Diagnosis of common health conditions among autistic adults in the UK: evidence from a matched cohort study.

Background: Autistic people are disproportionately likely to experience premature mortality and most mental and physical health conditions. We measured the incidence of diagnosed conditions accounting for the most disability-adjusted life years in the UK population according to the Global Burden of Disease study (anxiety, depression, self-harm, harmful alcohol use, substance use, migraine, neck or back pain, and gynaecological conditions). Methods: Participants were aged 18 years or above and had an autism diagnosis recorded in the IQVIA Medical Research Database between 01/01/2000 and 16/01/2019. We included 15,675 autistic adults without intellectual disability, 6437 autistic adults with intellectual disability, and a comparison group matched (1:10) by age, sex, and primary care practice. We estimated crude incidences and incidence rate ratios (IRRs) adjusted for age and sex. Findings: Autistic adults without intellectual disability experienced a higher incidence (IRR, 95% CI) of self-harm (2.07, 1.79-2.40), anxiety (1.91, 1.76-2.06), depressive disorders (1.79, 1.67-1.92), and substance use (1.24, 1.02-1.51) relative to comparison participants. Incidences of harmful alcohol use (1.01, 0.85-1.18), migraine (0.99, 0.84-1.17), and gynaecological conditions (1.19, 0.95-1.49) did not differ. Neck or back pain incidence was lower (0.88, 0.82-0.95). Autistic adults with intellectual disability experienced a higher incidence of self-harm (2.08, 1.69-2.56). Incidences of anxiety (1.14, 1.00-1.30), gynaecological conditions (1.22, 0.93-1.62), and substance use (1.08, 0.80-1.47) did not differ, and lower incidences were found for depressive disorders (0.73, 0.64-0.83), harmful alcohol use (0.65, 0.50-0.84), migraine (0.55, 0.42-0.74), and neck or back pain (0.49, 0.44-0.55). Interpretation: Although our findings cannot be directly compared to previous prevalence studies, they contrast with the higher frequency of mental and physical health conditions in autistic adults reported in studies that directly assessed and/or surveyed autistic people about co-occurring conditions. The present findings may suggest under-diagnosis of common conditions in autistic people, particularly those with intellectual disability. Improved detection should be a clinical and policy priority to reduce health inequalities. Funding: Dunhill Medical Trust, Economic and Social Research Council, National Institute of Health and Care Research.

Fruit and Vegetable Intake, Food Security, Barriers to Healthy Eating, and Empowerment among Dietetic Interns and Physician Assistant Interns: A Cross-Sectional Pilot Study.

Students are required to complete supervised practice hours prior to becoming Registered Dietitians and Physician Assistants. Research suggests that environmental and social factors affect dietetic interns' diets during their internship, although these factors have not been studied among physician assistant interns. This cross-sectional study utilized an online survey to compare dietetic interns' (n = 81) and physician assistant interns' (n = 79) fruit and vegetable intake, food security, barriers to healthy eating, and empowerment for making healthy dietary choices during an internship. Differences were assessed via independent t-tests and chi-square distributions. The significance was set at p < 0.05. Dietetic interns had a higher vegetable intake (p = 0.002) while physician assistant interns had higher rates of food insecurity (p = 0.040). Dietetic interns reported a greater impact on their dietary choices due to mental fatigue (p = 0.006), while physician assistant interns' dietary choices were more heavily impacted by peer influence, interactions with patients, and interactions with preceptors (p < 0.05). There was not a group difference in overall empowerment (p = 0.157), although both groups rated empowerment for asking for help with food and nutrition challenges the lowest of the empowerment sub-items. Addressing interns' unique needs may support students' educational success and wellbeing once they are professionals, promote a diverse workforce, and ensure optimal care for patients.

Estimating life expectancy and years of life lost for autistic people in the UK: a matched cohort study.

