1. |
- Bang Madsen, Kathrine, et al.
(författare)
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Attention-Deficit Hyperactivity Disorder (ADHD) Medication Use Trajectories Among Women in the Perinatal Period
- 2024
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Ingår i: CNS Drugs. - : Adis International Ltd.. - 1172-7047 .- 1179-1934. ; 38, s. 301-314
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: An increasing number of women of reproductive age are treated with attention-deficit hyperactivity disorder (ADHD) medication; however, patterns of ADHD medication use for women in the perinatal period have not been well described.OBJECTIVE: This study aimed to describe ADHD medication use patterns from 1 year before pregnancy to 1 year after delivery, and to describe sociodemographic characteristics and clinical features by medication trajectories.METHODS: The population-based cohort study included pregnancies in Denmark between 1997 and 2020, from the Medical Birth Register, by women who filled at least one prescription for ADHD medication from 12 months before pregnancy until 12 months after delivery. We applied group-based trajectory modeling to classify women into subgroups based on the identification of heterogeneous ADHD medication treatment patterns, and described the characteristics associated with these groups.RESULTS: Overall, we included 4717 pregnancies leading to liveborn singletons by 4052 mothers with a mean (standard deviation) age of 27.5 (5.6) years. We identified four treatment trajectories across pregnancy and the postpartum period: continuers (23.3%), discontinuers (41.8%), interrupters who ceased filling prescriptions during pregnancy but resumed postpartum (17.2%), and postpartum initiators (17.7%). Continuers were older at the time of conception, gave birth in more recent years, were more likely to smoke during pregnancy, and used other psychotropic medications during pregnancy. A large proportion of continuers used methylphenidate (89.1%) compared with the other groups (75.9-84.1%) and had switched ADHD medication type during the whole period (16.4% vs. 7.4-14.8%).CONCLUSION: We found that approximately 60% of women discontinued or interrupted their ADHD medication around pregnancy, and those who continued differed in sociodemographic and clinical factors that may reflect more severe ADHD.
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2. |
- Brikell, Isabell
(författare)
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ADHD, epilepsy, and related childhood psychopathology : understanding shared genetic risk, developmental trajectories, and pharmacological treatment safety
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder, affecting 5-7% of children and 2.5-5% of adults worldwide. The disorder is characterized by excessive and age-inappropriate symptoms of inattention, hyperactivity, and impulsivity, which impair everyday functioning across several settings (home, school, work). Although great advances have been made in ADHD research during the past decades, many questions remain regarding the causes and consequences of ADHD. ADHD is conceptualized as an early onset disorder, underpinned by varying degrees of neurological delay or dysfunction that may be exacerbated by environmental factors. The disorder is developmentally complex, and extensive comorbidity with other psychiatric and non-psychiatric disorders is the rule rather than the exception. In this thesis, quantitative and molecular genetic research designs were used to explore important and poorly understood questions regarding development, treatment safety, and comorbidity in ADHD, epilepsy and related childhood psychopathology. In Study 1, we addressed the question of whether perceived immaturity is related to the developmental course of ADHD from childhood to early adulthood. Using data from a longitudinal twin study, we estimated the overlap between ADHD and immaturity from ages 8-9 to 19-20 years. Results showed that immaturity plays a small but significant role in ADHD in childhood and adolescence, largely due to shared genetic factors that diminish in importance with age. We also showed evidence for ADHD-related genetic stability across ages, and genetic innovation during adolescence and early adulthood. These findings may partly explain why some children show a decrease in ADHD symptoms from childhood to early adulthood, whereas others show a more persistent, chronic, disorder expression. In Study 2, we explore whether common genetic risk variants associated with ADHD also influences a broad range of related childhood psychopathology. Results suggested that genetic risk for ADHD, summed to a polygenic risk score (PRS), is associated with higher levels of neurodevelopmental, externalizing, and to a lesser extent, internalizing problems. Importantly, these associations could largely be attributed to a general psychopathology factor, capturing covariance across symptoms dimensions. These findings provide evidence for wide-spread genetic pleiotropy across psychiatric conditions, and support the notion that many identified genetic risk variants associated with ADHD are likely to non-specifically increase liability towards broad childhood psychiatric problems. In Study 3, we broaden our focus beyond psychiatric conditions to address the overlap between ADHD and epilepsy using a family co-aggregation design. Results from this large, population based cohort suggest that ADHD and epilepsy commonly co-occur and that this risk increase extends to family members of epilepsy patients. Quantitative genetic analyses revealed only a moderate genetic overlap across the disorder. These findings suggest that, although highly comorbid, epilepsy may be less genetically related to ADHD as compared to traditional neurodevelopmental disorders. In Study 4, we address the safety of ADHD pharmacological treatment in patients with a history of epileptic seizures. Using a within-individual comparison design to adjust for time-constant confounders that vary between individuals (e.g. baseline disorder severity, shared genetic liability), we found that ADHD medications were not associated with an increased risk ofacute epileptic seizures. Despite long-standing concerns regarding the safety of stimulant ADHD medications in epilepsy patients, these findings suggest that ADHD medication treatment may be a safe and viable option even in patients with a seizure history. The main findings from this thesis suggest that ADHD is related to both later maturation and a wide range of comorbid psychiatric conditions, partly due to shared genetic risk factors. Importantly, the shared genetic liability between ADHD and related psychiatric conditions appears to be in part attributable to a general liability towards broad childhood psychopathology. In contrast, epilepsy and ADHD comorbidity seems to be less influenced by shared genetic factors and more strongly influenced by environmental factors not shared by family members. ADHD medication does however not appear to be a risk factor for acute epileptic seizures among individuals with a seizure history. Taken together, results from this thesis highlight important aspects of development and comorbidity in ADHD, and lends support to the hypothesis ADHD may be considered part of broader continuum of psychopathology that is underpinned by partly shared genetic factors. Based on evidence thus far, this genetic shared liability appears less strongly related to epilepsy.
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3. |
- Brikell, Isabell, et al.
(författare)
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ADHD medication discontinuation and persistence across the lifespan : a retrospective observational study using population-based databases
- 2024
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Ingår i: Lancet psychiatry. - : Elsevier. - 2215-0374 .- 2215-0366. ; 11:1, s. 16-26
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although often intended for long-term treatment, discontinuation of medication for ADHD is common. However, cross-national estimates of discontinuation are missing due to the absence of standardised measures. The aim of this study was to determine the rate of ADHD treatment discontinuation across the lifespan and to describe similarities and differences across countries to guide clinical practice.METHODS: We did a retrospective, observational study using population-based databases from eight countries and one Special Administrative Region (Australia, Denmark, Hong Kong, Iceland, the Netherlands, Norway, Sweden, the UK, and the USA). We used a common analytical protocol approach and extracted prescription data to identify new users of ADHD medication. Eligible individuals were aged 3 years or older who had initiated ADHD medication between 2010 and 2020. We estimated treatment discontinuation and persistence in the 5 years after treatment initiation, stratified by age at initiation (children [age 4-11 years], adolescents [age 12-17 years], young adults [age 18-24 years], and adults [age ≥25 years]) and sex. Ethnicity data were not available.FINDINGS: 1 229 972 individuals (735 503 [60%] males, 494 469 females [40%]; median age 8-21 years) were included in the study. Across countries, treatment discontinuation 1-5 years after initiation was lowest in children, and highest in young adults and adolescents. Within 1 year of initiation, 65% (95% CI 60-70) of children, 47% (43-51) of adolescents, 39% (36-42) of young adults, and 48% (44-52) of adults remained on treatment. The proportion of patients discontinuing was highest between age 18 and 19 years. Treatment persistence for up to 5 years was higher across countries when accounting for reinitiation of medication; at 5 years of follow-up, 50-60% of children and 30-40% of adolescents and adults were covered by treatment in most countries. Patterns were similar across sex.INTERPRETATION: Early medication discontinuation is prevalent in ADHD treatment, particularly among young adults. Although reinitiation of medication is common, treatment persistence in adolescents and young adults is lower than expected based on previous estimates of ADHD symptom persistence in these age groups. This study highlights the scope of medication treatment discontinuation and persistence in ADHD across the lifespan and provides new knowledge about long-term ADHD medication use.FUNDING: European Union Horizon 2020 Research and Innovation Programme.
