unmeasured factors shared between full siblings into account. A population-based birth cohort, consisting of all singletons born in Sweden in 1973-2003, was followed until December 2013. A total of 3 026 861 individuals were identified, 5597 of which had a registered TD/CTD diagnosis. We then studied differentially exposed full siblings from 947 942 families; of these, 3563 families included siblings that were discordant for TD/CTD. Perinatal data were collected from the Medical Birth Register and TD/CTD diagnoses were collected from the National Patient Register, using a previously validated algorithm. In the fully adjusted models, impaired fetal growth, preterm birth, breech presentation and cesarean section were associated with a higher risk of TD/CTD, largely independent from shared family confounders and measured covariates. Maternal smoking during pregnancy was associated with risk of TD/CTD in a dose-response manner but the association was no longer statistically significant in the sibling comparison models or after the exclusion of comorbid attention-deficit/hyperactivity disorder. A dose-response relationship between the number of adverse perinatal events and increased risk for TD/CTD was also observed, with hazard ratios ranging from 1.41 (95% confidence interval (CI): 1.33-1.50) for one event to 2.42 (95% CI: 1.65-3.53) for five or more events. These results pave the way for future gene by environment interaction and epigenetic studies in TD/CTD.
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| 7. |
- Brikell, Isabell, et al.
(författare)
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Familial Liability to Epilepsy and Attention-Deficit/Hyperactivity Disorder : A Nationwide Cohort Study
- 2018
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 83:2, s. 173-180
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epilepsy and attention-deficit/hyperactivity disorder (ADHD) are strongly associated; however, the underlying factors contributing to their co-occurrence remain unclear. A shared genetic liability has been proposed as one possible mechanism. Therefore, our goal in this study was to investigate the familial coaggregation of epilepsy and ADHD and to estimate the contribution of genetic and environmental risk factors to their co-occurrence.METHODS: We identified 1,899,654 individuals born between 1987 and 2006 via national Swedish registers and linked each individual to his or her biological relatives. We used logistic regression to estimate the association between epilepsy and ADHD within individual and across relatives. Quantitative genetic modeling was used to decompose the cross-disorder covariance into genetic and environmental factors.RESULTS: Individuals with epilepsy had a statistically significant increased risk of ADHD (odds ratio [OR] = 3.47, 95% confidence interval [CI] = 3.33-3.62). This risk increase extended to children whose mothers had epilepsy (OR = 1.85, 95% CI = 1.75-1.96), children whose fathers had epilepsy (OR = 1.64, 95% CI = 1.54-1.74), full siblings (OR = 1.56, 95% CI = 1.46-1.67), maternal half siblings (OR = 1.28, 95% CI = 1.14-1.43), paternal half siblings (OR = 1.10, 95% CI = 0.96-1.25), and cousins (OR = 1.15, 95% CI = 1.10-1.20). The genetic correlation was 0.21 (95% CI = 0.02-0.40) and explained 40% of the phenotypic correlation between epilepsy and ADHD, with the remaining variance largely explained by nonshared environmental factors (49%, nonshared environmental correlation = 0.36, 95% CI = 0.23-0.49). The contribution of shared environmental factors to the cross-disorder overlap was not statistically significant (11%, shared environmental correlation = 0.32, 95% CI = 20.16-0.79).CONCLUSIONS: This study demonstrates a strong and etiologically complex association between epilepsy and ADHD, with shared familial factors and risk factors unique to the individual contributing to co-occurrence of the disorders. Our findings suggest that epilepsy and ADHD may share less genetic risk as compared with other neurodevelopmental disorders.
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| 8. |
- 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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| 9. |
- Butwicka, Agnieszka, et al.