Background: Previous research has shown that people who have been diagnosed autistic are more likely to die prematurely than the general population. However, statistics on premature mortality in autistic people have often been misinterpreted. In this study we aimed to estimate the life expectancy and years of life lost experienced by autistic people living in the UK. Methods: We studied people in the IQVIA Medical Research Database with an autism diagnosis between January 1, 1989 and January 16, 2019. For each participant diagnosed autistic, we included ten comparison participants without an autism diagnosis, matched by age, sex, and primary care practice. We calculated age- and sex-standardised mortality ratios comparing people diagnosed autistic to the reference group. We used Poisson regression to estimate age-specific mortality rates, and life tables to estimate life expectancy at age 18 and years of life lost. We analysed the data separately by sex, and for people with and without a record of intellectual disability. We discuss the findings in the light of the prevalence of recorded diagnosis of autism in primary care compared to community estimates. Findings: From a cohort of nearly 10 million people, we identified 17,130 participants diagnosed autistic without an intellectual disability (matched with 171,300 comparison participants), and 6450 participants diagnosed autistic with an intellectual disability (matched with 64,500 comparison participants). The apparent estimates indicated that people diagnosed with autism but not intellectual disability had 1.71 (95% CI: 1.39-2.11) times the mortality rate of people without these diagnoses. People diagnosed with autism and intellectual disability had 2.83 (95% CI: 2.33-3.43) times the mortality rate of people without these diagnoses. Likewise, the apparent reduction in life expectancy for people diagnosed with autism but not intellectual disability was 6.14 years (95% CI: 2.84-9.07) for men and 6.45 years (95% CI: 1.37-11.58 years) for women. The apparent reduction in life expectancy for people diagnosed with autism and intellectual disability was 7.28 years (95% CI: 3.78-10.27) for men and 14.59 years (95% CI: 9.45-19.02 years) for women. However, these findings are likely to be subject to exposure misclassification biases: very few autistic adults and older-adults have been diagnosed, meaning that we could only study a fraction of the total autistic population. Those who have been diagnosed may well be those with greater support needs and more co-occurring health conditions than autistic people on average. Interpretation: The findings indicate that there is a group of autistic people who experience premature mortality, which is of significant concern. There is an urgent need for investigation into the reasons behind this. However, our estimates suggest that the widely reported statistic that autistic people live 16-years less on average is likely incorrect. Nine out of 10 autistic people may have been undiagnosed across the time-period studied. Hence, the results of our study do not generalise to all autistic people. Diagnosed autistic adults, and particularly older adults, are likely those with greater-than-average support needs. Therefore, we may have over-estimated the reduction in life expectancy experienced by autistic people on average. The larger reduction in life expectancy for women diagnosed with autism and intellectual disability vs. men may in part reflect disproportionate underdiagnosis of autism and/or intellectual disability in women. Funding: Dunhill Medical Trust, Medical Research Council, National Institute for Health and Care Research, and the Royal College of Psychiatrists.

Increased anticholinergic medication use in middle-aged and older autistic adults and its associations with self-reported memory difficulties and cognitive decline.

Many commonly used prescription and over-the-counter medicines have potent anticholinergic (AC) effects. Among older adults, AC medications are associated with cognitive impairment and risk for cognitive disorders, including Alzheimer's disease. Collectively, the impact of AC medications is known as anticholinergic cognitive burden (ACB). Because of the high rates of co-occurring medical and psychiatric conditions, autistic adults may have high AC exposure and, thus, may experience elevated ACB. However, no research has characterized AC exposure or examined its associations with cognitive outcomes in autistic adults. Autistic adults (40-83 years) recruited via Simons Powering Autism Research's (SPARK) Research Match service self-reported their medication use (N = 415) and memory complaints (N = 382) at Time (T)1. At T2, 2 years later, a subset of T1 participants (N = 197) self-reported on decline in cognition. Medications were coded using two scales of AC potency. A high proportion (48.2%-62.9%, depending upon the AC potency scale) of autistic adults reported taking at least one medication with AC effects, and 20.5% to 26.5% of autistic adults reported clinically-relevant levels of AC medication (potency ≥3). After controlling for birth-sex, and age, hierarchical linear regression models showed total ACB scores and AC potency values of ≥3 predicted greater memory complaints. Logistic regression models showed that AC medicines at T1 were associated with self-reported cognitive decline at follow-up 2 years later. Understanding AC medications-including potentially earlier AC polypharmacy-and their impacts on cognition (e.g., dementia risk) in autistic adults is warranted.

A Qualitative Study of Autistic Adults' Quality of Life During the COVID-19 Pandemic and Lockdowns.