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4. |
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5. |
- 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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6. |
- Brikell, Isabell, et al.
(författare)
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Heritability of attention-deficit hyperactivity disorder in adults
- 2015
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Ingår i: American Journal of Medical Genetics Part B. - Hoboken, USA : Wiley-Blackwell. - 1552-4841 .- 1552-485X. ; 168:6, s. 406-413
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Forskningsöversikt (refereegranskat)abstract
- Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Symptoms often persist into adulthood, with a prevalence of 2.5-5% in adult populations. Twin studies in childhood consistently report high heritabilities of 70-80%, while studies in adult samples show only moderate heritability of 30-40% when estimated from self-ratings. This review summarizes the available research on the heritability of ADHD in adults. Three key findings are outlined: (i) self-ratings lead to relatively low heritability estimates of ADHD, independent of age and whether ratings refer to current or retrospective symptoms; (ii) studies relying on different informants to rate each twin within a pair (i.e., self-ratings and different parents/teachers rating each twin in a pair) consistently yield lower heritability estimates than studies relying on ratings from a single informant; (iii) studies using cross-informant data via either combined parent and self-ratings or clinical diagnoses information suggest that the heritability of ADHD in adults could be as high as 70-80%. Together, the reviewed studies suggest that the previously reported low heritability of ADHD in adults is unlikely to reflect a true developmental change. Instead, the drop in heritability is better explained by rater effects related to a switch from using one rater for both twins in a pair (parent/teacher) in childhood, to relying on self-ratings (where each twin rates themselves) of ADHD symptoms in adulthood. When rater effects are addressed using cross-informant approaches, the heritability of ADHD in adults appears to be comparable to the heritability of ADHD in childhood.
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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. |
- Brikell, Isabell, et al.
(författare)
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Relative Immaturity in Childhood and Attention-Deficit/Hyperactivity Disorder Symptoms From Childhood to Early Adulthood : Exploring Genetic and Environmental Overlap Across Development
- 2016
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Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier. - 0890-8567 .- 1527-5418. ; 55:10, s. 886-895
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Attention-deficit/hyperactivity disorder (ADHD) has been linked to immaturity relative to peers in childhood, yet it is unclear how such immaturity is associated with ADHD across development. This longitudinal twin study examined the genetic and environmental contributions to the association between parents' perception of their child's immaturity relative to peers (RI) in childhood and ADHD symptoms across development.Method: 1,302 twin pairs from the Swedish Twin Study of Child and Adolescent Development were followed prospectively from childhood to early adulthood. Parent ratings of RI were collected at 8 to 9 years and parent and self-ratings of ADHD symptoms were collected at 8 to 9, 13 to 14, 16 to 17, and 19 to 20 years using the Child Behavior Checklist Attention Problems scale. In addition, ADHD symptoms corresponding to DSM criteria were used for sensitivity analysis. Analyses were conducted using longitudinal structural equation modeling with multiple raters.Results: RI-related etiologic factors, predominantly influenced by genes, explained 10-14% of the variance in ADHD symptoms from 8 to 9 up to 16 to 17 years. The influence of these RI-related factors on ADHD symptoms attenuated to 4% by 19 to 20 years of age. The remaining variance in ADHD symptoms was primarily explained by genetic factors independent of RI, which remained relatively stable across development, explaining 19% to 30% of the variance in ADHD symptoms from 13 to 14 up to 19 to 20 years.Conclusion: The results show that RI is significantly associated with ADHD symptoms, particularly during childhood and adolescence, and that the association is primarily explained by a shared genetic liability. Nevertheless, the magnitude of associations across development was modest, highlighting that RI is merely one aspect contributing to the complex etiology of ADHD symptoms.
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9. |
- Brikell, Isabell, et al.
(författare)
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The contribution of ADHD genetic risk to somatic health in late life
- 2019
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Ingår i: Behavior Genetics. - : Springer. - 0001-8244 .- 1573-3297. ; 49:6, s. 514-514
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Genetic risk variants associated with ADHD have been linked to comorbid psychiatric health problems, however less is known about how these genetic factors contribute to somatic health across the life-span. The aim of this study is to assess whether polygenic risk scores (PRS) for ADHD are associated with late-life somatic health problems in a general population sample never diagnosed with ADHD.We derived ADHD PRS for 15,701 Swedish twins born 1911–1958 using results from an independent ADHD genome-wide association study meta-analysis (Demontis et al, 2018). Somatic health outcomes in cardiovascular, metabolic, autoimmune, and neurological domains were defined via self-report in the Screening Across the Lifespan Twin study (Lichtenstein et al. 2006) and from clinical diagnoses in the National Swedish Patient Register. Associations between ADHD PRS and somatic health problems were estimated using generalized estimating equations.Higher ADHD PRS were associated with a small increased risk of coronary heart disease based on self-report (OR = 1.11, 95% CI = 1.02–1.20) and clinical diagnoses (OR = 1.09, 95% CI = 1.02–1.16), after false discovery rate correction. We also found statistically significant associations between ADHD PRS and obesity, type 1 diabetes, arthritis, psoriasis, and migraine, although results varied by information source. Our results suggest that polygenic risk for ADHD is associated with small increases to risk of somatic health problems in cardiovascular and autoimmune domains. These findings warrant further research into mechanisms influencing long-term health outcomes in ADHD. Next, we will test for mediation via socioeconomic variables, evaluate genetic causality using twin-comparison methods, and test for replication in a younger, clinical ADHD sample.
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10. |
- Brikell, Isabell, et al.
(författare)
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The contribution of common genetic risk variants for ADHD to a general factor of childhood psychopathology
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:8, s. 1809-1821
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Tidskriftsartikel (refereegranskat)abstract
- Common genetic risk variants have been implicated in the etiology of clinical attention-deficit/hyperactivity disorder (ADHD) diagnoses and symptoms in the general population. However, given the extensive comorbidity across ADHD and other psychiatric conditions, the extent to which genetic variants associated with ADHD also influence broader psychopathology dimensions remains unclear. The aim of this study was to evaluate the associations between ADHD polygenic risk scores (PRS) and a broad range of childhood psychiatric symptoms, and to quantify the extent to which such associations can be attributed to a general factor of childhood psychopathology. We derived ADHD PRS for 13,457 children aged 9 or 12 from the Child and Adolescent Twin Study in Sweden, using results from an independent meta-analysis of genome-wide association studies of ADHD diagnosis and symptoms. We estimated associations between ADHD PRS, a general psychopathology factor, and several dimensions of neurodevelopmental, externalizing, and internalizing symptoms, using structural equation modeling. Higher ADHD PRS were statistically significantly associated with elevated neurodevelopmental, externalizing, and depressive symptoms (R 2 = 0.26-1.69%), but not with anxiety. After accounting for a general psychopathology factor, on which all symptoms loaded positively (mean loading = 0.50, range = 0.09-0.91), an association with specific hyperactivity/impulsivity remained significant. ADHD PRS explained ~ 1% (p value < 0.0001) of the variance in the general psychopathology factor and ~ 0.50% (p value < 0.0001) in specific hyperactivity/impulsivity. Our results suggest that common genetic risk variants associated with ADHD, and captured by PRS, also influence a general genetic liability towards broad childhood psychopathology in the general population, in addition to a specific association with hyperactivity/impulsivity symptoms.
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11. |
- Chen, Qi, et al.
