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Proceedings. Biological Sciences Oct 2023Synaesthesia is a sensory phenomenon where external stimuli, such as sounds or letters, trigger additional sensations (e.g. colours). Synaesthesia aggregates in families...
Synaesthesia is a sensory phenomenon where external stimuli, such as sounds or letters, trigger additional sensations (e.g. colours). Synaesthesia aggregates in families but its heritability is unknown. The phenomenon is more common in people on the autism spectrum compared with the general population and associated with higher autistic traits. Using classical twin design, we assessed the heritability of individual differences in self-reported synaesthesia and the genetic and environmental contributions to their association with autistic traits within a population twin cohort ( = 4262, age = 18 years). We estimated individual differences in synaesthesia to be heritable and influenced by environmental factors not shared between twins. The association between individual differences in synaesthesia and autistic traits was estimated to be predominantly under genetic influence and seemed to be mainly driven by non-social autistic traits (repetitive behaviours, restricted interests and attention to detail). Our study suggests that the link between synaesthesia and autism might reside in shared genetic causes, related to non-social autistic traits such as alterations in perception. Future studies building on these findings may attempt to identify specific groups of genes that influence both autism, synaesthesia and perception.
Topics: Humans; Adolescent; Autistic Disorder; Sensation; Self Report; Autism Spectrum Disorder
PubMed: 37876199
DOI: 10.1098/rspb.2023.1888 -
Brain and Behavior Dec 2023The mechanism underlying autism spectrum disorder (ASD) remains incompletely understood, but researchers have identified over a thousand genes involved in complex...
BACKGROUND
The mechanism underlying autism spectrum disorder (ASD) remains incompletely understood, but researchers have identified over a thousand genes involved in complex interactions within the brain, nervous, and immune systems, particularly during the mechanism of brain development. Various contributory environmental effects including circadian rhythm have also been studied in ASD. Thus, capturing the global picture of the ASD-clock network in combined form is critical.
METHODS
We reconstructed the protein-protein interaction network of ASD and circadian rhythm to understand the connection between autism and the circadian clock. A graph theoretical study is undertaken to evaluate whether the network attributes are biologically realistic. The gene ontology enrichment analyses provide information about the most important biological processes.
RESULTS
This study takes a fresh look at metabolic mechanisms and the identification of potential key proteins/pathways (ribosome biogenesis, oxidative stress, insulin/IGF pathway, Wnt pathway, and mTOR pathway), as well as the effects of specific conditions (such as maternal stress or disruption of circadian rhythm) on the development of ASD due to environmental factors.
CONCLUSION
Understanding the relationship between circadian rhythm and ASD provides insight into the involvement of these essential pathways in the pathogenesis/etiology of ASD, as well as potential early intervention options and chronotherapeutic strategies for treating or preventing the neurodevelopmental disorder.
Topics: Humans; Circadian Clocks; Autism Spectrum Disorder; Autistic Disorder; Circadian Rhythm; Neurodevelopmental Disorders
PubMed: 37807632
DOI: 10.1002/brb3.3273 -
Developmental Medicine and Child... Jan 2024Motor features of autism have long been acknowledged by clinicians, researchers, and community stakeholders. Current DSM-5 and ICD-11 guidelines allow clinicians to... (Review)
Review
Motor features of autism have long been acknowledged by clinicians, researchers, and community stakeholders. Current DSM-5 and ICD-11 guidelines allow clinicians to assign a co-occurring diagnosis of developmental [motor] coordination disorder (DCD) for autistic individuals with significant motor problems. DCD is characterized by poor motor proficiency with an onset of symptoms in early development. Studies have shown considerable overlap in the behavioral motor features observed in autism and DCD. However, others indicate that motor problems in autism and DCD may stem from different underlying sensorimotor mechanisms. Regardless of whether autism has a unique motor phenotype or an overlap with DCD, changes need to be made in the clinical pipeline to address motor problems in autism at the stages of recognition, assessment, diagnosis, and intervention. Consensus is needed to address unmet needs in research on the etiology of motor problems in autism and their overlap with DCD, to optimize clinical practice guidelines. The development of screening and assessment tools for motor problems that are valid and reliable for use with autistic individuals is essential, and an evidence-based clinical pipeline for motor problems in autism is urgently needed. WHAT THIS PAPER ADDS: Motor problems in autism are highly prevalent, yet underdiagnosed and poorly managed. An evidence-based clinical pipeline for motor problems in autism is urgently needed.
