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  • Butwicka, Agnieszka, et al. (författare)
  • Hypospadias and increased risk for neurodevelopmental disorders.
  • 2015
  • Ingår i: Journal of child psychology and psychiatry, and allied disciplines. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1469-7610. ; 56:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypospadias (aberrant opening of the urethra on the underside of the penis) occurs in 1 per 300 newborn boys. It has been previously unknown whether this common malformation is associated with increased psychiatric morbidity later in life. Studies of individuals with hypospadias also provide an opportunity to examine whether difference in androgen signaling is related to neurodevelopmental disorders. To elucidate the mechanisms behind a possible association, we also studied psychiatric outcomes among brothers of the hypospadias patients.
  • Dinkler, Lisa, et al. (författare)
  • Maltreatment-associated neurodevelopmental disorders: a co-twin control analysis.
  • 2017
  • Ingår i: Journal of child psychology and psychiatry, and allied disciplines. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1469-7610. ; 58:6, s. 691-701
  • Tidskriftsartikel (refereegranskat)abstract
    • Childhood maltreatment (CM) is strongly associated with psychiatric disorders in childhood and adulthood. Previous findings suggest that the association between CM and psychiatric disorders is partly causal and partly due to familial confounding, but few studies have investigated the mechanisms behind the association between CM and neurodevelopmental disorders (NDDs). Our objective was to determine whether maltreated children have an elevated number of NDDs and whether CM is a risk factor for an increased NDD 'load' and increased NDD symptoms when controlling for familial effects.We used a cross-sectional sample from a population-representative Swedish twin study, comprising 8,192 nine-year-old twins born in Sweden between 1997 and 2005. CM was defined as parent-reported exposure to emotional abuse/neglect, physical neglect, physical abuse, and/or sexual abuse. Four NDDs were measured with the Autism-Tics, AD/HD, and other comorbidities inventory.Maltreated children had a greater mean number of NDDs than nonmaltreated children. In a co-twin control design, CM-discordant monozygotic twins did not differ significantly for their number of NDDs, suggesting that CM is not associated with an increased load of NDDs when genetic and shared environmental factors are taken into account. However, CM was associated with a small increase in symptoms of attention-deficit/hyperactivity disorder and autism spectrum disorder in CM-discordant MZ twins, although most of the covariance of CM with NDD symptoms was explained by common genetic effects.Maltreated children are at higher risk of having multiple NDDs. Our findings are, however, not consistent with the notion that CM causes the increased NDD load in maltreated children. Maltreated children should receive a full neurodevelopmental assessment, and clinicians should be aware that children with multiple NDDs are at higher risk of maltreatment.
  • Halldner, Linda, et al. (författare)
  • Relative immaturity and ADHD : findings from nationwide registers, parent- and self-reports
  • 2014
  • Ingår i: Journal of Child Psychology and Psychiatry and Allied Disciplines. - Stockholm : Wiley-Blackwell. - 0021-9630 .- 1469-7610. ; 55:8, s. 897-904
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: We addressed if immaturity relative to peers reflected in birth month increases the likelihood of ADHD diagnosis and treatment.METHODS: We linked nationwide Patient and Prescribed Drug Registers and used prospective cohort and nested case-control designs to study 6-69 year-old individuals in Sweden from July 2005 to December 2009 (Cohort 1). Cohort 1 included 56,263 individuals diagnosed with ADHD or ever used prescribed ADHD-specific medication. Complementary population-representative cohorts provided DSM-IV ADHD symptom ratings; parent-reported for 10,760 9-year-old twins born 1995-2000 from the CATSS study (Cohort 2) and self-reported for 6,970 adult twins age 20-47 years born 1959-1970 from the STAGE study (Cohort 3). We calculated odds ratios (OR:s) for ADHD across age for individuals born in November/December compared to January/February (Cohort 1). ADHD symptoms in Cohorts 2 and 3 were studied as a function of calendar birth month.RESULTS: ADHD diagnoses and medication treatment were both significantly more common in individuals born in November/December versus January/February; peaking at ages 6 (OR: 1.8; 95% CI: 1.5-2.2) and 7 years (OR: 1.6; 95% CI: 1.3-1.8) in the Patient and Prescribed Drug Registers, respectively. We found no corresponding differences in parent- or self-reported ADHD symptoms by calendar birth month.CONCLUSION: Relative immaturity compared to class mates might contribute to ADHD diagnosis and pharmacotherapy despite absence of parallel findings in reported ADHD symptom loads by relative immaturity. Increased clinical awareness of this phenomenon may be warranted to decrease risk for imprecise diagnostics and treatment. We speculate that flexibility regarding age at school start according to individual maturity could reduce developmentally inappropriate demands on children and improve the precision of ADHD diagnostic practice and pharmacological treatment.
