Materiały źródłowe

• #1 Autism spectrum disorder (ASD) in children and adolescents: Terminology, epidemiology, and pathogenesis – UpToDate

  https://www.uptodate.com/contents/autism-spectrum-disorder-asd-in-children-and-adolescents-terminology-epidemiology-and-pathogenesis

  Autism spectrum disorder (ASD) is a biologically based neurodevelopmental disorder characterized by persistent deficits in social communication and social interaction and restricted, repetitive patterns of behavior, interests, and activities. […] The terminology, epidemiology, and pathogenesis of ASD will be reviewed here. […] PATHOGENESIS […] Genetic factors […] Neurobiologic factors […] Parental age […] Environmental and perinatal factors […] Maternal medication use during pregnancy […] Lack of association with immunizations.

• #2 Autism Spectrum Disorders: Etiology and Pathology – Autism Spectrum Disorders – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK573613/

  Autism spectrum disorders (ASD) are a group of neurodevelopmental diseases. The cause of ASD is unknown, but several genetic and non-genetic risk factors have been characterized that, alone or in combination, are implicated in the development of ASD. […] Several pathomechanisms such as alterations in brain development and function, and synaptic defects have been proposed to contribute to these behaviors. […] The etiology of ASD is likely to be multifactorial, with both genetic and non-genetic factors playing a role. ASD can be syndromic or non-syndromic. Syndromic ASD is often associated with chromosomal abnormalities or monogenic alterations. Such examples include Rett syndrome, fragile X syndrome, and MECP2 duplication syndrome. Contrary to syndromic ASD, the etiology of non-syndromic ASD is still relatively undefined due to its genetic heterogeneity. A collaboration of de novo mutations and prenatal plus postnatal environmental factors are likely to play a role.

• #3 Mechanism of autism – Wikipedia

  https://en.wikipedia.org/wiki/Mechanism_of_autism

  The mechanisms of autism are the molecular and cellular processes believed to cause or contribute to the symptoms of autism. Multiple processes are hypothesized to explain different autism spectrum features. These hypotheses include defects in synapse structure and function, reduced synaptic plasticity, disrupted neural circuit function, gut-brain axis dyshomeostasis, neuroinflammation, and altered brain structure or connectivity. Autism symptoms stem from maturation-related changes in brain systems. The mechanisms of autism are divided into two main areas: pathophysiology of brain structures and processes, and neuropsychological linkages between brain structures and behaviors, with multiple pathophysiologies linked to various autism behaviors. […] Evidence suggests gut-brain axis abnormalities may contribute to autism.

• #4 The pathogenesis of autism spectrum disorder

  http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S1665-50442021000600248

  ASD is multifactorial: a mother and an embryo with genetic susceptibility, probably exposed to external triggers such as infections, toxins, environmental pollutants, and nutritional deficiencies, and/or to internal factors (autoimmune diseases) that condition an inflammatory state in which the microglia and numerous cytokines, especially interleukin 6 (IL-6), exert actions that negatively affect the structure and functionality of the developing brain. […] The genetic factor is important. […] Neurodevelopment is influenced by innate and environmental factors that can modify synapse plasticity, brain structures, cognition, and behavior. […] There is an interaction between multiple genes to give the autistic phenotype. […] Heritability in ASD is about 50 or 55%. […] Genes related to neurodevelopment such as TEX 49 (LINC00935) and CCNT1 are implicated in ASD and in reading disabilities.

• #5 Autism Spectrum Disorders: Etiology and Pathology – Autism Spectrum Disorders – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK573613/

  Autism spectrum disorders (ASD) are a group of neurodevelopmental diseases. The cause of ASD is unknown, but several genetic and non-genetic risk factors have been characterized that, alone or in combination, are implicated in the development of ASD. […] Several pathomechanisms such as alterations in brain development and function, and synaptic defects have been proposed to contribute to these behaviors. […] The etiology of ASD is likely to be multifactorial, with both genetic and non-genetic factors playing a role. ASD can be syndromic or non-syndromic. Syndromic ASD is often associated with chromosomal abnormalities or monogenic alterations. Such examples include Rett syndrome, fragile X syndrome, and MECP2 duplication syndrome. Contrary to syndromic ASD, the etiology of non-syndromic ASD is still relatively undefined due to its genetic heterogeneity. A collaboration of de novo mutations and prenatal plus postnatal environmental factors are likely to play a role.

• #6

  https://scite.ai/reports/10.2217/fnl.09.29

  11 Recent studies have implicated multiple and different genes, which have in common that they damage neurodevelopment. […] A mutation of this gene was found, it encodes an abnormal protein responsible for synaptic or dendritic changes leading to autism with sever language and social deficits (Durand et al, 2007; Losh et al, 2008; Benvenuto et al, 2009). Neuroligins, cell adhesion molecules that play a prominent role in synaptic maturation and function are regarded as plausible candidates implicated in autism (Grigorenko, 2009). A link between neuroligins and autism was first supported by findings of mutations in the X-linked neuroligins, NLGN3 and NLGN4 in two autistic sib pairs (Losh et al, 2008; Grigorenko, 2009). […] Autism spectrum disorders are neurodevelopmental disorders characterized by significant deficits in reciprocal social interactions, impaired communication and restricted, repetitive behaviors. As autism spectrum disorders are among the most heritable of neuropsychiatric disorders, much of autism research has focused on the search for genetic variants in protein-coding genes (i.e., the trees). However, no single gene can account for more than 1% of the cases of autism spectrum disorders. Yet, genome-wide association studies have often identified statistically significant associations of genetic variations in regions of DNA that do not code for proteins (i.e., intergenic regions). There is increasing evidence that such noncoding regions are actively transcribed and may participate in the regulation of genes, including genes on different chromosomes. This article summarizes evidence that suggests that the research spotlight needs to be expanded to encompass far-reaching gene-regulatory mechanisms that include a variety of epigenetic modifications, as well as noncoding RNA (i.e., the forest). Given that noncoding RNA represents over 90% of the transcripts in most cells, we may be observing just the tip of the iceberg or the edge of the forest in the genomic landscape of autism.

• #7 Mount Sinai Researchers Learn Mechanism Behind Genetic Mutation Associated with Autism | Mount Sinai – New York

  https://www.mountsinai.org/about/newsroom/2010/mount-sinai-researchers-learn-mechanism-behind-genetic-mutation-associated-with-autism

  Researchers from Mount Sinai School of Medicine have found that when one copy of the SHANK3 gene in mice is missing, nerve cells do not effectively communicate and do not show cellular properties associated with normal learning. This discovery may explain how mutations affecting SHANK3 may lead to autism spectrum disorders (ASDs). […] „These data provide critical insight into the mechanism behind the development of the cognitive and social changes associated with autism.” […] „These results have helped us determine a pathological mechanism behind neurodevelopmental disorders like autism,” said Dr. Buxbaum. […] „Armed with this breakthrough, we can begin testing drug compounds that treat the disease at its root cause, improving nerve cell communication.”

• #8 The pathogenesis of autism spectrum disorder

  http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S1665-50442021000600248

  However, heterozygous mutations in RELN are related with the ASD. […] It encodes a protein that acts as a scaffold that supports the connections between neurons, ensuring communication between them; the protein participates in the formation and maturation of dendritic spines. […] Alterations in this gene, including the 22q13.3 deletion, appear to be related to ASD. […] The MET gene encodes a member of the receptor tyrosine kinase family of proteins. […] In the human brain, this gene is highly expressed in temporal, occipital, and medial portions of the parietal lobes. […] At least, two common risk alleles have been identified. […] MET signaling has a role not only in neocortical and cerebellar growth and maturation, but also in gastrointestinal repair, and immunological competence, functions that have been reported as abnormal in children with autism.

• #9 The pathogenesis of autism spectrum disorder

  http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S1665-50442021000600248

  Furthermore, genes that code for proteins related to the immune system are involved. […] A large exome sequencing study showed 102 genes involved in risk for ASD. […] The DR4 allele of the MHC is one of the susceptibility markers for certain autoimmune diseases, such as rheumatoid arthritis, hypothyroidism, and autoimmune diabetes. […] Compared to controls, children with ASD had significantly increased numbers of HLA-DR+CD4+, HLA-DR+CD8+, CD28+HLA-DR+, HLA-DR+CXCR4+, and HLA-DR+CCR7+ cells. […] Increased relative risk for autism has been observed with HLA hypervariable region 3 of DRB1*0401 in children from North America and China. […] The RELN gene codifies a protein called reelin that activates a signaling pathway that triggers neurons to migrate to their proper locations. […] The homozygous mutations lead to brain hypoplasia, developmental delay, and epilepsy.

• #10 The pathogenesis of autism spectrum disorder

  http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S1665-50442021000600248

  However, heterozygous mutations in RELN are related with the ASD. […] It encodes a protein that acts as a scaffold that supports the connections between neurons, ensuring communication between them; the protein participates in the formation and maturation of dendritic spines. […] Alterations in this gene, including the 22q13.3 deletion, appear to be related to ASD. […] The MET gene encodes a member of the receptor tyrosine kinase family of proteins. […] In the human brain, this gene is highly expressed in temporal, occipital, and medial portions of the parietal lobes. […] At least, two common risk alleles have been identified. […] MET signaling has a role not only in neocortical and cerebellar growth and maturation, but also in gastrointestinal repair, and immunological competence, functions that have been reported as abnormal in children with autism.

• #11 Autism Spectrum Disorders: Etiology and Pathology – Autism Spectrum Disorders – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK573613/

  The clearest neuropathology of ASD is synaptic dysfunction. Many of the 207 SFARI genes associated with high risk (syndromic and category 1) for ASD encode for proteins that play a crucial role in synaptic function in the brain. […] Therefore, ASD is also classified as a synaptopathy. At synapses, two signaling pathways seem to be critical to the ASD pathology. The mTOR/PI3K pathway that is particularly associated with syndromic ASD and the NRXN-NLGN-SHANK pathway. Together, these pathways are key regulators of synaptogenesis. However, their presence is vastly limited to excitatory synapses, which ultimately may result in an imbalance between excitatory and inhibitory transmission. It has been speculated that many genetic and non-genetic risk factors for ASD mechanistically converge at synaptic level.

• #12 Autism Spectrum Disorders: Etiology and Pathology – Autism Spectrum Disorders – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK573613/

  The clearest neuropathology of ASD is synaptic dysfunction. Many of the 207 SFARI genes associated with high risk (syndromic and category 1) for ASD encode for proteins that play a crucial role in synaptic function in the brain. […] Therefore, ASD is also classified as a synaptopathy. At synapses, two signaling pathways seem to be critical to the ASD pathology. The mTOR/PI3K pathway that is particularly associated with syndromic ASD and the NRXN-NLGN-SHANK pathway. Together, these pathways are key regulators of synaptogenesis. However, their presence is vastly limited to excitatory synapses, which ultimately may result in an imbalance between excitatory and inhibitory transmission. It has been speculated that many genetic and non-genetic risk factors for ASD mechanistically converge at synaptic level.

• #13 Mechanism of autism – Wikipedia

  https://en.wikipedia.org/wiki/Mechanism_of_autism

  Synaptic dysfunction also appears to be implicated in autism, with some mutations disrupting synaptic pathways involving cell adhesion. […] Neuroanatomical studies support that autism may involve abnormal neuronal growth and pruning, leading to brain enlargement in some areas and reduction in others. […] Autism appears to result from developmental factors that affect many or all functional brain systems. […] Some factors may disturb the timing of brain development rather than the final product. […] The immune system is thought to play an important role in autism. […] It is proposed that inflammation within the brain promoted by inflammatory responses to harmful gut microbiome impacts brain development. […] Several lines of evidence indicate abnormalities of folate metabolism in ASD.

• #14 Mechanism of autism – Wikipedia

  https://en.wikipedia.org/wiki/Mechanism_of_autism

  Synaptic dysfunction also appears to be implicated in autism, with some mutations disrupting synaptic pathways involving cell adhesion. […] Neuroanatomical studies support that autism may involve abnormal neuronal growth and pruning, leading to brain enlargement in some areas and reduction in others. […] Autism appears to result from developmental factors that affect many or all functional brain systems. […] Some factors may disturb the timing of brain development rather than the final product. […] The immune system is thought to play an important role in autism. […] It is proposed that inflammation within the brain promoted by inflammatory responses to harmful gut microbiome impacts brain development. […] Several lines of evidence indicate abnormalities of folate metabolism in ASD.

• #15 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Autism-Mechanism.aspx

  Autism is a spectrum of disorders with no specific only cause. This is the reason why its mechanism of pathophysiology is difficult to understand. […] While a genetic basis is recognised, the pathophysiology of autism is unknown. […] This suggests that autistic symptoms may be a consequence of abnormal function in these structures. […] The early overgrowth seems to be most prominent in areas underlying the development of higher cognitive specialization. This may lead to disturbed neuronal migration during early gestation and a imbalance between excitatory-inhibitory networks. […] Disrupted synaptic development may also contribute to epilepsy, which may explain why the two conditions are associated. […] There are excessive cells in the limbic system and they are too small. […] At the subcellular level research shows that there is an elevation in a major neurotransmitter, serotonin, which affects potentiation at synapses and may play a role in the development of the nervous system.