(författare)
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Familial aggregation of attention-deficit/hyperactivity disorder
- 2017
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Ingår i: Journal of Child Psychology and Psychiatry. - : Wiley-Blackwell. - 0021-9630 .- 1469-7610. ; 58:3, s. 231-239
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Tidskriftsartikel (refereegranskat)abstract
- Background: Attention-deficit/hyperactivity disorder (ADHD) aggregates in families. To date, the strength, pattern, and characteristics of the familial aggregation have not been thoroughly assessed in a population-based family sample.Methods: In this cohort study, we identified relative pairs of twins, full and half-siblings, and full and half cousins from 1,656,943 unique individuals born in Sweden between 1985 and 2006. The relatives of index persons were followed from their third birthday to 31 December 2009 for ADHD diagnosis. Birth year adjusted hazard ratio (HR), that is, the rate of ADHD in relatives of ADHD-affected index persons compared with the rate of ADHD in relatives of unaffected index persons, was estimated in the different types of relatives using Cox proportional hazards model.Results: During the follow-up, 31,865 individuals were diagnosed with ADHD (male to female ratio was 3.7). The birth year adjusted HRs were as follows: 70.45 for monozygotic twins; 8.44 for dizygotic twins; 8.27 for full siblings; 2.86 for maternal half-siblings; 2.31 for paternal half-siblings; 2.24 for full cousins; 1.47 for half cousins. Maternal half-siblings had significantly higher HR than in paternal half-siblings. The HR did not seem to be affected by index person's sex. Full siblings of index persons with ADHD diagnosis present at age 18 or older had a higher rate of ADHD (HR: 11.49) than full siblings of index persons with ADHD diagnosis only before age 18 (HR: 4.68).Conclusions: Familial aggregation of ADHD increases with increasing genetic relatedness. The familial aggregation is driven by not only genetic factors but also a small amount of shared environmental factors. Persistence of ADHD into adulthood indexes stronger familial aggregation of ADHD.
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12. |
- Dobrosavljevic, Maja, 1986-, et al.
(författare)
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Risk prediction model for cardiovascular diseases in adults initiating pharmacological treatment for attention-deficit/hyperactivity disorder
- 2022
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Ingår i: Evidence-Based Mental Health. - : BMJ Publishing Group Ltd. - 1362-0347 .- 1468-960X. ; 25, s. 185-190
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Tidskriftsartikel (refereegranskat)abstract
- Background: Available prediction models ofcardiovascular diseases (CVDs) may not accuratelypredict outcomes among individuals initiatingpharmacological treatment for attention-deficit/hyperactivity disorder (ADHD).Objective: To improve the predictive accuracyof traditional CVD risk factors for adults initiatingpharmacological treatment of ADHD, by consideringnovel CVD risk factors associated with ADHD (comorbidpsychiatric disorders, sociodemographic factors andpsychotropic medication).Methods: The cohort composed of 24 186 adultsresiding in Sweden without previous CVDs, born between1932 and 1990, who started pharmacological treatmentof ADHD between 2008 and 2011, and were followedfor up to 2 years. CVDs were identified using diagnosesaccording to the International Classification of Diseases,and dispended medication prescriptions from Swedishnational registers. Cox proportional hazards regressionwas employed to derive the prediction model.Findings: The developed model included eighttraditional and four novel CVD risk factors. Themodel showed acceptable overall discrimination (Cindex=0.72, 95% CI 0.70 to 0.74) and calibration(Brier score=0.008). The Integrated DiscriminationImprovement index showed a significant improvementafter adding novel risk factors (0.003 (95% CI 0.001 to0.007), p<0.001).Conclusions: The inclusion of the novel CVD riskfactors may provide a better prediction of CVDs in thispopulation compared with traditional CVD predictorsonly, when the model is used with a continuous riskscore. External validation studies and studies assessingclinical impact of the model are warranted.Clinical implications: Individuals initiatingpharmacological treatment of ADHD at higher risk ofdeveloping CVDs should be more closely monitored.
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13. |
- Du Rietz, Ebba, et al.
(författare)
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Associations between ADHD and medical disorders in adulthood : a large-scale genetically informed Swedish register study
- 2020
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Ingår i: Behavior Genetics. - : Springer. - 0001-8244 .- 1573-3297. ; 50:6, s. 452-452
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Only a limited number of medical disorders have been thoroughly studied in relation to ADHD, and knowledge is especially lacking for disorders that develop in older ages. This study aimed to map out the phenotypic and aetiologic associations between ADHD and a wide range of medical disorders across adulthood.Full- and maternal half-siblings (N = 4,288,451 pairs), aged 18–81 years, were identified from Swedish Population Registers and linked to ICD-diagnoses from National Patient Registers. Logistic regression was used to estimate associations between ADHD and 35 medical disorders (8 disease groups) within-individuals, and across full- and half-siblings. Quantitative genetic modelling was performed to estimate genetic and environmental contributions to the associations with ADHD.Adults with ADHD had increased risk for most medical disorders (34/35), showing the strongest associations with nervous system (OR = 3.27) and respiratory (OR = 2.49) disease groups. Significantly (P < 0.001) stronger associations were found between full-siblings than half-siblings for nervous system, respiratory, musculoskeletal and metabolic disease groups. Subsequent quantitative genetic modelling showed that these associations with ADHD were largely explained by shared genetic factors, with the exception for nervous system disorders.Individuals with ADHD are at increased risk for a range of medical disorders, with long-term aspects into adult life. While numerous associations between ADHD and medical disorders were largely driven by genetic factors, others, such as nervous system and ageing disorders were mainly driven by individual-specific environmental factors. This mapping of aetiological sources of covariance can guide future research aiming to identify specific mechanisms that contribute to risk for medical disorders in ADHD
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14. |
- Du Rietz, Ebba, et al.
(författare)
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Mapping phenotypic and aetiological associations between ADHD and physical conditions in adulthood in Sweden : a genetically informed register study
- 2021
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Ingår i: Lancet psychiatry. - : Elsevier. - 2215-0374 .- 2215-0366. ; 8:9, s. 774-783
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Emerging evidence suggests increased risk of several physical health conditions in people with ADHD. Only a few physical conditions have been thoroughly studied in relation to ADHD, and there is little knowledge on associations in older adults in particular. We aimed to investigate the phenotypic and aetiological associations between ADHD and a wide range of physical health conditions across adulthood.METHODS: We did a register study in Sweden and identified full-sibling and maternal half-sibling pairs born between Jan 1, 1932, and Dec 31, 1995, through the Population and Multi-Generation Registers. We excluded individuals who died or emigrated before Jan 1, 2005, and included full-siblings who were not twins and did not have half-siblings. ICD diagnoses were obtained from the National Patient Register. We extracted ICD diagnoses for physical conditions, when participants were aged 18 years or older, from inpatient (recorded 1973-2013) and outpatient (recorded 2001-13) services. Diagnoses were regarded as lifetime presence or absence. Logistic regression models were used to estimate the associations between ADHD (exposure) and 35 physical conditions (outcomes) in individuals and across sibling pairs. Quantitative genetic modelling was used to estimate the extent to which genetic and environmental factors accounted for the associations with ADHD.FINDINGS: 4 789 799 individuals were identified (2 449 146 [51%] men and 2 340 653 [49%] women), who formed 4 288 451 unique sibling pairs (3 819 207 full-sibling pairs and 469 244 maternal half-sibling pairs) and 1 841 303 family clusters (siblings, parents, cousins, spouses). The mean age at end of follow-up was 47 years (range 18-81; mean birth year 1966); ethnicity data were not available. Adults with ADHD had increased risk for most physical conditions (34 [97%] of 35) compared with adults without ADHD; the strongest associations were with nervous system disorders (eg, sleep disorders, epilepsy, dementia; odds ratios [ORs] 1·50-4·62) and respiratory diseases (eg, asthma, chronic obstructive pulmonary disease; ORs 2·42-3·24). Sex-stratified analyses showed similar patterns of results in men and women. Stronger cross-disorder associations were found between full-siblings than between half-siblings for nervous system, respiratory, musculoskeletal, and metabolic diseases (p<0·007). Quantitative genetic modelling showed that these associations were largely explained by shared genetic factors (60-69% of correlations), except for associations with nervous system disorders, which were mainly explained by non-shared environmental factors.INTERPRETATION: This mapping of aetiological sources of cross-disorder overlap can guide future research aiming to identify specific mechanisms contributing to risk of physical conditions in people with ADHD, which could ultimately inform preventive and lifestyle intervention efforts. Our findings highlight the importance of assessing the presence of physical conditions in patients with ADHD.FUNDING: Swedish Research Council; Swedish Brain Foundation; Swedish Research Council for Health, Working Life, and Welfare; Stockholm County Council; StratNeuro; EU Horizon 2020 research and innovation programme; National Institute of Mental Health.
