| 1. |
- Lichtenstein, P., et al.
(författare)
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Associations between conduct problems in childhood and adverse outcomes in emerging adulthood: a longitudinal Swedish nationwide twin cohort
- 2020
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Ingår i: Journal of Child Psychology and Psychiatry and Allied Disciplines. - : Wiley. - 0021-9630 .- 1469-7610. ; 61:7, s. 798-806
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Tidskriftsartikel (refereegranskat)abstract
- Background We examined whether childhood conduct problems predicted a wide range of adverse outcomes in emerging adulthood and whether the association with internalizing problems remained after adjusting for general comorbidity and externalizing problems. Methods Participants were 18,649 twins from the Child and Adolescent Twin Study in Sweden. At age 9/12, parents rated their children on eight conduct problems. Adverse outcomes were retrieved from national registers in emerging adulthood (median follow‐up time = 9.2 years), including diagnoses of six psychiatric disorders, prescriptions of antidepressants, suicide attempts, criminality, high school ineligibility, and social welfare recipiency. We estimated risk for the separate outcomes and examined if conduct problems predicted an internalizing factor above and beyond a general comorbidity and an externalizing factor. We used twin analyses to estimate genetic and environmental contributions to these associations. Results On the average, each additional conduct symptom in childhood was associated with a 32% increased risk of the adverse outcomes in emerging adulthood (mean hazard ratio = 1.32; range = 1.16, 1.56). A latent childhood conduct problems factor predicted the internalizing factor in emerging adulthood (βboys = .24, standard error, SE = 0.03; βgirls = .17, SE = 0.03), above and beyond its association with the externalizing (βboys = 0.21, SE = 0.04; βgirls = 0.17, SE = 0.05) and general factors (βboys = 0.45, SE = 0.03; βgirls = 0.34, SE = 0.04). These associations were differentially influenced by genetic and environmental factors. Conclusions It is important to monitor boys and girls with conduct problems not only for future externalizing problems, but also for future internalizing problems. Prevention of specific outcomes, however, might require interventions at different levels.
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| 2. |
- Ronald, A., et al.
(författare)
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A twin study of autism symptoms in Sweden
- 2011
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Ingår i: Molecular Psychiatry. - London, United Kingdom : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 16:10, s. 1039-1047
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to identify empirically the number of factors underlying autism symptoms-social impairments, communication impairments, and restricted repetitive behaviors and interests-when assessed in a general population sample. It also investigated to what extent these autism symptoms are caused by the same or different genetic and environmental influences. Autistic symptoms were assessed in a population-based twin cohort of >12,000 (9- and 12-year-old) children by parental interviews. Confirmatory factor analyses, principal component analyses and multivariate structural equation model fitting were carried out. A multiple factor solution was suggested, with nearly all analyses pointing to a three-factor model for both boys and girls and at both ages. A common pathway twin model fit the data best, which showed that there were some underlying common genetic and environmental influences across the different autism dimensions, but also significant specific genetic effects on each symptom type. These results suggest that the autism triad consists of three partly independent dimensions when assessed in the general population, and that these different autism symptoms, to a considerable extent, have partly separate genetic influences. These findings may explain the large number of children who do not meet current criteria for autism but who show some autism symptoms. Molecular genetic research may benefit from taking a symptom-specific approach to finding genes associated with autism.
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| 3. |
- Ronald, A., et al.
(författare)
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Symptoms of Autism and ADHD: A Swedish Twin Study Examining Their Overlap
- 2014
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Ingår i: Journal of Abnormal Psychology. - Washington DC, USA : American Psychological Association (APA). - 0021-843X .- 1939-1846. ; 123:2, s. 440-451
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) show high comorbidity. The following questions were addressed regarding their specific symptoms: What is the factor structure of ASD and ADHD symptoms, to what degree do different symptom domains cluster together, to what extent are these domains caused by the same genetic and environmental influences, and what is the best model of their co-occurrence? A population-based twin cohort of over 17,000 9- and 12-year-olds were assessed using the Autism-Tics, AD/HD, and other Comorbidities parental interview inventory. Principal component analyses were conducted, and symptom domain clustering was assessed. Four multivariate twin models were compared. Factors split into three ASD (social impairments, communication impairments, and restricted repetitive behaviors and interests), and three ADHD (inattention, hyperactivity, and impulsivity) symptom domains. Some ASD-ADHD symptom domain combinations clustered together often, although others not at all. A two-factor common pathway model fit the data, suggesting that ASD and ADHD symptom domains tap into separate "ASD" and "ADHD" latent factors that showed high genetic overlap. All subdomains also showed significant specific genetic and environmental influences, reflecting the etiological heterogeneity both within and between ASD and ADHD. These findings support the conceptual distinction of ASD and ADHD, and demonstrate the considerable natural co-occurrence of particular ASD/ADHD symptom domains. The results imply that more children with 1 condition show features of the other condition than show complete comorbidity. Emphasis on symptom co-occurrence, rather than complete comorbidity between disorders, may help focus clinical approaches and advance molecular genetic research.
