Retinal GABAergic Alterations in Adults with Autism Spectrum Disorder

Alterations in γ-aminobutyric acid (GABA) have been implicated in sensory differences in individuals with autism spectrum disorder (ASD). Visual signals are initially processed in the retina, and in this study, we explored the hypotheses that the GABA-dependent retinal response to light is altered in individuals with ASD. Light-adapted electroretinograms were recorded from 61 adults (38 males and 23 females; n = 22 ASD) in response to three stimulus protocols: (1) the standard white flash, (2) the standard 30 Hz flickering protocol, and (3) the photopic negative response protocol. Participants were administered an oral dose of placebo, 15 or 30 mg of arbaclofen (STX209, GABAB agonist) in a randomized, double-blind, crossover order before the test. At baseline (placebo), the a-wave amplitudes in response to single white flashes were more prominent in ASD, relative to typically developed (TD) participants. Arbaclofen was associated with a decrease in the a-wave amplitude in ASD, but an increase in TD, eliminating the group difference observed at baseline. The extent of this arbaclofen-elicited shift significantly correlated with the arbaclofen-elicited shift in cortical responses to auditory stimuli as measured by using an electroencephalogram in our prior study and with broader autistic traits measured with the autism quotient across the whole cohort. Hence, GABA-dependent differences in retinal light processing in ASD appear to be an accessible component of a wider autistic difference in the central processing of sensory information, which may be upstream of more complex autistic phenotypes.</p

Familial risk of autism alters subcortical and cerebellar brain anatomy in infants and predicts the emergence of repetitive behaviors in early childhood.

Autism spectrum disorder (ASD) is a common neurodevelopmental condition, and infant siblings of children with ASD are at a higher risk of developing autistic traits or an ASD diagnosis, when compared to those with typically developing siblings. Reports of differences in brain anatomy and function in high-risk infants which predict later autistic behaviors are emerging, but although cerebellar and subcortical brain regions have been frequently implicated in ASD, no high-risk study has examined these regions. Therefore, in this study, we compared regional MRI volumes across the whole brain in 4-6-month-old infants with (high-risk, n = 24) and without (low-risk, n = 26) a sibling with ASD. Within the high-risk group, we also examined whether any regional differences observed were associated with autistic behaviors at 36 months. We found that high-risk infants had significantly larger cerebellar and subcortical volumes at 4-6-months of age, relative to low-risk infants; and that larger volumes in high-risk infants were linked to more repetitive behaviors at 36 months. Our preliminary observations require replication in longitudinal studies of larger samples. If correct, they suggest that the early subcortex and cerebellum volumes may be predictive biomarkers for childhood repetitive behaviors. Autism Res 2019, 12: 614-627. © 2019 The Authors. Autism Research published by International Society for Autism Research published byWiley Periodicals, Inc. LAY SUMMARY: Individuals with a family history of autism spectrum disorder (ASD) are at risk of ASD and related developmental difficulties. This study revealed that 4-6-month-old infants at high-risk of ASD have larger cerebellum and subcortical volumes than low-risk infants, and that larger volumes in high-risk infants are associated with more repetitive behaviors in childhood

Familial risk of autism alters subcortical and cerebellar brain anatomy in infants and predicts the emergence of repetitive behaviors in early childhood

Autism spectrum disorder (ASD) is a common neurodevelopmental condition, and infant siblings of children with ASD are at a higher risk of developing autistic traits or an ASD diagnosis, when compared to those with typically developing siblings. Reports of differences in brain anatomy and function in high‐risk infants which predict later autistic behaviors are emerging, but although cerebellar and subcortical brain regions have been frequently implicated in ASD, no high‐risk study has examined these regions. Therefore, in this study, we compared regional MRI volumes across the whole brain in 4–6‐month‐old infants with (high‐risk, n = 24) and without (low‐risk, n = 26) a sibling with ASD. Within the high‐risk group, we also examined whether any regional differences observed were associated with autistic behaviors at 36 months. We found that high‐risk infants had significantly larger cerebellar and subcortical volumes at 4–6‐months of age, relative to low‐risk infants; and that larger volumes in high‐risk infants were linked to more repetitive behaviors at 36 months. Our preliminary observations require replication in longitudinal studies of larger samples. If correct, they suggest that the early subcortex and cerebellum volumes may be predictive biomarkers for childhood repetitive behaviors

Bridge-building between communities: Imagining the future of biomedical autism research

A paradigm shift of research culture is required to ease perceived tensions between autistic people and the biomedical research community. As a group of autistic and non-autistic scientists and stakeholders, we contend that through participatory research we can reject a deficit-based conceptualisation of autism whilst building a shared vision for a neurodiversity-affirmative biomedical research paradigm

An investigation into the functions of the septohippocampal cholinergic system

SIGLEAvailable from British Library Document Supply Centre-DSC:D063873 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

High rate of prevalence of clock 3′UTR polymorphism rs1801260 and a novel variation: Association with diurnal preference

There are a number of reports which show CLOCK 3111 T/C SNP rs1801260 is associated with ‘eveningness’ circadian type, but the results are not consistent across different populations. The present study tried to address the effect of CLOCK polymorphisms on Diurnal preference in the South Indian population. 108 subjects were genotyped for rs1801260 polymorphism by direct sequencing. Demographic data was collected from genotypically stratified groups of subjects using a modified sleep wake cycle questionnaire. Data from the questionnaire recorded the subjects sleep wake pattern and their peak performance time of the day. The sequencing data was aligned and analyzed using Mutation Survey software for new mutations. We found a new variation in the 3′UTR region of the CLOCK gene (BankIt1368312 Seq1 HM626403, BankIt1368312 Seq2 HM626404) which may be a possible miRNA binding site. Our study found that CLOCK 3111 T/C polymorphism is negatively associated with Eveningness with a significance of 0.038. We found that the prevalence rate of rs1801260 is high and the ancestral genotype is associated with eveningness. Though the sample size was small this was a homogenous group from south India selected for the study. It is the first study in south Indian population to document the effect of CLOCK polymorphisms on Circadian rhythm.</jats:p

The ‘PSILAUT’ protocol:an experimental medicine study of autistic differences in the function of brain serotonin targets of psilocybin

Background: The underlying neurobiology of the complex autism phenotype remains obscure, although accumulating evidence implicates the serotonin system and especially the 5HT2A receptor. However, previous research has largely relied upon association or correlation studies to link differences in serotonin targets to autism. To directly establish that serotonergic signalling is involved in a candidate brain function our approach is to change it and observe a shift in that function. We will use psilocybin as a pharmacological probe of the serotonin system in vivo. We will directly test the hypothesis that serotonergic targets of psilocybin – principally, but not exclusively, 5HT2A receptor pathways—function differently in autistic and non-autistic adults. Methods: The ‘PSILAUT’ “shiftability” study is a case–control study autistic and non-autistic adults. How neural responses ‘shift’ in response to low doses (2 mg and 5 mg) of psilocybin compared to placebo will be examined using multimodal techniques including functional MRI and EEG. Each participant will attend on up to three separate visits with drug or placebo administration in a double-blind and randomized order. Results: This study will provide the first direct evidence that the serotonin targets of psilocybin function differently in the autistic and non-autistic brain. We will also examine individual differences in serotonin system function. Conclusions: This work will inform our understanding of the neurobiology of autism as well as decisions about future clinical trials of psilocybin and/or related compounds including stratification approaches. Trial registration: NCT05651126.</p