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Journal of Autism and Developmental... Dec 2021In the last 40 years, there has been a huge increase in autism genetics research and a rapidly growing number of discoveries. We now know autism is one of the most... (Review)
Review
In the last 40 years, there has been a huge increase in autism genetics research and a rapidly growing number of discoveries. We now know autism is one of the most highly heritable disorders with negligible shared environmental contributions. Recent discoveries also show that rare variants of large effect size as well as small effect common gene variants all contribute to autism risk. These discoveries challenge traditional diagnostic boundaries and highlight huge heterogeneity in autism. In this review, we consider some of the key findings that are shaping current understanding of autism and what these discoveries mean for clinicians.
Topics: Autism Spectrum Disorder; Autistic Disorder; Genetic Predisposition to Disease; Humans
PubMed: 32940822
DOI: 10.1007/s10803-020-04685-z -
Genes Mar 2023Autism spectrum disorder (ASD) consists of a group of heterogeneous genetic neurobehavioral disorders associated with developmental impairments in social communication... (Review)
Review
Autism spectrum disorder (ASD) consists of a group of heterogeneous genetic neurobehavioral disorders associated with developmental impairments in social communication skills and stereotypic, rigid or repetitive behaviors. We review common behavioral, psychiatric and genetic associations related to ASD. Autism affects about 2% of children with 4:1 male-to-female ratio and a heritability estimate between 70 and 90%. The etiology of ASD involves a complex interplay between inheritance and environmental factors influenced by epigenetics. Over 800 genes and dozens of genetic syndromes are associated with ASD. Novel gene-protein interactions with pathway and molecular function analyses have identified at least three functional pathways including chromatin modeling, Wnt, Notch and other signaling pathways and metabolic disturbances involving neuronal growth and dendritic spine profiles. An estimated 50% of individuals with ASD are diagnosed with chromosome deletions or duplications (e.g., 15q11.2, BP1-BP2, 16p11.2 and 15q13.3), identified syndromes (e.g., Williams, Phelan-McDermid and Shprintzen velocardiofacial) or single gene disorders. Behavioral and psychiatric conditions in autism impacted by genetics influence clinical evaluations, counseling, diagnoses, therapeutic interventions and treatment approaches. Pharmacogenetics testing is now possible to help guide the selection of psychotropic medications to treat challenging behaviors or co-occurring psychiatric conditions commonly seen in ASD. In this review of the autism spectrum disorder, behavioral, psychiatric and genetic observations and associations relevant to the evaluation and treatment of individuals with ASD are discussed.
Topics: Child; Humans; Male; Female; Autism Spectrum Disorder; Autistic Disorder; Syndrome; Chromosome Deletion; Epigenesis, Genetic
PubMed: 36980949
DOI: 10.3390/genes14030677 -
Neurologic Clinics May 2023Relative to males, women with autism spectrum disorder (ASD) have neurobiological and clinical presentation differences. Recent research suggests that the male/female... (Review)
Review
Relative to males, women with autism spectrum disorder (ASD) have neurobiological and clinical presentation differences. Recent research suggests that the male/female ASD prevalence gap is smaller than previously reported. Sex differences in symptom presentation as well as the male bias of ASD account for delayed/missed diagnosis among women. Investigating ASD and providing psychological evaluation referrals for women who are struggling socially and present with complex mental health conditions (e.g., ADHD, depression), even when they do not show typical autistic characteristics, is important. Accurate diagnosis facilitates understanding of challenges, increases access to treatments, and alleviates the burden of ASD.
Topics: Humans; Male; Female; Autistic Disorder; Autism Spectrum Disorder; Prevalence
PubMed: 37030965
DOI: 10.1016/j.ncl.2022.10.006 -
British Journal of Hospital Medicine... Dec 2021Recognition of autism and the associated co-occurring physical and mental health issues has increased over recent years. However, undergraduate and postgraduate...
Recognition of autism and the associated co-occurring physical and mental health issues has increased over recent years. However, undergraduate and postgraduate curricula take time to adapt and to impact on what is delivered in training so healthcare professionals, including doctors, report little training on these topics. Doctors need to know when someone might be autistic in order to respond to them appropriately. This article sets out the reasons why recognition of autism is important and the positive impacts of recognising and understanding autism on health outcomes, service delivery and patient experience. The negative consequences of not recognising autism or understanding the impact of autistic traits on the person are also explored. A companion article then covers how practice can be made more appropriate for autistic people to improve outcomes.
