Genetic analysis of the postsynaptic transmembrane X-linked neuroligin 3 gene in autism

Autism is a complex neurodevelopmental disorder, the prevalence of which has increased drastically in India in recent years. Neuroligin is a type I transmembrane protein that plays a crucial role in synaptogenesis. Alterations in synaptic genes are most commonly implicated in autism and other cognitive disorders. The present study investigated the neuroligin 3 gene in the Indian autistic population by sequencing and in silico pathogenicity prediction of molecular changes. In total, 108 clinically described individuals with autism were included from the North Karnataka region of India, along with 150 age-, sex-, and ethnicity-matched healthy controls. Genomic DNA was extracted from peripheral blood, and exonic regions were sequenced. The functional and structural effects of variants of the neuroligin 3 protein were predicted. One coding sequence variant (a missense variant) and four non-coding variants (two 5'-untranslated region [UTR] variants and two 3'-UTR variants) were recorded. The novel missense variant was found in 25% of the autistic population. The C/C genotype of c.551T>C was significantly more common in autistic children than in controls (p = 0.001), and a significantly increased risk of autism (24.7-fold) was associated with this genotype (p = 0.001). The missense variant showed pathogenic effects and high evolutionary conservation over the functions of the neuroligin 3 protein. In the present study, we reported a novel missense variant, V184A, which causes abnormal neuroligin 3 and was found with high frequency in the Indian autistic population. Therefore, neuroligin is a candidate gene for future molecular investigations and functional analysis in the Indian autistic population.

Reexamining Empathy in Autism: The Role of Empathic Disequilibrium in Autism and Autistic Traits

Background: While many autistics report feelings of excessive empathy, their experience is not reflected by most of the current literature, which typically, but not always, suggests that autism is characterized by intact emotional empathy and reduced cognitive empathy. To try and bridge this gap in empirical findings and with respect to individuals' experiences, we examined a novel conceptualization of empathy termed empathic disequilibrium, i.e., the imbalance between emotional and cognitive empathy. Empathic disequilibrium was previously found to predict autistic traits in non-autistic population, suggesting it is an important empathy measure. Here, we aimed to extend the generalizability of empathic disequilibrium to the autistic population and to provide a better analytical approach to examine this construct.Methods: We analyzed self-reports of empathy and autistic traits in a large cohort (N = 4,914) of autistic and non-autistic individuals. We applied a polynomial regression with response surface analysis to examine empathic disequilibrium and total empathy as predictors of an autism diagnosis and autistic traits. Results: Total empathy and empathic disequilibrium each predicted autism. There was a higher probability for diagnosis in individuals with lower total empathy, but also in individuals with higher emotional relative to cognitive empathy. Linear and non-linear patterns linked empathy, empathic disequilibrium, and autistic traits and diagnosis, with empathic disequilibrium being more prominent in females. Conclusions: Empathic disequilibrium might allow for a more nuanced and sensitive understanding of empathy and its link with autism. This study provides empirical evidence that empathic disequilibrium is at least as informative as empathy for assessing autism, and offers a novel analytical approach for examining the role of empathy at the phenomenological level.

"I'm trying to reach out, I'm trying to find my people": Loneliness and loneliness distress in autistic adults

Despite the persistent stereotype that autistic individuals are not motivated to seek meaningful social relationships, rates of loneliness among the autistic population are higher than in the non-autistic population. In this two-part, mixed methods study, we sought to 1) quantify the level of distress associated with loneliness in autistic and non-autistic adults and 2) gain qualitative insight into autistic experiences of loneliness. In Study A, 209 participants (encompassing a group of autistic individuals and a group of non-autistic comparison participants) completed questionnaire ratings of their level of loneliness, associated distress, trait anxiety, depression, and sensory sensitivity. Results indicated that the autistic group scored higher levels across all measures. Both groups manifest strong correlations between loneliness and loneliness distress. In the autistic group, but not the non-autistic group, regression analyses showed that loneliness and sensory sensitivity predicted levels of anxiety, wherein the effect of loneliness on anxiety was partially mediated by the level of sensory sensitivity. In Study B, nine autistic adults took part in ten-minute, unstructured dyadic conversations around the topic of loneliness. Inductive and deductive analyses enriched qualitative understanding of the experiences of loneliness of autistic individuals. Our results broadly oppose the social motivation deficit hypothesis and we instead frame our findings within the larger context of ‘ethical loneliness’, concluding that a concerted effort is needed to overcome the fundamental disconnect with the neurotypical world experienced by many autistic people.