• #16 The Pathogenesis of Autism

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3160002/

  The theory of unbalanced excitability-inhibitory networks in autism also carries certain credibility. […] The abnormal assembly of synapses and dendritic spines may also be a contributing factor in autisms pathogenesis. […] The topic of neuroimmune disturbance and its impact on the pathogenesis of autism has also been widely researched. […] Calcium signalling may also contribute to autism via the important nature of activity-dependant calcium influx into neurons which subsequently regulates (via transcription) numerous cortical excitatory synapses. […] The favourable mirror neurone system theory links neuropathology to autism on a more symptomatic level. […] Overall it seems most likely that the anomaly encountered in neurodevelopment that leads to autism is not merely localised to a single functional neural defect as many theories have suggested, but more distributed across numerous levels of study (genetic, immunopathogenic, neurofunctional etc.) becoming a multi-domain disorder.

• #17 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  In patients with autism, neuroanatomic and neuroimaging studies reveal abnormalities of cellular configurations in several regions of the brain, including the frontal and temporal lobes and the cerebellum. Enlargements of the amygdala and the hippocampus are common in childhood. Markedly more neurons are present in select divisions of the prefrontal cortex of autopsy specimens of some children with ASD, compared with those without ASD. […] Magnetic resonance imaging (MRI) studies have suggested evidence for differences in neuroanatomy and connectivity in people with ASD compared with normal controls. Specifically, these studies have found reduced or atypical connectivity in frontal brain regions, as well as thinning of the corpus callosum in children and adults with ASD and related conditions.

• #18 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  Importantly, some of the regional differences in neuroanatomy correlate significantly with the severity of specific autistic symptoms. For example, social and language deficits of people with ASD likely are related to dysfunction of the frontal and temporal lobes. […] In a study of postmortem brain tissue from 11 children with ASD and 11 unaffected controls, researchers found focal disruption of cortical laminar architecture in the cortexes of 10 of the children with ASD and 1 of the controls, suggesting that brain irregularities in ASD may have prenatal origins. […] The patches of abnormal neurons were found in the frontal and temporal lobes, regions involved in social, emotional, communication, and language functions. Since the changes were in the form of patches, the researchers believe that early treatment could rewire the brain and improve ASD symptoms.

• #19 The Pathogenesis of Autism

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3160002/

  One specific theory emphasises that early brain overgrowth and neural overconnectivity are key in the pathogenesis. It is speculated that excess neuron numbers (inducing cerebral overgrowth) may promote defects in neural patterning and wiring, with subsequent over energetic short-distance cortical interactions hindering long-distance interactions that communicate between critical brain regions. […] Conversely another related theory postulates that the neuropathological basis of disrupted cognition in autism is linked to reduced intracortical connectivity which subsequently promotes a lower degree of information integration across multiple cortical regions. […] Cerebral cortical malformations observed in autism may result from defective neural migration to the cerebral cortex during the first 6 months of gestation.

• #20 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Autism-Mechanism.aspx

  Autism is a spectrum of disorders with no specific only cause. This is the reason why its mechanism of pathophysiology is difficult to understand. […] While a genetic basis is recognised, the pathophysiology of autism is unknown. […] This suggests that autistic symptoms may be a consequence of abnormal function in these structures. […] The early overgrowth seems to be most prominent in areas underlying the development of higher cognitive specialization. This may lead to disturbed neuronal migration during early gestation and a imbalance between excitatory-inhibitory networks. […] Disrupted synaptic development may also contribute to epilepsy, which may explain why the two conditions are associated. […] There are excessive cells in the limbic system and they are too small. […] At the subcellular level research shows that there is an elevation in a major neurotransmitter, serotonin, which affects potentiation at synapses and may play a role in the development of the nervous system.

• #21 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Autism-Mechanism.aspx

  The under-connectivity theory of autism hypothesizes that autism is marked by under-functioning high-level neural connections and synchronization, along with an excess of low-level processes. […] Disturbed immune activity during critical periods of neurodevelopment is part of the mechanism of some forms of ASD. However, as autoantibodies are found in conditions other than ASD, and are not always present in ASD, the relationship between immune disturbances and autism remains unclear.

• #22 The Pathogenesis of Autism

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3160002/

  One specific theory emphasises that early brain overgrowth and neural overconnectivity are key in the pathogenesis. It is speculated that excess neuron numbers (inducing cerebral overgrowth) may promote defects in neural patterning and wiring, with subsequent over energetic short-distance cortical interactions hindering long-distance interactions that communicate between critical brain regions. […] Conversely another related theory postulates that the neuropathological basis of disrupted cognition in autism is linked to reduced intracortical connectivity which subsequently promotes a lower degree of information integration across multiple cortical regions. […] Cerebral cortical malformations observed in autism may result from defective neural migration to the cerebral cortex during the first 6 months of gestation.

• #23 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Autism-Mechanism.aspx

  Autism is a spectrum of disorders with no specific only cause. This is the reason why its mechanism of pathophysiology is difficult to understand. […] While a genetic basis is recognised, the pathophysiology of autism is unknown. […] This suggests that autistic symptoms may be a consequence of abnormal function in these structures. […] The early overgrowth seems to be most prominent in areas underlying the development of higher cognitive specialization. This may lead to disturbed neuronal migration during early gestation and a imbalance between excitatory-inhibitory networks. […] Disrupted synaptic development may also contribute to epilepsy, which may explain why the two conditions are associated. […] There are excessive cells in the limbic system and they are too small. […] At the subcellular level research shows that there is an elevation in a major neurotransmitter, serotonin, which affects potentiation at synapses and may play a role in the development of the nervous system.

• #24 Mechanism of autism – Wikipedia

  https://en.wikipedia.org/wiki/Mechanism_of_autism

  An imbalance in glutathione-dependent redox metabolism has been shown to be associated with autism spectrum disorder (ASD). […] Reduced NMDA receptor function has been linked to reduced social interactions, locomotor hyperactivity, self-injury, prepulse inhibition (PPI) deficits, and sensory hypersensitivity, among others. Results suggest that NMDA dysregulation could contribute to core ASD symptoms.

• #25 Mechanism of autism – Wikipedia

  https://en.wikipedia.org/wiki/Mechanism_of_autism

  An imbalance in glutathione-dependent redox metabolism has been shown to be associated with autism spectrum disorder (ASD). […] Reduced NMDA receptor function has been linked to reduced social interactions, locomotor hyperactivity, self-injury, prepulse inhibition (PPI) deficits, and sensory hypersensitivity, among others. Results suggest that NMDA dysregulation could contribute to core ASD symptoms.

• #26 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  On MRI scans, the brains of children with ASD demonstrate greater myelination in bilateral medial frontal cortices and less myelination in the left temporoparietal junction. […] Similarly, region-specific differences in the concentrations of gray matter, made up of neuronal cell bodies, dendrites, unmyelinated axons and glial cells, are also found in the brains of people with autism. […] Reductions in cerebral GABA likely contribute to the sensorimotor and behavioral anomalies of individuals with ASD. […] Reductions in sensorimotor GABA were observed by magnetic resonance spectroscopy (MRS) in participants with ASD in contrast to matched controls without ASD. […] Postmortem specimens of the brains of people with ASD demonstrated reductions for gamma-aminobutyric acidB (GABAB) receptors in the cingulate cortex, a key region for the evaluation of social relationships, emotions, and cognition, and in the fusiform gyrus, a crucial region to evaluate faces and facial expressions.

• #27 The Pathogenesis of Autism

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3160002/

  The theory of unbalanced excitability-inhibitory networks in autism also carries certain credibility. […] The abnormal assembly of synapses and dendritic spines may also be a contributing factor in autisms pathogenesis. […] The topic of neuroimmune disturbance and its impact on the pathogenesis of autism has also been widely researched. […] Calcium signalling may also contribute to autism via the important nature of activity-dependant calcium influx into neurons which subsequently regulates (via transcription) numerous cortical excitatory synapses. […] The favourable mirror neurone system theory links neuropathology to autism on a more symptomatic level. […] Overall it seems most likely that the anomaly encountered in neurodevelopment that leads to autism is not merely localised to a single functional neural defect as many theories have suggested, but more distributed across numerous levels of study (genetic, immunopathogenic, neurofunctional etc.) becoming a multi-domain disorder.

• #28 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  On MRI scans, the brains of children with ASD demonstrate greater myelination in bilateral medial frontal cortices and less myelination in the left temporoparietal junction. […] Similarly, region-specific differences in the concentrations of gray matter, made up of neuronal cell bodies, dendrites, unmyelinated axons and glial cells, are also found in the brains of people with autism. […] Reductions in cerebral GABA likely contribute to the sensorimotor and behavioral anomalies of individuals with ASD. […] Reductions in sensorimotor GABA were observed by magnetic resonance spectroscopy (MRS) in participants with ASD in contrast to matched controls without ASD. […] Postmortem specimens of the brains of people with ASD demonstrated reductions for gamma-aminobutyric acidB (GABAB) receptors in the cingulate cortex, a key region for the evaluation of social relationships, emotions, and cognition, and in the fusiform gyrus, a crucial region to evaluate faces and facial expressions.

• #29 Autism Spectrum Disorder: Neurodevelopmental Risk Factors, Biological Mechanism, and Precision Therapy

  https://www.mdpi.com/1422-0067/24/3/1819

  The molecular biological mechanisms and neural circuits associated with autism spectrum disorders were also integrated to explore further the critical circuit elements and underlying molecular mechanisms involved in each set of symptoms of ASD disorders. […] The PI3K-AKT/mTOR signaling pathway is highly associated with autism and various neurodegenerative diseases. […] Studies have identified a mutated PI3K-AKT-mTOR pathway in nearly 50% of kids with brain malformations and delayed development/autism. […] Abnormalities in transcription and translation exacerbate abnormal neuronal function in ASD, further affecting synaptic transmission and plasticity, and dysregulation of the gut flora affects peripheral immune response function also influences brain dysfunction. […] In general, it is believed that associated gene variants in ASD patients and animal models are likely focused on similar molecular or cellular pathways.

• #30 Impaired neurodevelopmental pathways in autism spectrum disorder: a review of signaling mechanisms and crosstalk | Journal of Neurodevelopmental Disorders | Full Text

  https://jneurodevdisorders.biomedcentral.com/articles/10.1186/s11689-019-9268-y

  Several genetic loci/mutations linked to and/or reported in ASD patients are either core components of canonical WNT signaling, such as -catenin (CTNNB1) and adenomatous polyposis coli (APC), or non-canonical WNT signaling, suggesting crucial roles of both canonical and non-canonical WNT signaling pathways in the etiologies of ASD. […] The tumor suppressor APC is a key component of the -catenin-destruction complex. […] Human APC inactivating gene mutations have been linked to ASD. […] These results also indicate that overactivation of WNT/-catenin signaling may be a cause of ASD. […] -Catenin is a key intracellular molecule in the canonical WNT signaling pathway and plays significant roles in development and disease. […] De novo CTNNB1 mutations have been reported in individuals with ASD, intellectual disability, microcephaly, motor delay, and speech impairment.

• #31 Impaired neurodevelopmental pathways in autism spectrum disorder: a review of signaling mechanisms and crosstalk | Journal of Neurodevelopmental Disorders | Full Text

  https://jneurodevdisorders.biomedcentral.com/articles/10.1186/s11689-019-9268-y

  Conditional ablation of -catenin in parvalbumin interneurons in mice leads to impaired object recognition and social interactions, as well as elevated repetitive behaviors, which are core symptoms of ASD patients. […] Dysregulation of BMP signaling has been suggested to play a role in the pathogenesis of ASD. […] The TGF-/activin and the bone morphogenetic protein (BMP)/growth and differentiation factor (GDF) are the two subgroups of TGF- superfamily and are critical in the development of the nervous system. […] Their signaling has been shown to be dysregulated in ASD. […] Dysregulation of FGF signaling has been suggested to play a role in the pathogenesis of ASD. […] Dysregulation of SHH signaling in the brain leads to neurological disorders like ASD. […] Significantly higher levels of oxygen free radicals (OFR) and serum SHH protein have been demonstrated in autistic children, suggesting a pathological role of oxidative stress and SHH in ASD.