Topics: Autistic Disorder; Delivery of Health Care; Health Personnel; Humans
PubMed: 34983217
DOI: 10.12968/hmed.2021.0313 -
International Review of Psychiatry... May 2021Individuals with autism experience substantially higher rates of mood problems compared to the general population, which contribute to reduced quality of life and... (Review)
Review
Individuals with autism experience substantially higher rates of mood problems compared to the general population, which contribute to reduced quality of life and increased mortality through suicide. Here, we reviewed evidence for the clinical presentation, aetiology and therapeutic approaches for mood problems in autism. We identified a lack of validated tools for accurately identifying mood problems in individuals with autism, who may present with 'atypical' features (e.g. severe irritability). Risk factors for mood problems in autism appear to be largely overlapping with those identified in the general population, including shared genetic, environmental, cognitive, physiological/neurobiological mechanisms. However, these mechanisms are exacerbated directly/indirectly by lived experiences of autism, including increased vulnerability for chronic stress - often related to social-communication difficulties(/bullying) and sensory sensitivities. Lastly, current therapeutic approaches are based on recommendations for primary mood disorders, with little reference to the neurobiological/cognitive differences associated with autism. Thus, we recommend: 1) the development and validation of (objective) tools to identify mood problems in autism and measure therapeutic efficacy; 2) an interactive approach to investigating aetiologies in large-scale longitudinal studies, integrating different levels of analysis (e.g. cognitive, neurobiological) and lived experience; 3) testing potential treatments through high-quality (e.g. sufficiently powered, blinded) clinical trials, specifically for individuals with autism.
Topics: Autistic Disorder; Bullying; Humans; Mood Disorders; Quality of Life; Suicide
PubMed: 33648430
DOI: 10.1080/09540261.2021.1872506 -
Neuroscience and Biobehavioral Reviews Mar 2020Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Several genetic causes of ASD have been identified and this has enabled researchers to construct mouse... (Review)
Review
Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Several genetic causes of ASD have been identified and this has enabled researchers to construct mouse models. Mouse behavioral tests reveal impaired social interaction and communication, as well as increased repetitive behavior and behavioral inflexibility in these mice, which correspond to core behavioral deficits observed in individuals with ASD. However, the connection between these behavioral abnormalities and the underlying dysregulation in neuronal circuits and synaptic function is poorly understood. Moreover, different components of the ASD phenotype may be linked to dysfunction in different brain regions, making it even more challenging to chart the pathophysiological mechanisms involved in ASD. Here we summarize the research on mouse models of ASD and their contribution to understanding pathophysiological mechanisms. Specifically, we emphasize abnormal serotonin production and regulation, as well as the disruption in circadian rhythms and sleep that are observed in a subset of ASD, and propose that spatiotemporal disturbances in brainstem development may be a primary cause of ASD that propagates towards the cerebral cortex.
Topics: Animals; Autism Spectrum Disorder; Autistic Disorder; Brain; Circadian Rhythm; Humans; Phenotype; Social Behavior
PubMed: 31059731
DOI: 10.1016/j.neubiorev.2019.04.012 -
Molecular Psychiatry Dec 2020The current diagnostic practices are linked to a 20-fold increase in the reported prevalence of ASD over the last 30 years. Fragmenting the autism phenotype into... (Review)
Review
The current diagnostic practices are linked to a 20-fold increase in the reported prevalence of ASD over the last 30 years. Fragmenting the autism phenotype into dimensional "autistic traits" results in the alleged recognition of autism-like symptoms in any psychiatric or neurodevelopemental condition and in individuals decreasingly distant from the typical population, and prematurely dismisses the relevance of a diagnostic threshold. Non-specific socio-communicative and repetitive DSM 5 criteria, combined with four quantitative specifiers as well as all their possible combinations, render limitless variety of presentations consistent with the categorical diagnosis of ASD. We propose several remedies to this problem: maintain a line of research on prototypical autism; limit the heterogeneity compatible with a categorical diagnosis to situations with a phenotypic overlap and a validated etiological link with prototypical autism; reintroduce the qualitative properties of autism presentations and of current dimensional specifiers, language, intelligence, comorbidity, and severity in the criteria used to diagnose autism in replacement of quantitative "social" and "repetitive" criteria; use these qualitative features combined with the clinical intuition of experts and machine-learning algorithms to differentiate coherent subgroups in today's autism spectrum; study these subgroups separately, and then compare them; and question the autistic nature of "autistic traits".
