Is There a Female Protective Effect Against Attention-Deficit/Hyperactivity Disorder? Evidence From Two Representative Twin Samples

Taylor, Mark J.; Lichtenstein, Paul; Larsson, Henrik; Anckarsäter, Henrik; Greven, Corina U.; Ronald, Angelica

doi:10.1016/j.jaac.2016.04.004

Cited by 58 publications

(49 citation statements)

References 33 publications

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“…We found both weak and insignificant differences between males and females in the effect of PI-PTVs on 4 neurodevelopmental/psychiatric disorders (Supplementary Table 8). Interestingly, we did not observe differences in ADHD-affected males and females, in contrast with the hypothesis that affected females might be enriched for rare deleterious variants 19 . We cannot exclude that differences in the diagnostic criteria used in these European studies compared to those of previous studies, which were mostly conducted in the U.S., might explain these results.…”

Section: Introductioncontrasting

confidence: 99%

Quantifying the impact of rare and ultra-rare coding variation across the phenotypic spectrum

Ganna

Satterstrom

Zekavat

et al. 2017

Preprint

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There is a limited understanding about the impact of rare protein truncating variants across multiple phenotypes. We explore the impact of this class of variants on 13 quantitative traits and 10 diseases using whole-exome sequencing data from 100,296 individuals. Protein truncating variants in genes intolerant to this class of mutations increased risk of autism, schizophrenia, bipolar disorder, intellectual disability, ADHD. In individuals without these disorders, there was an association with shorter height, lower education, increased hospitalization and reduced age. Gene sets implicated from GWAS did not show a significant protein truncating variants-burden beyond what captured by established Mendelian genes. In conclusion, we provide the most thorough investigation to date of the impact of rare deleterious coding variants on complex traits, suggesting widespread pleiotropic risk.Main abbreviationsPTV= Protein Truncating VariantsPI= Protein Truncating IntolerantPI-PTV= Protein Truncating Variant in genes that are Intolerant to Protein Truncating Variants

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Section: Introductioncontrasting

confidence: 99%

Quantifying the impact of rare and ultra-rare coding variation across the phenotypic spectrum

Ganna

Satterstrom

Zekavat

et al. 2017

Preprint

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“…The closer cross‐sectional and longitudinal HCC‐ADHD links in boys than in girls might further characterize the specific pathway of preschool ADHD. Although the predictive effect by HCC did not prove to differ significantly between boys and girls, the closer and significant association in boys fits well with a female protective effect in ADHD described by Taylor et al (), and should thus be taken as a hint for further investigations of HCC in larger samples of children showing ADHD symptoms.…”

Section: Discussionsupporting

confidence: 82%

“…We found a significant interaction effect between gender and ADHD symptoms on the hair cortisol concentration (HCC) of the child, indicating a negative association between ADHD symptoms and HCC in preschool boys but not in girls (Pauli‐Pott et al, ). We speculated that the identification of the moderator effect by gender was facilitated by the use of HCC, and that the less pronounced link in girls might reflect the female protective effect against ADHD recently described by Taylor et al (): Several genetic and environmental factors explained less variance in ADHD symptoms in girls than in boys. Hence, it seems possible that the putative association between HPA axis activity and an increase in ADHD symptoms is closer in boys than in girls.…”

Section: Introductionmentioning

confidence: 94%

Low hair cortisol concentration and emerging attention‐deficit/hyperactivity symptoms in preschool age

Schloß

Ruhl

Müller

et al. 2018

Developmental Psychobiology

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Previous research demonstrated hypoactivity of the HPA axis in children with attention-deficit/hyperactivity disorder (ADHD) or externalizing symptoms. We analyzed the predictive association between the long-term HPA axis activity and increasing symptoms of ADHD in the preschool period. The sample consisted of n = 125 4-year-old children and their families (including n = 64 children with elevated ADHD symptoms). ADHD symptoms were assessed by a structured clinical interview with the mother and by parent- and teacher-report questionnaires. The long-term HPA axis activity was assessed by the hair cortisol concentration (HCC) (over a 3-month period). After controlling for potential confounders, low HCC predicted an increase in ADHD symptoms between the age of 4 and 5 years. Exploration of gender effects revealed that cross-sectional and predictive associations were significant in boys but not in girls. Low HCC might thus be regarded as an early marker of a possibly gender-related developmental pathway to ADHD.

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“…Biological sex is an important source of heterogeneity in NDDs [11] and aspects of sex-specific brain structure and functional connectivity patterns have been found in ASD [51] and to a lesser degree in ADHD [52] or OCD [53]. Previous evidence has suggested a protective effect for females, or required increased biological 'hit' related to resilience to developing NDDs [54,55]. However, interpretation of any differences found amongst males versus females in the current study is limited due to the small numbers of represented females with NDDs.…”

Section: Discussionmentioning

confidence: 99%

Integration of Brain and Behavior Measures for Identification of Data-Driven Groups Cutting Across Children with ASD, ADHD, or OCD

Jacobs

Voineskos

Hawco

et al. 2020

Preprint

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Autism spectrum disorder (ASD), obsessive-compulsive disorder (OCD) and attentiondeficit/hyperactivity disorder (ADHD) are clinically and biologically heterogeneous neurodevelopmental disorders (NDDs). The objective of the present study was to integrate brain imaging and behavioral measures to identify new brain-behavior subgroups cutting across these disorders. A subset of the data from the Province of Ontario Neurodevelopmental Disorder (POND) Network including participants with different NDDs (aged 6-16 years) that underwent cross-sectional T1-weighted and diffusion-weighted magnetic resonance imaging (MRI) scanning on the same 3T scanner, and behavioral/cognitive assessments was used. Similarity Network Fusion was applied to integrate cortical thickness, subcortical volume, white matter fractional anisotropy (FA), and behavioral measures in 176 children with ASD, ADHD or OCD with complete data that passed quality control. Normalized mutual information (NMI) was used to determine top contributing model features. Bootstrapping, out-of-model outcome measures and supervised machine learning were each used to examine stability and evaluate the new groups. Cortical thickness in socio-emotional and attention/executive networks and inattention symptoms comprised the top ten features driving participant similarity and differences between four transdiagnostic groups. Subcortical volumes (pallidum, nucleus accumbens, thalamus) were also different among groups, although white matter FA showed limited differences. Features driving participant similarity remained stable across resampling, and the new groups showed significantly different scores on everyday adaptive functioning. Our findings open the possibility of studying new data-driven groups that represent children with NDDs more similar to each other than others within their own diagnostic group. Such new groups can be evaluated longitudinally for prognostic utility and could be stratified for clinical trials targeted toward each group's unique brain and behavioral profiles.

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Is There a Female Protective Effect Against Attention-Deficit/Hyperactivity Disorder? Evidence From Two Representative Twin Samples

Cited by 58 publications

References 33 publications

Quantifying the impact of rare and ultra-rare coding variation across the phenotypic spectrum

Quantifying the impact of rare and ultra-rare coding variation across the phenotypic spectrum

Low hair cortisol concentration and emerging attention‐deficit/hyperactivity symptoms in preschool age

Integration of Brain and Behavior Measures for Identification of Data-Driven Groups Cutting Across Children with ASD, ADHD, or OCD

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