• #32 Impaired neurodevelopmental pathways in autism spectrum disorder: a review of signaling mechanisms and crosstalk | Journal of Neurodevelopmental Disorders | Full Text

  https://jneurodevdisorders.biomedcentral.com/articles/10.1186/s11689-019-9268-y

  Conditional ablation of -catenin in parvalbumin interneurons in mice leads to impaired object recognition and social interactions, as well as elevated repetitive behaviors, which are core symptoms of ASD patients. […] Dysregulation of BMP signaling has been suggested to play a role in the pathogenesis of ASD. […] The TGF-/activin and the bone morphogenetic protein (BMP)/growth and differentiation factor (GDF) are the two subgroups of TGF- superfamily and are critical in the development of the nervous system. […] Their signaling has been shown to be dysregulated in ASD. […] Dysregulation of FGF signaling has been suggested to play a role in the pathogenesis of ASD. […] Dysregulation of SHH signaling in the brain leads to neurological disorders like ASD. […] Significantly higher levels of oxygen free radicals (OFR) and serum SHH protein have been demonstrated in autistic children, suggesting a pathological role of oxidative stress and SHH in ASD.

• #33 Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01081-0

  Key literature from recent years has suggested that ASD-associated genes enriched in aspect of transcription and translation, synapse, epigenetics, immunity and inflammation. […] These types of signalling pathways can interact or participate in the pathophysiology of ASD in a cascading manner rather than acting independently. […] Current evidence suggests that there is a complex level of dynamic regulation between translation and transcription that likely contributes to ASD pathophysiology. […] In summary, current evidence suggests that there is a complex level of dynamic regulation between translation and transcription that likely contributes to ASD pathophysiology. […] The neuropeptide theory of autism is backed up by evidence from animal research. […] The neuropeptide hormones OT and AVP belong to the same superfamily, and genetic variants in OXT, OXTR, arginine vasopressin receptor 1a (AVPR1a) and CD38 have been verified to be associated with autism. […] The development of strategies to intervene in or block the transduction of key signalling molecules involved in the pathogenesis of autism is a primary research direction.

• #34 Mechanism of autism – Wikipedia

  https://en.wikipedia.org/wiki/Mechanism_of_autism

  Synaptic dysfunction also appears to be implicated in autism, with some mutations disrupting synaptic pathways involving cell adhesion. […] Neuroanatomical studies support that autism may involve abnormal neuronal growth and pruning, leading to brain enlargement in some areas and reduction in others. […] Autism appears to result from developmental factors that affect many or all functional brain systems. […] Some factors may disturb the timing of brain development rather than the final product. […] The immune system is thought to play an important role in autism. […] It is proposed that inflammation within the brain promoted by inflammatory responses to harmful gut microbiome impacts brain development. […] Several lines of evidence indicate abnormalities of folate metabolism in ASD.

• #35 Pathogenesis of Brain: Autism Spectrum Disorders | Auctores

  https://auctoresonline.org/article/pathogenesis-of-brain-autism-spectrum-disorders

  Autism spectrum disorders (ASDs) affect as many as 1 in 45 children and are characterized by deficits in sociability and communication, as well as stereotypic movements. Many children also show severe anxiety. […] The lack of distinct pathogenesis and reliable biomarkers hampers the development of effective treatments. As a result, most children with ASD are prescribed psychopharmacologic agents that do not address the core symptoms of ASD. Autoantibodies against brain epitopes in mothers of children with ASD and many such children strongly correlate with allergic symptoms and indicate an aberrant immune response, as well as disruption of the bloodbrain barrier (BBB). Recent epidemiological studies have shown a strong statistical correlation between risk for ASD and either maternal or infantile atopic diseases, such as asthma, eczema, food allergies and food intolerance, all of which involve activation of mast cells (MCs). These unique tissue immune cells are located perivascularly in all tissues, including the thalamus and hypothalamus, which regulate emotions. MC-derived inflammatory and vasoactive mediators increase BBB permeability. Expression of the inflammatory molecules interleukin (IL-1), IL-6, 1L-17 and tumor necrosis factor (TNF) is increased in the brain, cerebrospinal fluid and serum of some patients with ASD, while NF-kB is activated in brain samples and stimulated peripheral blood immune cells of other patients; however, these molecules are not specific. Instead the peptide neurotensin is uniquely elevated in the serum of children with ASD, as is corticotropin-releasing hormone, secreted from the hypothalamus under stress. Both peptides trigger MC to release IL-6 and TNF, which in turn, stimulate microglia proliferation and activation, leading to disruption of neuronal connectivity. MC-derived IL-6 and TGF induce maturation of Th17 cells and MCs also secrete IL-17, which is increased in ASD. Serum IL-6 and TNF may define an ASD subgroup that benefits most from treatment with the natural flavonoid luteolin. Atopic diseases may create a phenotype susceptible to ASD and formulations targeting focal inflammation of the brain could have great promise in the treatment of ASD.

• #36 Pathogenesis of Brain: Autism Spectrum Disorders | Auctores

  https://auctoresonline.org/article/pathogenesis-of-brain-autism-spectrum-disorders

  Autism spectrum disorders (ASDs) affect as many as 1 in 45 children and are characterized by deficits in sociability and communication, as well as stereotypic movements. Many children also show severe anxiety. […] The lack of distinct pathogenesis and reliable biomarkers hampers the development of effective treatments. As a result, most children with ASD are prescribed psychopharmacologic agents that do not address the core symptoms of ASD. Autoantibodies against brain epitopes in mothers of children with ASD and many such children strongly correlate with allergic symptoms and indicate an aberrant immune response, as well as disruption of the bloodbrain barrier (BBB). Recent epidemiological studies have shown a strong statistical correlation between risk for ASD and either maternal or infantile atopic diseases, such as asthma, eczema, food allergies and food intolerance, all of which involve activation of mast cells (MCs). These unique tissue immune cells are located perivascularly in all tissues, including the thalamus and hypothalamus, which regulate emotions. MC-derived inflammatory and vasoactive mediators increase BBB permeability. Expression of the inflammatory molecules interleukin (IL-1), IL-6, 1L-17 and tumor necrosis factor (TNF) is increased in the brain, cerebrospinal fluid and serum of some patients with ASD, while NF-kB is activated in brain samples and stimulated peripheral blood immune cells of other patients; however, these molecules are not specific. Instead the peptide neurotensin is uniquely elevated in the serum of children with ASD, as is corticotropin-releasing hormone, secreted from the hypothalamus under stress. Both peptides trigger MC to release IL-6 and TNF, which in turn, stimulate microglia proliferation and activation, leading to disruption of neuronal connectivity. MC-derived IL-6 and TGF induce maturation of Th17 cells and MCs also secrete IL-17, which is increased in ASD. Serum IL-6 and TNF may define an ASD subgroup that benefits most from treatment with the natural flavonoid luteolin. Atopic diseases may create a phenotype susceptible to ASD and formulations targeting focal inflammation of the brain could have great promise in the treatment of ASD.

• #37 Pathogenesis of Brain: Autism Spectrum Disorders | Auctores

  https://auctoresonline.org/article/pathogenesis-of-brain-autism-spectrum-disorders

  Autism spectrum disorders (ASDs) affect as many as 1 in 45 children and are characterized by deficits in sociability and communication, as well as stereotypic movements. Many children also show severe anxiety. […] The lack of distinct pathogenesis and reliable biomarkers hampers the development of effective treatments. As a result, most children with ASD are prescribed psychopharmacologic agents that do not address the core symptoms of ASD. Autoantibodies against brain epitopes in mothers of children with ASD and many such children strongly correlate with allergic symptoms and indicate an aberrant immune response, as well as disruption of the bloodbrain barrier (BBB). Recent epidemiological studies have shown a strong statistical correlation between risk for ASD and either maternal or infantile atopic diseases, such as asthma, eczema, food allergies and food intolerance, all of which involve activation of mast cells (MCs). These unique tissue immune cells are located perivascularly in all tissues, including the thalamus and hypothalamus, which regulate emotions. MC-derived inflammatory and vasoactive mediators increase BBB permeability. Expression of the inflammatory molecules interleukin (IL-1), IL-6, 1L-17 and tumor necrosis factor (TNF) is increased in the brain, cerebrospinal fluid and serum of some patients with ASD, while NF-kB is activated in brain samples and stimulated peripheral blood immune cells of other patients; however, these molecules are not specific. Instead the peptide neurotensin is uniquely elevated in the serum of children with ASD, as is corticotropin-releasing hormone, secreted from the hypothalamus under stress. Both peptides trigger MC to release IL-6 and TNF, which in turn, stimulate microglia proliferation and activation, leading to disruption of neuronal connectivity. MC-derived IL-6 and TGF induce maturation of Th17 cells and MCs also secrete IL-17, which is increased in ASD. Serum IL-6 and TNF may define an ASD subgroup that benefits most from treatment with the natural flavonoid luteolin. Atopic diseases may create a phenotype susceptible to ASD and formulations targeting focal inflammation of the brain could have great promise in the treatment of ASD.

• #38 Pathogenesis of Brain: Autism Spectrum Disorders | Auctores

  https://auctoresonline.org/article/pathogenesis-of-brain-autism-spectrum-disorders

  Autism spectrum disorders (ASDs) affect as many as 1 in 45 children and are characterized by deficits in sociability and communication, as well as stereotypic movements. Many children also show severe anxiety. […] The lack of distinct pathogenesis and reliable biomarkers hampers the development of effective treatments. As a result, most children with ASD are prescribed psychopharmacologic agents that do not address the core symptoms of ASD. Autoantibodies against brain epitopes in mothers of children with ASD and many such children strongly correlate with allergic symptoms and indicate an aberrant immune response, as well as disruption of the bloodbrain barrier (BBB). Recent epidemiological studies have shown a strong statistical correlation between risk for ASD and either maternal or infantile atopic diseases, such as asthma, eczema, food allergies and food intolerance, all of which involve activation of mast cells (MCs). These unique tissue immune cells are located perivascularly in all tissues, including the thalamus and hypothalamus, which regulate emotions. MC-derived inflammatory and vasoactive mediators increase BBB permeability. Expression of the inflammatory molecules interleukin (IL-1), IL-6, 1L-17 and tumor necrosis factor (TNF) is increased in the brain, cerebrospinal fluid and serum of some patients with ASD, while NF-kB is activated in brain samples and stimulated peripheral blood immune cells of other patients; however, these molecules are not specific. Instead the peptide neurotensin is uniquely elevated in the serum of children with ASD, as is corticotropin-releasing hormone, secreted from the hypothalamus under stress. Both peptides trigger MC to release IL-6 and TNF, which in turn, stimulate microglia proliferation and activation, leading to disruption of neuronal connectivity. MC-derived IL-6 and TGF induce maturation of Th17 cells and MCs also secrete IL-17, which is increased in ASD. Serum IL-6 and TNF may define an ASD subgroup that benefits most from treatment with the natural flavonoid luteolin. Atopic diseases may create a phenotype susceptible to ASD and formulations targeting focal inflammation of the brain could have great promise in the treatment of ASD.

• #39 Pathogenesis of Brain: Autism Spectrum Disorders | Auctores

  https://auctoresonline.org/article/pathogenesis-of-brain-autism-spectrum-disorders

  Autism spectrum disorders (ASDs) affect as many as 1 in 45 children and are characterized by deficits in sociability and communication, as well as stereotypic movements. Many children also show severe anxiety. […] The lack of distinct pathogenesis and reliable biomarkers hampers the development of effective treatments. As a result, most children with ASD are prescribed psychopharmacologic agents that do not address the core symptoms of ASD. Autoantibodies against brain epitopes in mothers of children with ASD and many such children strongly correlate with allergic symptoms and indicate an aberrant immune response, as well as disruption of the bloodbrain barrier (BBB). Recent epidemiological studies have shown a strong statistical correlation between risk for ASD and either maternal or infantile atopic diseases, such as asthma, eczema, food allergies and food intolerance, all of which involve activation of mast cells (MCs). These unique tissue immune cells are located perivascularly in all tissues, including the thalamus and hypothalamus, which regulate emotions. MC-derived inflammatory and vasoactive mediators increase BBB permeability. Expression of the inflammatory molecules interleukin (IL-1), IL-6, 1L-17 and tumor necrosis factor (TNF) is increased in the brain, cerebrospinal fluid and serum of some patients with ASD, while NF-kB is activated in brain samples and stimulated peripheral blood immune cells of other patients; however, these molecules are not specific. Instead the peptide neurotensin is uniquely elevated in the serum of children with ASD, as is corticotropin-releasing hormone, secreted from the hypothalamus under stress. Both peptides trigger MC to release IL-6 and TNF, which in turn, stimulate microglia proliferation and activation, leading to disruption of neuronal connectivity. MC-derived IL-6 and TGF induce maturation of Th17 cells and MCs also secrete IL-17, which is increased in ASD. Serum IL-6 and TNF may define an ASD subgroup that benefits most from treatment with the natural flavonoid luteolin. Atopic diseases may create a phenotype susceptible to ASD and formulations targeting focal inflammation of the brain could have great promise in the treatment of ASD.

