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- Ip, H. F., et al.
(författare)
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Genetic association study of childhood aggression across raters, instruments, and age
- 2021
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGG(overall). The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from r(g)= 0.46 between self- and teacher-assessment to r(g)d= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range r(g): 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r(g)=-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |r(g)| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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| 2. |
- Singh, K. P., et al.
(författare)
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Clinical standards for the management of adverse effects during treatment for TB
- 2023
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Ingår i: The International Journal of Tuberculosis and Lung Disease. - : International Union Against Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 27:7, s. 506-519
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitiv-ity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person -centred, consensus-based approach to minimise the impact of AE TB treatment.
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| 5. |
- Bartels, M., et al.
(författare)
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Childhood aggression and the co-occurrence of behavioural and emotional problems: results across ages 3-16years from multiple raters in six cohorts in the EU-ACTION project
- 2018
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Ingår i: European Child & Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 27:9, s. 1105-1121
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Tidskriftsartikel (refereegranskat)abstract
- Childhood aggression and its resulting consequences inflict a huge burden on affected children, their relatives, teachers, peers and society as a whole. Aggression during childhood rarely occurs in isolation and is correlated with other symptoms of childhood psychopathology. In this paper, we aim to describe and improve the understanding of the co-occurrence of aggression with other forms of childhood psychopathology. We focus on the co-occurrence of aggression and other childhood behavioural and emotional problems, including other externalising problems, attention problems and anxiety-depression. The data were brought together within the EU-ACTION (Aggression in Children: unravelling gene-environment interplay to inform Treatment and InterventiON strategies) project. We analysed the co-occurrence of aggression and other childhood behavioural and emotional problems as a function of the child's age (ages 3 through 16years), gender, the person rating the behaviour (father, mother or self) and assessment instrument. The data came from six large population-based European cohort studies from the Netherlands (2x), the UK, Finland and Sweden (2x). Multiple assessment instruments, including the Child Behaviour Checklist (CBCL), the Strengths and Difficulties Questionnaire (SDQ) and Multidimensional Peer Nomination Inventory (MPNI), were used. There was a good representation of boys and girls in each age category, with data for 30,523 3- to 4-year-olds (49.5% boys), 20,958 5- to 6-year-olds (49.6% boys), 18,291 7- to 8-year-olds (49.0% boys), 27,218 9- to 10-year-olds (49.4% boys), 18,543 12- to 13-year-olds (48.9% boys) and 10,088 15- to 16-year-olds (46.6% boys). We replicated the well-established gender differences in average aggression scores at most ages for parental ratings. The gender differences decreased with age and were not present for self-reports. Aggression co-occurred with the majority of other behavioural and social problems, from both externalising and internalising domains. At each age, the co-occurrence was particularly prevalent for aggression and oppositional and ADHD-related problems, with correlations of around 0.5 in general. Aggression also showed substantial associations with anxiety-depression and other internalizing symptoms (correlations around 0.4). Co-occurrence for self-reported problems was somewhat higher than for parental reports, but we found neither rater differences, nor differences across assessment instruments in co-occurrence patterns. There were large similarities in co-occurrence patterns across the different European countries. Finally, co-occurrence was generally stable across age and sex, and if any change was observed, it indicated stronger correlations when children grew older. We present an online tool to visualise these associations as a function of rater, gender, instrument and cohort. In addition, we present a description of the full EU-ACTION projects, its first results and the future perspectives.
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| 6. |
- Bolhuis, K, et al.
(författare)
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Hospital Presentation for Self-Harm in Youth as a Risk Marker for Later Psychotic and Bipolar Disorders: A Cohort Study of 59 476 Finns
- 2021
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Ingår i: Schizophrenia bulletin. - : Oxford University Press (OUP). - 1745-1701 .- 0586-7614. ; 47:6, s. 1685-1694
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Tidskriftsartikel (refereegranskat)abstract
- Expanding clinical strategies to identify high risk groups for psychotic and bipolar disorders is a research priority. Considering that individuals diagnosed with psychotic and bipolar disorder are at high risk of self-harm, we hypothesised the reverse order relationship would also be true (ie, self-harm would predict psychotic/bipolar disorder). Specifically, we hypothesised that hospital presentation for self-harm would be a marker of high risk for subsequent development of psychotic/bipolar disorder and sought to test this hypothesis in a large population sample. This prospective register-based study included everyone born in Finland in 1987, followed until age 28 years (N = 59 476). We identified all hospital records of self-harm presentations, as well as all ICD-10 healthcare registrations of first diagnoses of psychotic and bipolar disorders. Cox proportional hazards models were used to assess the relationship between self-harm and psychotic/bipolar disorders. Of all individuals who presented to hospital with self-harm (n = 481), 12.8% went on to receive a diagnosis of psychosis (hazard ratio [HR] = 6.03, 95% confidence interval [CI] 4.56–7.98) and 9.4% a diagnosis of bipolar disorder (HR = 7.85, 95% CI 5.73–10.76) by age 28 years. Younger age of first self-harm presentation was associated with higher risk—for individuals who presented before age 18 years, 29.1% developed a psychotic or bipolar disorder by age 28 years. Young people who present to hospital with self-harm are at high risk of future psychotic and bipolar disorders. They represent an important cohort for the prevention of serious mental illness.
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| 7. |
- Derks, I. P. M., et al.
(författare)
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Testing Bidirectional Associations Between Childhood Aggression and BMI: Results from Three Cohorts
- 2019
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 27:5, s. 822-829
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Tidskriftsartikel (refereegranskat)abstract
- Objective This study examined the prospective, potentially bidirectional association of aggressive behavior with BMI and body composition across childhood in three population-based cohorts. Methods Repeated measures of aggression and BMI were available from the Generation R Study between ages 6 and 10 years (N = 3,974), the Netherlands Twin Register (NTR) between ages 7 and 10 years (N = 10,328), and the Swedish Twin Study of Child and Adolescent Development (TCHAD) between ages 9 and 14 years (N = 1,462). In all samples, aggression was assessed with the Child Behavior Checklist. Fat mass and fat-free mass were available in the Generation R Study. Associations were examined with cross-lagged modeling. Results Aggressive behavior at baseline was associated with higher BMI at follow-up in the Generation R Study (beta = 0.02, 95% CI: 0.00 to 0.04), in NTR (beta = 0.04, 95% CI: 0.02 to 0.06), and in TCHAD (beta = 0.03, 95% CI: -0.02 to 0.07). Aggressive behavior was prospectively associated with higher fat mass (beta = 0.03, 95% CI: 0.01 to 0.05) but not fat-free mass. There was no evidence that BMI or body composition preceded aggressive behavior. Conclusions More aggressive behavior was prospectively associated with higher BMI and fat mass. This suggests that aggression contributes to the obesity problem, and future research should study whether these behavioral pathways to childhood obesity are modifiable.
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