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15. |
- Du Rietz, Ebba, et al.
(författare)
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Overlap between attention-deficit hyperactivity disorder and neurodevelopmental, externalising and internalising disorders : separating unique from general psychopathology effects
- 2021
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Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatry. - 0007-1250 .- 1472-1465. ; 218:1, s. 35-42
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although attention-deficit hyperactivity disorder (ADHD) is classified as a neurodevelopmental disorder in the latest diagnostic manuals, it shows phenotypic and genetic associations of similar magnitudes across neurodevelopmental, externalising and internalising disorders.AIMS: To investigate if ADHD is aetiologically more closely related to neurodevelopmental than externalising or internalising disorder clusters, after accounting for a general psychopathology factor.METHOD: Full and maternal half-sibling pairs (N = 774 416), born between 1980 and 1995, were identified from the Swedish Medical Birth and Multi-Generation Registers, and ICD diagnoses were obtained from the Swedish National Patient Register. A higher-order confirmatory factor analytic model was fitted to examine associations between ADHD and a general psychopathology factor, as well as a neurodevelopmental, externalising and internalising subfactor. Quantitative genetic modelling was performed to estimate the extent to which genetic, shared and non-shared environmental effects influenced the associations with ADHD.RESULTS: ADHD was significantly and strongly associated with all three factors (r = 0.67-0.75). However, after controlling for a general psychopathology factor, only the association between ADHD and the neurodevelopmental-specific factor remained moderately strong (r = 0.43, 95% CI = 0.42-0.45) and was almost entirely influenced by genetic effects. In contrast, the association between ADHD and the externalising-specific factor was smaller (r = 0.25, 95% CI = 0.24-0.27), and largely influenced by non-shared environmental effects. There remained no internalising-specific factor after accounting for a general factor.CONCLUSIONS: Findings suggest that ADHD comorbidity is largely explained by genetically influenced general psychopathology, but the strong link between ADHD and other neurodevelopmental disorders is also substantially driven by unique genetic influences.
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16. |
- Du Rietz, Ebba, et al.
(författare)
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Phenotypic, genetic and environmental correlations between diagnosed ADHD, neurodevelopmental, internalizing and externalizing disorders
- 2019
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Ingår i: Behavior Genetics. - : Springer. - 0001-8244 .- 1573-3297. ; 49:6, s. 513-513
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- ADHD is currently classified as a neurodevelopmental disorder (NDD) and clustered together with Autism Spectrum Disorder and intellectual disabilities in the recently updated diagnostic manuals (DSM-5/ICD-11). There is, however, evidence for strong genetic overlap of ADHD with not only NDDs but also with internalizing and externalizing disorders, as well as with a general psychopathology-factor. These genetic findings challenge the accuracy of the current nosology of ADHD. In this study we therefore aimed to compare the strength of phenotypic, genetic and environmental correlations of ADHD with NDDs, internalizing and externalizing disorders, to explore if ADHD is more closely linked to one of these disorder domains. We further aimed to determine the etiological overlap between ADHD and the domains after accounting for a general psychopathology-factor. We identified full and maternal half siblings in the Swedish population and linked diagnostic data from the National Patient Register. Through structural equation modeling we fitted a confirmatory factor model, where one general factor loaded onto all disorders, and disorder clusters (NDD, internalizing, externalizing) each had a factor loading onto the disorders. We allowed ADHD to have loading from each of the cluster factors and the general factor. Initial findings showed similar magnitudes of genetic overlap of ADHD with NDDs (rg= 0.52–0.70) and internalizing disorders (rg= 0.58–0.68). Further analyses will be extended to include externalizing disorders, and to estimate etiological overlap after accounting for a general psychopathology-factor. Our findings may be informative for the nosology of ADHD as well as for increasing our understanding of the etiology of psychiatric disorders.
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17. |
- Du Rietz, Ebba, et al.
(författare)
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Predictive validity of parent- and self-rated ADHD symptoms in adolescence on adverse socioeconomic and health outcomes
- 2017
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Ingår i: European Child and Adolescent Psychiatry. - : Springer. - 1018-8827 .- 1435-165X. ; 26:7, s. 857-867
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Tidskriftsartikel (refereegranskat)abstract
- There is scarcity of research investigating the validity of self-report of attention deficit hyperactivity disorder (ADHD) symptoms compared to other informants, such as parents. This study aimed to compare the predictive associations of ADHD symptoms rated by parents and their children across adolescence on a range of adverse socioeconomic and health outcomes in early adulthood. Parent- and self-rated ADHD symptoms were assessed in 2960 individuals in early (13-14 years) and late adolescence (16-17 years). Logistic regression analyses were used to compare the associations between parent- and self-rated ADHD symptoms at both time points and adverse life outcomes in young adulthood obtained from Swedish national registries. Both parent- and self-ratings of ADHD symptoms were associated with increased risk for adverse outcomes, although associations of parent-ratings were more often statistically significant and were generally stronger (OR = 1.12-1.49, p < 0.05) than self-ratings (OR = 1.07-1.17, p < 0.05). After controlling for the other informant, parent-ratings of ADHD symptoms in both early and late adolescence significantly predicted academic and occupational failure, criminal convictions and traffic-related injuries, while self-ratings of ADHD symptoms only in late adolescence predicted substance use disorder and academic failure. Our findings suggest that both parent- and self-ratings of ADHD symptoms in adolescence provides valuable information on risk of future adverse socioeconomic and health outcomes, however, self-ratings are not valuable once parent-ratings have been taken into account in predicting most outcomes. Thus, clinicians and researchers should prioritize parent-ratings over self-ratings.
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18. |
- Fernández de la Cruz, Lorena, et al.
(författare)
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All cause and cause specific mortality in obsessive-compulsive disorder : nationwide matched cohort and sibling cohort study
- 2024
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Ingår i: BMJ (Clinical Research Edition). - : BMJ Publishing Group Ltd. - 0959-8138 .- 1756-1833. ; 384
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To estimate the risk of all cause and cause specific mortality in people with obsessive-compulsive disorder (OCD) compared with matched unaffected people from the general population and with their unaffected siblings. DESIGN: Population based matched cohort and sibling cohort study. SETTING: Register linkage in Sweden.PARTICIPANTS: Population based cohort including 61 378 people with OCD and 613 780 unaffected people matched (1:10) on sex, birth year, and county of residence; sibling cohort consisting of 34 085 people with OCD and 47 874 unaffected full siblings. Cohorts were followed up for a median time of 8.1 years during the period from 1 January 1973 to 31 December 2020. MAIN OUTCOME MEASURES: All cause and cause specific mortality.RESULTS: 4787 people with OCD and 30 619 unaffected people died during the study period (crude mortality rate 8.1 and 5.1 per 1000 person years, respectively). In stratified Cox proportional hazards models adjusted for birth year, sex, county, migrant status (born in Sweden versus abroad), and sociodemographic variables (latest recorded education, civil status, and family income), people with OCD had an increased risk of all cause mortality (hazard ratio 1.82, 95% confidence interval 1.76 to 1.89) and mortality due to natural causes (1.31, 1.27 to 1.37) and unnatural causes (3.30, 3.05 to 3.57). Among the natural causes of death, those due to endocrine, nutritional, and metabolic diseases, mental and behavioural disorders, and diseases of the nervous, circulatory, respiratory, digestive, and genitourinary systems were higher in the OCD cohort. Conversely, the risk of death due to neoplasms was lower in the OCD cohort compared with the unaffected cohort. Among the unnatural causes, suicide showed the highest hazard ratio, followed by accidents. The results were robust to adjustment for psychiatric comorbidities and familial confounding.CONCLUSIONS: Non-communicable diseases and external causes of death, including suicides and accidents, were major contributors to the risk of mortality in people with OCD. Better surveillance, prevention, and early intervention strategies should be implemented to reduce the risk of fatal outcomes in people with OCD.