  • Hedman, Anna, et al. (författare)
  • Bidirectional relationship between eating disorders and autoimmune diseases
  • 2019
  • Ingår i: Journal of Child Psychology and Psychiatry and Allied Disciplines. - Stockholm : Blackwell Publishing. - 0021-9630 .- 1469-7610. ; 60:7, s. 803-812
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Immune system dysfunction may be associated with eating disorders (ED) and could have implications for detection, risk assessment, and treatment of both autoimmune diseases and EDs. However, questions regarding the nature of the relationship between these two disease entities remain. We evaluated the strength of associations for the bidirectional relationships between EDs and autoimmune diseases.METHODS: In this nationwide population-based study, Swedish registers were linked to establish a cohort of more than 2.5 million individuals born in Sweden between January 1, 1979 and December 31, 2005 and followed up until December 2013. Cox proportional hazard regression models were used to investigate: (a) subsequent risk of EDs in individuals with autoimmune diseases; and (b) subsequent risk of autoimmune diseases in individuals with EDs.RESULTS: We observed a strong, bidirectional relationship between the two illness classes indicating that diagnosis in one illness class increased the risk of the other. In women, the diagnoses of autoimmune disease increased subsequent hazards of anorexia nervosa (AN), bulimia nervosa (BN), and other eating disorders (OED). Similarly, AN, BN, and OED increased subsequent hazards of autoimmune diseases.Gastrointestinal-related autoimmune diseases such as, celiac disease and Crohn's disease showed a bidirectional relationship with AN and OED. Psoriasis showed a bidirectional relationship with OED. The previous occurence of type 1 diabetes increased the risk for AN, BN, and OED. In men, we did not observe a bidirectional pattern, but prior autoimmune arthritis increased the risk for OED.CONCLUSIONS: The interactions between EDs and autoimmune diseases support the previously reported associations. The bidirectional risk pattern observed in women suggests either a shared mechanism or a third mediating variable contributing to the association of these illnesses.
  • Kuja-Halkola, Ralf, et al. (författare)
  • Codevelopment of ADHD and externalizing behavior from childhood to adulthood
  • 2015
  • Ingår i: Journal of Child Psychology and Psychiatry and Allied Disciplines. - Stockholm : Wiley-Blackwell. - 0021-9630 .- 1469-7610. ; 56:6, s. 640-647
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) frequently co-occurs with externalizing disorders, but a clear understanding of the etiologic underpinnings is hampered by the limited understanding of the codevelopment of the traits from childhood into early adulthood.METHODS: Using a birth cohort of 2600 twins, the Swedish Twin study of Child and Adolescent Development study, assessed at ages 8-9, 13-14, 16-17, and 19-20, we investigated the codevelopment of ADHD and externalizing behavior from childhood to adulthood. The analyses examined ADHD-like and externalizing traits, as rated by twins and their parents using the Attention Problems scale and Externalizing scale of the Child Behavior Checklist, and estimated cross-lagged effects (one trait at one time-point predicting the other at the next). The covariation between the traits were decomposed into stable (effects carried over from the prior time-points) and innovative (new effects for each time-point) sources; each source was further decomposed into additive genetics, shared and nonshared environment.RESULTS: The analysis suggested that externalizing traits in middle childhood (age 8-9) predicted ADHD-like traits in early adolescence (age 13-14), whereas the reverse association was nonsignificant. In contrast, ADHD-like traits in lateadolescence (age 16-17) predicted externalizing traits in early adulthood (age 19-20). The correlation between ADHD-like and externalizing traits increased over time. At all time-points, innovative sources contributed substantially to maintained comorbidity. Genetic effects explained 67% of the covariation at each time-point; importantly, nearly 50% of these effects were innovative.CONCLUSIONS: This study challenges the belief that ADHD generally precedes externalizing behaviors; rather, change in the etiologic factors across the development is the rule. The effects were due to both new genetic and environmental factors emerging up to young adulthood. Clinicians and researchers needs to consider complex etiologic and developmental models for the comorbidity between ADHD and externalizing behaviors.