• #40 Pathogenesis of Brain: Autism Spectrum Disorders | Auctores

  https://auctoresonline.org/article/pathogenesis-of-brain-autism-spectrum-disorders

  Autism spectrum disorders (ASDs) affect as many as 1 in 45 children and are characterized by deficits in sociability and communication, as well as stereotypic movements. Many children also show severe anxiety. […] The lack of distinct pathogenesis and reliable biomarkers hampers the development of effective treatments. As a result, most children with ASD are prescribed psychopharmacologic agents that do not address the core symptoms of ASD. Autoantibodies against brain epitopes in mothers of children with ASD and many such children strongly correlate with allergic symptoms and indicate an aberrant immune response, as well as disruption of the bloodbrain barrier (BBB). Recent epidemiological studies have shown a strong statistical correlation between risk for ASD and either maternal or infantile atopic diseases, such as asthma, eczema, food allergies and food intolerance, all of which involve activation of mast cells (MCs). These unique tissue immune cells are located perivascularly in all tissues, including the thalamus and hypothalamus, which regulate emotions. MC-derived inflammatory and vasoactive mediators increase BBB permeability. Expression of the inflammatory molecules interleukin (IL-1), IL-6, 1L-17 and tumor necrosis factor (TNF) is increased in the brain, cerebrospinal fluid and serum of some patients with ASD, while NF-kB is activated in brain samples and stimulated peripheral blood immune cells of other patients; however, these molecules are not specific. Instead the peptide neurotensin is uniquely elevated in the serum of children with ASD, as is corticotropin-releasing hormone, secreted from the hypothalamus under stress. Both peptides trigger MC to release IL-6 and TNF, which in turn, stimulate microglia proliferation and activation, leading to disruption of neuronal connectivity. MC-derived IL-6 and TGF induce maturation of Th17 cells and MCs also secrete IL-17, which is increased in ASD. Serum IL-6 and TNF may define an ASD subgroup that benefits most from treatment with the natural flavonoid luteolin. Atopic diseases may create a phenotype susceptible to ASD and formulations targeting focal inflammation of the brain could have great promise in the treatment of ASD.

• #41 Mechanism of action and therapeutic targeting of microglia in autism spectrum disorder

  https://accscience.com/journal/AN/1/3/10.36922/an.v1i3.167

  Autism spectrum disorder (ASD) is a complex mental illness with a high incidence and considerable impact. […] The underlying pathogenesis of ASD is still unclear, and effective interventions are lacking. Microglia are key immune cells in the central nervous system (CNS), and they function far beyond classical innate immunity, as they can affect normal neuronal activity by secreting cytokines and pruning synapses through phagocytosis. On the one hand, the abnormal activity of microglia may contribute to the development of ASD; on the other hand, it provides a potential target for intervention and treatment. In this review, we comprehensively analyze the mechanism of action of microglia in ASD development and summarize the current methods for targeting microglia in treating ASD.

• #42 Mechanism of action and therapeutic targeting of microglia in autism spectrum disorder

  https://accscience.com/journal/AN/1/3/10.36922/an.v1i3.167

  Autism spectrum disorder (ASD) is a complex mental illness with a high incidence and considerable impact. […] The underlying pathogenesis of ASD is still unclear, and effective interventions are lacking. Microglia are key immune cells in the central nervous system (CNS), and they function far beyond classical innate immunity, as they can affect normal neuronal activity by secreting cytokines and pruning synapses through phagocytosis. On the one hand, the abnormal activity of microglia may contribute to the development of ASD; on the other hand, it provides a potential target for intervention and treatment. In this review, we comprehensively analyze the mechanism of action of microglia in ASD development and summarize the current methods for targeting microglia in treating ASD.

• #43 When autism spectrum disorder occurs with intellectual disability, convergent mechanism for two top-ranking risk genes may be cause – UBNow: News and views for UB faculty and staff – University at Buffalo

  https://www.buffalo.edu/ubnow/campus.host.html/content/shared/university/news/ub-reporter-articles/stories/2022/07/autism-intellectual-disability.detail.html

  UB scientists have discovered a convergent mechanism that may be responsible for how two top-ranked genetic risk factors for autism spectrum disorder/intellectual disability (ASD/ID) lead to these neurodevelopmental disorders. […] The research demonstrates that mutations in these genes result in abnormal activation and overexpression of immune response genes and genes for a type of immune cell in the brain called microglia. […] The hypothesized result is the abnormal function of synapses in the brain, a characteristic of ASD/ID. […] When that repression is weakened, these immune and inflammatory genes are then able to be expressed in large quantities. […] The upregulated genes in the mouse prefrontal cortex caused by the deficiencies in ADNP or POGZ activated the pro-inflammatory response. […] Aberrant activation of microglia, which we demonstrate occurs as a result of deficiency in ADNP or POGZ, could lead to the damage and loss of synapses and neurons. […] We found that changes in two risk genes lead to a convergent mechanism, likely involving immune activation, Conrow-Graham says.

• #44 When autism spectrum disorder occurs with intellectual disability, convergent mechanism for two top-ranking risk genes may be cause – UBNow: News and views for UB faculty and staff – University at Buffalo

  https://www.buffalo.edu/ubnow/campus.host.html/content/shared/university/news/ub-reporter-articles/stories/2022/07/autism-intellectual-disability.detail.html

  UB scientists have discovered a convergent mechanism that may be responsible for how two top-ranked genetic risk factors for autism spectrum disorder/intellectual disability (ASD/ID) lead to these neurodevelopmental disorders. […] The research demonstrates that mutations in these genes result in abnormal activation and overexpression of immune response genes and genes for a type of immune cell in the brain called microglia. […] The hypothesized result is the abnormal function of synapses in the brain, a characteristic of ASD/ID. […] When that repression is weakened, these immune and inflammatory genes are then able to be expressed in large quantities. […] The upregulated genes in the mouse prefrontal cortex caused by the deficiencies in ADNP or POGZ activated the pro-inflammatory response. […] Aberrant activation of microglia, which we demonstrate occurs as a result of deficiency in ADNP or POGZ, could lead to the damage and loss of synapses and neurons. […] We found that changes in two risk genes lead to a convergent mechanism, likely involving immune activation, Conrow-Graham says.

• #45

  https://link.springer.com/article/10.1007/s10753-024-02061-y

  It has emphasized the potential role of neuroinflammatory intermediates linked to gut microbiota alterations in individuals with ASD. […] Evidence indicates neuroinflammation induced by dysregulated gut microbiota in ASD, yet there is little clarity based on analysis of the circulating immune profile. […] The interaction between the gut and the brain, along with alterations in microbiota and neuroinflammatory biomarkers, serves as a foundational background for understanding the etiology, diagnosis, prognosis, and treatment of autism spectrum disorder. […] Inflammatory elements that contribute to ASD include unusual microglia activation and polarization phenotypes, higher systemic levels of pro-inflammatory mediators, and altered patterns of immune cell responsiveness to activation triggers.

• #46

  https://link.springer.com/article/10.1007/s10753-024-02061-y

  Neuroinflammatory factors in ASD result from changes in the regulation of intestinal barriers, activation and function of microglia, and levels of neurotransmitters. […] Biomarkers based on neuroinflammatory processes associated with gut microbiota may provide a more objective and precise way of detecting ASD. […] Overall, gut microbiota seems to play a crucial role in ASD through inflammation. […] The changes in GM-CSF levels in ASD can indicate that an inflammatory process may be involved in developmental and neuroimmune impairment. […] It is suggested that neuroinflammation is strongly related to ASD occurrence through activating the inflammasome system as a mechanism. […] The effect of probiotics and gut microbiota alteration on HMGB1 levels in ASD patients can strengthen the idea and can be further studied. […] Overall, these findings support that probiotics may serve as a promising therapy due to their beneficial impact on symptoms of ASD.

• #47 Mechanism of autism – Wikipedia

  https://en.wikipedia.org/wiki/Mechanism_of_autism

  The mechanisms of autism are the molecular and cellular processes believed to cause or contribute to the symptoms of autism. Multiple processes are hypothesized to explain different autism spectrum features. These hypotheses include defects in synapse structure and function, reduced synaptic plasticity, disrupted neural circuit function, gut-brain axis dyshomeostasis, neuroinflammation, and altered brain structure or connectivity. Autism symptoms stem from maturation-related changes in brain systems. The mechanisms of autism are divided into two main areas: pathophysiology of brain structures and processes, and neuropsychological linkages between brain structures and behaviors, with multiple pathophysiologies linked to various autism behaviors. […] Evidence suggests gut-brain axis abnormalities may contribute to autism.

• #48 Autism Spectrum Disorder Pathogenesis—A Cross-Sectional Literature Review Emphasizing Molecular Aspects

  https://www.mdpi.com/1422-0067/25/20/11283

  Autism spectrum disorder (ASD) was first described by Leo Kanner in 1943. The mechanism of ASD remains unclear. It is currently suspected to have a multilineage etiology. In summary, to date, molecular research has confirmed multigene dysfunction as the causative factor of ASD, the multigene model with metabolomic influence would explain the heterogeneity in ASD, and it is proposed that ion channel dysfunction could play a core role in ASD pathogenesis. […] The collected studies allowed us to present a multilineage approach to explain ASD pathogenesis. The first highlighted idea was the gut–brain axis theory with an emphasis on gut microbiota, especially the fungal colonization of the colonic mucosa. […] The signaling pathway of lipid molecules contributes to the pathophysiology of autism spectrum disorder (ASD) and provides hope for alternative therapeutic strategies.

• #49 Autism Spectrum Disorder: Neurodevelopmental Risk Factors, Biological Mechanism, and Precision Therapy

  https://www.mdpi.com/1422-0067/24/3/1819

  The molecular biological mechanisms and neural circuits associated with autism spectrum disorders were also integrated to explore further the critical circuit elements and underlying molecular mechanisms involved in each set of symptoms of ASD disorders. […] The PI3K-AKT/mTOR signaling pathway is highly associated with autism and various neurodegenerative diseases. […] Studies have identified a mutated PI3K-AKT-mTOR pathway in nearly 50% of kids with brain malformations and delayed development/autism. […] Abnormalities in transcription and translation exacerbate abnormal neuronal function in ASD, further affecting synaptic transmission and plasticity, and dysregulation of the gut flora affects peripheral immune response function also influences brain dysfunction. […] In general, it is believed that associated gene variants in ASD patients and animal models are likely focused on similar molecular or cellular pathways.

• #50 Mechanism of autism – Wikipedia

  https://en.wikipedia.org/wiki/Mechanism_of_autism

  Synaptic dysfunction also appears to be implicated in autism, with some mutations disrupting synaptic pathways involving cell adhesion. […] Neuroanatomical studies support that autism may involve abnormal neuronal growth and pruning, leading to brain enlargement in some areas and reduction in others. […] Autism appears to result from developmental factors that affect many or all functional brain systems. […] Some factors may disturb the timing of brain development rather than the final product. […] The immune system is thought to play an important role in autism. […] It is proposed that inflammation within the brain promoted by inflammatory responses to harmful gut microbiome impacts brain development. […] Several lines of evidence indicate abnormalities of folate metabolism in ASD.

• #51 Impaired Microbial Detoxification May Be Involved in Pathogenesis of Autism Spectrum Disorder – Gastroenterology Advisor

  https://www.gastroenterologyadvisor.com/news/impaired-microbial-detoxification-may-be-involved-in-pathogenesis-of-autism-spectrum-disorder/

  Impaired microbial detoxification may be involved in the pathogenesis of autism spectrum disorder (ASD), according to research recently reported in Science Advances. […] The impaired microbial detoxification is correlated with the clinical rating of ASD and the extent of mitochondrial dysfunction, one of the main pathological alterations of ASD, which strongly suggests that impaired microbial detoxification is deeply involved in the pathogenesis of ASD, the researchers concluded.

• #52 Exploring the molecular mechanism of comorbidity of autism spectrum disorder and inflammatory bowel disease by combining multiple data sets | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04218-z

  Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is difficult to diagnose. Inflammatory bowel disease (IBD) is a common chronic digestive disease. Previous studies have shown a potential correlation between ASD and IBD, but the pathophysiological mechanism remains unclear. […] This research reveals the shared pathogenesis of ASD and IBD. […] Although there is evidence that IBD and ASD may be related, the precise mechanism explaining the coexistence of the two conditions is yet unknown. […] The putative gut-brain connection has frequently been invoked to explain the potential connection between ASD and IBD. […] According to studies in mice, maternal immune activation (MIA) causes the offspring to display an autism-like phenotype as well as become immunologically sensitive and more vulnerable to bacteria-caused intestinal inflammation.

• #53 Research finds potential mechanism linking autism, intestinal inflammation | MIT News | Massachusetts Institute of Technology

  https://news.mit.edu/2021/research-finds-potential-mechanism-linking-autism-intestinal-inflammation-1209

  Changes to a mothers microbiome after infection and the consequent immune response involving the molecule IL-17a can both lead to autism-like behavioral symptoms in her offspring, and can postnatally impact a newborns immune system potentially leading to an inflammatory response to infection later in life, a study in mice suggests. […] When a mother experiences an infection during pregnancy and her immune system produces elevated levels of the molecule Interleukin-17a (IL-17a), this can not only alter brain development in her fetus, but also alter her microbiome such that after birth the newborns immune system can become primed for future inflammatory attacks. […] Their new research, published Dec. 7 in Immunity, shows how IL-17a can act to also alter the trajectory of immune system development.