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19. |
- Garcia-Argibay, Miguel, 1988-, et al.
(författare)
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Attention deficit/hyperactivity disorder and major depressive disorder : evidence from multiple genetically informed designs
- 2024
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 95:5, s. 444-452
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) are two highly prevalent disorders that frequently co-occur. Prior evidence from genetic and cohort studies supports an association between ADHD and MDD. However, the direction and mechanisms underlying their association remain unclear. As ADHD onsets in early life, it has been hypothesized that ADHD may cause MDD.METHODS: In this study, we examined the association of ADHD with MDD using three different genetically informed methods to disentangle causality from confounding: 1) a nationwide longitudinal register-based full sibling comparison (N=1,018,489) adjusting for shared familial confounding; 2) a prospective co-twin control study comprising 16,447 twins (5,084 monozygotic and 11,393 dizygotic); and 3) a two-sample Mendelian randomization analysis using the largest available ADHD (N=225,534) and MDD (N=500,199) genome wide association (GWAS) summary statistics, adjusting for correlated and uncorrelated horizontal pleiotropy.RESULTS: Sibling and twin comparisons indicated that individuals with ADHD have an increased risk for subsequent development of MDD (HR=4.12 [3.62-4.69]) after adjusting for shared genetic and familial factors, and that ADHD scores endorsed by parents are positively associated with subsequent MDD scores at ages 15 and 18 years (b=0.07 [0.05-0.08]) and b=0.09 [0.08-0.11], respectively). Mendelian randomization analyses showed that genetic liability for ADHD is causally related to MDD (OR=1.15 [1.08-1.23]).CONCLUSIONS: Our study provided consistent results across three different genetically informative approaches, strengthening the hypothesis that ADHD is causally related to MDD.
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20. |
- Garcia-Argibay, Miguel, 1988-, et al.
(författare)
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The association between type 2 diabetes and attention- deficit/hyperactivity disorder : a systematic review, meta-analysis, and population-based sibling study
- 2023
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Ingår i: Neuroscience and Biobehavioral Reviews. - : Pergamon Press. - 0149-7634 .- 1873-7528. ; 147
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Forskningsöversikt (refereegranskat)abstract
- We conducted a systematic review and a meta-analysis to quantitatively summarize evidence on the association between attention-deficit/hyperactivity disorder (ADHD) and type 2 diabetes (T2D). Moreover, a register-based sibling study was conducted to simultaneously control for confounding factors. A systematic search identified four eligible observational studies (N=5,738,287). The meta-analysis showed that individuals with ADHD have a more than doubled risk of T2D when considering adjusted estimates (OR=2.29 [1.48-3.55], d=0.46). Results from the register-based Swedish data showed a significant association between ADHD and T2D (HR=2.35 [2.14-2.58]), with substance use disorder, depression, and anxiety being the main drivers of the association, and cardiovascular and familiar risk playing a smaller role. While results from the meta-analysis provide evidence for an increased risk of T2D in individuals with ADHD, the register-based analyses show that the association between ADHD and T2D is largely explained by psychiatric comorbidities. Pending further evidence of causal association, our findings suggest that early identification and treatment of ADHD comorbidities might greatly reduce the risk of developing T2D in individuals with ADHD.
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21. |
- Garcia-Argibay, Miguel, 1988-, et al.
(författare)
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The role of ADHD genetic risk in mid-to-late life somatic health conditions
- 2022
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Growing evidence suggests that ADHD, an early onset neurodevelopmental disorder, is associated with poor somatic health in adulthood. However, the mechanisms underlying these associations are poorly understood. Here, we tested whether ADHD polygenic risk scores (PRS) are associated with mid-to-late life somatic health in a general population sample. Furthermore, we explored whether potential associations were moderated and mediated by life-course risk factors. We derived ADHD-PRS in 10,645 Swedish twins born between 1911 and 1958. Sixteen cardiometabolic, autoimmune/inflammatory, and neurological health conditions were evaluated using self-report (age range at measure 42-88 years) and clinical diagnoses defined by International Classification of Diseases codes in national registers. We estimated associations of ADHD-PRS with somatic outcomes using generalized estimating equations, and tested moderation and mediation of these associations by four life-course risk factors (education level, body mass index [BMI], tobacco use, alcohol misuse). Results showed that higher ADHD-PRS were associated with increased risk of seven somatic outcomes (heart failure, cerebro- and peripheral vascular disease, obesity, type 1 diabetes, rheumatoid arthritis, and migraine) with odds ratios ranging 1.07 to 1.20. We observed significant mediation effects by education, BMI, tobacco use, and alcohol misuse, primarily for associations of ADHD-PRS with cardiometabolic outcomes. No moderation effects survived multiple testing correction. Our findings suggests that higher ADHD genetic liability confers a modest risk increase for several somatic health problems in mid-to-late life, particularly in the cardiometabolic domain. These associations were observable in the general population, even in the absence of medical treatment for ADHD, and appear to be in part mediated by life-course risk factors.
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22. |
- Haan, Elis, et al.
(författare)
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Associations between attention-deficit hyperactivity disorder genetic liability and ICD-10 medical conditions in adults : utilizing electronic health records in a Phenome-Wide Association Study
- 2024
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is often comorbid with other medical conditions in adult patients. However, ADHD is extremely underdiagnosed in adults and little is known about the medical comorbidities in undiagnosed adult individuals with high ADHD liability. In this study we investigated associations between ADHD genetic liability and electronic health record (EHR)-based ICD-10 diagnoses across all diagnostic categories, in individuals without ADHD diagnosis history.METHODS: We used data from the Estonian Biobank cohort (N = 111 261) and generated polygenic risk scores (PRS) for ADHD (PRSADHD) based on the ADHD genome-wide association study. We performed a phenome-wide association study (PheWAS) to test for associations between standardized PRSADHD and 1515 EHR-based ICD-10 diagnoses in the full and sex-stratified sample. We compared the observed significant ICD-10 associations to associations with (1) ADHD diagnosis and (2) questionnaire-based high ADHD risk analyses.RESULTS: After Bonferroni correction (p = 3.3 × 10-5) we identified 80 medical conditions associated with PRSADHD. The strongest evidence was seen with chronic obstructive pulmonary disease (OR 1.15, CI 1.11-1.18), obesity (OR 1.13, CI 1.11-1.15), and type 2 diabetes (OR 1.11, CI 1.09-1.14). Sex-stratified analysis generally showed similar associations in males and females. Out of all identified associations, 40% and 78% were also observed using ADHD diagnosis or questionnaire-based ADHD, respectively, as the predictor.CONCLUSIONS: Overall our findings indicate that ADHD genetic liability is associated with an increased risk of a substantial number of medical conditions in undiagnosed individuals. These results highlight the need for timely detection and improved management of ADHD symptoms in adults.
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23. |
- Jangmo, Andreas, et al.
