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JAMA Jan 2024
Topics: Humans; Autistic Disorder
PubMed: 38227035
DOI: 10.1001/jama.2023.24158 -
Endocrine Regulations Jan 2019Current understanding of the neuroanatomical abnormalities in autism includes gross anatomical changes in several brain areas and microstructural alterations in neuronal... (Review)
Review
Current understanding of the neuroanatomical abnormalities in autism includes gross anatomical changes in several brain areas and microstructural alterations in neuronal cells as well. There are many controversies in the interpretation of the imaging data, evaluation of volume and size of particular brain areas, and their functional translation into a broad autism phenotype. Critical questions of neuronal pathology in autism include the concept of the reversible plasticity of morphological changes, volume alterations of brain areas, and both short- and long-term consequences of adverse events present during the brain development. At the cellular level, remodeling of the actin cytoskeleton is considered as one of the critical factors associated with the autism spectrum disorders. Alterations in the composition of the neuronal cytoskeleton, in particular abnormalities in the polymerization of actin filaments and their associated proteins underlie the functional consequences in behavior resulting in symptoms and clinical correlates of autism spectrum disorder. In the present review, a special attention is devoted to the role of oxytocin in experimental models of neurodevelopmental disorders manifesting alterations in neuronal morphology.
Topics: Animals; Autism Spectrum Disorder; Autistic Disorder; Brain; Cell Shape; Cell Size; Humans; Magnetic Resonance Imaging; Neurons; Oxytocin
PubMed: 31517618
DOI: 10.2478/enr-2019-0006 -
Current Topics in Behavioral... 2016Animal models provide preclinical tools to investigate the causal role of genetic mutations and environmental factors in the etiology of autism spectrum disorder (ASD).... (Review)
Review
Animal models provide preclinical tools to investigate the causal role of genetic mutations and environmental factors in the etiology of autism spectrum disorder (ASD). Knockout and humanized knock-in mice, and more recently knockout rats, have been generated for many of the de novo single gene mutations and copy number variants (CNVs) detected in ASD and comorbid neurodevelopmental disorders. Mouse models incorporating genetic and environmental manipulations have been employed for preclinical testing of hypothesis-driven pharmacological targets, to begin to develop treatments for the diagnostic and associated symptoms of autism. In this review, we summarize rodent behavioral assays relevant to the core features of autism, preclinical and clinical evaluations of pharmacological interventions, and strategies to improve the translational value of rodent models of autism.
Topics: Animals; Autistic Disorder; Behavior, Animal; Disease Models, Animal; Mice; Mice, Knockout; Phenotype; Social Behavior; Translational Research, Biomedical
PubMed: 27305922
DOI: 10.1007/7854_2015_5003 -
Autism Research : Official Journal of... Oct 2015Most research into the epidemiology, etiology, clinical manifestations, diagnosis and treatment of autism is based on studies in high income countries. Moreover, within... (Review)
Review
Most research into the epidemiology, etiology, clinical manifestations, diagnosis and treatment of autism is based on studies in high income countries. Moreover, within high income countries, individuals of high socioeconomic status are disproportionately represented among participants in autism research. Corresponding disparities in access to autism screening, diagnosis, and treatment exist globally. One of the barriers perpetuating this imbalance is the high cost of proprietary tools for diagnosing autism and for delivering evidence-based therapies. Another barrier is the high cost of training of professionals and para-professionals to use the tools. Open-source and open access models provide a way to facilitate global collaboration and training. Using these models and technologies, the autism scientific community and clinicians worldwide should be able to work more effectively and efficiently than they have to date to address the global imbalance in autism knowledge and at the same time advance our understanding of autism and our ability to deliver cost-effective services to everyone in need.
Topics: Autistic Disorder; Developing Countries; Global Health; Health Services Accessibility; Humans; Internationality; Research
PubMed: 26437907
DOI: 10.1002/aur.1575 -
Revista de Neurologia 2016Research into autism, based mainly on the categorical model in the Diagnostic and statistical manual of mental disorders, has focused above all on the epidemiology,... (Review)
Review
INTRODUCTION
Research into autism, based mainly on the categorical model in the Diagnostic and statistical manual of mental disorders, has focused above all on the epidemiology, clinical manifestations, cognitive mechanisms and the biological-environmental determining factors. Yet, little attention has been paid to the developmental trajectories, which play a decisive role when it comes to establishing a medium- and long-term prognosis.