Topics: Humans; Autistic Disorder; Motor Skills Disorders; Autism Spectrum Disorder
PubMed: 37332143
DOI: 10.1111/dmcn.15674 -
Molecular Autism Jul 2023Septo-optic dysplasia (SOD) is a rare condition diagnosed in children with two or more of the following: hypopituitarism, midline brain abnormalities, and optic nerve... (Review)
Review
BACKGROUND
Septo-optic dysplasia (SOD) is a rare condition diagnosed in children with two or more of the following: hypopituitarism, midline brain abnormalities, and optic nerve hypoplasia. Children with SOD experience varied visual impairment and endocrine dysfunction. Autistic-like behaviours have been reported; however, their nature and prevalence remain to be fully understood. The present systematic review aimed to explore the type and prevalence of neurodevelopmental impairments in children with SOD spectrum conditions.
METHODS
The search was conducted in PubMed, EMBASE, and PsycInfo. Hand-searching reference lists of included studies was conducted. All peer-reviewed, observational studies assessing behavioural and cognitive impairments or autism spectrum disorder (ASD) symptoms in children (< 18 years) with SOD, optic nerve hypoplasia, and SOD-plus were included. Studies were excluded if they did not report standardised measures of neurodevelopmental impairments or ASD outcomes.
RESULTS
From 2132 screened articles, 20 articles reporting data from a total of 479 children were included in prevalence estimates. Of 14 studies assessing cognitive-developmental outcomes, 175 of 336 (52%) children presented with intellectual disability or developmental delay. A diagnosis of ASD or clinical level of symptoms was observed in 65 of 187 (35%) children across five studies. Only five studies assessed for dysfunction across behavioural, emotional, or social domains and reported impairments in 88 of 184 (48%) of children assessed.
LIMITATIONS
Importantly, high heterogeneity among the samples in relation to their neuroanatomical, endocrine, and optic nerve involvement meant that it was not possible to statistically assess the relative contribution of these confounding factors to the specific neurodevelopmental phenotype. This was further limited by the variation in study designs and behavioural assessments used across the included studies, which may have increased the risk of information bias.
CONCLUSIONS
This systematic review suggests that the prevalence of neurodevelopmental impairments in children within the SOD spectrum may be high. Clinicians should therefore consider including formal assessments of ASD symptoms and neurodevelopmental impairments alongside routine care. There is, additionally, a need for further research to define and validate a standardised battery of tools that accurately identify neurodevelopmental impairments in SOD spectrum conditions, and for research to identify the likely causal mechanisms.
Topics: Humans; Septo-Optic Dysplasia; Autism Spectrum Disorder; Optic Nerve Hypoplasia; Hypopituitarism; Autistic Disorder
PubMed: 37491272
DOI: 10.1186/s13229-023-00559-0 -
Translational Psychiatry Dec 2023Narrative reviews have described various resting-state EEG power differences in autism across all five canonical frequency bands, with increased power for low and high... (Meta-Analysis)
Meta-Analysis
Narrative reviews have described various resting-state EEG power differences in autism across all five canonical frequency bands, with increased power for low and high frequencies and reduced power for middle frequencies. However, these differences have yet to be quantified using effect sizes and probed robustly for consistency, which are critical next steps for clinical translation. Following PRISMA guidelines, we conducted a systematic review of published and gray literature on resting-state EEG power in autism. We performed 10 meta-analyses to synthesize and quantify differences in absolute and relative resting-state delta, theta, alpha, beta, and gamma EEG power in autism. We also conducted moderator analyses to determine whether demographic characteristics, methodological details, and risk-of-bias indicators might account for heterogeneous study effect sizes. Our literature search and study selection processes yielded 41 studies involving 1,246 autistic and 1,455 neurotypical individuals. Meta-analytic models of 135 effect sizes demonstrated that autistic individuals exhibited reduced relative alpha (g = -0.35) and increased gamma (absolute: g = 0.37, relative: g = 1.06) power, but similar delta (absolute: g = 0.06, relative: g = 0.10), theta (absolute: g = -0.03, relative: g = -0.15), absolute alpha (g = -0.17), and beta (absolute: g = 0.01, relative: g = 0.08) power. Substantial heterogeneity in effect sizes was observed across all absolute (I: 36.1-81.9%) and relative (I: 64.6-84.4%) frequency bands. Moderator analyses revealed that age, biological sex, IQ, referencing scheme, epoch duration, and use of gold-standard autism diagnostic instruments did not moderate study effect sizes. In contrast, resting-state paradigm type (eyes-closed versus eyes-open) moderated absolute beta, relative delta, and relative alpha power effect sizes, and resting-state recording duration moderated relative alpha power effect sizes. These findings support further investigation of resting-state alpha and gamma power as potential biomarkers for autism.