(författare)
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Genetic and environmental influences on the association between ADHD and school achievement
- 2019
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Ingår i: Behavior Genetics. - : Springer. - 0001-8244 .- 1573-3297. ; 49:6, s. 531-531
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Twin research has suggested that genetic factors are important for ADHD. Likewise, a recent twin study in suggested that school achievement at age 16 could be attributed by 52–58% to genetic factors, 24–31% to shared environmental effects, and 11–18% to unique environmental effects. Polygenic risk scores (PRS) for educational attainment (EA) has been found to predict educational achievement and ADHD symptoms in children, and PRS for ADHD predicts educational outcomes in the general population. Few twin studies have explored the overlap between ADHD and school achievement, and no study has explored this overlap using school grades.We linked parent rated DSM-IV ADHD-symptoms at age 9 and PRS for ADHD and educational attainment, from a sample of 11,242t wins in the Child and Adolescent Twin Study in Sweden, to measures of school achievement (e.g., GPA) from Swedish national registers. Multivariate twin modeling was used to estimate the heritability of each trait, and the genetic correlation between the traits. ADHD-symptoms correlated negatively with school performance,-0.30. The heritability of ADHD-symptoms and school achievement were estimated to 62 and 58 percent respectively. The genetic correlation between ADHD symptoms and school performance was estimated to -0.40 and the genetic contribution to the phenotypic correlation was 75 percent.These findings suggest a strong, shared genetic influence between ADHD and school performance.
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24. |
- Kittel-Schneider, Sarah, et al.
(författare)
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Non-mental diseases associated with ADHD across the lifespan : Fidgety Philipp and Pippi Longstocking at risk of multimorbidity?
- 2022
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Ingår i: Neuroscience and Biobehavioral Reviews. - : Pergamon Press. - 0149-7634 .- 1873-7528. ; 132, s. 1157-1180
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Forskningsöversikt (refereegranskat)abstract
- Several non-mental diseases seem to be associated with an increased risk of ADHD and ADHD seems to be associated with increased risk for non-mental diseases. The underlying trajectories leading to such brain-body co-occurrences are often unclear - are there direct causal relationships from one disorder to the other, or does the sharing of genetic and/or environmental risk factors lead to their occurring together more frequently or both? Our goal with this narrative review was to provide a conceptual synthesis of the associations between ADHD and non-mental disease across the lifespan. We discuss potential shared pathologic mechanisms and genetic background and treatments in co-occurring diseases. For those co-occurrences for which published studies with sufficient sample sizes exist, meta-analyses have been published by others and we discuss those in detail. We conclude that non-mental diseases are common in ADHD and vice versa and add to the disease burden of the patient across the lifespan. Insufficient attention to such co-occurring conditions may result in missed diagnoses and suboptimal treatment in the affected individuals.
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25. |
- Li, Lin, et al.
(författare)
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ADHD Pharmacotherapy and Mortality in Individuals With ADHD
- 2024
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 331:10, s. 850-860
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Attention-deficit/hyperactivity disorder (ADHD) is associated with increased risks of adverse health outcomes including premature death, but it is unclear whether ADHD pharmacotherapy influences the mortality risk. OBJECTIVE: To investigate whether initiation of ADHD pharmacotherapy was associated with reduced mortality risk in individuals with ADHD. DESIGN,SETTING, AND PARTICIPANTS: In an observational nationwide cohort study in Sweden applying the target trial emulation framework, we identified individuals aged 6 through 64 years with an incident diagnosis of ADHD from 2007 through 2018 and no ADHD medication dispensation prior to diagnosis. Follow-up started from ADHD diagnosis until death, emigration, 2 years after ADHD diagnosis, or December 31, 2020, whichever came first.EXPOSURES: ADHD medication initiation was defined as dispensing of medication within 3 months of diagnosis. MAIN OUTCOMES AND MEASURES: We assessed all-cause mortality within 2 years of ADHD diagnosis, as well as natural-cause (eg, physical conditions) and unnatural-cause mortality (eg, unintentional injuries, suicide, and accidental poisonings).RESULTS: Of 148 578 individuals with ADHD (61 356 females [41.3%]), 84 204 (56.7%) initiated ADHD medication. The median age at diagnosis was 17.4 years (IQR, 11.6-29.1 years). The 2-year mortality risk was lower in the initiation treatment strategy group (39.1 per 10 000 individuals) than in the noninitiation treatment strategy group (48.1 per 10 000 individuals), with a risk difference of -8.9 per 10 000 individuals (95% CI, -17.3 to -0.6). ADHD medication initiation was associated with significantly lower rate of all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.70 to 0.88) and unnatural-cause mortality (2-year mortality risk, 25.9 per 10 000 individuals vs 33.3 per 10 000 individuals; risk difference, -7.4 per 10 000 individuals; 95% CI, -14.2 to -0.5; HR, 0.75; 95% CI, 0.66 to 0.86), but not natural-cause mortality (2-year mortality risk, 13.1 per 10 000 individuals vs 14.7 per 10 000 individuals; risk difference, -1.6 per 10 000 individuals; 95% CI, -6.4 to 3.2; HR, 0.86; 95% CI, 0.71 to 1.05).CONCLUSIONS AND RELEVANCE: Among individuals diagnosed with ADHD, medication initiation was associated with significantly lower all-cause mortality, particularly for death due to unnatural causes.
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26. |
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27. |
- Li, Lin, 1989-, et al.
(författare)
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Attention-deficit/hyperactivity disorder as a risk factor for cardiovascular diseases : a nationwide population-based cohort study
- 2022
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Ingår i: World Psychiatry. - : Masson SpA. - 1723-8617 .- 2051-5545. ; 21:3, s. 452-459
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence suggests a higher risk for cardiovascular diseases among individuals with mental disorders, but very little is known about the risk for overall and specific groups of cardiovascular diseases in people with attention-deficit/hyperactivity disorder (ADHD). To fill this knowledge gap, we investigated the prospective associations between ADHD and a wide range of cardiovascular diseases in adults. In a nationwide population-based cohort study, we identified 5,389,519 adults born between 1941 and 1983, without pre-existing cardiovascular diseases, from Swedish registers. The study period was from January 1, 2001 to December 31, 2013. Incident cardiovascular disease events were identified according to ICD codes. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox proportional hazards regression model, with ADHD as a time-varying exposure. After an average 11.80 years of follow-up, 38.05% of individuals with ADHD versus 23.57% of those without ADHD had at least one diagnosis of cardiovascular disease (p<0.0001). ADHD was significantly associated with increased risk of any cardiovascular disease (HR=2.05, 95% CI: 1.98-2.13) after adjusting for sex and year of birth. Further adjustments for education level, birth country, type 2 diabetes mellitus, obesity, dyslipidemia, sleep problems and heavy smoking attenuated the association, which however remained significant (HR=1.84, 95% CI: 1.77-1.91). Further adjustment for psychiatric comorbidities attenuated but could not fully explain the association (HR=1.65, 95% CI: 1.59-1.71). The strongest associations were found for cardiac arrest (HR=2.28, 95% CI: 1.81-2.87), hemorrhagic stroke (HR=2.16, 95% CI: 1.68-2.77), and peripheral vascular disease/arteriosclerosis (HR=2.05, 95% CI: 1.76-2.38). Stronger associations were observed in males and younger adults, while comparable associations were found among individuals with or without psychotropic medications and family history of cardiovascular diseases. These data suggest that ADHD is an independent risk factor for a wide range of cardiovascular diseases. They highlight the importance of carefully monitoring cardiovascular health and developing age-appropriate and individualized strategies to reduce the cardiovascular risk in individuals with ADHD.
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28. |
- Li, Lin, et al.
