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Lancet (London, England) Aug 2018Autism spectrum disorder is a term used to describe a constellation of early-appearing social communication deficits and repetitive sensory-motor behaviours associated... (Review)
Review
Autism spectrum disorder is a term used to describe a constellation of early-appearing social communication deficits and repetitive sensory-motor behaviours associated with a strong genetic component as well as other causes. The outlook for many individuals with autism spectrum disorder today is brighter than it was 50 years ago; more people with the condition are able to speak, read, and live in the community rather than in institutions, and some will be largely free from symptoms of the disorder by adulthood. Nevertheless, most individuals will not work full-time or live independently. Genetics and neuroscience have identified intriguing patterns of risk, but without much practical benefit yet. Considerable work is still needed to understand how and when behavioural and medical treatments can be effective, and for which children, including those with substantial comorbidities. It is also important to implement what we already know and develop services for adults with autism spectrum disorder. Clinicians can make a difference by providing timely and individualised help to families navigating referrals and access to community support systems, by providing accurate information despite often unfiltered media input, and by anticipating transitions such as family changes and school entry and leaving.
Topics: Adolescent; Adult; Autism Spectrum Disorder; Child; Humans; Risk Factors
PubMed: 30078460
DOI: 10.1016/S0140-6736(18)31129-2 -
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 -
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 -
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 -
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 -
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 -
American Family Physician Dec 2016Autism spectrum disorder is characterized by difficulty with social communication and restricted, repetitive patterns of behavior, interest, or activities. The... (Review)
Review
Autism spectrum disorder is characterized by difficulty with social communication and restricted, repetitive patterns of behavior, interest, or activities. The Diagnostic and Statistical Manual of Mental Disorders, 5th ed., created an umbrella diagnosis that includes several previously separate conditions: autistic disorder, Asperger syndrome, childhood disintegrative disorder, and pervasive developmental disorder not otherwise specified. There is insufficient evidence to recommend screening for autism spectrum disorder in children 18 to 30 months of age in whom the disorder is not suspected; however, there is a growing body of evidence that early intensive behavioral intervention based on applied behavior analysis improves cognitive ability, language, and adaptive skills. Therefore, early identification of autism spectrum disorder is important, and experts recommend the use of a validated screening tool at 18- and 24-month well-child visits. Medications can be used as adjunctive treatment for maladaptive behaviors and comorbid psychiatric conditions, but there is no single medical therapy that is effective for all symptoms of autism spectrum disorder. Prognosis is heavily affected by the severity of diagnosis and the presence of intellectual disability. Children with optimal outcomes receive earlier, more intensive behavioral interventions and less pharmacologic treatment.
Topics: Antipsychotic Agents; Aripiprazole; Asperger Syndrome; Autism Spectrum Disorder; Autistic Disorder; Behavior Therapy; Child Development Disorders, Pervasive; Child, Preschool; Early Diagnosis; Early Medical Intervention; Humans; Infant; Primary Health Care; Referral and Consultation; Risperidone
PubMed: 28075089
DOI: No ID Found -
Neuroscience Bulletin Apr 2017Since the documented observations of Kanner in 1943, there has been great debate about the diagnoses, the sub-types, and the diagnostic threshold that relates to what is... (Review)
Review
Since the documented observations of Kanner in 1943, there has been great debate about the diagnoses, the sub-types, and the diagnostic threshold that relates to what is now known as autism spectrum disorder (ASD). Reflecting this complicated history, there has been continual refinement from DSM-III with 'Infantile Autism' to the current DSM-V diagnosis. The disorder is now widely accepted as a complex, pervasive, heterogeneous condition with multiple etiologies, sub-types, and developmental trajectories. Diagnosis remains based on observation of atypical behaviors, with criteria of persistent deficits in social communication and restricted and repetitive patterns of behavior. This review provides a broad overview of the history, prevalence, etiology, clinical presentation, and heterogeneity of ASD. Factors contributing to heterogeneity, including genetic variability, comorbidity, and gender are reviewed. We then explore current evidence-based pharmacological and behavioral treatments for ASD and highlight the complexities of conducting clinical trials that evaluate therapeutic efficacy in ASD populations. Finally, we discuss the potential of a new wave of research examining objective biomarkers to facilitate the evaluation of sub-typing, diagnosis, and treatment response in ASD.
Topics: Autism Spectrum Disorder; Disease Management; Humans; Prevalence
PubMed: 28213805
DOI: 10.1007/s12264-017-0100-y -
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 -
Seminars in Speech and Language Aug 2019Difficulties with both executive functions and language skills are common but variable in autism spectrum disorder (ASD). Executive functions and language skills are... (Review)
Review
Difficulties with both executive functions and language skills are common but variable in autism spectrum disorder (ASD). Executive functions and language skills are related to one another, such that vocabulary, syntax, and pragmatics are related to domains of working memory, shifting, and inhibition in ASD, although the directionality of these relationships remains unclear. Moreover, interventions that target pragmatic ability have been found to improve executive function skills, and conversely, executive function interventions are linked with improvements in social skills in children with ASD. We review the literature on executive functions, language skills, and their relationship in ASD; discuss factors that may be driving inconsistent findings; and explore clinical applications from the research thus far.
Topics: Autism Spectrum Disorder; Child; Child, Preschool; Comorbidity; Executive Function; Female; Humans; Inhibition, Psychological; Language Development Disorders; Male; Memory, Short-Term; Reference Values; Verbal Learning; Vocabulary
PubMed: 31311054
DOI: 10.1055/s-0039-1692964