Topics: Humans; Electroencephalography; Autism Spectrum Disorder; Attention Deficit Disorder with Hyperactivity; Autistic Disorder
PubMed: 38097538
DOI: 10.1038/s41398-023-02681-2 -
Journal of Psychiatric Research Aug 2023People with mental disorders, such as psychosis or autism spectrum disorder (ASD), often present impairments in social cognition (SC), which may cause significant... (Review)
Review
People with mental disorders, such as psychosis or autism spectrum disorder (ASD), often present impairments in social cognition (SC), which may cause significant difficulties in real-world functioning. SC deficits are seen also in unaffected relatives, indicating a genetic substratum. The present review evaluated the evidence on the association between SC and the polygenic risk score (PRS), a single metric of the molecular genetic risk to develop a specific disorder. In July 2022, we conducted systematic searches in Scopus and PubMed following the PRISMA-ScR guidelines. We selected original articles written in English reporting results on the association between PRSs for any mental disorder and domains of SC either in people with mental disorders or controls. The search yielded 244 papers, of which 13 were selected for inclusion. Studies tested mainly PRSs for schizophrenia, ASD, and attention-deficit hyperactivity disorder. Emotion recognition was the most investigated domain of SC. Overall, evidence revealed that currently available PRSs for mental disorders do not explain variation in SC performances. To enhance the understanding of mechanisms underlying SC in mental disorders, future research should focus on the development of transdiagnostic PRSs, study their interaction with environmental risk factors, and standardize outcome measurement.
Topics: Humans; Social Cognition; Autism Spectrum Disorder; Psychotic Disorders; Attention Deficit Disorder with Hyperactivity; Risk Factors
PubMed: 37418886
DOI: 10.1016/j.jpsychires.2023.06.029 -
Cell Communication and Signaling : CCS Nov 2023The GPCR HCAR1 is known to be the sole receptor for lactate, which modulates its metabolic effects. Despite its significant role in many processes, mice deficient in...
The GPCR HCAR1 is known to be the sole receptor for lactate, which modulates its metabolic effects. Despite its significant role in many processes, mice deficient in HCAR1 exhibit no visible phenotype and are healthy and fertile. We performed transcriptomic analysis on HCAR1 deficient cells, in combination with lactate, to explore pathophysiologically altered processes. Processes such as immune regulation, various cancers, and neurodegenerative diseases were significantly enriched for HCAR1 transcriptomic signature. However, the most affected process of all was autism spectrum disorder. We performed behavioral tests on HCAR1 KO mice and observed that these mice manifest autistic-like behavior. Our data opens new avenues for research on HCAR1 and lactate effect at a pathological level. Video Abstract.
Topics: Mice; Animals; Lactic Acid; Autistic Disorder; Autism Spectrum Disorder; Signal Transduction; Receptors, G-Protein-Coupled
PubMed: 37940970
DOI: 10.1186/s12964-023-01188-z -
Autism : the International Journal of... Aug 2023It is now recognised that autism spectrum disorder (ASD) and personality disorders (PDs) have a variety of factors in common. However, the exact nature of the...
