Inattention and hyperactivity/impulsivity among children with attention-deficit/hyperactivity-disorder, autism spectrum disorder, and intellectual disability

Purpose: We describe a novel neurobehavioral syndrome of autism spectrum disorder, intellectual disability, and attention deficit/hyperactivity disorder associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. Methods: We assembled a cohort of 36 individuals (from 31 unrelated families) with de novo mutations in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. Results: These individuals share neurobehavioral features including autism spectrum disorder (ASD), intellectual disability, and attention-deficit/hyperactivity disorder (ADHD); other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. Conclusion: These results establish deleterious variation in RFX3, RFX4, and RFX7 as important causes of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.

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Pharmacotherapy of attention deficit/hyperactivity disorder in individuals with autism spectrum disorder: A systematic review of the literature

Journal of Psychopharmacology ◽

10.1177/0269881120972336 ◽

2020 ◽

pp. 026988112097233

Author(s):

Gagan Joshi ◽

Timothy Wilens ◽

Elizabeth S Firmin ◽

Barbora Hoskova ◽

Joseph Biederman

Keyword(s):

Autism Spectrum Disorder ◽

Attention Deficit Hyperactivity Disorder ◽

Intellectual Disability ◽

Attention Deficit ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Controlled Trials ◽

Sample Sizes ◽

Hyperactivity Disorder ◽

Mood Lability

Aim: To assess the empirical evidence for the treatment of attention deficit/hyperactivity disorder (ADHD) in populations with autism spectrum disorder (ASD). Methods: A systemic PubMed, PsychINFO, Embase, and Medline database search of peer-reviewed literature was conducted. Included in the review were controlled trials published in English with sample sizes ⩾10 participants examining the safety and efficacy of anti-ADHD medication in ASD populations. Data was extracted on relevant variables of study design, demographics, associated psychopathology, medication dose, efficacy, and tolerability. Results: Nine controlled trials met the inclusion and exclusion criteria: five with methylphenidate, three with atomoxetine, and one with guanfacine. Sample sizes ranged from 10 to 128 with 430 children participating across all the trials. In all the trials, treatment response was significantly superior to placebo. However, almost all trials assessed only hyperactivity, and most included only participants with intellectual disability with high levels of irritability. None of the trials distinguished agitation from hyperactivity. The response on hyperactivity for methylphenidate and atomoxetine was less than that observed in the neurotypical population; however, the response for guanfacine surpassed results observed in neurotypical populations. Treatment-emergent mood lability (i.e. mood dysregulation and mood-related adverse events) was frequently associated with methylphenidate and guanfacine treatments. Worse treatment outcomes were associated with individuals with lower intellectual capability compared with those with higher IQs. Conclusions: here is a scarcity of controlled trials examining ADHD treatments in ASD populations, particularly in intellectually capable individuals with ASD and in adults. Response to ADHD medications in ASD were adversely moderated by the presence of intellectual disability and mood lability.

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ANTI-PCA/YO AND ANTI-GAD LEVELS IN AUTISM SPECTRUM DISORDER AND ATTENTION DEFICIT HYPERACTIVITY DISORDER

10.21506/j.ponte.2018.4.4 ◽

2018 ◽

Vol 74 (4) ◽

Author(s):

Cagatay Ugur ◽

Ozden Sukran Uneri ◽

Esra Yurumez

Keyword(s):

Autism Spectrum Disorder ◽

Attention Deficit Hyperactivity Disorder ◽

Attention Deficit ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Hyperactivity Disorder

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Attention Deficit Hyperactivity Disorder in Autism Spectrum Disorder

The Oxford Handbook of Autism and Co-Occurring Psychiatric Conditions ◽

10.1093/oxfordhb/9780190910761.013.9 ◽

2020 ◽

pp. 158-176

Author(s):

Karen Bearss ◽

Aaron J. Kaat

Keyword(s):

Autism Spectrum Disorder ◽

Attention Deficit Hyperactivity Disorder ◽

Attention Deficit ◽

Autism Spectrum ◽

Developmental Trajectory ◽

Spectrum Disorder ◽

Adhd Symptoms ◽

Functional Impairments ◽

Hyperactivity Disorder ◽

Delayed Recognition

This chapter will review the available evidence on individuals with co-occurring diagnoses of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). This chapter contends that children diagnosed with both disorders (ASD+ADHD) are a subset of the ASD population that is at risk for delayed recognition of their ASD diagnosis, poor treatment response, and poorer functional outcomes compared to those with ASD without ADHD. Specifically, the chapter highlights the best estimates of the prevalence of the comorbidity, the developmental trajectory of people with co-occurring ASD and ADHD, how ADHD symptoms change across development, overlapping genetic and neurobiological risk factors, psychometrics of ADHD diagnostic instruments in an ASD population, neuropsychological and functional impairments associated with co-occurring ASD and ADHD, and the current state of evidence-based treatment for both ASD and ADHD symptoms. Finally, the chapter discusses fruitful avenues of research for improving understanding of this high-risk comorbidity so that mechanism-to-treatment pathways for ADHD in children with ASD can be better developed.

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Medications for attention-deficit/hyperactivity disorder in individuals with or without coexisting autism spectrum disorder: analysis of data from the Swedish prescribed drug register

Journal of Neurodevelopmental Disorders ◽

10.1186/s11689-020-09352-z ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Viktoria Johansson ◽

Sven Sandin ◽

Zheng Chang ◽

Mark J. Taylor ◽

Paul Lichtenstein ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Attention Deficit Hyperactivity Disorder ◽

Attention Deficit ◽

Clinical Studies ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Prescribing Patterns ◽

Adhd Medication ◽

Hyperactivity Disorder ◽

Drug Register

Abstract Background Clinical studies found that medication for attention-deficit/hyperactivity disorder (ADHD) is effective in coexisting autism spectrum disorder (ASD), but current research is based on small clinical studies mainly performed on children or adolescents. We here use register data to examine if individuals with ADHD and coexisting ASD present differences in the prescribing patterns of ADHD medication when compared to individuals with pure ADHD. Methods Data with information on filled prescriptions and diagnoses was retrieved from the Swedish Prescribed Drug Register and the National Patient Register. We identified 34,374 individuals with pure ADHD and 5012 individuals with ADHD and coexisting ASD, aged between 3 and 80 years. The first treatment episode with ADHD medications (≥ 2 filled prescriptions within 90 days) and daily doses of methylphenidate during a 3-year period was measured. Odds ratios (ORs) were calculated for the likelihood of being prescribed ADHD medication in individuals with and without ASD and Wilcoxon rank-sum test was used to compare group differences in dose per day. Results Individuals with ADHD and coexisting ASD were less likely to start continuous treatment with ADHD medication (ADHD 80.5%; ADHD with ASD 76.2%; OR, 0.80; 95% confidence interval, 0.75-0.86), were less likely to be prescribed methylphenidate, and were more commonly prescribed second line treatments such as dexamphetamine, amphetamine, or modafinil. No group difference was observed for atomoxetine. In adults with ADHD and coexisting ASD, methylphenidate was prescribed in lower daily doses over three years as compared to individuals with pure ADHD. Conclusions The findings indicate that there are differences in the medical treatment of individuals with or without ASD. If these differences are due to different medication responses in ASD or due to other factors such as clinicians’ perceptions of medication effects in patients with ASD, needs to be further studied.

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