(författare)
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Attention-deficit/hyperactivity disorder is associated with increased risk of cardiovascular diseases : A systematic review and meta-analysis
- 2023
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Ingår i: JCPP Advances. - : John Wiley & Sons. - 2692-9384. ; 3:3
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Forskningsöversikt (refereegranskat)abstract
- Attention-deficit/hyperactivity disorder (ADHD) often co-occurs with other psychiatric and physical diseases. However, available evidence on associations between ADHD and cardiovascular diseases (CVDs) is mixed. To systematically review, quantitatively synthesize, and appraise available evidence on the link between ADHD with CVDs, we searched relevant articles in PubMed, Embase, PsycINFO, and Web of Science from inception to May 1, 2022. Study quality was assessed by using the Newcastle-Ottawa Scale, and random-effects model meta-analyses were performed. A total of 18,391,169 (ADHD: n = 421,224) individuals from 11 studies were included in our systematic review and 8,196,648 (ADHD = 332,619) individuals from five studies were included in the main meta-analysis of adjusted estimates. Pooled estimates showed that ADHD was significantly associated with an increased risk of CVDs in analyses based on adjusted effect size (odds ratio (OR) = 1.96; 95% confidence interval (CI) = 1.19-2.23, Q = 140.74, P Q < 0.001, I 2 = 97.2%). When restricted among adults, the heterogeneity declined to null (OR = 1.73; 95% CI = 1.14-2.62, Q = 6.28, P Q = 0.10, I 2 = 6.28%), suggesting age might be the main source of heterogeneity. In subgroup analyses, we found increased risk of CVDs associated with ADHD across age groups, type of CVDs, and data sources. This systematic review and meta-analyses indicate that ADHD is associated with increased risk for CVDs, but further studies with various study designs are warranted to advance the understanding of the underlying mechanisms for the observed association between ADHD and CVDs. Additional research is also needed to resolve the role of ADHD medications which remains unclear due to the limited number of primary studies exploring this issue.
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29. |
- Martin, Joanna, et al.
(författare)
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A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder
- 2018
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 83:12, s. 1044-1053
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is two to seven times more common in male individuals than in female individuals. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases.METHODS: We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (n = 20,183 cases, n = 35,191 controls) and Swedish population register data (n = 77,905 cases, n = 1,874,637 population controls).RESULTS: Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with r(g) estimates close to 1. Analyses of population data, however, indicated that female individuals with ADHD may be at especially high risk for certain comorbid developmental conditions (i.e., autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score analysis did not support a higher burden of ADHD common risk variants in female cases (odds ratio [confidence interval] = 1.02 [0.98-1.06], p = .28). In contrast, epidemiological sibling analyses revealed that the siblings of female individuals with ADHD are at higher familial risk for ADHD than the siblings of affected male individuals (odds ratio [confidence interval] = 1.14 [1.11-1.18], p = 1.5E-15).CONCLUSIONS: Overall, this study supports a greater familial burden of risk in female individuals with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence.
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30. |
- Mataix-Cols, David, et al.
(författare)
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Early-Life and Family Risk Factors for Tic Disorder Persistence into Adulthood
- 2023
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Ingår i: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257. ; 38:8, s. 1419-1427
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Many children with tic disorders outgrow their tics, but little is known about the proportion of individuals who will continue to require specialist services in adulthood and which variables are associated with tic persistence. OBJECTIVES: The aims were to estimate the proportion of individuals first diagnosed with tic disorders in childhood who continued to receive tic disorder diagnoses after age 18 years and to identify risk factors for persistence.METHODS: In this Swedish nationwide cohort study including 3761 individuals diagnosed with tic disorders in childhood, we calculated the proportion of individuals whose diagnoses persisted into adulthood. Minimally adjusted logistic regression models examined the associations between sociodemographic, clinical, and family variables and tic disorder persistence. A multivariable model was then fitted, including only variables that were statistically significant in the minimally adjusted models.RESULTS: Seven hundred and fifty-four (20%) children with tic disorders received a diagnosis of a chronic tic disorder in adulthood. Psychiatric comorbidity in childhood (particularly attention-deficit hyperactivity disorder, obsessive-compulsive disorder, pervasive developmental disorders, and anxiety disorders) and psychiatric disorders in first-degree relatives (particularly tic and anxiety disorders) were the strongest risk factors for persistence. We did not observe statistically significant associations with socioeconomic variables, perinatal complications, comorbid autoimmune diseases, or family history of autoimmune diseases. All statistically significant variables combined explained approximately 10% of the variance in tic disorder persistence (P < 0.0001).CONCLUSIONS: Childhood psychiatric comorbidities and family history of psychiatric disorders were the strongest risk factors associated with tic disorder persistence into adulthood. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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31. |
- Rautio, Daniel, et al.
(författare)
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Intentional self-harm and death by suicide in body dysmorphic disorder : A nationwide cohort study
- 2024
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Body dysmorphic disorder (BDD) is thought to be associated with considerable suicide risk. This nationwide cohort study quantified the risks of intentional self-harm - including non-suicidal self-injuries and suicide attempts - and death by suicide in BDD.METHODS: Individuals with a validated ICD-10 diagnosis of BDD in the Swedish National Patient Register, registered between January 1, 1997 and December 31, 2020, were matched with 10 unexposed individuals from the general population on birth year, sex, and county of residence. Conditional Poisson regression models estimated incidence rate ratios (IRR) and 95% confidence intervals (CIs) for intentional self-harm and stratified Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs for death by suicide. Models adjusted for sociodemographic variables and lifetime psychiatric comorbidities.RESULTS: Among 2,833 individuals with BDD and 28,330 unexposed matched individuals, 466 (16.45%) and 1,071 (3.78%) had at least one record of intentional self-harm during the study period, respectively (IRR=3.37; 95% CI, 3.02-3.76). In the BDD cohort, about two thirds (n=314; 67%) had their first recorded self-harm event before their first BDD diagnosis. A total of 17 (0.60%) individuals with BDD and 27 (0.10%) unexposed individuals died by suicide (HR=3.47; 95% CI, 1.76-6.85). All results remained robust to additional adjustment for lifetime psychiatric comorbidities. A higher proportion of individuals with BDD who died by suicide had at least one previous record of intentional self-harm, compared to unexposed individuals (52.94% vs. 22.22%; p=0.0363).CONCLUSIONS: BDD was associated with a three-fold increased risk of intentional self-harm and death by suicide.
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32. |
- Taylor, Mark J., et al.
(författare)
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Association of Genetic Risk Factors for Psychiatric Disorders and Traits of These Disorders in a Swedish Population Twin Sample
- 2019
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Ingår i: JAMA psychiatry. - : American Medical Association. - 2168-6238 .- 2168-622X. ; 76:3, s. 280-289
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Psychiatric traits associated with categorically defined psychiatric disorders are heritable and present to varying degrees in the general population. It is commonly assumed that diagnoses represent the extreme end of continuously distributed traits in the population, but this assumption has yet to be robustly tested for many psychiatric phenotypes.Objective: To assess whether genetic risk factors associated with psychiatric disorders are also associated with continuous variation in milder population traits.Design, Setting, and Participants: This study combined a novel twin analytic approach with polygenic risk score (PRS) analyses in a large population-based twin sample. Phenotypic and genetic data were available from the Child and Adolescent Twin Study in Sweden. Inpatient data were available for January 1, 1987, to December 31, 2014, and outpatient data for January 1, 2001, to December 31, 2013. The last day of follow-up was December 31, 2014. Data analysis was performed from January 1, 2017, to September 30, 2017.Main Outcomes and Measures: Questionnaires that assessed traits of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), learning difficulties, tic disorders (TDs), obsessive-compulsive disorder (OCD), anxiety, major depressive disorder (MDD), mania, and psychotic experiences were administered to a large Swedish twin sample. Individuals with clinical psychiatric diagnoses were identified using the Swedish National Patient Register. Joint categorical/continuous twin modeling was used to estimate genetic correlations between psychiatric diagnoses and continuous traits. The PRSs for psychiatric disorders were calculated based on independent discovery genetic data. The association between PRSs for each disorder and associated continuous traits was tested.Results: Phenotype data were available for 13 923 twin pairs (35.1% opposite sex and 31.7% same-sex females) at 9 years of age, 5165 pairs (36.9% opposite sex and 34.0% same-sex females) at 15 years of age, and 4273 pairs (36.5% opposite sex and 34.4% same-sex females) at 18 years of age. Genetic data were available for 13 412 individuals (50.2% females). Twin genetic correlations between numerous psychiatric diagnoses and corresponding traits ranged from 0.31 to 0.69. Disorder PRSs were associated with related population traits for ASD (β [SE] = 0.04 [0.01] at 9 years of age), ADHD (β [SE] = 0.27 [0.03] at 9 years of age), TDs (β [SE] = 0.02 [0.004] at 9 years of age), OCD (β [SE] = 0.13 [0.05] at 18 years of age), anxiety (β [SE] = 0.18 [0.08] at 9 years of age; β [SE] = 0.07 [0.02] at 15 years of age; and β [SE] = 0.40 [0.17] at 18 years of age), MDD (β [SE] = 0.10 [0.03] at 9 years of age; β [SE] = 0.11 [0.02] at 15 years of age; and β [SE] = 0.41 [0.10] at 18 years of age), and schizophrenia (β [SE] = 0.02 [0.01] at 18 years of age). Polygenic risk scores for depressive symptoms were associated with MDD diagnoses (odds ratio, 1.16; 95% CI, 1.02-1.32).Conclusions and Relevance: These results suggest that genetic factors associated with psychiatric disorders are also associated with milder variation in characteristic traits throughout the general population for many psychiatric phenotypes. This study suggests that many psychiatric disorders are likely to be continuous phenotypes rather than the categorical entities currently defined in diagnostic manuals, which has strong implications for genetic research in particular.