Topics: Artifacts; Autism Spectrum Disorder; Autistic Disorder; Child; Child Development Disorders, Pervasive; Comorbidity; Diagnostic and Statistical Manual of Mental Disorders; Humans
PubMed: 32355335
DOI: 10.1038/s41380-020-0748-y -
Evidence-Based Practices for Children, Youth, and Young Adults with Autism: Third Generation Review.Journal of Autism and Developmental... Nov 2021This systematic review describes a set of practices that have evidence of positive effects with autistic children and youth. This is the third iteration of a review of...
This systematic review describes a set of practices that have evidence of positive effects with autistic children and youth. This is the third iteration of a review of the intervention literature (Odom et al. in J Autism Dev Disorders 40(4):425-436, 2010a; Prevent School Fail 54(4):275-282, 2010b; Wong et al. in https://autismpdc.fpg.unc.edu/sites/autismpdc.fpg.unc.edu/files/imce/documents/2014-EBP-Report.pdf ; J Autism Dev Disorders 45(7):1951-1966, 2015), extending coverage to articles published between 1990 and 2017. A search initially yielded 31,779 articles, and the subsequent screening and evaluation process found 567 studies to include. Combined with the previous review, 972 articles were synthesized, from which the authors found 28 focused intervention practices that met the criteria for evidence-based practice (EBP). Former EBPs were recategorized and some manualized interventions were distinguished as meeting EBP criteria. The authors discuss implications for current practices and future research.
Topics: Adolescent; Autism Spectrum Disorder; Autistic Disorder; Child; Evidence-Based Practice; Humans; Schools; Young Adult
PubMed: 33449225
DOI: 10.1007/s10803-020-04844-2 -
Journal of Neural Transmission (Vienna,... Mar 2023This article reviews the current knowledge state on pragmatic and structural language abilities in autism and their potential relation to extralinguistic abilities and... (Review)
Review
This article reviews the current knowledge state on pragmatic and structural language abilities in autism and their potential relation to extralinguistic abilities and autistic traits. The focus is on questions regarding autism language profiles with varying degrees of (selective) impairment and with respect to potential comorbidity of autism and language impairment: Is language impairment in autism the co-occurrence of two distinct conditions (comorbidity), a consequence of autism itself (no comorbidity), or one possible combination from a series of neurodevelopmental properties (dimensional approach)? As for language profiles in autism, three main groups are identified, namely, (i) verbal autistic individuals without structural language impairment, (ii) verbal autistic individuals with structural language impairment, and (iii) minimally verbal autistic individuals. However, this tripartite distinction hides enormous linguistic heterogeneity. Regarding the nature of language impairment in autism, there is currently no model of how language difficulties may interact with autism characteristics and with various extralinguistic cognitive abilities. Building such a model requires carefully designed explorations that address specific aspects of language and extralinguistic cognition. This should lead to a fundamental increase in our understanding of language impairment in autism, thereby paving the way for a substantial contribution to the question of how to best characterize neurodevelopmental disorders.
Topics: Humans; Autistic Disorder; Cognition; Comorbidity; Language Development Disorders
PubMed: 36922431
DOI: 10.1007/s00702-023-02592-y -
Progress in Molecular Biology and... 2020Since the initial psychological report by Leo Kanner in 1943, relatively little formal biochemical/neurological research on the cause of autism, other than peripheral... (Review)
Review
Since the initial psychological report by Leo Kanner in 1943, relatively little formal biochemical/neurological research on the cause of autism, other than peripheral searches for genomic mutations, had been carried until the end of the 20th century. As a result of studies on twin sets and the conclusion that autism was largely a hereditary defect, numerous investigations have sought various genetic faults in particular. However, such studies were able to reveal a plausible etiology for this malady in only a small percentage of instances. Key bio-molecular characteristics of this syndrome have been uncovered when the potential roles of the glia were studied in depth. Findings related to biochemical deficiencies appearing early in the newborn, such as depressed IGF-1 (insulin-like growth factor #1) in neurogenesis/myelination, are becoming emphasized in many laboratories. Progress leading to timely diagnoses and subsequent prevention of central nervous system dysconnectivity now seems plausible. The tendency for an infant to develop autism may currently be determinable and preventable before irreversible psychosocial disturbances become established. These discussions about glial function will be inter-spersed with comments about their apparent relevance to autism. The concluding portion of this presentation will be a detailed review and summation of this diagnosis and prevention proposition.
Topics: Animals; Autistic Disorder; Biomarkers; Humans; Insulin-Like Growth Factor I; Myelin Sheath; Nerve Net; Polymorphism, Genetic
PubMed: 32711807
DOI: 10.1016/bs.pmbts.2020.04.013