| 1. |
- Bang Madsen, Kathrine, et al.
(författare)
-
Attention-Deficit Hyperactivity Disorder (ADHD) Medication Use Trajectories Among Women in the Perinatal Period
- 2024
-
Ingår i: CNS Drugs. - : Adis International Ltd.. - 1172-7047 .- 1179-1934. ; 38, s. 301-314
-
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.
|
|
| 2. |
- Brikell, Isabell
(författare)
-
ADHD, epilepsy, and related childhood psychopathology : understanding shared genetic risk, developmental trajectories, and pharmacological treatment safety
- 2018
-
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.
|
|
| 3. |
- Brikell, Isabell, et al.
(författare)
-
ADHD medication discontinuation and persistence across the lifespan : a retrospective observational study using population-based databases
- 2024
-
Ingår i: Lancet psychiatry. - : Elsevier. - 2215-0374 .- 2215-0366. ; 11:1, s. 16-26
-
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.
|
|
| 4. |
|
|
| 5. |
- Brikell, Isabell, et al.
(författare)
-
Familial Liability to Epilepsy and Attention-Deficit/Hyperactivity Disorder : A Nationwide Cohort Study
- 2018
-
Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 83:2, s. 173-180
-
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.
|
|
| 6. |
- Brikell, Isabell, et al.
(författare)
-
Heritability of attention-deficit hyperactivity disorder in adults
- 2015
-
Ingår i: American Journal of Medical Genetics Part B. - Hoboken, USA : Wiley-Blackwell. - 1552-4841 .- 1552-485X. ; 168:6, s. 406-413
-
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.
|
|
| 7. |
- Brikell, Isabell, et al.
(författare)
-
Medication treatment for attention-deficit/hyperactivity disorder and the risk of acute seizures in individuals with epilepsy
- 2019
-
Ingår i: Epilepsia. - : Wiley-Blackwell. - 0013-9580 .- 1528-1167. ; 60:2, s. 284-293
-
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.
|
|
| 8. |
- Brikell, Isabell, et al.
(författare)
-
Relative Immaturity in Childhood and Attention-Deficit/Hyperactivity Disorder Symptoms From Childhood to Early Adulthood : Exploring Genetic and Environmental Overlap Across Development
- 2016
-
Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier. - 0890-8567 .- 1527-5418. ; 55:10, s. 886-895
-
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.
|
|
| 9. |
- Brikell, Isabell, et al.
(författare)
-
The contribution of ADHD genetic risk to somatic health in late life
- 2019
-
Ingår i: Behavior Genetics. - : Springer. - 0001-8244 .- 1573-3297. ; 49:6, s. 514-514
-
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.
|
|
| 10. |
- Brikell, Isabell, et al.
(författare)
-
The contribution of common genetic risk variants for ADHD to a general factor of childhood psychopathology
- 2020
-
Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:8, s. 1809-1821
-
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.
|
|