  • Lundström, Sebastian, et al. (författare)
  • Autism spectrum disorders and coexisting disorders in a nationwide Swedish twin study.
  • 2015
  • Ingår i: Journal of child psychology and psychiatry, and allied disciplines. - Stockholm : Wiley-Blackwell. - 1469-7610 .- 0021-9630. ; 56:6
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Evidence from twin and molecular genetic studies is accumulating that Autism Spectrum Disorder (ASD) shares substantial etiological factors with other disorders. This is mirrored in clinical practice where ASD without coexisting disorders is rare. The present study aims to examine the range of coexisting disorders in ASD in a genetically informative cohort. METHODS: Parents of all Swedish 9-year-old twins born between 1992 and 2001 (n = 19,130) underwent a telephone interview designed to screen for child psychiatric disorders, including ASD. To ensure full coverage of child psychiatric disorders, data were also retrieved from population-based health registers. We investigated the coexistence of eight psychiatric disorders known to coexist with ASDs in probands and their co-twins. RESULTS: Half of the individuals with ASDs (50.3%) had four or more coexisting disorders and only 4% did not have any concomitant disorder. The 'healthy co-twin' in ASD discordant monozygotic twin pairs was very often (79% of boys and 50% of girls) affected by at least one non-ASD disorder. The corresponding figures for ASD discordant dizygotic twin pairs were significantly lower (46% of males and 30% of females). CONCLUSIONS: Detailed phenotypic descriptions including symptoms of problems associated with a wide range of child psychiatric disorders may aid in unraveling the genetic architecture of ASD and should guide the development of intervention strategies addressing each problem type specifically.
  • Pettersson, Erik, et al. (författare)
  • Birth weight as an independent predictor of ADHD symptoms : a within-twin pair analysis
  • 2015
  • Ingår i: Journal of Child Psychology and Psychiatry and Allied Disciplines. - Hoboken, USA : Wiley-Blackwell. - 0021-9630 .- 1469-7610. ; 56:4, s. 453-459
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Studies have found an association between low birth weight and ADHD, but the nature of this relation is unclear. First, it is uncertain whether birth weight is associated with both of the ADHD dimensions, inattentiveness and hyperactivity-impulsivity. Second, it remains uncertain whether the association between birth weight and ADHD symptom severity is confounded by familial factors.Method: Parents of all Swedish 9- and 12-year-old twins born between 1992 and 2000 were interviewed for DSM-IV inattentive and hyperactive-impulsive ADHD symptoms by the Autism - Tics, AD/HD and other Comorbidities (A-TAC) inventory (N = 21,775 twins). Birth weight was collected prospectively through the Medical Birth Registry. We used a within-twin pair design to control for genetic and shared environmental factors.Results: Reduced birth weight was significantly associated with a mean increase in total ADHD (β = -.42; 95% CI: -.53, -.30), inattentive (β = -.26; 95% CI: -.33, -.19), and hyperactive-impulsive (β = -.16; 95% CI: -.22, -.10) symptom severity. These results imply that a change of one kilogram of birth weight corresponded to parents rating their child nearly one unit higher (going from "no" to "yes, to some extent" on a given symptom) on the total ADHD scale. These associations remained within pairs of MZ and DZ twins, and were also present when restricting the analyses to full term births.Conclusions: There is an independent association between low birth weight and all forms of ADHD symptoms, even after controlling for all environmental and genetic confounds shared within twin pairs. These results indicate that fetal growth restriction (as reflected in birth weight differences within twin pairs) and/or the environmental factors which influence it is in the casual pathway leading to ADHD.
  • Rydell, Mina, et al. (författare)
  • Has the attention deficit hyperactivity disorder phenotype become more common in children between 2004 and 2014? Trends over 10 years from a Swedish general population sample.
