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Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder.

ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders. Evidence indicates both disorders co-occur with a high frequency, in 20-50% of children with ADHD meeting criteria for ASD and in 30-80% of ASD children meeting criteria for ADHD. This review will provide an overview on all available studies [family based, twin, candidate gene, linkage, and genome wide association (GWA) studies] shedding light on the role of shared genetic underpinnings of ADHD and ASD. It is concluded that family and twin studies do provide support for the hypothesis that ADHD and ASD originate from partly similar familial/genetic factors. Only a few candidate gene studies, linkage studies and GWA studies have specifically addressed this co-occurrence, pinpointing to some promising pleiotropic genes, loci and single nucleotide polymorphisms (SNPs), but the research field is in urgent need for better designed and powered studies to tackle this complex issue. We propose that future studies examining shared familial etiological factors for ADHD and ASD use a family-based design in which the same phenotypic (ADHD and ASD), candidate endophenotypic, and environmental measurements are obtained from all family members. Multivariate multi-level models are probably best suited for the statistical analysis.

SUBMITTER: Rommelse NN

PROVIDER: S-EPMC2839489 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder.

Rommelse Nanda N J NN Franke Barbara B Geurts Hilde M HM Hartman Catharina A CA Buitelaar Jan K JK

European child & adolescent psychiatry 20100211 3

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders. Evidence indicates both disorders co-occur with a high frequency, in 20-50% of children with ADHD meeting criteria for ASD and in 30-80% of ASD children meeting criteria for ADHD. This review will provide an overview on all available studies [family based, twin, candidate gene, linkage, and genome wide association (GWA) studies] shedding light on the role of ...[more]

PMID: 20148275

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Project description:Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorders (ASD) are two of the most represented neurodevelopmental conditions in childhood. The diagnostic shift introduced by the DSM-5, allowing a combined diagnosis of ADHD and ASD, poses different clinical challenges related to diagnostic overshadowing, accuracy of clinical judgment and potential delay in an ASD diagnosis in children presenting with ADHD. Here we tried to disentangle the clinical phenotype and specificity of the two co-occurring conditions in relation to autism traits and empathy, by comparing children with ASD with and without comorbid ADHD with children presenting ADHD only and children with typical development. The child versions of the Autism Quotient (C-AQ) and Empathy Quotient (C-EQ) were administered to a total sample of 198 male children between 6 and 14 years old with age appropriate language skills and normal intelligence. Univariate analysis demonstrated no significant differences in the C-AQ total and subscale scores as well as the C-EQ between children with ASD and children with ASD + ADHD, while children with ADHD alone presented an intermediate phenotype between ASD and TD. Furthermore, a receiver operating characteristic (ROC) analysis was applied to discriminate among the different phenotypes. We found that the C-AQ and C-EQ were accurate at distinguishing with satisfactory reliability between: (a) ASD vs. non- ASD (N-ASD) groups comprising both ADHD and TD children (Area Under the Curve AUC 88% for C-AQ and 81% for C-EQ); (b) ASD and TD (AUC 92% for C-AQ and 95% for C-EQ); (c) ASD and ADHD (AUC 80% for C-AQ and 68% for C-EQ). Our data confirm the reliability of the C-AQ and C-EQ as behavioral markers to differentiate ASD (regardless of comorbid ADHD) from an ADHD condition and TD. Interestingly, in our sample an ADHD condition does not increase the severity of the clinical phenotype in terms of autism traits distribution and empathy, suggesting that the psychological measures detected by the two quantitative instruments are independent of ADHD traits. This evidence will contribute to the translational efforts in developing better tailored treatments and preventive strategies.

Project description:Symptoms of autism spectrum disorder and attention-deficit/hyperactivity disorder often co-occur. Among these, sensory impairment, which is a core diagnostic feature of autism spectrum disorder, is often observed in children with attention-deficit/hyperactivity disorder. However, the underlying mechanisms of symptoms that are shared across disorders remain unknown. To examine the neural correlates of sensory symptoms that are associated with autism spectrum disorder and attention-deficit/hyperactivity disorder, we analysed resting-state functional MRI data obtained from 113 people with either autism spectrum disorder or attention-deficit/hyperactivity disorder (n = 78 autism spectrum disorder, mean age = 29.5; n = 35 attention-deficit/hyperactivity disorder, mean age = 31.2) and 96 neurotypical controls (mean age = 30.6, range: 20-55 years) using a cross-sectional study design. First, we used a multi-dimensional approach to examine intrinsic brain functional connectivity related to sensory symptoms in four domains (i.e. low registration, sensation seeking, sensory sensitivity and sensation avoidance), after controlling for age, handedness and head motion. Then, we used a partial least squares correlation to examine the link between sensory symptoms related to intrinsic brain functional connectivity and neurodevelopmental symptoms measured using the Autism Spectrum Quotient and Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale, regardless of diagnosis. To test whether observed associations were specific to sensory symptoms related to intrinsic brain functional connectivity, we conducted a control analysis using a bootstrap framework. The results indicated that transdiagnostic yet distinct intrinsic brain functional connectivity neural bases varied according to the domain of the examined sensory symptom. Partial least squares correlation analysis revealed two latent components (latent component 1: q < 0.001 and latent component 2: q < 0.001). For latent component 1, a set of intrinsic brain functional connectivity was predominantly associated with neurodevelopmental symptom-related composite score (r = 0.64, P < 0.001), which was significantly correlated with Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale total T scores (r = -0.99, q < 0.001). For latent component 2, another set of intrinsic brain functional connectivity was positively associated with neurodevelopmental symptom-related composite score (r = 0.58, P < 0.001), which was eventually positively associated with Autism Spectrum Quotient total scores (r = 0.92, q < 0.001). The bootstrap analysis showed that the relationship between intrinsic brain functional connectivity and neurodevelopmental symptoms was relative to sensory symptom-related intrinsic brain functional connectivity (latent component 1: P = 0.003 and latent component 2: P < 0.001). The current results suggest that sensory symptoms in individuals with autism spectrum disorder and those with attention-deficit/hyperactivity disorder have shared neural correlates. The neural correlates of the sensory symptoms were associated with the severity of both autism spectrum disorder and attention-deficit/hyperactivity disorder symptoms, regardless of diagnosis.

Dataset Information

Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder.

Publications

Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder.

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