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33. |
- Virtanen, Suvi, et al.
(författare)
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Antidepressant Use and Risk of Manic Episodes in Children and Adolescents With Unipolar Depression
- 2024
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Ingår i: JAMA Psychiatry. - 2168-622X .- 2168-6238. ; 8081:111, s. 25-33
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Antidepressants are increasingly prescribed to pediatric patients with unipolar depression, but little is known about the risk of treatment-emergent mania. Previous research suggests pediatric patients may be particularly vulnerable to this adverse outcome. OBJECTIVE To estimate whether pediatric patients treated with antidepressants have an increased incidence of mania/hypomania compared with patients not treated with antidepressants and to identify patient characteristics associated with the risk of mania/hypomania. DESIGN, SETTING, AND PARTICIPANTS In a cohort study applying the target trial emulation framework, nationwide inpatient and outpatient care in Sweden from July 1, 2006, to December 31, 2019, was evaluated. Follow-up was conducted for 12 and 52 weeks after treatment initiation, with administrative follow-up ending December 31, 2020. Data were analyzed between May 1, 2022, and June 28, 2023. Individuals aged 4 to 17 years with a diagnosis of depression, but without a prior diagnosis of mania/hypomania, bipolar disorder, or psychosis or treatment with mood stabilizer (lithium, valproate, or carbamazepine), prescriptions were included. EXPOSURES The treatment group included patients who initiated any antidepressant medication within 90 days of diagnosis. The control group included patients who did not initiate antidepressants within 90 days. MAIN OUTCOMES AND MEASURES Diagnosis of mania/hypomania or initiation of mood stabilizer therapy. Incidences were estimated with Kaplan-Meier estimator, and inverse probability of treatment weighting was used to adjust for group differences at baseline. RESULTS The cohort included 43 677 patients (28 885 [66%] girls); 24 573 in the treatment group and 19 104 in the control group. The median age was 15 (IQR, 14-16) years. The outcome occurred in 96 individuals by 12 weeks and in 291 by 52 weeks. The cumulative incidence of mania was 0.26% (95% CI, 0.19%-0.33%) in the treatment group and 0.20% (95% CI, 0.13%-0.27%) in the control group at 12 weeks, with a risk difference of 0.06% (95% CI, −0.04% to 0.16%). At 52 weeks, the cumulative incidence was 0.79% (95% CI, 0.68%-0.91%) in the treatment group and 0.52% (95% CI, 0.40%-0.63%) in the control group (risk difference, 0.28%; 95% CI, 0.12%-0.44%). Hospitalizations, parental bipolar disorder, and use of antipsychotics and antiepileptics were the most important predictors of mania/hypomania by 12 weeks. CONCLUSION This cohort study found no evidence of treatment-emergent mania/hypomania by 12 weeks in children and adolescents. This corresponds to the time frame for antidepressants to exert their psychotropic effect. A small risk difference was found only with longer follow-up. Certain patient characteristics were associated with mania/hypomania, which warrants clinical attention.
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34. |
- 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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35. |
- Zhang, Le, et al.
(författare)
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Attention-Deficit/Hyperactivity Disorder Medications and Long-Term Risk of Cardiovascular Diseases
- 2024
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 81:2, s. 178-187
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Use of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades. However, the potential risk of cardiovascular disease (CVD) associated with long-term ADHD medication use remains unclear.OBJECTIVE: To assess the association between long-term use of ADHD medication and the risk of CVD.DESIGN, SETTING, AND PARTICIPANTS: This case-control study included individuals in Sweden aged 6 to 64 years who received an incident diagnosis of ADHD or ADHD medication dispensation between January 1, 2007, and December 31, 2020. Data on ADHD and CVD diagnoses and ADHD medication dispensation were obtained from the Swedish National Inpatient Register and the Swedish Prescribed Drug Register, respectively. Cases included individuals with ADHD and an incident CVD diagnosis (ischemic heart diseases, cerebrovascular diseases, hypertension, heart failure, arrhythmias, thromboembolic disease, arterial disease, and other forms of heart disease). Incidence density sampling was used to match cases with up to 5 controls without CVD based on age, sex, and calendar time. Cases and controls had the same duration of follow-up.EXPOSURE: Cumulative duration of ADHD medication use up to 14 years.MAIN OUTCOMES AND MEASURES: The primary outcome was incident CVD. The association between CVD and cumulative duration of ADHD medication use was measured using adjusted odds ratios (AORs) with 95% CIs.RESULTS: Of 278 027 individuals with ADHD aged 6 to 64 years, 10 388 with CVD were identified (median [IQR] age, 34.6 [20.0-45.7] years; 6154 males [59.2%]) and matched with 51 672 control participants without CVD (median [IQR] age, 34.6 [19.8-45.6] years; 30 601 males [59.2%]). Median (IQR) follow-up time in both groups was 4.1 (1.9-6.8) years. Longer cumulative duration of ADHD medication use was associated with an increased risk of CVD compared with nonuse (0 to ≤1 year: AOR, 0.99 [95% CI, 0.93-1.06]; 1 to ≤2 years: AOR, 1.09 [95% CI, 1.01-1.18]; 2 to ≤3 years: AOR, 1.15 [95% CI, 1.05-1.25]; 3 to ≤5 years: AOR, 1.27 [95% CI, 1.17-1.39]; and >5 years: AOR, 1.23 [95% CI, 1.12-1.36]). Longer cumulative ADHD medication use was associated with an increased risk of hypertension (eg, 3 to ≤5 years: AOR, 1.72 [95% CI, 1.51-1.97] and >5 years: AOR, 1.80 [95% CI, 1.55-2.08]) and arterial disease (eg, 3 to ≤5 years: AOR, 1.65 [95% CI, 1.11-2.45] and >5 years: AOR, 1.49 [95% CI, 0.96-2.32]). Across the 14-year follow-up, each 1-year increase of ADHD medication use was associated with a 4% increased risk of CVD (AOR, 1.04 [95% CI, 1.03-1.05]), with a larger increase in risk in the first 3 years of cumulative use (AOR, 1.08 [95% CI, 1.04-1.11]) and stable risk over the remaining follow-up. Similar patterns were observed in children and youth (aged <25 years) and adults (aged ≥25 years).CONCLUSIONS AND RELEVANCE: This case-control study found that long-term exposure to ADHD medications was associated with an increased risk of CVDs, especially hypertension and arterial disease. These findings highlight the importance of carefully weighing potential benefits and risks when making treatment decisions about long-term ADHD medication use. Clinicians should regularly and consistently monitor cardiovascular signs and symptoms throughout the course of treatment.
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