Using human pluripotent stem cell models to study autism in the era of big data
AbstractAdvances in human pluripotent stem cell (hPSC) biology coupled with protocols to generate diverse brain cell types in vitro have provided neuroscientists with opportunities to dissect basic and disease mechanisms in increasingly relevant cellular substrates. At the same time, large data collections and analyses have facilitated unprecedented insights into autism genetics, normal human genetic variation, and the molecular landscape of the developing human brain. While such insights have enabled the investigation of key mechanistic questions in autism, they also highlight important limitations associated with the use...
Source: Molecular Autism - March 22, 2020 Category: Molecular Biology Source Type: research
Effects of oxytocin administration on salivary sex hormone levels in autistic and neurotypical women
ConclusionsThis study provides the first evidence that oxytocin influences endogenous testosterone levels in autistic individuals, with autistic women showing increases similar to previous reports of neurotypical men. These findings highlight the need to consider sex steroid hormones as a variable in future oxytocin trials. (Source: Molecular Autism)
Source: Molecular Autism - March 17, 2020 Category: Molecular Biology Source Type: research
A DLG2 deficiency in mice leads to reduced sociability and increased repetitive behavior accompanied by aberrant synaptic transmission in the dorsal striatum
ConclusionThese results suggest that homozygousDlg2 deletion in mice leads to ASD-like behavioral phenotypes, including social deficits and increased repetitive behaviors, as well as reductions in excitatory synaptic input onto dorsolateral spiny projection neurons, implying that the dorsal striatum is one of the brain regions vulnerable to the developmental dysregulation of DLG2. (Source: Molecular Autism)
Source: Molecular Autism - March 11, 2020 Category: Molecular Biology Source Type: research
Revised scored Sensory Perception Quotient reveals sensory hypersensitivity in women with autism
ConclusionsThe present findings revealed greater sensory hypersensitivity, but not hyposensitivity, in females with ASC compared to BAP and control female groups, and that a greater degree of autism traits relates to higher hypersensitivity in ASC females. The results offer support for the enhanced perceptual functioning model using large samples of females, who are an understudied population, and demonstrate the validity of the SPQ-RS as a valuable new research tool for exploring self-reported hypersensitivity and hyposensitivity. (Source: Molecular Autism)
Source: Molecular Autism - March 1, 2020 Category: Molecular Biology Source Type: research
Social brain activation during mentalizing in a large autism cohort: the Longitudinal European Autism Project
ConclusionsContrary to prior reports, this large-scale study does not support the assumption that altered social brain activation during mentalizing forms a common neural marker of ASD, at least with the paradigm we employed. Yet, autistic individuals show socio-behavioral deficits. Our work therefore highlights the need to interrogate social brain function with other brain measures, such as connectivity and network-based approaches, using other paradigms, or applying complementary analysis approaches to assess individual differences in this heterogeneous condition. (Source: Molecular Autism)
Source: Molecular Autism - February 21, 2020 Category: Molecular Biology Source Type: research
Recent advances in human stem cell-based modeling of Tuberous Sclerosis Complex
AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by epilepsy, intellectual disability, and benign tumors of the brain, heart, skin, and kidney. Animal models have contributed to our understanding of normal and abnormal human brain development, but the construction of models that accurately recapitulate a human pathology remains challenging. Recent advances in stem cell biology with the derivation of human-induced pluripotent stem cells (hiPSCs) from somatic cells from patients have opened new avenues to the study of TSC. This approach combined with gene-editing tools such as CRISPR/C...
Source: Molecular Autism - February 18, 2020 Category: Molecular Biology Source Type: research
Quantifying compensatory strategies in adults with and without diagnosed autism
ConclusionsTogether, our findings suggest that many intellectually able adults, with and without a clinical diagnosis of autism, report using compensatory strategies to modify their social behaviour. We discuss the clinical utility of measuring self-reported compensation (e.g., using our checklist), with important implications for the accurate diagnosis and management of autism and related conditions. (Source: Molecular Autism)
Source: Molecular Autism - February 11, 2020 Category: Molecular Biology Source Type: research
Links between self-injury and suicidality in autism
ConclusionsThese preliminary data suggest that while individuals might frame their self-injury as a positive or neutral thing, there remains a concerning relationship between self-injury and suicidality which exists regardless of individual feelings on self-injury. This is consistent with the theoretical perspective that self-injury can be a “gateway” through which individuals acquire capability for lethal suicidal behaviors. The data highlight that particular methods (cutting) and reasons for self-injury may be of significant concern, but this information, which might be of extreme value for clinicians, requires furth...
