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JAMA Jan 2023Autism spectrum disorder (ASD), characterized by deficits in social communication and the presence of restricted, repetitive behaviors or interests, is a... (Review)
Review
IMPORTANCE
Autism spectrum disorder (ASD), characterized by deficits in social communication and the presence of restricted, repetitive behaviors or interests, is a neurodevelopmental disorder affecting approximately 2.3% children aged 8 years in the US and approximately 2.2% of adults. This review summarizes evidence on the diagnosis and treatment of ASD.
OBSERVATIONS
The estimated prevalence of ASD has been increasing in the US, from 1.1% in 2008 to 2.3% in 2018, which is likely associated with changes in diagnostic criteria, improved performance of screening and diagnostic tools, and increased public awareness. No biomarkers specific to the diagnosis of ASD have been identified. Common early signs and symptoms of ASD in a child's first 2 years of life include no response to name when called, no or limited use of gestures in communication, and lack of imaginative play. The criterion standard for the diagnosis of ASD is a comprehensive evaluation with a multidisciplinary team of clinicians and is based on semistructured direct observation of the child's behavior and semistructured caregiver interview focused on the individual's development and behaviors using standardized measures, such as the Autism Diagnostic Observation Schedule-Second Edition and the Autism Diagnostic Interview. These diagnostic measures have sensitivity of 91% and 80% and specificity of 76% and 72%, respectively. Compared with people without ASD, individuals with ASD have higher rates of depression (20% vs 7%), anxiety (11% vs 5%), sleep difficulties (13% vs 5%), and epilepsy (21% with co-occurring intellectual disability vs 0.8%). Intensive behavioral interventions, such as the Early Start Denver Model, are beneficial in children 5 years or younger for improvement in language, play, and social communication (small to medium effect size based on standardized mean difference). Pharmacotherapy is indicated for co-occurring psychiatric conditions, such as emotion dysregulation or attention-deficit/hyperactivity disorder. Risperidone and aripiprazole can improve irritability and aggression (standardized mean difference of 1.1, consistent with a large effect size) compared with placebo. Psychostimulants are effective for attention-deficit/hyperactivity disorder (standardized mean difference of 0.6, consistent with a moderate effect size) compared with placebo. These medications are associated with adverse effects including, most commonly, changes in appetite, weight, and sleep.
CONCLUSIONS AND RELEVANCE
ASD affects approximately 2.3% of children aged 8 years and approximately 2.2% of adults in the US. First-line therapy consists of behavioral interventions, while co-occurring psychiatric conditions, such as anxiety or aggression, may be treated with specific behavioral therapy or medication.
Topics: Adult; Child; Humans; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Central Nervous System Stimulants; Irritable Mood; United States
PubMed: 36625807
DOI: 10.1001/jama.2022.23661 -
International Journal of Molecular... Jan 2023Autism spectrum disorder (ASD) is a heterogeneous, behaviorally defined neurodevelopmental disorder. Over the past two decades, the prevalence of autism spectrum... (Review)
Review
Autism spectrum disorder (ASD) is a heterogeneous, behaviorally defined neurodevelopmental disorder. Over the past two decades, the prevalence of autism spectrum disorders has progressively increased, however, no clear diagnostic markers and specifically targeted medications for autism have emerged. As a result, neurobehavioral abnormalities, neurobiological alterations in ASD, and the development of novel ASD pharmacological therapy necessitate multidisciplinary collaboration. In this review, we discuss the development of multiple animal models of ASD to contribute to the disease mechanisms of ASD, as well as new studies from multiple disciplines to assess the behavioral pathology of ASD. In addition, we summarize and highlight the mechanistic advances regarding gene transcription, RNA and non-coding RNA translation, abnormal synaptic signaling pathways, epigenetic post-translational modifications, brain-gut axis, immune inflammation and neural loop abnormalities in autism to provide a theoretical basis for the next step of precision therapy. Furthermore, we review existing autism therapy tactics and limits and present challenges and opportunities for translating multidisciplinary knowledge of ASD into clinical practice.
Topics: Animals; Autism Spectrum Disorder; Autistic Disorder; Risk Factors; Inflammation; Biological Factors
PubMed: 36768153
DOI: 10.3390/ijms24031819 -
Pediatric Clinics of North America Jun 2020Autism spectrum disorder (ASD) is characterized by deficits in social communication and interaction and the presence of restricted and repetitive patterns of behavior... (Review)
Review
Autism spectrum disorder (ASD) is characterized by deficits in social communication and interaction and the presence of restricted and repetitive patterns of behavior and interests. Currently, ASD affects 1 in 59 individuals and can be a costly disorder across one's lifetime. Because of the prevalence, costs, and range of behavioral needs, early intervention is vital to teach skills across a variety of domains and prevent the development or exacerbation of behavioral deficits and excesses. Interventions based on applied behavior analysis have the most empirical support; several strategies to teach social skills, communication, and adaptive skills are discussed.