AIMS
The purpose of this study is to review the developmental course of children diagnosed with autism who, despite preserving behavioural traits consistent with the initial profile in the medium- and long-term, accomplish a satisfactory social and occupational adaptation, and additionally no longer meet the criteria that gave rise to the initial diagnosis.
DEVELOPMENT
A review was conducted of the bibliography on autism focused on the analysis of the development of the clinical manifestations and their repercussions from the earliest ages to adulthood. Likewise, we have also taken into consideration conceptual aspects about autism that facilitate the comprehension and the meaning of the developmental patterns.
CONCLUSIONS
Around 20% of the children diagnosed with autism cease to meet the criteria on which their diagnosis was based and, furthermore, achieve a satisfactory social and occupational adjustment. The following were identified as favouring factors: normal intelligence, good level of language and low incidence of 'comorbidities'; conversely, in the series that were reported, early and intensive therapeutic interventions were not shown to be determining factors. Lastly, mention is made of the concept of neurodiversity, where recovery is centred on the optimal development of each individual's capacities within a facilitating environment.
Topics: Autistic Disorder; Child; Humans; Remission Induction
PubMed: 26922958
DOI: No ID Found -
Communications Biology 2019The core diagnostic criteria for autism comprise two symptom domains - social and communication difficulties, and unusually repetitive and restricted behaviour,...
The core diagnostic criteria for autism comprise two symptom domains - social and communication difficulties, and unusually repetitive and restricted behaviour, interests and activities. There is some evidence to suggest that these two domains are dissociable, though this hypothesis has not yet been tested using molecular genetics. We test this using a genome-wide association study ( = 51,564) of a non-social trait related to autism, systemising, defined as the drive to analyse and build systems. We demonstrate that systemising is heritable and genetically correlated with autism. In contrast, we do not identify significant genetic correlations between social autistic traits and systemising. Supporting this, polygenic scores for systemising are significantly and positively associated with restricted and repetitive behaviour but not with social difficulties in autistic individuals. These findings strongly suggest that the two core domains of autism are genetically dissociable, and point at how to fractionate the genetics of autism.
Topics: Autistic Disorder; Cohort Studies; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Male; Phenotype; Reproducibility of Results; Social Behavior
PubMed: 31508503
DOI: 10.1038/s42003-019-0558-4 -
Dialogues in Clinical Neuroscience Dec 2017Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and repetitive/restrictive interests. ASD is associated with... (Review)
Review
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and repetitive/restrictive interests. ASD is associated with multiple comorbidities, including intellectual disability, anxiety, and epilepsy. Evidence that ASD is highly heritable has spurred major efforts to unravel its genetics, revealing possible contributions from hundreds of genes through rare and common variation and through copy-number changes. In this perspective, we provide an overview of the current state of ASD genetics and of how genetic research has spurred the development of in vivo and in vitro models using animals and patient cells to evaluate the impact of genetic mutations on cellular function leading to disease. Efforts to translate these findings into successful therapies have yet to bear fruit. We discuss how the valuable insight into the disorder provided by these new models can be used to better understand ASD and develop future clinical trials.