• #54 Research finds potential mechanism linking autism, intestinal inflammation | MIT News | Massachusetts Institute of Technology

  https://news.mit.edu/2021/research-finds-potential-mechanism-linking-autism-intestinal-inflammation-1209

  Weve shown that IL-17a acting on the fetal brain can induce autism-like behavioral phenotypes such as social deficits, says Choi, the Mark Hyman Jr. Career Development Associate Professor in The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences at MIT. Now we are showing that the same IL-17a in mothers, through changes in the microbiome community, produces co-morbid symptoms such as a primed immune system. […] There has been no mechanistic understanding of why patients with a neurodevelopmental disorder have a dysregulated immune system, says Huh, an associate professor of immunology at Harvard Medical School. Weve tied these fragmented links together. It may be that the reason is that they were exposed to this increase in inflammation during pregnancy.

• #55 Research finds potential mechanism linking autism, intestinal inflammation | MIT News | Massachusetts Institute of Technology

  https://news.mit.edu/2021/research-finds-potential-mechanism-linking-autism-intestinal-inflammation-1209

  Weve shown that IL-17a acting on the fetal brain can induce autism-like behavioral phenotypes such as social deficits, says Choi, the Mark Hyman Jr. Career Development Associate Professor in The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences at MIT. Now we are showing that the same IL-17a in mothers, through changes in the microbiome community, produces co-morbid symptoms such as a primed immune system. […] There has been no mechanistic understanding of why patients with a neurodevelopmental disorder have a dysregulated immune system, says Huh, an associate professor of immunology at Harvard Medical School. Weve tied these fragmented links together. It may be that the reason is that they were exposed to this increase in inflammation during pregnancy.

• #56 Research finds potential mechanism linking autism, intestinal inflammation | MIT News | Massachusetts Institute of Technology

  https://news.mit.edu/2021/research-finds-potential-mechanism-linking-autism-intestinal-inflammation-1209

  The results showed that while neurodevelopment is altered before birth, the immune response is altered postnatally. […] These results indicated that the altered microbiome of MIA moms leads to the immune priming of offspring. […] Thus, increase in IL-17a in moms during pregnancy leads to susceptibility to produce more IL-17a in offspring upon an immune challenge, Choi says. […] This also held true when the researchers repeated the experiment of transplanting MIA stool to germ-free moms, this time including stool from MIA-moms with IL-17a blockers. Again, blocking IL-17a amid maternal infection led to a microbiome that did not mis-prime the immune system of offspring.

• #57 Research finds potential mechanism linking autism, intestinal inflammation | MIT News | Massachusetts Institute of Technology

  https://news.mit.edu/2021/research-finds-potential-mechanism-linking-autism-intestinal-inflammation-1209

  The results showed that while neurodevelopment is altered before birth, the immune response is altered postnatally. […] These results indicated that the altered microbiome of MIA moms leads to the immune priming of offspring. […] Thus, increase in IL-17a in moms during pregnancy leads to susceptibility to produce more IL-17a in offspring upon an immune challenge, Choi says. […] This also held true when the researchers repeated the experiment of transplanting MIA stool to germ-free moms, this time including stool from MIA-moms with IL-17a blockers. Again, blocking IL-17a amid maternal infection led to a microbiome that did not mis-prime the immune system of offspring.

• #58 Gut Microbiota and Autism Spectrum Disorder: A Neuroinflammatory Mediated Mechanism of Pathogenesis? | springermedizin.de

  https://www.springermedizin.de/gut-microbiota-and-autism-spectrum-disorder-a-neuroinflammatory-/27423310

  Evidence indicates neuroinflammation induced by dysregulated gut microbiota in ASD, yet there is little clarity based on analysis of the circulating immune profile. It deems the repair of microbiota load would lower inflammatory chaos in the GI tract, correct neuroinflammatory mediators, and modulate the neurotransmitters to attenuate autism. […] The interaction between the gut and the brain, along with alterations in microbiota and neuroinflammatory biomarkers, serves as a foundational background for understanding the etiology, diagnosis, prognosis, and treatment of autism spectrum disorder. […] Inflammatory deviations are potential etiology candidates in how gut microbiota can influence the gut-brain axis of ASD patients. Neuroinflammatory factors in ASD result from changes in the regulation of intestinal barriers, activation and function of microglia, and levels of neurotransmitters.

• #59 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  ASD is hypothesized to be caused by oxidative stress. […] Some children with ASD display hyperlacticacidemia as well as evidence of mitochondrial disorders including carnitine deficiency. […] Since mitochondrial function may be impaired in some individuals with ASD, a lack of dietary components containing key cofactors may play a role in the pathogenesis. […] A low concentration of anti-inflammatory cytokines may produce an imbalance between anti-inflammatory and pro-inflammatory cytokines to trigger inflammation in ASD.

• #60 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  ASD is hypothesized to be caused by oxidative stress. […] Some children with ASD display hyperlacticacidemia as well as evidence of mitochondrial disorders including carnitine deficiency. […] Since mitochondrial function may be impaired in some individuals with ASD, a lack of dietary components containing key cofactors may play a role in the pathogenesis. […] A low concentration of anti-inflammatory cytokines may produce an imbalance between anti-inflammatory and pro-inflammatory cytokines to trigger inflammation in ASD.

• #61 A Novel Thioredoxin-Mediated Mechanism in Autism Spectrum Disorder by Haitham Amal, Wisam Bazbaz, Maryam Kartawy, Wajeha Hamoudi, Shashank Kumar Ojha, Igor Khaliulin :: SSRN

  https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4844704

  Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by difficulties in social interaction and communication, repetitive behaviors, and restricted interests. […] Unfortunately, the underlying molecular mechanism behind ASD remains unknown. […] It has been reported that oxidative and nitrosative stress are strongly linked to ASD. […] We have recently found that nitric oxide (NO) and NO-meditated post-transitional modifications play a key role in ASD. […] Here we show that the Trx antioxidant system may have a crucial role in ASD pathology. […] We hypothesize that the Trx system is altered in the Shank3 KO mouse model of autism, which may lead to a decreased activity of the nuclear factor erythroid 2-related factor 2 (Nrf2), leading to oxidative stress, and thus, contributing to ASD-related phenotypes.

• #62 A Novel Thioredoxin-Mediated Mechanism in Autism Spectrum Disorder by Haitham Amal, Wisam Bazbaz, Maryam Kartawy, Wajeha Hamoudi, Shashank Kumar Ojha, Igor Khaliulin :: SSRN

  https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4844704

  Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by difficulties in social interaction and communication, repetitive behaviors, and restricted interests. […] Unfortunately, the underlying molecular mechanism behind ASD remains unknown. […] It has been reported that oxidative and nitrosative stress are strongly linked to ASD. […] We have recently found that nitric oxide (NO) and NO-meditated post-transitional modifications play a key role in ASD. […] Here we show that the Trx antioxidant system may have a crucial role in ASD pathology. […] We hypothesize that the Trx system is altered in the Shank3 KO mouse model of autism, which may lead to a decreased activity of the nuclear factor erythroid 2-related factor 2 (Nrf2), leading to oxidative stress, and thus, contributing to ASD-related phenotypes.

• #63 A Novel Thioredoxin-Mediated Mechanism in Autism Spectrum Disorder by Haitham Amal, Wisam Bazbaz, Maryam Kartawy, Wajeha Hamoudi, Shashank Kumar Ojha, Igor Khaliulin :: SSRN

  https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4844704

  We showed significant changes in the levels and activity of Trx redox proteins in the Shank3 KO mice. […] A Trx1 inhibitor PX-12 decreased Trx1 and Nrf2 expression in wild-type mice, causing abnormal alterations in the levels of synaptic proteins and neurotransmission markers, and an elevation of nitrosative stress. […] The behavioral tests revealed that Trx inhibition results in an ASD-like behavioral phenotype, similar to that observed in the Shank3 KO mouse model of autism. […] Our findings confirm the strong link between Trx system and ASD, including the increased oxidative/nitrosative stress, and impaired synaptic and behavioral phenotype. […] The results of this study may pave the way for developing new ASD drug treatments.

• #64 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  In patients with autism, neuroanatomic and neuroimaging studies reveal abnormalities of cellular configurations in several regions of the brain, including the frontal and temporal lobes and the cerebellum. Enlargements of the amygdala and the hippocampus are common in childhood. Markedly more neurons are present in select divisions of the prefrontal cortex of autopsy specimens of some children with ASD, compared with those without ASD. […] Magnetic resonance imaging (MRI) studies have suggested evidence for differences in neuroanatomy and connectivity in people with ASD compared with normal controls. Specifically, these studies have found reduced or atypical connectivity in frontal brain regions, as well as thinning of the corpus callosum in children and adults with ASD and related conditions.

• #65 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  In patients with autism, neuroanatomic and neuroimaging studies reveal abnormalities of cellular configurations in several regions of the brain, including the frontal and temporal lobes and the cerebellum. Enlargements of the amygdala and the hippocampus are common in childhood. Markedly more neurons are present in select divisions of the prefrontal cortex of autopsy specimens of some children with ASD, compared with those without ASD. […] Magnetic resonance imaging (MRI) studies have suggested evidence for differences in neuroanatomy and connectivity in people with ASD compared with normal controls. Specifically, these studies have found reduced or atypical connectivity in frontal brain regions, as well as thinning of the corpus callosum in children and adults with ASD and related conditions.

• #66 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  In patients with autism, neuroanatomic and neuroimaging studies reveal abnormalities of cellular configurations in several regions of the brain, including the frontal and temporal lobes and the cerebellum. Enlargements of the amygdala and the hippocampus are common in childhood. Markedly more neurons are present in select divisions of the prefrontal cortex of autopsy specimens of some children with ASD, compared with those without ASD. […] Magnetic resonance imaging (MRI) studies have suggested evidence for differences in neuroanatomy and connectivity in people with ASD compared with normal controls. Specifically, these studies have found reduced or atypical connectivity in frontal brain regions, as well as thinning of the corpus callosum in children and adults with ASD and related conditions.

• #67 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  In patients with autism, neuroanatomic and neuroimaging studies reveal abnormalities of cellular configurations in several regions of the brain, including the frontal and temporal lobes and the cerebellum. Enlargements of the amygdala and the hippocampus are common in childhood. Markedly more neurons are present in select divisions of the prefrontal cortex of autopsy specimens of some children with ASD, compared with those without ASD. […] Magnetic resonance imaging (MRI) studies have suggested evidence for differences in neuroanatomy and connectivity in people with ASD compared with normal controls. Specifically, these studies have found reduced or atypical connectivity in frontal brain regions, as well as thinning of the corpus callosum in children and adults with ASD and related conditions.

• #68 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  Importantly, some of the regional differences in neuroanatomy correlate significantly with the severity of specific autistic symptoms. For example, social and language deficits of people with ASD likely are related to dysfunction of the frontal and temporal lobes. […] In a study of postmortem brain tissue from 11 children with ASD and 11 unaffected controls, researchers found focal disruption of cortical laminar architecture in the cortexes of 10 of the children with ASD and 1 of the controls, suggesting that brain irregularities in ASD may have prenatal origins. […] The patches of abnormal neurons were found in the frontal and temporal lobes, regions involved in social, emotional, communication, and language functions. Since the changes were in the form of patches, the researchers believe that early treatment could rewire the brain and improve ASD symptoms.

• #69 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  Importantly, some of the regional differences in neuroanatomy correlate significantly with the severity of specific autistic symptoms. For example, social and language deficits of people with ASD likely are related to dysfunction of the frontal and temporal lobes. […] In a study of postmortem brain tissue from 11 children with ASD and 11 unaffected controls, researchers found focal disruption of cortical laminar architecture in the cortexes of 10 of the children with ASD and 1 of the controls, suggesting that brain irregularities in ASD may have prenatal origins. […] The patches of abnormal neurons were found in the frontal and temporal lobes, regions involved in social, emotional, communication, and language functions. Since the changes were in the form of patches, the researchers believe that early treatment could rewire the brain and improve ASD symptoms.

• #70 The Pathogenesis of Autism

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3160002/

  One specific theory emphasises that early brain overgrowth and neural overconnectivity are key in the pathogenesis. It is speculated that excess neuron numbers (inducing cerebral overgrowth) may promote defects in neural patterning and wiring, with subsequent over energetic short-distance cortical interactions hindering long-distance interactions that communicate between critical brain regions. […] Conversely another related theory postulates that the neuropathological basis of disrupted cognition in autism is linked to reduced intracortical connectivity which subsequently promotes a lower degree of information integration across multiple cortical regions. […] Cerebral cortical malformations observed in autism may result from defective neural migration to the cerebral cortex during the first 6 months of gestation.

