| 1. |
- Jami, E. S., et al.
(författare)
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Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms
- 2022
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Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567 .- 1527-5418. ; 61:7, s. 934-945
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. Results: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, n(effective) = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (vertical bar r(g)vertical bar > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range vertical bar r(g)vertical bar = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.
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| 2. |
- Roetman, P. J., et al.
(författare)
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Children With Early-Onset Disruptive Behavior: Parental Mental Disorders Predict Poor Psychosocial Functioning in Adolescence
- 2019
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Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567 .- 1527-5418. ; 58:8, s. 806-817
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Parental mental disorders (MD) and child early-onset disruptive behavior (DB) are well-established risk factors for poor outcomes in adolescence. However, it is not clear whether parental MD increases risk of future maladjustment among children who already display DB. Method: Parents of 9-year-old children reported on child DB, whereas a patient registry was used to determine parental MD. At follow-ups at ages 15 (n = 6,319) and 18 (n = 3,068) years, information about various problems were collected via registries, parent-, and self-reports. Results: In the total sample, child DB was related to all outcomes (mean odds ratio [OR] = 1.18; range = 1.07−1.51; p values <.01), paternal MD to criminality, aggression, truancy, poor school performance, and a cumulative risk index of poor functioning, and maternal MD to peer problems, rule breaking, and truancy (mean OR = 1.67; range = 1.19−2.71; p values <.05). In the subsample of children with DB, paternal MD predicted criminality, consequences of antisocial behavior, truancy, poor school performance, and cumulative risk, whereas maternal MD predicted peer problems (mean OR = 1.94; range = 1.30−2.40; p values <.05). Conclusion: This study provides novel evidence that parental MD places 9-year-olds with DB at risk for negative outcomes in adolescence. In addition, paternal MD is a better predictor than maternal MD, regardless of child DB at age 9, suggesting that fathers should be given increased attention in future research. Treatment-as-usual of children with DB could be augmented with additional screening and, if necessary, treatment of mental health problems in their parents. © 2019 American Academy of Child and Adolescent Psychiatry
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| 3. |
- Taylor, M. J., et al.
(författare)
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Examining the Association Between Autistic Traits and Atypical Sensory Reactivity: A Twin Study
- 2018
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Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567 .- 1527-5418. ; 57:2, s. 96-102
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Atypical responses to sensory stimuli are common features of autism spectrum disorders (ASD). Consequently, atypical sensory reactivity (SR) is now a diagnostic feature of ASD. Quantitative genetic research on ASD has overlooked these symptoms, however. We therefore investigated the association between autistic traits and SR using twin methods. Method: Autistic traits and SR were assessed by 2 separate scales in 12,419 Swedish twin pairs (n = 3,586 monozygotic [MZ], n = 8,833 dizygotic [DZ]) when the twins were 9 or 12 years of age. The classic twin design estimated the degree to which etiological factors associated with autistic traits were also associated with SR, and the degree to which such shared factors explained the covariance between these phenotypes. DeFries Fulker analysis estimated the genetic correlation between screening diagnoses of ASD, defined broadly and strictly, and SR. Results: Autistic traits and SR were both highly heritable (62%-75% and 66%-71%, respectively). There was a moderate phenotypic correlation between autistic traits and SR (r = 0.47). Genetic influences on these phenotypes correlated moderately (genetic correlation = 0.60). These overlapping genetic factors explained most of the correlation between autistic traits and SR. Genetic correlations with SR increased for broad ASD (genetic correlation = 0.72) and strict ASD (genetic correlation = 0.80). Conclusion: The genetic overlap observed between autistic traits and SR lends quantitative genetic support to the notion that ASD and SR are strongly linked. Stich symptoms may thus comprise part of the ASD genotype, as well as phenotype. Associations persisted across all definitions of ASD, indicating a genetic link between the broader ASD phenotype and SR.
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| 4. |
- Virtanen, S., et al.
(författare)
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Longitudinal Associations of Childhood Internalizing Psychopathology With Substance Misuse: A Register-Based Twin and Sibling Study
- 2021
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Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567 .- 1527-5418. ; 60:5, s. 593-603
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The pathways from internalizing psychopathology to substance misuse remain largely unclear. We estimated associations between childhood internalizing problems and subsequent substance misuse in two family-based samples. We also investigated sex differences and the role of externalizing comorbidity. Method: We studied associations of childhood internalizing psychopathology with register-based substance misuse after age 13 years. Sample 1 included all individuals born in Sweden from 1984 to 2000 (N = 1,768,516). Depressive and anxiety disorders were included as register-based International Classification of Diseases Ninth Revision (ICD-9) or Tenth Revision (ICD-10) diagnoses before age 13. Sample 2 was a subsample within the population sample, the Child and Adolescent Twin Study in Sweden (CATSS) twin cohort (n = 12,408; born 1992–1998), with mood and anxiety problems assessed at age 9/12 by parents. In both samples, substance misuse was defined as an ICD-9/10 alcohol/drug use disorder or an alcohol/drug-related criminal conviction until December 2013. To account for familial effects, stratified analyses were conducted within siblings and twin pairs. Results: In the population sample, both depressive (hazard ratio [HR] = 2.75, 95% CI = 2.36–3.20) and anxiety disorders (HR = 1.52, 95% CI = 1.35–1.73) were associated with substance misuse. Childhood mood problems (HR = 2.28, 95% CI = 1.69–3.08) were associated with substance misuse in the CATSS sample. The associations were partially explained by familial factors, and comorbid externalizing disorders explained the associations in men but not in women. Conclusion: Childhood mood problems were associated with substance misuse, but familial factors shared by siblings partially explained the associations. The relationship of anxiety with substance misuse was complex and depended on measurement and the type of anxiety disorder. Internalizing problems may be especially important for substance misuse risk in women. © 2020 American Academy of Child and Adolescent Psychiatry
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