The familial co-aggregation of ASD and ADHD: a register-based cohort study

Ghirardi, Laura; Brikell, Isabell; Kuja‐Halkola, Ralf; Freitag, Christine M.; Franke, Barbara; Asherson, Philip; Lichtenstein, Paul; Larsson, Henrik

doi:10.1038/mp.2017.17

Cited by 181 publications

(165 citation statements)

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“…Conversely, the excess cross-aggregation in siblings indicates shared etiologic (familial) factors. This finding is consistent with numerous studies using genetically informed methods that have suggested shared genetic influences on both ASD and ADHD traits and diagnoses, 5,6,9 and several that have highlighted shared copy number variants, 10,25 although other studies have not identified genetic overlap. 8,26 …”

Section: Discussionsupporting

confidence: 91%

Sibling Recurrence Risk and Cross-aggregation of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

et al. 2019

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IMPORTANCE Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are believed to partially share genetic factors and biological influences. As the number of children with these diagnoses rises, so does the number of younger siblings at presumed risk for ADHD and ASD; reliable recurrence risk estimates within and across diagnoses may aid screening and early detection efforts and enhance understanding of potential shared causes. OBJECTIVE To examine within-diagnosis sibling recurrence risk and sibling cross-aggregation of ADHD and ASD among later-born siblings of children with either disorder. DESIGN, SETTING, AND PARTICIPANTS Using data extracted from medical records of 2 large health care systems in the United States, estimates of recurrence risk and cross-aggregation in later-born siblings of children with ADHD or ASD were compared with later-born siblings of children without these diagnoses. One data set included children seen between January 1, 1995, and December 31, 2013; the other included children born between January 1, 1998, and May 17, 2010. Participants included 15 175 later-born siblings of children with ADHD, ASD, and no known diagnosis. The study was conducted from October 2, 2017, to August 14, 2018. MAIN OUTCOMES AND MEASURES Diagnoses of ASD or ADHD in the later-born sibling, ascertained from medical records, were the primary outcomes of interest; moderators included sex, gestational age, and maternal age. RESULTS A total of 15 175 later-born siblings were classified by familial risk status based on the older child’s diagnostic status: ADHD risk (n = 730; male [51.92%]), ASD risk (n = 158; male [48.10%]), and no known risk (n = 14 287; male [50.73%]). Compared with later-born siblings of children without ADHD or ASD, later-born siblings of children with ASD were more likely to be diagnosed with ASD (odds ratio [OR], 30.38; 95% CI, 17.73–52.06) or ADHD in the absence of ASD (OR, 3.70; 95% CI, 1.67–8.21). Compared with later-born siblings of children without a diagnosis, later-born siblings of children with ADHD were more likely to be diagnosed with ADHD (OR, 13.05; 95% CI, 9.86–17.27) or ASD in the absence of ADHD (OR, 4.35; 95% CI, 2.43–7.79). CONCLUSIONS AND RELEVANCE Later-born siblings of children with ASD or ADHD appear to be at elevated risk for the same disorder, but also of being diagnosed with the other disorder. These findings provide further support for shared familial mechanisms underlying ASD and ADHD, which may be useful for genetic and prospective developmental studies. Later-born siblings of children with ADHD or ASD should be monitored for both conditions.

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Section: Discussionsupporting

confidence: 91%

Sibling Recurrence Risk and Cross-aggregation of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

et al. 2019

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“…A register-based study in Sweden found that individuals with ASD and their relatives were at increased risk of ADHD. The pattern of association across relatives supported the existence of a genetic overlap between clinically ascertained ASD and ADHD [50]. Some features of ASD are differentially linked to either the inattentive or the hyperactive-impulsive components of ADHD [51,52].…”