Topics: Autism Spectrum Disorder; Behavior Therapy; Child; Child, Preschool; Early Intervention, Educational; Humans; Problem Behavior
PubMed: 32443991
DOI: 10.1016/j.pcl.2020.02.007 -
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 -
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 -
International Journal of Molecular... Jul 2020Autism spectrum disorder (ASD) consists of a genetically heterogenous group of neurobehavioral disorders characterized by impairment in three behavioral domains... (Review)
Review
Autism spectrum disorder (ASD) consists of a genetically heterogenous group of neurobehavioral disorders characterized by impairment in three behavioral domains including communication, social interaction, and stereotypic repetitive behaviors. ASD affects more than 1% of children in Western societies, with diagnoses on the rise due to improved recognition, screening, clinical assessment, and diagnostic testing. We reviewed the role of genetic and metabolic factors which contribute to the causation of ASD with the use of new genetic technology. Up to 40 percent of individuals with ASD are now diagnosed with genetic syndromes or have chromosomal abnormalities including small DNA deletions or duplications, single gene conditions, or gene variants and metabolic disturbances with mitochondrial dysfunction. Although the heritability estimate for ASD is between 70 and 90%, there is a lower molecular diagnostic yield than anticipated. A likely explanation may relate to multifactorial causation with etiological heterogeneity and hundreds of genes involved with a complex interplay between inheritance and environmental factors influenced by epigenetics and capabilities to identify causative genes and their variants for ASD. Behavioral and psychiatric correlates, diagnosis and genetic evaluation with testing are discussed along with psychiatric treatment approaches and pharmacogenetics for selection of medication to treat challenging behaviors or comorbidities commonly seen in ASD. We emphasize prioritizing treatment based on targeted symptoms for individuals with ASD, as treatment will vary from patient to patient based on diagnosis, comorbidities, causation, and symptom severity.
Topics: Autism Spectrum Disorder; Comorbidity; Humans
PubMed: 32630718
DOI: 10.3390/ijms21134726 -
Signal Transduction and Targeted Therapy Jul 2022Autism spectrum disorder (ASD) is a prevalent and complex neurodevelopmental disorder which has strong genetic basis. Despite the rapidly rising incidence of autism,... (Review)
Review
Autism spectrum disorder (ASD) is a prevalent and complex neurodevelopmental disorder which has strong genetic basis. Despite the rapidly rising incidence of autism, little is known about its aetiology, risk factors, and disease progression. There are currently neither validated biomarkers for diagnostic screening nor specific medication for autism. Over the last two decades, there have been remarkable advances in genetics, with hundreds of genes identified and validated as being associated with a high risk for autism. The convergence of neuroscience methods is becoming more widely recognized for its significance in elucidating the pathological mechanisms of autism. Efforts have been devoted to exploring the behavioural functions, key pathological mechanisms and potential treatments of autism. Here, as we highlight in this review, emerging evidence shows that signal transduction molecular events are involved in pathological processes such as transcription, translation, synaptic transmission, epigenetics and immunoinflammatory responses. This involvement has important implications for the discovery of precise molecular targets for autism. Moreover, we review recent insights into the mechanisms and clinical implications of signal transduction in autism from molecular, cellular, neural circuit, and neurobehavioural aspects. Finally, the challenges and future perspectives are discussed with regard to novel strategies predicated on the biological features of autism.
Topics: Autism Spectrum Disorder; Epigenesis, Genetic; Humans; Signal Transduction
PubMed: 35817793
DOI: 10.1038/s41392-022-01081-0 -
The American Journal of Psychiatry Jan 2021Recent progress in the identification of genes and genomic regions contributing to autism spectrum disorder (ASD) has had a broad impact on our understanding of the... (Review)
Review
Recent progress in the identification of genes and genomic regions contributing to autism spectrum disorder (ASD) has had a broad impact on our understanding of the nature of genetic risk for a range of psychiatric disorders, on our understanding of ASD biology, and on defining the key challenges now facing the field in efforts to translate gene discovery into an actionable understanding of pathology. While these advances have not yet had a transformative impact on clinical practice, there is nonetheless cause for real optimism: reliable lists of risk genes are large and growing rapidly; the identified encoded proteins have already begun to point to a relatively small number of areas of biology, where parallel advances in neuroscience and functional genomics are yielding profound insights; there is strong evidence pointing to mid-fetal prefrontal cortical development as one nexus of vulnerability for some of the largest-effect ASD risk genes; and there are multiple plausible paths forward toward rational therapeutics development that, while admittedly challenging, constitute fundamental departures from what was possible prior to the era of successful gene discovery.
Topics: Autism Spectrum Disorder; Genes; Genetic Predisposition to Disease; Humans
PubMed: 33384012
DOI: 10.1176/appi.ajp.2020.20111608 -
Medicina Aug 2022The coexistence of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) definitely poses new challenges, such as making an early diagnosis,... (Review)
Review
The coexistence of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) definitely poses new challenges, such as making an early diagnosis, considering that the former is usually diagnosed 2 years later in children with ADHD comorbid with autism compared to those with ASD alone; this is a problem at a personal, family and social level, since they must receive timely intervention. This coexistence raises questions about the efficacy of treatment in ADHD in people with autism, genetic, anatomical and functional concordances, among others; these are the challenges that are currently posed. In this review, we present some responses to the challenges posed by such coexistence, and we highlight some pending issues to be solved, being these of great importance for their better understanding and management. In all patients with ADHD or ASD, a coexistence between them should be sought. There are shared functional brain alterations in both disorders identified by functional brain magnetic resonance imaging; the treatment established for ADHD is also effective in this comorbidity.
Topics: Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Autistic Disorder; Brain; Child; Comorbidity; Humans
PubMed: 36054861
DOI: No ID Found -
The American Journal of Medicine Jun 2021
Topics: Autism Spectrum Disorder; Humans
PubMed: 33181106
DOI: 10.1016/j.amjmed.2020.10.022