• #71 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  On MRI scans, the brains of children with ASD demonstrate greater myelination in bilateral medial frontal cortices and less myelination in the left temporoparietal junction. […] Similarly, region-specific differences in the concentrations of gray matter, made up of neuronal cell bodies, dendrites, unmyelinated axons and glial cells, are also found in the brains of people with autism. […] Reductions in cerebral GABA likely contribute to the sensorimotor and behavioral anomalies of individuals with ASD. […] Reductions in sensorimotor GABA were observed by magnetic resonance spectroscopy (MRS) in participants with ASD in contrast to matched controls without ASD. […] Postmortem specimens of the brains of people with ASD demonstrated reductions for gamma-aminobutyric acidB (GABAB) receptors in the cingulate cortex, a key region for the evaluation of social relationships, emotions, and cognition, and in the fusiform gyrus, a crucial region to evaluate faces and facial expressions.

• #72 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  On MRI scans, the brains of children with ASD demonstrate greater myelination in bilateral medial frontal cortices and less myelination in the left temporoparietal junction. […] Similarly, region-specific differences in the concentrations of gray matter, made up of neuronal cell bodies, dendrites, unmyelinated axons and glial cells, are also found in the brains of people with autism. […] Reductions in cerebral GABA likely contribute to the sensorimotor and behavioral anomalies of individuals with ASD. […] Reductions in sensorimotor GABA were observed by magnetic resonance spectroscopy (MRS) in participants with ASD in contrast to matched controls without ASD. […] Postmortem specimens of the brains of people with ASD demonstrated reductions for gamma-aminobutyric acidB (GABAB) receptors in the cingulate cortex, a key region for the evaluation of social relationships, emotions, and cognition, and in the fusiform gyrus, a crucial region to evaluate faces and facial expressions.

• #73 KBS_Icon_questionmark

  https://www.kcl.ac.uk/archive/news/ioppn/records/2013/april/epigenetics-autism

  Scientists from Kings College London have identified patterns of epigenetic changes involved in autism spectrum disorder (ASD) by studying genetically identical twins who differ in autism traits. […] The study, published in Molecular Psychiatry, is the largest of its kind and may shed light on the biological mechanism by which environmental influences regulate the activity of certain genes and in turn contribute to the development of ASD and related behaviour traits. […] Epigenetic changes affect the expression or activity of genes without changing the underlying DNA sequence they are believed to be one mechanism by which the environment can interact with the genome. […] Dr Chloe Wong, first author of the study from Kings College Londons Institute of Psychiatry, says: Weve identified distinctive patterns of DNA methylation associated with both autism diagnosis and related behaviour traits, and increasing severity of symptoms. Our findings give us an insight into the biological mechanism mediating the interaction between gene and environment in autism spectrum disorder.

• #74 Epigenetic changes shed light on biological mechanism of autism | Crick

  https://www.crick.ac.uk/news/2013-04-23-epigenetic-changes-shed-light-on-biological-mechanism-of-autism

  Scientists from King’s College London have identified patterns of epigenetic changes involved in autism spectrum disorder (ASD) by studying genetically identical twins who differ in autism traits. […] The study is the largest of its kind and may shed light on the biological mechanism by which environmental influences regulate the activity of certain genes and in turn contribute to the development of ASD and related behaviour traits. […] Epigenetic changes affect the expression or activity of genes without changing the underlying DNA sequence – they are believed to be one mechanism by which the environment can interact with the genome. Importantly, epigenetic changes are potentially reversible and may therefore provide targets for the development of new therapies. […] Chloe Wong, from King’s College London’s Institute of Psychiatry, said: „We’ve identified distinctive patterns of DNA methylation associated with both autism diagnosis and related behaviour traits, and increasing severity of symptoms. Our findings give us an insight into the biological mechanism mediating the interaction between gene and environment in autism spectrum disorder.”

• #75 Epigenetic changes shed light on biological mechanism of autism | Crick

  https://www.crick.ac.uk/news/2013-04-23-epigenetic-changes-shed-light-on-biological-mechanism-of-autism

  Scientists from King’s College London have identified patterns of epigenetic changes involved in autism spectrum disorder (ASD) by studying genetically identical twins who differ in autism traits. […] The study is the largest of its kind and may shed light on the biological mechanism by which environmental influences regulate the activity of certain genes and in turn contribute to the development of ASD and related behaviour traits. […] Epigenetic changes affect the expression or activity of genes without changing the underlying DNA sequence – they are believed to be one mechanism by which the environment can interact with the genome. Importantly, epigenetic changes are potentially reversible and may therefore provide targets for the development of new therapies. […] Chloe Wong, from King’s College London’s Institute of Psychiatry, said: „We’ve identified distinctive patterns of DNA methylation associated with both autism diagnosis and related behaviour traits, and increasing severity of symptoms. Our findings give us an insight into the biological mechanism mediating the interaction between gene and environment in autism spectrum disorder.”

• #76 Epigenetic changes shed light on biological mechanism of autism | Crick

  https://www.crick.ac.uk/news/2013-04-23-epigenetic-changes-shed-light-on-biological-mechanism-of-autism

  Jonathan Mill, from King’s College London’s Institute of Psychiatry and the University of Exeter, added: „Research into the intersection between genetic and environmental influences is crucial because risky environmental conditions can sometimes be avoided or changed. Epigenetic changes are potentially reversible, so our next step is to embark on larger studies to see whether we can identify key epigenetic changes common to the majority of people with autism to help us develop possible therapeutic interventions.”

• #77

  https://link.springer.com/article/10.1007/s11427-015-4941-1

  Autism spectrum disorder (ASD) is a spectral neurodevelopment disorder affecting approximately 1% of the population. […] Multiple factors, including genetic/genomic, epigenetic/epigenomic and environmental, are thought to be necessary for autism development. […] It has long been suspected that epigenetic mechanisms, including DNA methylation, chromatin structures and long non-coding RNAs may play important roles in the pathology of ASD. […] In addition to genetic/genomic alterations and epigenetic/epigenomic influences, environmental exposures have been widely accepted as an important role in autism etiology, among which immune dysregulation and gastrointestinal microbiota are two prominent ones.

• #78 Autism mechanism goes beyond genes | PET

  https://www.progress.org.uk/autism-mechanism-goes-beyond-genes/

  They also argue that their study highlights the notion that 'environmentally mediated effects on the epigenome may be relatively common and important for disease’. […] Optimistically, Dr Jonathan Mill of the Institute of Psychiatry and the University of Exeter, the paper’s lead author, said: 'Epigenetic changes are potentially reversible, so our next step is to embark on larger studies to see whether we can identify key epigenetic changes common to the majority of people with autism to help us develop possible therapeutic interventions’.

• #79 What causes autism? | Autism Speaks

  https://www.autismspeaks.org/what-causes-autism

  Changes in certain genes or your genome increase the risk that a child will develop autism. If a parent carries one or more of these gene changes, they may get passed to a child (even if the parent does not have autism). For some people, a high risk for ASD can be associated with a genetic disorder, such as Rett syndrome or fragile X syndrome. For the majority of autism, multiple changes in other regions of your DNA increase the risk of autism spectrum disorder. The majority of these DNA changes do not cause autism by themselves but work in conjunction with many other genes and environmental factors to cause autism. […] According to the National Institute of Environmental Health Sciences, certain environmental influences may increase autism risk: Advanced parental age, prenatal exposure to air pollution or certain pesticides, maternal obesity, diabetes or immune system disorders, extreme prematurity or very low birth weight, birth complications leading to periods of oxygen deprivation to the baby’s brain. […] Autism prevalence has risen due to increased awareness of autism, broader diagnostic criteria for autism, improved screening tools and standardized screening processes. These factors have led to earlier detection and more diagnoses.

• #80 What causes autism? | Autism Speaks

  https://www.autismspeaks.org/what-causes-autism

  Changes in certain genes or your genome increase the risk that a child will develop autism. If a parent carries one or more of these gene changes, they may get passed to a child (even if the parent does not have autism). For some people, a high risk for ASD can be associated with a genetic disorder, such as Rett syndrome or fragile X syndrome. For the majority of autism, multiple changes in other regions of your DNA increase the risk of autism spectrum disorder. The majority of these DNA changes do not cause autism by themselves but work in conjunction with many other genes and environmental factors to cause autism. […] According to the National Institute of Environmental Health Sciences, certain environmental influences may increase autism risk: Advanced parental age, prenatal exposure to air pollution or certain pesticides, maternal obesity, diabetes or immune system disorders, extreme prematurity or very low birth weight, birth complications leading to periods of oxygen deprivation to the baby’s brain. […] Autism prevalence has risen due to increased awareness of autism, broader diagnostic criteria for autism, improved screening tools and standardized screening processes. These factors have led to earlier detection and more diagnoses.

• #81 What causes autism? | Autism Speaks

  https://www.autismspeaks.org/what-causes-autism

  Changes in certain genes or your genome increase the risk that a child will develop autism. If a parent carries one or more of these gene changes, they may get passed to a child (even if the parent does not have autism). For some people, a high risk for ASD can be associated with a genetic disorder, such as Rett syndrome or fragile X syndrome. For the majority of autism, multiple changes in other regions of your DNA increase the risk of autism spectrum disorder. The majority of these DNA changes do not cause autism by themselves but work in conjunction with many other genes and environmental factors to cause autism. […] According to the National Institute of Environmental Health Sciences, certain environmental influences may increase autism risk: Advanced parental age, prenatal exposure to air pollution or certain pesticides, maternal obesity, diabetes or immune system disorders, extreme prematurity or very low birth weight, birth complications leading to periods of oxygen deprivation to the baby’s brain. […] Autism prevalence has risen due to increased awareness of autism, broader diagnostic criteria for autism, improved screening tools and standardized screening processes. These factors have led to earlier detection and more diagnoses.

• #82 What causes autism? | Autism Speaks

  https://www.autismspeaks.org/what-causes-autism

  Changes in certain genes or your genome increase the risk that a child will develop autism. If a parent carries one or more of these gene changes, they may get passed to a child (even if the parent does not have autism). For some people, a high risk for ASD can be associated with a genetic disorder, such as Rett syndrome or fragile X syndrome. For the majority of autism, multiple changes in other regions of your DNA increase the risk of autism spectrum disorder. The majority of these DNA changes do not cause autism by themselves but work in conjunction with many other genes and environmental factors to cause autism. […] According to the National Institute of Environmental Health Sciences, certain environmental influences may increase autism risk: Advanced parental age, prenatal exposure to air pollution or certain pesticides, maternal obesity, diabetes or immune system disorders, extreme prematurity or very low birth weight, birth complications leading to periods of oxygen deprivation to the baby’s brain. […] Autism prevalence has risen due to increased awareness of autism, broader diagnostic criteria for autism, improved screening tools and standardized screening processes. These factors have led to earlier detection and more diagnoses.

• #83 What causes autism? | Autism Speaks

  https://www.autismspeaks.org/what-causes-autism

  Changes in certain genes or your genome increase the risk that a child will develop autism. If a parent carries one or more of these gene changes, they may get passed to a child (even if the parent does not have autism). For some people, a high risk for ASD can be associated with a genetic disorder, such as Rett syndrome or fragile X syndrome. For the majority of autism, multiple changes in other regions of your DNA increase the risk of autism spectrum disorder. The majority of these DNA changes do not cause autism by themselves but work in conjunction with many other genes and environmental factors to cause autism. […] According to the National Institute of Environmental Health Sciences, certain environmental influences may increase autism risk: Advanced parental age, prenatal exposure to air pollution or certain pesticides, maternal obesity, diabetes or immune system disorders, extreme prematurity or very low birth weight, birth complications leading to periods of oxygen deprivation to the baby’s brain. […] Autism prevalence has risen due to increased awareness of autism, broader diagnostic criteria for autism, improved screening tools and standardized screening processes. These factors have led to earlier detection and more diagnoses.

• #84 What causes autism? | Autism Speaks

  https://www.autismspeaks.org/what-causes-autism

  Changes in certain genes or your genome increase the risk that a child will develop autism. If a parent carries one or more of these gene changes, they may get passed to a child (even if the parent does not have autism). For some people, a high risk for ASD can be associated with a genetic disorder, such as Rett syndrome or fragile X syndrome. For the majority of autism, multiple changes in other regions of your DNA increase the risk of autism spectrum disorder. The majority of these DNA changes do not cause autism by themselves but work in conjunction with many other genes and environmental factors to cause autism. […] According to the National Institute of Environmental Health Sciences, certain environmental influences may increase autism risk: Advanced parental age, prenatal exposure to air pollution or certain pesticides, maternal obesity, diabetes or immune system disorders, extreme prematurity or very low birth weight, birth complications leading to periods of oxygen deprivation to the baby’s brain. […] Autism prevalence has risen due to increased awareness of autism, broader diagnostic criteria for autism, improved screening tools and standardized screening processes. These factors have led to earlier detection and more diagnoses.