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| 4. |
- Taylor, M. J., et al.
(författare)
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Is There a Female Protective Effect Against Attention-Deficit/Hyperactivity Disorder? Evidence From Two Representative Twin Samples
- 2016
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Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - Stockholm : Elsevier BV. - 0890-8567 .- 1527-5418. ; 55:6, s. 504-512
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Attention-deficit/hyperactivity disorder (ADHD) is more frequent in males than in females. The "female protective effect" posits that females undergo greater exposure to etiological factors than males in order to develop ADHD, leading to the prediction that relatives of females with ADHD will display more ADHD behaviors. We thus tested whether cotwins of females displaying extreme ADHD traits would display more ADHD traits than cotwins of males displaying extreme ADHD traits. Method: Parents of approximately 7,000 pairs of nonidentical twins in Sweden, and approximately 4,000 pairs of twins in England and Wales, completed dimensional assessments of ADHD traits. Probands were selected on the basis of scoring within the highest 10% of the distribution in each sample. Dimensional scores of cotwins of probands, as well as the categorical recurrence rate, were investigated by proband sex. Results: Cotwins of female probands displayed higher mean ADHD trait scores (mean = 0.62-0.79) than cotwins of male probands (mean = 0.38-0.55) in both samples. This trend was significant in the Swedish sample (p <.01) and when the 2 samples were merged into a single, larger sample (p <.001). When the samples were merged, there was also a significant association between proband sex and cotwin's categorical status, with more cotwins of female probands also being probands than cotwins of male probands. Conclusion: These findings support a female protective effect against ADHD behaviors, suggesting that females require greater exposure to genetic and environmental factors associated with ADHD in order to develop the condition.
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| 5. |
- Arora, M., et al.
(författare)
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Fetal and postnatal metal dysregulation in autism
- 2017
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Ingår i: Nat Commun. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Genetic and environmental factors contribute to the etiologies of autism spectrum disorder (ASD), but evidence of specific environmental exposures and susceptibility windows is limited. Here we study monozygotic and dizygotic twins discordant for ASD to test whether fetal and postnatal metal dysregulation increases ASD risk. Using validated tooth-matrix biomarkers, we estimate pre- and post-natal exposure profiles of essential and toxic elements. Significant divergences are apparent in metal uptake between ASD cases and their control siblings, but only during discrete developmental periods. Cases have reduced uptake of essential elements manganese and zinc, and higher uptake of the neurotoxin lead. Manganese and lead are also correlated with ASD severity and autistic traits. Our study suggests that metal toxicant uptake and essential element deficiency during specific developmental windows increases ASD risk and severity, supporting the hypothesis of systemic elemental dysregulation in ASD. Independent replication in population-based studies is needed to extend these findings.
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| 6. |
- Bolte, S., et al.
(författare)
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The Roots of Autism and ADHD Twin Study in Sweden (RATSS)
- 2014
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Ingår i: Twin Research and Human Genetics. - Stockholm : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 17:3, s. 164-176
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Tidskriftsartikel (refereegranskat)abstract
- Neurodevelopmental disorders affect a substantial minority of the general population. Their origins are still largely unknown, but a complex interplay of genetic and environmental factors causing disturbances of the central nervous system's maturation and a variety of higher cognitive skills is presumed. Only limited research of rather small sample size and narrow scope has been conducted in neurodevelopmental disorders using a twin-differences design. The Roots of Autism and ADHD Twin Study in Sweden (RATSS) is an ongoing project targeting monozygotic twins discordant for categorical or dimensional autistic and inattentive/hyperactive-impulsive phenotypes as well as other neurodevelopmental disorders, and typically developing twin controls. Included pairs are 9 years of age or older, and comprehensively assessed for psychopathology, medical history, neuropsychology, and dysmorphology, as well as structural, functional, and molecular brain imaging. Specimens are collected for induced pluripotent (iPS) and neuroepithelial stem cells, genetic, gut bacteria, protein-/monoamine, and electron microscopy analyses. RATSS's objective is to generate a launch pad for novel surveys to understand the complexity of genotype-environment-phenotype interactions in autism spectrum disorder and attention-deficit hyperactivity disorder (ADHD). By October 2013, RATSS had collected data from 55 twin pairs, among them 10 monozygotic pairs discordant for autism spectrum disorder, seven for ADHD, and four for other neurodevelopmental disorders. This article describes the design, recruitment, data collection, measures, collected pairs' characteristics, as well as ongoing and planned analyses in RATSS. Potential gains of the study comprise the identification of environmentally mediated biomarkers, the emergence of candidates for drug development, translational modeling, and new leads for prevention of incapacitating outcomes.