Source: Molecular Autism - February 9, 2020 Category: Molecular Biology Source Type: research
Transcriptomics of Gabra4 knockout mice reveals common NMDAR pathways underlying autism, memory, and epilepsy
AbstractAutism spectrum disorder (ASD) is a neuronal developmental disorder with impaired social interaction and communication, often with abnormal intelligence and comorbidity with epilepsy. Disturbances in synaptic transmission, including the GABAergic, glutamatergic, and serotonergic systems, are known to be involved in the pathogenesis of this disorder, yet we do not know if there is a common molecular mechanism. As mutations in the GABAergic receptor subunit geneGABRA4 are reported in patients with ASD, we eliminated theGabra4 gene in mice and found that theGabra4 knockout mice showed autistic-like behavior, enhanced ...
Source: Molecular Autism - February 6, 2020 Category: Molecular Biology Source Type: research
Serotonergic innervation of the amygdala is increased in autism spectrum disorder and decreased in Williams syndrome
ConclusionsDifferential alterations to serotonergic innervation of the amygdala may contribute to differences in sociobehavioral phenotype in WS and ASD. These findings will inform future work identifying targets for future therapeutics in these and other disorders characterized by atypical social behavior. (Source: Molecular Autism)
Source: Molecular Autism - February 4, 2020 Category: Molecular Biology Source Type: research
Reduced nonverbal interpersonal synchrony in autism spectrum disorder independent of partner diagnosis: a motion energy study
ConclusionsThe present results do not provide support for the Interactional Heterogeneity Hypothesis given that autistic individuals do not coordinate better when interacting with another autistic individual, compared to when interacting with a typical individual. (Source: Molecular Autism)
Source: Molecular Autism - February 2, 2020 Category: Molecular Biology Source Type: research
Profiling parvalbumin interneurons using iPSC: challenges and perspectives for Autism Spectrum Disorder (ASD)
AbstractAutism spectrum disorders (ASD) are persistent conditions resulting from disrupted/altered neurodevelopment. ASD multifactorial etiology —and its numerous comorbid conditions—heightens the difficulty in identifying its underlying causes, thus obstructing the development of effective therapies. Increasing evidence from both animal and human studies suggests an altered functioning of the parvalbumin (PV)-expressing inhibitory inter neurons as a common and possibly unifying pathway for some forms of ASD. PV-expressing interneurons (short: PVALB neurons) are critically implicated in the regulation of cortical netwo...
Source: Molecular Autism - January 28, 2020 Category: Molecular Biology Source Type: research
Age-variant and age-invariant features of functional brain organization in middle-aged and older autistic adults
ConclusionThese results highlight the complexity of aging in ASC with both parallel and divergent trajectories across different aspects of functional network organization. (Source: Molecular Autism)
Source: Molecular Autism - January 21, 2020 Category: Molecular Biology Source Type: research
Persistence and predictors of self-injurious behaviour in autism: a ten-year prospective cohort study
ConclusionsIn this unique longitudinal investigation into the persistence of self-injury in a non-clinical sample of individuals with autism over a 10 year period, we have identified a novel, robust and stable profile of behavioural characteristics associated with persistent self-injury. Findings support an early intervention strategy targeted towards individuals identified to be at a higher risk of developing self-injurious behaviour. (Source: Molecular Autism)
Source: Molecular Autism - January 19, 2020 Category: Molecular Biology Source Type: research
Maternal blood folate status during early pregnancy and occurrence of autism spectrum disorder in offspring: a study of 62 serum biomarkers
ConclusionsOur findings suggest that high maternal serum folate status during early pregnancy may be associated with the occurrence of ASD in offspring. No inference about physiological mechanisms behind this observation can be made at the present time because blood folate levels may have complex relations with nutritional intake, the cellular folate status and status of other B-vitamins. Therefore, further investigations, which may clarify the potential role and mechanisms of maternal blood folate status in ASD risk and the interplay with other potential risk factors, in larger materials are warranted. (Source: Molecular Autism)
Source: Molecular Autism - January 15, 2020 Category: Molecular Biology Source Type: research