• #85 Different Factors and the Occurrence of of Autism and ADHD | PRBM

  https://www.dovepress.com/a-review-on-the-mechanism-between-different-factors-and-the-occurrence-peer-reviewed-fulltext-article-PRBM

  The incidence of neurodevelopmental disorders especially in children has been on the rise in recent decades, which is possibly caused by many different factors. […] This review will specifically elaborate genetic aspects and pathogenic hypothesis of these two kinds of neurodevelopmental diseases in children, autism and attention deficit hyperactivity disorder (ADHD) while analyzing the relationship between different environmental toxins and these two disorders. […] The effects of these pathogenic factors such as heavy metal lead, mercury, polyvinyl chloride (PVC) and polychlorinated biphenyls (PCBs) and their strong pathogenicity will be explained in detail through literature data retrieval and analysis. […] Since these environmental toxins and other harmful substances discussed in the paper have been linked to an increasing number of children with autism and ADHD in recent decades, from the medical perspective, this review will put forward certain succinct points to the aspects of minimizing relevant exposure or risks in clinical and daily life.

• #86 Different Factors and the Occurrence of of Autism and ADHD | PRBM

  https://www.dovepress.com/a-review-on-the-mechanism-between-different-factors-and-the-occurrence-peer-reviewed-fulltext-article-PRBM

  Air pollutants, especially PM2.5 and PM10, may increase the risk of developing Autism, but there may exist bias in the results of epidemiological studies. […] The mechanism of fetal brain dysplasia induced by nicotine exposure is considered to be caused by stimulation of acetylcholine release. […] To sum up, there may exist a possible link between the harmful effects of certain environmental toxins and neurotoxins in the pathogenesis of neurodevelopmental disorders, in this review, autism and ADHD.

• #87 Different Factors and the Occurrence of of Autism and ADHD | PRBM

  https://www.dovepress.com/a-review-on-the-mechanism-between-different-factors-and-the-occurrence-peer-reviewed-fulltext-article-PRBM

  Studies have shown that many neurodevelopmental diseases may be caused by neurotoxic chemicals such as lead, mercury, polyvinyl chloride and PCBs. […] PCB and mercury emissions are strongly associated with Autism in terms of neurotoxin pathogenicity. […] It is generally agreed that most of the industrial chemicals present in the environment today are known carcinogens, so caution is warranted in public health areas. […] The role of genetic factors in the development of autism has been demonstrated in earlier twin studies: the prevalence of autism in the monozygotic twins is significantly higher than in the dizygotic twins. […] Studies have confirmed the occurrence of autism some gene variations may be due to the influence caused by the biological signaling pathways related to brain development.

• #88 Different Factors and the Occurrence of of Autism and ADHD | PRBM

  https://www.dovepress.com/a-review-on-the-mechanism-between-different-factors-and-the-occurrence-peer-reviewed-fulltext-article-PRBM

  Air pollutants, especially PM2.5 and PM10, may increase the risk of developing Autism, but there may exist bias in the results of epidemiological studies. […] The mechanism of fetal brain dysplasia induced by nicotine exposure is considered to be caused by stimulation of acetylcholine release. […] To sum up, there may exist a possible link between the harmful effects of certain environmental toxins and neurotoxins in the pathogenesis of neurodevelopmental disorders, in this review, autism and ADHD.

• #89 Key breakthrough in autism: pivotal role of CPEB4 condensates revealed | IRB Barcelona

  https://www.irbbarcelona.org/en/news/scientific/key-breakthrough-autism-pivotal-role-cpeb4-condensates-revealed

  A study by IRB Barcelona unveils how the lack of a fraction of the CPEB4 protein causes a decrease in the expression of genes that are crucial for neuronal development. […] A team of scientists led by Dr. Ral Mndez and Dr. Xavier Salvatella at IRB Barcelona has identified a molecular mechanism that explains why certain alternations of the neuronal protein CPEB4 are associated with idiopathic autism. […] The work published today in the journal Nature reveals that this small fragment is key for neuronal activity because it preserves the flexibility of CPEB4 to assemble into condensates and disassemble them. […] This study provides new insights into how small modifications in proteins that regulate gene expression can have a significant impact on neuronal development, opening new avenues to explore future therapies, explains Dr. Mndez.

• #90 Key breakthrough in autism: pivotal role of CPEB4 condensates revealed | IRB Barcelona

  https://www.irbbarcelona.org/en/news/scientific/key-breakthrough-autism-pivotal-role-cpeb4-condensates-revealed

  Proper regulation of these genes is essential during brain development. If these CPEB4 condensates do not function correctly due to the absence of the neuronal microexon, it can lead to disruptions of neuronal development, which are manifested as symptoms of autism. […] Our results suggest that even small decreases in the percentage of microexon inclusion can have significant effects. This would explain why some individuals without a gene mutation develop idiopathic autism, explain Dr. Carla Garcia-Cabau and Dr. Anna Bartomeu. […] The study represents an important step in understanding the molecular mechanisms underlying idiopathic autism and highlights the significance of short genetic sequences in the regulation of critical cellular functions.

• #91 Unraveling autism spectrum disorder mechanisms through rigid-autonomous phase sequences | EurekAlert!

  https://www.eurekalert.org/news-releases/1008723

  Researchers propose „rigid-autonomous phase sequences (RAPS)” as a novel theoretical framework to explain the diverse symptoms and challenges associated with autism spectrum disorder (ASD). […] RAPS may be responsible for the cognitive, sensory-motor, and memory-related challenges faced by individuals with ASD. […] This paper proposes that RAPS can explain a wide range of symptoms in individuals with ASD, encompassing social, cognitive, and motor difficulties. […] The theory suggests that RAPS interferes with the activation of other neural circuits, leading to the observed impairments in various functions. […] By explaining the vast array of symptoms associated with ASD through the lens of RAPS, the theory opens doors for the development of innovative treatments targeting these neural patterns.

• #92 Aberrant causal inference and presence of a compensatory mechanism in autism spectrum disorder | eLife

  https://elifesciences.org/articles/71866

  Autism spectrum disorder (ASD) is characterized by a panoply of social, communicative, and sensory anomalies. […] Here, we posit causal inference the process of inferring a causal structure linking sensory signals to hidden world causes as one such computation. […] Together, this pattern of results suggests (i) different internal models in attributing world causes to sensory signals in ASD relative to neurotypical individuals given identical sensory cues, and (ii) the presence of an explicit compensatory mechanism in ASD, with these individuals putatively having learned to compensate for their bias to integrate in explicit reports. […] Indeed, the hypothesis that causal inference may be anomalous in ASD is supported by a multitude of tangential evidence, particularly within the study of multisensory perception.

• #93 The pathogenesis of autism spectrum disorder

  http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S1665-50442021000600248

  Deficits in synaptic pruning play a role in ASD where either hyperconnectivity and/or hypoconnectivity are observed across the amygdala, pre-frontal cortex, and components of the default-mode network. […] Children with ASD have significantly fewer Treg cells, but also a larger number of activated Th17 and myeloid dendritic cells (mDCs) compared to children without autism. […] There is an imbalance in the Th17/Treg relationship with marked deviation towards Th17; furthermore, the number of Th17 cells correlates positively with the severity of the disease. […] The transcription factor Nrf2 is related to antioxidant and anti-inflammatory genes; sulforaphane is an activator of Nrf2. […] Inflammation is capable of altering neural stem cells and progenitors, thereby altering neurodevelopment and the proper functioning of neural circuits. […] The moment of appearance of the insult and its intensity will determine the degree of damage to neurogenesis and astrogenesis and to neuronal circuits and therefore, the clinical spectrum of the disease.

• #94

  https://mjosht.usim.edu.my/index.php/mjosht/article/view/120

  Autism Spectrum Disorder or ASD refers to a broad range of neurodevelopmental disorder characterised by persistent deficits in social abilities, repetitive behavioural pattern and restricted interest propensity that usually developed throughout childhood. […] The genesis of it is incompletely comprehensible despite numerous studies have been done to elucidate the pathogenic mechanisms beneath this whole range of impaired neurodevelopmental condition. […] Given the complexity of ASD with diversity of clinical manifestations, it can be considered as multifactorial aetiopathogenesis disorder that is associated with diverse genetic factors that may also be predisposed by environmental exposures and prenatal factors. […] A growing number of reports have supported the involvement of microRNA in the mechanism of ASD.

• #95 Study of Different Autism Types Finds Shared Mechanism That May Respond to Drugs | Robert Wood Johnson Medical School

  https://rwjms.rutgers.edu/news/study-different-autism-types-finds-shared-mechanism-may-respond-drugs

  An analysis of how brains with different forms of autism develop has revealed common underlying mechanisms that may respond to existing medications. […] Although some cell lines exhibited too much activity in this mTOR pathway, while others exhibited too little, the researchers could correct both problems and spur better cell differentiation with existing drugs that either stimulate or inhibit the activity of mTOR (mechanistic target of rapamycin). […] Subsequent analysis showed that the mTOR signaling disruptions in some patients stemmed from excessive amounts of a particular molecule, while the disruptions in others stemmed from insufficient amounts. In either case, the researchers could use existing medications approved for use in other conditions to correct the problem and stimulate normal development.

• #96 Study of Different Autism Types Finds Shared Mechanism That May Respond to Drugs | Rutgers University

  https://www.rutgers.edu/news/study-different-autism-types-finds-shared-mechanism-may-respond-drugs

  An analysis of how brains with different forms of autism develop has revealed common underlying mechanisms that may respond to existing medications. […] As the precursor cells from both groups matured in the lab, defects in a common signaling pathway that controls structural proteins led them to struggle with an important step in cell differentiation, the growth of neurites, and the cell migration needed for proper brain architecture. […] Although some cell lines exhibited too much activity in this mTOR pathway, while others exhibited too little, the researchers could correct both problems and spur better cell differentiation with existing drugs that either stimulate or inhibit the activity of mTOR (mechanistic target of rapamycin). […] The researchers then gained access to blood cells from another three patients with ASD caused by a particular genetic abnormality associated with about 1 percent of ASD, deletion of genes on chromosome 16, called 16p11.2 deletion.

• #97 Study of Different Autism Types Finds Shared Mechanism That May Respond to Drugs | Robert Wood Johnson Medical School

  https://rwjms.rutgers.edu/news/study-different-autism-types-finds-shared-mechanism-may-respond-drugs

  If mTOR signaling disruption proves a common feature of ASD, tests of mTOR function could help clinicians diagnose the condition more accurately and differentiate it from other conditions with similar effects. […] These findings also echo something that has appeared in studies of other conditions, that not all people with mTOR dysregulation have excessive activation that needs inhibition.

• #98 Essential Pathways and Circuits of Autism Pathogenesis

  https://search.lib.asu.edu/discovery/fulldisplay?docid=alma991048141337403841&context=L&vid=01ASU_INST:01ASU&lang=en&adaptor=Local%20Search%20Engine&tab=Everything&query=sub%2Cexact%2Ccell%20signaling%2CAND&mode=advanced&offset=0

  Essential Pathways and Circuits of Autism Pathogenesis […] The Centers for Disease Control and Prevention estimate that 1 in 68 children in the United states is afflicted with autism spectrum disorders (ASD), yet at this time, there is no cure for the disease. Autism is characterized by delays in the development of many basic skills, most notably the ability to socialize and adapt to novelty. The condition is typically identified in children around 3 years of age, however the high heritability of autism suggests that the disease process begins at conception. The identification of over 500 ASD risk genes, has enabled the molecular genetic dissection of the pathogenesis of the disease in model organisms such as mice. Despite the genetic heterogeneity of ASD etiology, converging evidence suggests that these disparate genetic lesions may result in the disruption of a limited number of key biochemical pathways or circuits. Classification of patients into groups by pathogenic rather than etiological categories, will likely aid future therapeutic development and clinical trials. In this set of papers, we explore the existing evidence supporting this view. Specifically, we focus on biochemical cascades such as mTOR and ERK signaling, the mRNA network bound by FMRP and UBE3A, dorsal and ventral striatal circuits, cerebellar circuits, hypothalamic projections, as well as prefrontal and anterior cingulate cortical circuits. Special attention will be given to studies that demonstrate the necessity and/or sufficiency of genetic disruptions (e.g. by molecular deletion and/or replacement) in these pathways and circuits for producing characteristic behavioral features of autism. Necessarily these papers will be heavily weighted towards basic mechanisms elucidated in animal models, but may also include investigations in patients.