It is now recognised that autism spectrum disorder (ASD) and personality disorders (PDs) have a variety of factors in common. However, the exact nature of the relationship between ASD and the PDs remains unclear. The overlapping symptom profiles of ASD and PDs can lead to diagnostic uncertainty - features of ASD and PD can be misattributed and easily lead to misdiagnosis of ASD patients. Since differentiating between ASD and PD is such a complex task, it has been argued that there is a need for additional understanding and markers for facilitating diagnostic procedures. There is an urgent need to explore, first, how clinicians make diagnostic decisions and, second, how to effectively deal with the challenges and difficulties they face when making decisions. Also, where there are clear overlaps, how do clinicians choose how to attribute labels in order to understand the person.
Topics: Humans; Autism Spectrum Disorder; Diagnosis, Differential; Personality Disorders; Diagnostic Errors; Uncertainty
PubMed: 36708368
DOI: 10.1177/13623613231151356 -
Frontiers in Immunology 2024Autism spectrum disorder (ASD) is a disease characterized by social disorder. Recently, the population affected by ASD has gradually increased around the world. There...
BACKGROUND
Autism spectrum disorder (ASD) is a disease characterized by social disorder. Recently, the population affected by ASD has gradually increased around the world. There are great difficulties in diagnosis and treatment at present.
METHODS
The ASD datasets were obtained from the Gene Expression Omnibus database and the immune-relevant genes were downloaded from a previously published compilation. Subsequently, we used WGCNA to screen the modules related to the ASD and immune. We also choose the best combination and screen out the core genes from Consensus Machine Learning Driven Signatures (CMLS). Subsequently, we evaluated the genetic correlation between immune cells and ASD used GNOVA. And pleiotropic regions identified by PLACO and CPASSOC between ASD and immune cells. FUMA was used to identify pleiotropic regions, and expression trait loci (EQTL) analysis was used to determine their expression in different tissues and cells. Finally, we use qPCR to detect the gene expression level of the core gene.
RESULTS
We found a close relationship between neutrophils and ASD, and subsequently, CMLS identified a total of 47 potential candidate genes. Secondly, GNOVA showed a significant genetic correlation between neutrophils and ASD, and PLACO and CPASSOC identified a total of 14 pleiotropic regions. We annotated the 14 regions mentioned above and identified a total of 6 potential candidate genes. Through EQTL, we found that the CFLAR gene has a specific expression pattern in neutrophils, suggesting that it may serve as a potential biomarker for ASD and is closely related to its pathogenesis.
CONCLUSIONS
In conclusion, our study yields unprecedented insights into the molecular and genetic heterogeneity of ASD through a comprehensive bioinformatics analysis. These valuable findings hold significant implications for tailoring personalized ASD therapies.
Topics: Humans; Autism Spectrum Disorder; Computational Biology; Quantitative Trait Loci; Genetic Predisposition to Disease; Gene Expression Profiling; Gene Regulatory Networks; Machine Learning; Databases, Genetic; Immunogenetics; Neutrophils; Transcriptome
PubMed: 38726016
DOI: 10.3389/fimmu.2024.1347139 -
International Journal of Molecular... Aug 2023Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restrictive interests and/or repetitive behaviors and deficits in social interaction and...
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restrictive interests and/or repetitive behaviors and deficits in social interaction and communication. ASD is a multifactorial disease with a complex polygenic genetic architecture. Its genetic contributing factors are not yet fully understood, especially large structural variations (SVs). In this study, we aimed to assess the contribution of SVs, including copy number variants (CNVs), insertions, deletions, duplications, and mobile element insertions, to ASD and related language impairments in the New Jersey Language and Autism Genetics Study (NJLAGS) cohort. Within the cohort, ~77% of the families contain SVs that followed expected segregation or de novo patterns and passed our filtering criteria. These SVs affected 344 brain-expressed genes and can potentially contribute to the genetic etiology of the disorders. Gene Ontology and protein-protein interaction network analysis suggested several clusters of genes in different functional categories, such as neuronal development and histone modification machinery. Genes and biological processes identified in this study contribute to the understanding of ASD and related neurodevelopment disorders.
Topics: Humans; Autism Spectrum Disorder; Autistic Disorder; Language; Brain; Language Development Disorders
PubMed: 37686052
DOI: 10.3390/ijms241713248