Genetic Analysis of Neuroligin 4Y Gene in Autism Population of India

Background Autism is one of the most complex, heterogeneous neurological disorders. It is characterized mainly by abnormal communication, impaired social interaction, and restricted behaviors. Prevalence of autism is not clear in Indian population. Aim The present study hypothesizes that Y chromosome plays role in sex bias of autism in Indian autistic population. To investigate our hypothesis, we underwent genetic analysis of neuroligin 4Y [NLGN4Y] gene by sequencing 85 male autistic children after screening large population of 1,870 mentally ill children from North Karnataka region of India. Result Detailed sequencing of the single targeted gene revealed nine variants including, one novel missense mutation and eight synonymous variants; this accounts for 88.9% of synonymous variants. A single novel missense mutation is predicted to be nonpathogenic on the functions of neuroligin4Y protein but it slightly affects the local configuration by altering the original structure of a protein by changing charge and size of amino acid. Conclusion Probably NLGN4Y gene may not be the risk factor for autism in male children in Indian autistic population. Functional analysis was an important limitation of our study. Therefore, detailed functional analysis is necessary to determine the exact role of novel missense mutation of neuroligin 4Y [NLGN4Y] gene especially in the male predominance of autism in Indian autistic population.

Prevalence of Strabismus in Individuals on the Autism Spectrum: A Meta-analysis

Background and Objectives: Strabismus, a misalignment of the eyes, is an important risk factor for amblyopia and visual impairment in the pediatric population. Several studies have reported an increased likelihood of strabismus in persons on the autism spectrum, but prevalence estimates in this group vary greatly. Methods: We searched multiple databases to identify peer-reviewed articles published in English through November 1, 2020 that provided estimates of strabismus prevalence in autistic individuals. Prevalence estimates were synthesized using Bayesian random-effects meta-analysis, and sensitivity analysis was also performed using only the subset of studies that recruited participants from non-ophthalmologic settings and identified strabismus using structured ocular exams. Bayesian meta-regression was used to assess potential moderators of prevalence across studies. Results: A total of 151 nonduplicate articles were screened, of which 22 were included in the meta-analysis (k=28 samples, nAUT=113,227). The meta-analytic point prevalence of strabismus in autistic individuals was 13.4% (95% CrI [8.3, 19.4]), and sensitivity analysis produced a very similar estimate (14.0% [7.0, 22.0], nAUT=581). Esotropia was the predominant subtype of strabismus reported, accounting for approximately 55% of cases. Reported prevalence rates were higher in younger samples (BF10=13.43, R2Het=0.273) and samples recruited from optometry/ophthalmology clinics (BF10=11.47, R2Het=0.238). Conclusion: This meta-analysis found a high prevalence of strabismus in autistic individuals, with rates 3-10 times that of the general population. As untreated strabismus is a major risk factor for amblyopia in young children, these findings underscore the importance of timely screening and assessment of ocular problems in persons on the autism spectrum. What's Known on This Subject: Strabismus has been reported to be more prevalent in individuals on the autism spectrum, but estimates have been very imprecise, ranging from 3-84% across studies. What This Study Adds: This study performs the first quantitative synthesis of strabismus prevalence in over 100,000 autistic individuals, generating more precise estimates of the prevalence of strabismus in the autistic population. Factors contributing to the large differences between studies are also examined using meta-regression.