• #99 Essential Pathways and Circuits of Autism Pathogenesis

  https://search.lib.asu.edu/discovery/fulldisplay?docid=alma991048141337403841&context=L&vid=01ASU_INST:01ASU&lang=en&adaptor=Local%20Search%20Engine&tab=Everything&query=sub%2Cexact%2Ccell%20signaling%2CAND&mode=advanced&offset=0

  Essential Pathways and Circuits of Autism Pathogenesis […] The Centers for Disease Control and Prevention estimate that 1 in 68 children in the United states is afflicted with autism spectrum disorders (ASD), yet at this time, there is no cure for the disease. Autism is characterized by delays in the development of many basic skills, most notably the ability to socialize and adapt to novelty. The condition is typically identified in children around 3 years of age, however the high heritability of autism suggests that the disease process begins at conception. The identification of over 500 ASD risk genes, has enabled the molecular genetic dissection of the pathogenesis of the disease in model organisms such as mice. Despite the genetic heterogeneity of ASD etiology, converging evidence suggests that these disparate genetic lesions may result in the disruption of a limited number of key biochemical pathways or circuits. Classification of patients into groups by pathogenic rather than etiological categories, will likely aid future therapeutic development and clinical trials. In this set of papers, we explore the existing evidence supporting this view. Specifically, we focus on biochemical cascades such as mTOR and ERK signaling, the mRNA network bound by FMRP and UBE3A, dorsal and ventral striatal circuits, cerebellar circuits, hypothalamic projections, as well as prefrontal and anterior cingulate cortical circuits. Special attention will be given to studies that demonstrate the necessity and/or sufficiency of genetic disruptions (e.g. by molecular deletion and/or replacement) in these pathways and circuits for producing characteristic behavioral features of autism. Necessarily these papers will be heavily weighted towards basic mechanisms elucidated in animal models, but may also include investigations in patients.

• #100 Essential Pathways and Circuits of Autism Pathogenesis

  https://search.lib.asu.edu/discovery/fulldisplay?docid=alma991048141337403841&context=L&vid=01ASU_INST:01ASU&lang=en&adaptor=Local%20Search%20Engine&tab=Everything&query=sub%2Cexact%2Ccell%20signaling%2CAND&mode=advanced&offset=0

  Essential Pathways and Circuits of Autism Pathogenesis […] The Centers for Disease Control and Prevention estimate that 1 in 68 children in the United states is afflicted with autism spectrum disorders (ASD), yet at this time, there is no cure for the disease. Autism is characterized by delays in the development of many basic skills, most notably the ability to socialize and adapt to novelty. The condition is typically identified in children around 3 years of age, however the high heritability of autism suggests that the disease process begins at conception. The identification of over 500 ASD risk genes, has enabled the molecular genetic dissection of the pathogenesis of the disease in model organisms such as mice. Despite the genetic heterogeneity of ASD etiology, converging evidence suggests that these disparate genetic lesions may result in the disruption of a limited number of key biochemical pathways or circuits. Classification of patients into groups by pathogenic rather than etiological categories, will likely aid future therapeutic development and clinical trials. In this set of papers, we explore the existing evidence supporting this view. Specifically, we focus on biochemical cascades such as mTOR and ERK signaling, the mRNA network bound by FMRP and UBE3A, dorsal and ventral striatal circuits, cerebellar circuits, hypothalamic projections, as well as prefrontal and anterior cingulate cortical circuits. Special attention will be given to studies that demonstrate the necessity and/or sufficiency of genetic disruptions (e.g. by molecular deletion and/or replacement) in these pathways and circuits for producing characteristic behavioral features of autism. Necessarily these papers will be heavily weighted towards basic mechanisms elucidated in animal models, but may also include investigations in patients.

• #101 Biomarkers start telling us a story: Autism pathophysiology revisited – Autism Research Institute

  https://autism.org/biomarkers-and-pathophysiology/

  Persico states that there is no such thing as an autism gene because, depending on the affected pathways and protein functions, candidate genes could result in a variety of neurodevelopmental conditions. […] He considers how these findings may help broaden the focus of biomarker research to encompass intergenerational drivers and patterns. […] The speaker discusses the mTOR pathway in autism, noting the implications of immune activation and inflammation associated with hyperconnectivity. […] Persico therefore claims that altered brain connectivity can be due to genetics, epigenetics, neuroinflammation, microbiome composition, and/or altered protein expression. He reiterates that we cannot use biomarker research alone if we want to understand complex conditions. Researchers and clinicians must respect the complexities of neurodevelopment and assemble information to unravel autism pathophysiology and inform proper care.

• #102 Biomarkers start telling us a story: Autism pathophysiology revisited – Autism Research Institute

  https://autism.org/biomarkers-and-pathophysiology/

  Persico states that there is no such thing as an autism gene because, depending on the affected pathways and protein functions, candidate genes could result in a variety of neurodevelopmental conditions. […] He considers how these findings may help broaden the focus of biomarker research to encompass intergenerational drivers and patterns. […] The speaker discusses the mTOR pathway in autism, noting the implications of immune activation and inflammation associated with hyperconnectivity. […] Persico therefore claims that altered brain connectivity can be due to genetics, epigenetics, neuroinflammation, microbiome composition, and/or altered protein expression. He reiterates that we cannot use biomarker research alone if we want to understand complex conditions. Researchers and clinicians must respect the complexities of neurodevelopment and assemble information to unravel autism pathophysiology and inform proper care.

• #103 Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01081-0

  Key literature from recent years has suggested that ASD-associated genes enriched in aspect of transcription and translation, synapse, epigenetics, immunity and inflammation. […] These types of signalling pathways can interact or participate in the pathophysiology of ASD in a cascading manner rather than acting independently. […] Current evidence suggests that there is a complex level of dynamic regulation between translation and transcription that likely contributes to ASD pathophysiology. […] In summary, current evidence suggests that there is a complex level of dynamic regulation between translation and transcription that likely contributes to ASD pathophysiology. […] The neuropeptide theory of autism is backed up by evidence from animal research. […] The neuropeptide hormones OT and AVP belong to the same superfamily, and genetic variants in OXT, OXTR, arginine vasopressin receptor 1a (AVPR1a) and CD38 have been verified to be associated with autism. […] The development of strategies to intervene in or block the transduction of key signalling molecules involved in the pathogenesis of autism is a primary research direction.

• #104 Impaired neurodevelopmental pathways in autism spectrum disorder: a review of signaling mechanisms and crosstalk | Journal of Neurodevelopmental Disorders | Full Text

  https://jneurodevdisorders.biomedcentral.com/articles/10.1186/s11689-019-9268-y

  The understanding of mechanisms behind various signaling pathways in the etiology of ASD may help to facilitate the identification of potential therapeutic targets and design of new treatment methods. […] Dysregulation of sonic hedgehog (SHH), fibroblast growth factor (FGF), transforming growth factor (TGF-), and retinoic acid (RA) signaling pathways have also been implicated in the pathogenesis of ASD. […] Studies in genetically modified animal models and human induced pluripotent stem cell (hiPSC) models, along with large-scale human genomic studies in several neurodevelopmental disorders over the last few decades, have revealed the importance of spatiotemporal regulation of WNT signaling throughout the lifespan of an animal. […] Moreover, dysregulation of WNT signaling has been reported in several psychiatric disorders, including ASD, bipolar disorder, and schizophrenia, as well as in case of intellectual disability.

• #105 Deregulation of EIF4E: a novel mechanism for autism | Journal of Medical Genetics

  https://jmg.bmj.com/content/46/11/759

  Autism is a common childhood onset neurodevelopmental disorder, characterised by severe and sustained impairment of social interaction and social communication, as well as a notably restricted repertoire of activities and interests. Its aetiology is multifactorial with a strong genetic basis. […] EIF4E is the rate limiting component of eukaryotic translation initiation, and plays a key role in learning and memory through its control of translation within the synapse. […] These observations implicate EIF4E, and more specifically control of EIF4E activity, directly in autism. The findings raise the exciting possibility that pharmacological manipulation of EIF4E may provide therapeutic benefit for those with autism caused by disturbance of the converging pathways controlling EIF4E activity.

• #106 SFARI | Parvalbumin down-regulation as a common pathophysiological mechanism in autism spectrum disorders

  https://www.sfari.org/funded-project/parvalbumin-down-regulation-as-a-common-pathophysiological-mechanism-in-autism-spectrum-disorders/

  Beat Schwallers laboratory thus argues that upregulating PV expression might serve as a useful therapeutic approach for ASD. To address this systematically, Schwallers laboratory will take advantage of a transgenic mouse model in which PV expression can be modulated in a temporally precise manner. PV levels will be decreased at different time points during postnatal development, and behaviors will be assessed to see whether any changes in ASD core symptoms are observed. These experiments are expected to reveal windows of opportunities with respect to time periods of PV upregulation that may prove therapeutically beneficial for ASD.

• #107 Mechanism of action and therapeutic targeting of microglia in autism spectrum disorder

  https://accscience.com/journal/AN/1/3/10.36922/an.v1i3.167

  Autism spectrum disorder (ASD) is a complex mental illness with a high incidence and considerable impact. […] The underlying pathogenesis of ASD is still unclear, and effective interventions are lacking. Microglia are key immune cells in the central nervous system (CNS), and they function far beyond classical innate immunity, as they can affect normal neuronal activity by secreting cytokines and pruning synapses through phagocytosis. On the one hand, the abnormal activity of microglia may contribute to the development of ASD; on the other hand, it provides a potential target for intervention and treatment. In this review, we comprehensively analyze the mechanism of action of microglia in ASD development and summarize the current methods for targeting microglia in treating ASD.

• #108 Study reveals new genetic mechanism behind autism development

  https://www.sickkids.ca/en/news/archive/2025/study-reveals-new-genetic-mechanism-behind-autism-development/

  As the tandem repeat expands in the DMPK gene, the research team, including collaborators at the University of Florida and Adam Mickiewicz University (Poland), found its altered RNA binds to a protein that is involved in gene splicing regulation during brain development. […] This so-called toxic RNA depletes the protein and prevents it from binding to other RNA molecules in important areas of the genome, causing a protein imbalance which results in mis-splicing other genes. […] TREs are like a sponge that absorbs all these important proteins from the genome. Without this protein, other areas of the genome dont function properly, explains Yuen. […] The Yuen Lab and Sznajder Lab are already exploring whether this mis-splicing is happening in other genes associated with ASD, as well as how their findings could inform precision therapies that release these proteins back into the genome.

• #109 Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01081-0

  These advances in disease mechanism research provide the basis for the design of drugs such as rapamycin (mTOR) inhibitors […] In addition to the downregulation of synapse-related genes, microglia and immune-related genes were increased in the brains of autistic patients. […] The correlations among astrocytes, microglial activation, neuroinflammation caused by gut microbiota and immune dysregulation in ASD patients are also involved in the pathological mechanism. […] Another pathological mechanism of ASD that has garnered much attention is the functional impairment of brain regions and neural circuits. […] In this review, we integrate recent advances from genetic, neuropathological, and neurobiochemical studies on ASD to further elucidate the pathogenetic mechanism at the molecular, cellular, and neural circuit levels.

• #110

  https://link.springer.com/article/10.1007/s10753-024-02061-y

  Neuroinflammatory factors in ASD result from changes in the regulation of intestinal barriers, activation and function of microglia, and levels of neurotransmitters. […] Biomarkers based on neuroinflammatory processes associated with gut microbiota may provide a more objective and precise way of detecting ASD. […] Overall, gut microbiota seems to play a crucial role in ASD through inflammation. […] The changes in GM-CSF levels in ASD can indicate that an inflammatory process may be involved in developmental and neuroimmune impairment. […] It is suggested that neuroinflammation is strongly related to ASD occurrence through activating the inflammasome system as a mechanism. […] The effect of probiotics and gut microbiota alteration on HMGB1 levels in ASD patients can strengthen the idea and can be further studied. […] Overall, these findings support that probiotics may serve as a promising therapy due to their beneficial impact on symptoms of ASD.

• #111 Epigenetic changes shed light on biological mechanism of autism | Crick

  https://www.crick.ac.uk/news/2013-04-23-epigenetic-changes-shed-light-on-biological-mechanism-of-autism

  Jonathan Mill, from King’s College London’s Institute of Psychiatry and the University of Exeter, added: „Research into the intersection between genetic and environmental influences is crucial because risky environmental conditions can sometimes be avoided or changed. Epigenetic changes are potentially reversible, so our next step is to embark on larger studies to see whether we can identify key epigenetic changes common to the majority of people with autism to help us develop possible therapeutic interventions.”

• #112

  https://neurolaunch.com/pathophysiology-of-autism/

  The interaction between genetic predisposition and environmental triggers is a key area of research in ASD etiology. […] Several proposed models for autism pathogenesis attempt to integrate the diverse findings in ASD research. […] The multifactorial nature of ASD etiology is now widely recognized. […] In summary, the pathophysiology of autism spectrum disorder involves a complex interplay of genetic, environmental, and developmental factors. Key findings include abnormalities in brain structure and connectivity, neurochemical imbalances, synaptic dysfunction, and immune system irregularities.

• #113

  https://neurolaunch.com/pathophysiology-of-autism/

  The interaction between genetic predisposition and environmental triggers is a key area of research in ASD etiology. […] Several proposed models for autism pathogenesis attempt to integrate the diverse findings in ASD research. […] The multifactorial nature of ASD etiology is now widely recognized. […] In summary, the pathophysiology of autism spectrum disorder involves a complex interplay of genetic, environmental, and developmental factors. Key findings include abnormalities in brain structure and connectivity, neurochemical imbalances, synaptic dysfunction, and immune system irregularities.

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