Topics: Animals; Autistic Disorder; Disease Models, Animal; Genetic Therapy; Humans; Mutation; Translational Research, Biomedical
PubMed: 29398929
DOI: 10.31887/DCNS.2017.19.4/cmanzini -
International Journal of Molecular... Jun 2016Schizophrenia and autism spectrum disorder (ASD) are multi-factorial and multi-symptomatic psychiatric disorders, each affecting 0.5%-1% of the population worldwide.... (Review)
Review
Schizophrenia and autism spectrum disorder (ASD) are multi-factorial and multi-symptomatic psychiatric disorders, each affecting 0.5%-1% of the population worldwide. Both are characterized by impairments in cognitive functions, emotions and behaviour, and they undermine basic human processes of perception and judgment. Despite decades of extensive research, the aetiologies of schizophrenia and ASD are still poorly understood and remain a significant challenge to clinicians and scientists alike. Adding to this unsatisfactory situation, patients with schizophrenia or ASD often develop a variety of peripheral and systemic disturbances, one prominent example of which is cancer, which shows a direct (but sometimes inverse) comorbidity in people affected with schizophrenia and ASD. Cancer is a disease characterized by uncontrolled proliferation of cells, the molecular origin of which derives from mutations of a cell's DNA sequence. To counteract such mutations and repair damaged DNA, cells are equipped with intricate DNA repair pathways. Oxidative stress, oxidative DNA damage, and deficient repair of oxidative DNA lesions repair have been proposed to contribute to the development of schizophrenia and ASD. In this article, we summarize the current evidence of cancer comorbidity in these brain disorders and discuss the putative roles of oxidative stress, DNA damage and DNA repair in the aetiopathology of schizophrenia and ASD.
Topics: Animals; Autism Spectrum Disorder; Autistic Disorder; Comorbidity; DNA Damage; DNA Repair; Humans; Neoplasms; Oxidative Stress; Risk; Schizophrenia
PubMed: 27258260
DOI: 10.3390/ijms17060856 -
Brain and Cognition Dec 2023Hyperlexia, a strong orientation towards written materials, along with a discrepancy between the precocious acquisition of decoding skills and weaker comprehension...
BACKGROUND
Hyperlexia, a strong orientation towards written materials, along with a discrepancy between the precocious acquisition of decoding skills and weaker comprehension abilities, characterizes up to 20% of autistic children. Sometimes perceived as an obstacle to oral language acquisition, hyperlexia may alternatively be the first step in a non-social pathway of language acquisition in autism.
METHOD
We describe two monozygotic twin brothers, both autistic and hyperlexic, from the ages of 4 to 8 years old. Following an in-depth diagnostic assessment, we investigated cross-sectionally and longitudinally their verbal and non-verbal cognitive abilities, language, reading and writing skills, interests, and strengths.
RESULTS
The twins' features, including their high non-verbal level of intelligence, their special interests, and their skills in various domains, were highly similar. Their language consisted exclusively of letters and numbers until their fourth year. After that, their vocabulary broadened until they developed full sentences, and their perception-related interests expanded and merged over time to serve the development of other skills.
CONCLUSION
Our results show that hyperlexic skills can be harnessed to favor oral language development. Given the strong concordance between the twins' cognitive and behavioral phenotypes, we discuss the environmental and genetic influence that could explain their abilities.
Topics: Child; Child, Preschool; Humans; Male; Autistic Disorder; Language Development; Longitudinal Studies; Reading; Twins, Monozygotic
PubMed: 37839243
DOI: 10.1016/j.bandc.2023.106099 -
Journal of Neural Transmission (Vienna,... Aug 2014Glutamate is the major excitatory neurotransmitter in the brain and may be a key neurotransmitter involved in autism. Literature pertaining to glutamate and autism or... (Review)
Review
Glutamate is the major excitatory neurotransmitter in the brain and may be a key neurotransmitter involved in autism. Literature pertaining to glutamate and autism or related disorders (e.g., Fragile X syndrome) is reviewed in this article. Interest in glutamatergic dysfunction in autism is high due to increasing convergent evidence implicating the system in the disorder from peripheral biomarkers, neuroimaging, protein expression, genetics and animal models. Currently, there are no pharmaceutical interventions approved for autism that address glutamate deficits in the disorder. New treatments related to glutamatergic neurotransmission, however, are emerging. In addition, older glutamate-modulating medications with approved indications for use in other disorders are being investigated for re-tasking as treatments for autism. This review presents evidence in support of glutamate abnormalities in autism and the potential for translation into new treatments for the disorder.
Topics: Animals; Autistic Disorder; Excitatory Amino Acid Antagonists; Glutamic Acid; Humans; Psychotropic Drugs; Receptors, Glutamate; Synaptic Transmission
PubMed: 24752754
DOI: 10.1007/s00702-014-1216-0