  • 2018
  • Ingår i: Journal of child psychology and psychiatry, and allied disciplines. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1469-7610. ; 59:8, s. 863-871
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies have reported increases in clinically diagnosed and treated attention deficit hyperactivity disorder (ADHD) during the last decade, but it is unclear if this reflects an increase in the underlying ADHD phenotype. We aimed to clarify if there has been an increase in the prevalence of ADHD-like traits in the general population from 2004 to 2014.Data were collected from 9-year-old twins (19,271), participating in the population-based Child and Adolescent Twin Study in Sweden between 2004 and 2014. We assessed lifetime ADHD symptoms using the Autism-Tics, ADHD and other Comorbidities inventory. Research proxies for diagnostic-level ADHD and subthreshold ADHD were derived from this scale. We modeled the lifetime prevalence of diagnostic-level and subthreshold ADHD with logistic regression, and assessed mean ADHD scores each year with linear regression. Lifetime prevalence of clinically diagnosed ADHD was retrieved from the National Patient Register and modeled with logistic regression.The prevalence of diagnostic-level ADHD based on parent ratings did not differ significantly over time from 2004 to 2014 (OR 1.37; 95% CI: 0.77-2.45; p-value .233). Both subthreshold ADHD and mean ADHD scores increased significantly over time (both p-values <.001). Clinically diagnosed ADHD increased more than fivefold from 2004 to 2014 (OR 5.27, 95% CI: 1.85-14.96).We found no evidence of an increase in ADHD-like traits at the extreme end of the distribution from 2004 to 2014, but small increases in normal and subthreshold variations of ADHD-like traits were observed. This suggests that the increased rates of clinically diagnosed ADHD might reflect changes in diagnostic and treatment practices of ADHD, administrative changes in reporting diagnoses, greater awareness of ADHD, better access to healthcare, or current overdiagnosis, rather than an increase in the ADHD phenotype.
  • Skoglund, Charlotte, et al. (författare)
  • Familial confounding of the association between maternal smoking during pregnancy and ADHD in offspring
  • 2014
  • Ingår i: Journal of Child Psychology and Psychiatry and Allied Disciplines. - Stockholm : Blackwell Publishing. - 0021-9630 .- 1469-7610. ; 55:1, s. 61-8
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Maternal Smoking During Pregnancy (SDP) has consistently been associated with increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring, but recent studies indicate that this association might be due to unmeasured familial confounding.METHODS: A total of 813,030 individuals born in Sweden between 1992 and 2000 were included in this nationwide population-based cohort study. Data on maternal SDP and ADHD diagnosis were obtained from national registers and patients were followed up from the age of 3 to the end of 2009. Hazard Ratios (HRs) were estimated using stratified Cox regression models. Cousin and sibling data were used to control for unmeasured familial confounding.RESULTS: At the population level maternal SDP predicted ADHD in offspring (HR(ModerateSDP) = 1.89; HR(HighSDP)= 2.50). This estimate gradually attenuated toward the null when adjusting for measured confounders (HR(ModerateSDP)= 1.62; HR(HighSDP)= 2.04), unmeasured confounders shared within the extended family (i.e., cousin comparison) (HR(ModerateSDP)= 1.45; HR(HighSDP)= 1.69), and unmeasured confounders within the nuclear family (i.e., sibling comparison) (HR(ModerateSDP)= 0.88; HR(HighSDP)= 0.84).CONCLUSIONS: Our results suggest that the association between maternal SDP and offspring ADHD are due to unmeasured familial confounding.
  • Larsson, Henrik, et al. (författare)
  • Childhood attention-deficit hyperactivity disorder as an extreme of a continuous trait: a quantitative genetic study of 8,500 twin pairs.
  • 2012
  • Ingår i: Journal of child psychology and psychiatry, and allied disciplines. - : Wiley-Blackwell. - 1469-7610 .- 0021-9630. ; 53:1, s. 73-80
  • Tidskriftsartikel (refereegranskat)abstract
    • Although the clinical utility of categorically defined attention-deficit hyperactivity disorder (ADHD) is well established, there is also strong evidence supporting the notion of ADHD as an extreme of a continuous trait. Nevertheless, the question of whether the etiology is the same for different levels of DSM-IV ADHD symptoms remains to be investigated. The aim of this study was to assess genetic links between the extreme and the subthreshold range of ADHD symptoms.
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