(författare)
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Association of Childhood-Onset Inflammatory Bowel Disease With Risk of Psychiatric Disorders and Suicide Attempt
- 2019
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Ingår i: JAMA pediatrics. - : American Medical Association. - 2168-6203 .- 2168-6211. ; 173:10, s. 969-978
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Inflammatory bowel disease (IBD) has been associated with psychiatric morbidity in adults, although previous studies have not accounted for familial confounding. In children, IBD has an even more severe course, but the association between childhood-onset IBD and psychiatric morbidity remains unclear.Objective: To examine the risk of psychiatric morbidity in individuals with childhood-onset IBD, controlling for potential confounding shared between siblings.Design, Setting, and Participants: A population-based cohort study was conducted using data from the Swedish national health care and population registers of all children younger than 18 years born from 1973 to 2013. The study included 6464 individuals with a diagnosis of childhood-onset IBD (3228 with ulcerative colitis, 2536 with Crohn disease, and 700 with IBD unclassified) who were compared with 323 200 matched reference individuals from the general population and 6999 siblings of patients with IBD. Cox proportional hazards regression was used to estimate hazard ratios (HRs) with 95% CIs. Statistical analysis was performed from January 1, 1973, to December 1, 2013.Main Outcomes and Measures: The primary outcome was any psychiatric disorder and suicide attempt. Secondary outcomes were the following specific psychiatric disorders: psychotic, mood, anxiety, eating, personality, and behavioral disorders; substance misuse; attention-deficit/hyperactivity disorder; autism spectrum disorders; and intellectual disability.Results: The study included 6464 individuals with a diagnosis of childhood-onset IBD (2831 girls and 3633 boys; mean [SD] age at diagnosis of IBD, 13 [4] years). During a median follow-up time of 9 years, 1117 individuals with IBD (17.3%) received a diagnosis of any psychiatric disorder (incidence rate, 17.1 per 1000 person-years), compared with 38 044 of 323 200 individuals (11.8%) in the general population (incidence rate, 11.2 per 1000 person-years), corresponding to an HR of 1.6 (95% CI, 1.5-1.7), equaling 1 extra case of any psychiatric disorder per 170 person-years. Inflammatory bowel disease was significantly associated with suicide attempt (HR, 1.4; 95% CI, 1.2-1.7) as well as mood disorders (HR, 1.6; 95% CI, 1.4-1.7), anxiety disorders (HR, 1.9; 95% CI, 1.7-2.0) eating disorders (HR, 1.6; 95% CI, 1.3-2.0), personality disorders (HR, 1.4; 95% CI, 1.1-1.8), attention-deficit/hyperactivity disorder (HR, 1.2; 95% CI, 1.1-1.4), and autism spectrum disorders (HR, 1.4; 95% CI, 1.1-1.7) Results were similar for boys and girls. Hazard ratios for any psychiatric disorder were highest in the first year of follow-up but remained statistically significant after more than 5 years. Psychiatric disorders were particularly common for patients with very early-onset IBD (<6 years) and for patients with a parental psychiatric history. Results were largely confirmed by sibling comparison, with similar estimates noted for any psychiatric disorder (HR, 1.6; 95% CI, 1.5-1.8) and suicide attempt (HR, 1.7; 95% CI, 1.2-2.3).Conclusions and Relevance: Overall, childhood-onset IBD was associated with psychiatric morbidity, confirmed by between-sibling results. Particularly concerning is the increased risk of suicide attempt, suggesting that long-term psychological support be considered for patients with childhood-onset IBD.
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| 10. |
- Chen, Qi, et al.
(författare)
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Attention-deficit/hyperactivity disorder and clinically diagnosed obesity in adolescence and young adulthood : a register-based study in Sweden
- 2019
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 49:11, s. 1841-1849
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A recent family study of young adult males suggests a shared familial liability between attention-deficit/hyperactivity disorder (ADHD) and high body mass index (BMI), and a genome-wide meta-analysis reported a genetic correlation of 0.26 between ADHD and BMI. To date, it is unclear whether these findings generalize to the relationship between ADHD and clinically diagnosed obesity.METHOD: By linking the Swedish national registers, we identified 25 38 127 individuals born between 1973 and 2000, together with their siblings and cousins. The risk of clinical obesity in individuals with ADHD was compared with the risk in those without ADHD. The relative contributions of genetic and environmental factors to the association between ADHD and clinical obesity were examined via assessment of the familial co-aggregation of the two conditions and quantitative genetic analysis.RESULTS: Individuals with ADHD were at an increased risk of clinical obesity compared with those without (risk difference 3.73%, 95% confidence interval (CI) 3.55-3.90%; risk ratio 3.05, 95% CI 2.95-3.15). Familial co-aggregation of ADHD and clinical obesity was detected and the strength of the co-aggregation decreased by decreasing genetic relatedness. The correlation between the liabilities to ADHD and clinical obesity can be entirely attributed to their genetic correlation (rg 0.30, 95% CI 0.17-0.44).CONCLUSION: The association between ADHD and clinical obesity in adolescence and young adulthood can be entirely attributed to genetic underpinnings shared by the two conditions. Children with ADHD should be monitored for weight gain so that preventive measures can be taken for those on a suboptimal trajectory.
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