Section: Psychiatric Comorbiditymentioning

confidence: 72%

Genetics of attention deficit hyperactivity disorder

2018

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Decades of research show that genes play an vital role in the etiology of attention deficit hyperactivity disorder (ADHD) and its comorbidity with other disorders. Family, twin, and adoption studies show that ADHD runs in families. ADHD's high heritability of 74% motivated the search for ADHD susceptibility genes. Genetic linkage studies show that the effects of DNA risk variants on ADHD must, individually, be very small. Genome-wide association studies (GWAS) have implicated several genetic loci at the genome-wide level of statistical significance. These studies also show that about a third of ADHD's heritability is due to a polygenic component comprising many common variants each having small effects. From studies of copy number variants we have also learned that the rare insertions or deletions account for part of ADHD's heritability. These findings have implicated new biological pathways that may eventually have implications for treatment development.Attention deficit hyperactivity disorder (ADHD) is a childhood-onset condition with impairing symptoms of inattention, impulsivity, and hyperactivity. Decades of research have documented and replicated key facts about the disorder (for a review, see ref.[1]). It occurs in about 5% of children with little geographic or cross-cultural variation in prevalence and often co-occurs with other conditions, including mood, anxiety, conduct, learning, and substance use disorders. Longitudinal studies show that two-thirds of ADHD youth will continue to have impairing symptoms of ADHD in adulthood. People with ADHD are at risk for a wide range of functional impairments: school failure, peer rejection, injuries due to accidents, criminal behavior, occupational failure, divorce, suicide, and premature death. Although many details of ADHD's pathophysiology are unknown, neuropsychological and neuroimaging studies implicate brain circuits regulating executive functioning, reward processing, timing, and temporal information processing.This article reviews data about the role that genes play in the etiology of ADHD from two perspectives. Family, twin, and adoption studies provide a firm foundation for asserting that genes are involved in the etiology of ADHD. The view from molecular genetics provides a basis for understanding mechanisms whereby genes affect biological pathways that lead to ADHD. Family, twin and adoption studies of ADHDEvidence for heritability from family, adoption, and twin studies A study of 894 ADHD probands and 1135 of their siblings aged 5-17 years old found a ninefold increased risk of ADHD in siblings of ADHD probands compared with siblings of controls [2]. Adoption studies suggest that the familial factors of ADHD are attributable to genetic factors rather than shared environmental factors [3,4] with the most recent one reporting rates of ADHD to be greater among biological relatives of non-adopted ADHD children than adoptive relatives of adopted ADHD children. The adoptive relatives had a risk for ADHD like the risk in relatives of control childr...

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“…However, sex differences regarding these disease phenotypes are gaining attention, as fewer girls have been reported to have ASD. Notably, the possibility of missed diagnoses or misdiagnoses among girls is mentioned DSM‐5 . Finally, the sample of the present study was small; hence, it was impossible to evaluate the relationship between ASD and ADHD symptoms.…”

Section: Discussionmentioning

confidence: 83%

“…However, considering the frequency of this comorbid presentation, the current literature on the comorbidity of ASD with ADHD remains insufficient. Approximately 50%–80% of individuals with ASD develop ADHD, and persons with ASD and their relatives are at higher risk of having ADHD . The pattern of association across different familial relationships supports a genetic overlap between clinically ascertained ASD and ADHD .…”

mentioning

confidence: 76%

“…Approximately 50%–80% of individuals with ASD develop ADHD, and persons with ASD and their relatives are at higher risk of having ADHD . The pattern of association across different familial relationships supports a genetic overlap between clinically ascertained ASD and ADHD . Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM‐5) has defined ASD and ADHD as neurodevelopmental disorders, making comorbid diagnoses possible.…”

mentioning

confidence: 99%

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Clinical characteristics of boys with comorbid autism spectrum disorder and attention deficit/hyperactivity disorder

Yamawaki¹,

Ishitsuka

Suyama

et al. 2020

Pediatrics International

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Background Autism spectrum disorder (ASD) and attention deficit / hyperactivity disorder (ADHD) are frequently comorbid and, as both are defined as neurodevelopmental disorders in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, simultaneous diagnosis is possible. However, despite the frequency of this comorbid state, its endophenotypic features remain unclear. This study thus aimed to describe the behavioral and emotional problems in boys with comorbid ASD and ADHD using the Strengths and Difficulties Questionnaire (SDQ). Methods In total, 102 boys (age, 6–12 years) diagnosed with one or both disorders were divided into three groups according to their clinical diagnosis: ASD + ADHD (N = 39), ASD (N = 37), and ADHD (N = 25). Symptoms and related behaviors were compared among the groups using parents’ ratings of the autism spectrum quotient, ADHD rating scale‐IV, and SDQ. Results In the ASD + ADHD group, the proportion of “clinical‐range” cases was as high as 76.9% for the SDQ total difficulties score (TDS). The ASD + ADHD and ADHD groups had significantly higher TDS as well as behavioral problems and hyperactivity subscale scores than did the ASD group; however, the ASD + ADHD group did not have significantly different scores on any subscale compared with the other two groups. The ASD + ADHD and ASD groups also had significantly lower prosocial behavior scores than the ADHD group. Conclusions When using the SDQ as a screening tool for neurodevelopmental disorders, a high TDS, conduct problems, hyperactivity, and low prosocial behavior can be considered characteristic of ASD and ADHD comorbidity in 6‐ to 12‐year‐old boys.

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The familial co-aggregation of ASD and ADHD: a register-based cohort study

Cited by 181 publications

References 43 publications

Sibling Recurrence Risk and Cross-aggregation of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

Sibling Recurrence Risk and Cross-aggregation of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

Genetics of attention deficit hyperactivity disorder

Clinical characteristics of boys with comorbid autism spectrum disorder and attention deficit/hyperactivity disorder

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