Investigating the structure of trait rumination in autistic adults: A network analysis

Rumination, a form of passive, repetitive negative thinking, predicts the development of depressive disorders in non-autistic individuals, and recent work suggests higher levels of rumination may contribute to elevated rates of depression in the autistic population. Using psychological network analysis, this study sought to investigate the structure of rumination in autistic individuals and the relationships between rumination and individual depressive symptoms. Non-regularized partial correlation networks were estimated using cross-sectional data from 608 autistic adults who completed the Ruminative Responses Scale and Beck Depression Inventory–II. Node centrality indices were calculated to determine which specific symptoms may have a disproportionate influence on the network of repetitive negative thoughts. Nodes were also grouped into communities, and specific “bridge” nodes were identified that most strongly connected these different communities. Results demonstrated strong positive relationships between all facets of ruminative thinking, similar to a prior study in non-autistic adults. Self-directed negative cognitions appeared to be particularly central in this network. The depression symptoms most strongly related to rumination in autistic adults were sadness and guilt. Although these findings are preliminary, they highlight specific facets of rumination that warrant future study as depression risk factors and potential intervention targets in the autistic population. Lay abstract Autistic adults are substantially more likely to develop depression than individuals in the general population, and recent research has indicated that certain differences in thinking styles associated with autism may play a role in this association. Rumination, the act of thinking about the same thing over and over without a functional outcome, is a significant risk factor for depression in both autistic and non-autistic adults. However, little is known about how different kinds of rumination relate to each other and to depressive symptoms in the autistic population specifically. To fill this gap in knowledge, we recruited a large online sample of autistic adults, who completed questionnaire measures of both the tendency to ruminate and symptoms of depression. By examining the interacting network of rumination and depression symptoms, this study was able to identify particular aspects of rumination—such as thinking repetitively about one’s guilty feelings or criticizing oneself—that may be particularly important in maintaining these harmful thought patterns in autistic adults. Although further study is needed, it is possible that the symptoms identified as most “influential” in the network may be particularly good targets for future interventions for mood and anxiety disorders in the autistic population.

Autistic voices from the workplace

Purpose The purpose of this paper is to give autistic employees a voice, evaluate their work-based experiences and to disseminate the relevant recommendations of the Westminster AchieveAbility Commission report. Design/methodology/approach These experiences were identified through a questionnaire answered by 600 neurodivergent employees, including 95 autistic respondents. This allowed us to compare experiences across neurodivergent categories. Findings The overwhelmingly negative work-place experience is consistent at every stage unless managers had a good understanding of neurodivergence. This deteriorated further the more categories of neurodivergence identified with, and minority ethnicity. Few reasonable adjustments were made. Psychometric tests are experienced as disabling. No statistically significant differences were found between genders. Research limitations/implications The target group are not representative of the wider autistic population and the sample is relatively small. Further research could look at how managers come to understand neurodivergence, the utilisation of reasonable adjustments and how to promote neurodivergence awareness. Practical implications There need to be wholesale changes in recruitment and reasonable adjustments in the workplace, which will require substantial changes in attitudes. Social implications The experience of neurodivergent people in the work-place, including autistic employees, was more consistently negative than expected. It was difficult to find any autistic employees without disabling experiences. This paper hopes this will alert wider society to the issues and may serve to support more solidarity amongst neurodivergent people in relation to employment. The findings have already influenced The Advisory, Conciliation and Arbitration Service. Originality/value There is very little detailed research focussed on the work-place experience and voices of autistic employees and less research that considers the implications of neurodivergent overlaps in the workplace.

Differences Between Autistic and Non-autistic Adults in the Recognition of Anger From Dynamic Expressions Remain After Controlling for Alexithymia.

A burgeoning literature suggests that alexithymia, and not autism, is responsible for the difficulties with static emotion recognition that are documented in the autistic population. Here we investigate whether alexithymia can also account for difficulties with dynamic facial expressions. Autistic and control adults (N=60) matched on age, gender, non-verbal reasoning ability and alexithymia, completed an emotion recognition task, which employed dynamic point light displays of emotional facial expressions that varied in speed and spatial exaggeration. The ASD group exhibited significantly lower recognition accuracy for angry, but not happy or sad, expressions with normal speed and spatial exaggeration. The level of autistic, and not alexithymic, traits was a significant predictor of accuracy for angry expressions with normal speed and spatial exaggeration.