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| 7. |
- Cederlof, M., et al.
(författare)
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Language and mathematical problems as precursors of psychotic-like experiences and juvenile mania symptoms
- 2014
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Ingår i: Psychological Medicine. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1469-8978. ; 44:6, s. 1293-1302
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Tidskriftsartikel (refereegranskat)abstract
- Background. Psychotic-like experiences (PLEs) and juvenile mania in adolescence index risk for severe psychopathology in adulthood. The importance of childhood problems with communication, reading, speech and mathematics for the development of PLEs and juvenile mania is not well understood. Method. Through the Child and Adolescent Twin Study in Sweden, we identified 5812 children. The parents were interviewed about their children's development at age 9 or 12 years. At age 15 or 18 years, children and parents completed questionnaires targeting current PLEs and juvenile mania symptoms. Logistic regressions were used to assess associations between problems with communication, reading, speech and mathematics and PLEs/juvenile mania symptoms. To evaluate the relative importance of genes and environment in these associations, we used bivariate twin analyses based on structural equation models. Results. Children with parent-endorsed childhood problems with communication, reading and mathematics had an increased risk of developing auditory hallucinations and parental-reported juvenile mania symptoms in adolescence. The most consistent finding was that children with childhood problems with communication, reading and mathematics had an increased risk of developing auditory hallucinations [for example, the risk for self-reported auditory hallucinations at age 15 was increased by 96% for children with communication problems: OR (odds ratio) 1.96, 95% confidence interval (CI) 1.33-2.88]. The twin analyses showed that genetic effects accounted for the increased risk of PLEs and juvenile mania symptoms among children with communication problems. Conclusions. Childhood problems with communication, reading and mathematics predict PLEs and juvenile mania symptoms in adolescence. Similar to the case for schizophrenia and bipolar disorder, PLEs and juvenile mania may share genetic aetiological factors.
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| 8. |
- Hovey, Daniel, et al.
(författare)
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Antisocial behavior and polymorphisms in the oxytocin receptor gene: findings in two independent samples.
- 2016
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Ingår i: Molecular psychiatry. - Stockholm : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 16, s. 983-988
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Tidskriftsartikel (refereegranskat)abstract
- The quantitative genetic contribution to antisocial behavior is well established, but few, if any, genetic variants are established as risk factors. Emerging evidence suggests that the neuropeptide oxytocin (OXT) may modulate interpersonal aggression. We here investigated whether single-nucleotide polymorphisms (SNPs) in the OXT receptor gene (OXTR) are associated with the expression of antisocial behavior. A discovery sample, including both sexes, was drawn from the Child and Adolescent Twin Study in Sweden (CATSS; n=2372), and a sample from the Twin Study of Child and Adolescent Development (TCHAD; n=1232) was used for replication. Eight SNPs in OXTR, selected on previous associations with social and antisocial behavior, were genotyped in the participants of CATSS. Significant polymorphisms were subsequently genotyped in TCHAD for replication. Participants completed self-assessment questionnaires-Life History of Aggression (LHA; available only in CATSS), and Self-Reported Delinquency (SRD; available in both samples)-designed to capture antisocial behavior as continuous traits. In the discovery sample, the rs7632287 AA genotype was associated with higher frequency of antisocial behavior in boys, and this was then replicated in the second sample. In particular, overt aggression (directly targeting another individual) was strongly associated with this genotype in boys (P=6.2 × 10(-7) in the discovery sample). Meta-analysis of the results for antisocial behavior from both samples yielded P=2.5 × 10(-5). Furthermore, an association between rs4564970 and LHA (P=0.00013) survived correction in the discovery sample, but there was no association with the SRD in the replication sample. We conclude that the rs7632287 and rs4564970 polymorphisms in OXTR may independently influence antisocial behavior in adolescent boys. Further replication of our results will be crucial to understanding how aberrant social behavior arises, and would support the OXT receptor as one potential target in the treatment of aggressive antisocial behavior.Molecular Psychiatry advance online publication, 22 September 2015; doi:10.1038/mp.2015.144.
