The state of research on the genetics of autism spectrum disorder: methodological, clinical and conceptual progress

Arnett, Anne B.; Trinh, Sandy; Bernier, Raphael

doi:10.1016/j.copsyc.2018.07.004

Cited by 31 publications

(38 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The genotype-first approach has led to the identification of ASD-specific genetic subtypes, variant-specific phenotypic spectra, and promising pharmacological treatment targets and psychosocial benefits to affected families. 39 One of the first subtypes to be described was that for heterogeneous, disruptive variants in CHD8. CDH8 is involved in chromatin remodeling and its targets include many other genes that have also been associated with ASD.…”

Section: Neurodevelopmental Disorder Diagnosis-history and Future -Momentioning

confidence: 99%

Neurodevelopmental disorders—the history and future of a diagnosticconcept

Morris-Rosendahl

Crocq

2020

Dialogues in Clinical Neuroscience

227

110

View full text Add to dashboard Cite

This article describes the history of the diagnostic class of neurodevelopmental disorders (NDDs) up to DSM-5. We further analyze how the development of genetics will transform the classification and diagnosis of NDDs. In DSM-5, NDDs include intellectual disability (ID), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). Physicians in German-, French- and English-speaking countries (eg, Weikard, Georget, Esquirol, Down, Asperger, and Kanner) contributed to the phenomenological definitions of these disorders throughout the 18th and 20th centuries. These diagnostic categories show considerable comorbidity and phenotypic overlap. NDDs are one of the chapters of psychiatric nosology most likely to benefit from the approach advocated by the National Institute of Mental Health’s Research Domain Criteria project. Genetic research supports the hypothesis that ID, ASD, ADHD, schizophrenia, and bipolar disorder lie on a neurodevelopmental continuum. The identification of recurrently observed copy number variants and disruptive gene variants in ASD (eg, CDH8, 16p11.2, SCN2A) led to the adoption of the genotype-first approach to characterize individuals at the etiological level.

show abstract

Section: Neurodevelopmental Disorder Diagnosis-history and Future -Momentioning

confidence: 99%

Neurodevelopmental disorders—the history and future of a diagnosticconcept

Morris-Rosendahl

Crocq

2020

Dialogues in Clinical Neuroscience

227

110

View full text Add to dashboard Cite

show abstract

“…Genetic subtypes of ASD are associated with unique behavioral, medical, and cognitive phenotypes [Arnett, Trinh, & Bernier, 2019]. Mutations in CHD8 are among the most commonly identified, and include relatively high rates of ASD, macrocephaly, and gastrointestinal slowing [Sugathan et al, 2014].…”

Section: Introductionmentioning

confidence: 99%

Developmental Predictors of Cognitive and Adaptive Outcomes in Genetic Subtypes of Autism Spectrum Disorder

et al. 2020

View full text Add to dashboard Cite

Approximately one-fourth of autism spectrum disorder (ASD) cases are associated with a disruptive genetic variant. Many of these ASD genotypes have been described previously, and are characterized by unique constellations of medical, psychiatric, developmental, and behavioral features. Development of precision medicine care for affected individuals has been challenging due to the phenotypic heterogeneity that exists even within each genetic subtype. In the present study, we identify developmental milestones that predict cognitive and adaptive outcomes for five of the most common ASD genotypes. Sixty-five youth with a known pathogenic variant involving ADNP, CHD8, DYRK1A, GRIN2B, or SCN2A genes participated in cognitive and adaptive testing. Exploratory linear regressions were used to identify developmental milestones that predicted cognitive and adaptive outcomes within each gene group. We hypothesized that the earliest and most predictive milestones would vary across gene groups, but would be consistent across outcomes within each genetic subtype. Within the ADNP group, age of walking predicted cognitive outcomes, while age of first words predicted adaptive behaviors. Age of phrases predicted adaptive functioning in the CHD8 group, but cognitive outcomes were not clearly associated with early developmental milestones. Verbal milestones were the strongest predictors of cognitive and adaptive outcomes for individuals with mutations to DYRK1A, GRIN2B, or SCN2A. These trends inform decisions about treatment planning and long-term expectations for affected individuals, and they add to the growing body of research linking molecular genetic function to brain development and phenotypic outcomes.

show abstract

“…Although ASD was once conceptualized as a rare, narrowly defined diagnosis, incredible heterogeneity among individuals with the same diagnosis has become increasingly clear in recent decades (Shen & Piven, 2017). This is evident across levels of analysis, from the genetic bases thought to underlie the disorder (Arnett, Trinh, & Bernier, 2018) to the range of cognitive profiles observed (e.g., Munson et al, 2008). Even within the core "social deficits" that define the disorder, there are individual differences in social interest, skill, and success (Wing & Gould, 1979).…”

mentioning

confidence: 99%

Linking social motivation with social skill: The role of emotion dysregulation in autism spectrum disorder

Neuhaus

Bernier

2019

Dev Psychopathol

View full text Add to dashboard Cite

Autism spectrum disorder (ASD) is associated with pervasive social deficits as well as marked emotion dysregulation across the life span. Decreased social motivation accounts in part for social difficulties, but factors moderating its influence are not fully understood. In this paper, we (a) characterize social and emotional functioning among children and adolescents with ASD, (b) explore contributions of social motivation and emotion dysregulation to social skill, and (c) consider biological sex and intellectual functioning as moderators of these associations. In a sample of 2,079 children and adolescents with ASD from the Simons Simplex Collection, we document direct effects of social motivation, internalizing symptoms, aggression, attention problems, irritability, and self-injurious behavior on children's social skills. Furthermore, dysregulation in several domains moderated the association between social motivation and social skill, suggesting a blunting effect on social motivation in the context of emotional difficulties. Moreover, when considering only individuals with intellectual skills in the average range or higher, biological sex further moderated these associations. Findings add to our understanding of social–emotional processes in ASD, suggest emotion dysregulation as a target of intervention in the service of social skill improvements, and build on efforts to understand sources of individual difference that contribute to heterogeneity among individuals with ASD.

show abstract

The state of research on the genetics of autism spectrum disorder: methodological, clinical and conceptual progress

Cited by 31 publications

References 47 publications

Neurodevelopmental disorders—the history and future of a diagnosticconcept

Neurodevelopmental disorders—the history and future of a diagnosticconcept

Developmental Predictors of Cognitive and Adaptive Outcomes in Genetic Subtypes of Autism Spectrum Disorder

Linking social motivation with social skill: The role of emotion dysregulation in autism spectrum disorder

Contact Info

Product

Resources

About