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| 9. |
- Kerekes, Nóra, et al.
(författare)
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Conduct disorder and somatic health in children: a nationwide genetically sensitive study
- 2020
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Ingår i: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Conduct disorder (CD), a serious behavioral and emotional disorder in childhood and adolescence, characterized by disruptive behavior and breaking societal rules. Studies have explored the overlap of CD with neurodevelopmental problems (NDP). The somatic health of children with NDP has been investigated; however, the prevalence of these problems in children with CD has not been sufficiently studied. Holistic assessment of children with CD is required for establishing effective treatment strategies. Aims: (1) Define the prevalence of selected neurological problems (migraine and epilepsy) and gastrointestinal problems (celiac disease, lactose intolerance, diarrhea, and constipation) in a population of twins aged 9 or 12; (2) Compare the prevalence of somatic problems in three subpopulations: (a) children without CD or NDP, (b) children with CD, and (c) children with both CD and NDP; (3) Select twin pairs where at least one child screened positive for CD but not NDP (proband) and map both children’s neurological and gastrointestinal problems. Method: Telephone interviews with parents of 20,302 twins in a cross-sectional, nationwide, ongoing study. According to their scores on the Autism-Tics, AD/HD, and Comorbidities inventory, screen-positive children were selected and divided into two groups: (1) children with CD Only, (2) children with CD and at least one NDP. Results: Children with CD had an increased prevalence of each neurological and gastrointestinal problem (except celiac disease), and the prevalence of somatic problems was further increased among children with comorbid CD and NDP. The presence of CD (without NDP) increased the odds of constipation for girls and the odds of epilepsy for boys. Girls with CD generally had more coexisting gastrointestinal problems than boys with CD. Female co-twins of probands with CD were strongly affected by gastrointestinal problems. Concordance analyses suggested genetic background factors in neurological and gastrointestinal problems, but no common etiology with CD could be concluded. Conclusion: Co-occurring NDP could explain most of the increased prevalence of somatic problems in CD. Our results raise a new perspective on CD in children and adolescents; their CD seems to be linked to a number of other health problems, ranging from neurodevelopmental and psychiatric disorders to somatic complaints. © 2020, The Author(s).
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| 10. |
- Kerekes, Nora, 1969, et al.
(författare)
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Neurodevelopmental problems and extremes in BMI
- 2015
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Ingår i: Peerj. - : PeerJ. - 2167-8359. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Background. Over the last few decades, an increasing number of studies have suggested a connection between neurodevelopmental problems (NDPs) and body mass index (BMI). Attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) both seem to carry an increased risk for developing extreme BMI. However, the results are inconsistent, and there have been only a few studies of the general population of children. Aims. We had three aims with the present study: (1) to define the prevalence of extreme (low or high) BMI in the group of children with ADHD and/or ASDs compared to the group of children without these NDPs; (2) to analyze whether extreme BMI is associated with the subdomains within the diagnostic categories of ADHD or ASD; and (3) to investigate the contribution of genetic and environmental factors to BMI in boys and girls at ages 9 and 12. Method. Parents of 9- or 12-year-old twins (n = 12,496) were interviewed using the Autism-Tics, ADHD and other Comorbidities (A-TAC) inventory as part of the Child and Adolescent Twin Study in Sweden (CATSS). Univariate and multivariate generalized estimated equation models were used to analyze associations between extremes in BMI and NDPs. Results. ADHD screen-positive cases followed BMI distributions similar to those of children without ADHD or ASD. Significant association was found between ADHD and BMI only among 12-year-old girls, where the inattention subdomain of ADHD was significantly associated with the high extreme BMI. ASD scores were associated with both the low and the high extremes of BMI. Compared to children without ADHD or ASD, the prevalence of ASD screen-positive cases was three times greater in the high extreme BMI group and double as much in the low extreme BMI group. Stereotyped and repetitive behaviors were significantly associated with high extreme BMIs. Conclusion. Children with ASD, with or without coexisting ADHD, are more prone to have low or high extreme BMIs than children without ADHD or ASD.
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