Background: Autistic people experience higher rates of most mental health conditions and report more difficulties with change than nonautistic people. As such, the periods of national stay-at-home orders (known in the United Kingdom as a "lockdown") endured since the beginning of the COVID-19 (coronavirus disease 2019) pandemic in March 2020 may have been particularly challenging for autistic people. Aim: This study explored autistic adults' experience of quality of life and well-being during the start of the COVID-19 pandemic (specifically March to August 2020) using open-text responses from an online survey. Methods: In total, 79 autistic adults from the United Kingdom (aged 21-75 years) took part. Participants completed an online survey, including open-text questions on how various factors influencing quality of life, such as social interactions, general health, well-being, and sensory experiences, were impacted by the COVID-19 pandemic and the first set of national lockdowns that occurred between March and August 2020. Results: Thematic analysis created four key themes, each illustrated by several subthemes. These four themes explore (1) health, (2) social changes, (3) support provisions, and (4) adopting new routines. Many participants discussed the impact that the COVID-19 pandemic and the first set of national lockdowns had on their health and expressed concerns regarding the transition out of periods of lockdown, including readjusting to new rules, going back to in-person interactions, and reacclimatizing to high-stimulation sensory environments. However, several participants reported positive experiences of the periods of lockdown, such as reduced commuting, more control over sensory environments, and more time to pursue personal interests and self-care. Conclusions: These findings highlight the importance of giving autistic individuals the support they need to transition back to "normality" as COVID-19 becomes endemic.

Why is this an important issue?: The COVID-19 pandemic and national stay-at-home order (known in the United Kingdom as a "lockdown") led to severe disruption and change in people's lives throughout 2020 and early 2021. However, only a few studies have examined the impact of the lockdowns on autistic people's well-being. What was the purpose of this study?: The abrupt changes caused by the COVID-19 pandemic and lockdowns may have had a more detrimental impact on the lives of autistic people compared with others. This study aimed to explore the impact of the pandemic on the lives of autistic people and to provide context and descriptions of their experiences. What did the researchers do?: We asked autistic adults a range of open-response questions using an online survey in July/August 2020 to understand how they experienced the COVID-19 pandemic and periods of national lockdown. A total of 79 autistic adults from the United Kingdom took part. The questions asked about participants' health and general well-being, their social lives, and sensory differences before (retrospectively) and during the U.K. national lockdowns that occurred between March and August 2020. What were the results of the study?: Overall, most people felt that the pandemic had a negative impact on their lives. Many felt isolated and lonely due to lockdowns, and many expressed feelings of distress and anxiety at the prospect of returning to normality. However, several participants did report positive aspects of the periods of lockdown, such as having more time for personal interests and practicing self-care, and having to deal with less noise and sensory overload. What do these findings add to what was already known?: To date, much of the research about the impact of the COVID-19 pandemic and lockdowns on autistic peoples' lives has been quantitative (e.g., using scores on questionnaires). This study uses qualitative data (responses to open-ended questions). This study provides important contextualization of how the pandemic and lockdowns have impacted the lives of autistic people and highlights the need for additional support in the years after the pandemic. What are potential weaknesses in the study?: This study only includes autistic people, so we cannot be sure whether these experiences are unique to autistic people. Additionally, these findings may not be generalizable to the wider autistic population, including those who were unable to participate (e.g., those with learning difficulties). How will these findings help autistic adults now or in the future?: The COVID-19 pandemic and lockdowns are likely to have a long-lasting impact on well-being, which may disproportionately impact autistic people. As such, autistic people may need additional, tailored, support as COVID-19 becomes endemic (i.e., no longer a pandemic but part of everyday life, somewhat like seasonal flu). Additionally, lessons may be learned from the pandemic about how society could be adapted to become more inclusive.

Repetitive Behaviours in Autistic and Non-Autistic Adults: Associations with Sensory Sensitivity and Impact on Self-Efficacy.

PURPOSE: Restricted and repetitive behaviours are a core feature of autism diagnoses but have not been widely studied in adulthood. This study examined the rates of and associations between repetitive behaviours and sensory sensitivity in autistic and non-autistic adults; and whether repetitive behaviours described as "stimming" impacted coping with difficulties (self-efficacy). METHODS: Diagnosed autistic (n = 182), undiagnosed autistic (n = 163) and non-autistic (n = 146) adults completed online measures of repetitive behaviours, sensory sensitivity, and self-efficacy for when able and not able to stim. RESULTS: Repetitive behaviours and sensory sensitivity correlated significantly in each group, although ratings were higher in autistic compared to non-autistic groups. When people were able to stim, no differences between the groups were observed on self-efficacy ratings. However when unable to stim, autistic people reported lower self-efficacy than non-autistic people. CONCLUSIONS: Results suggest that repetitive behaviours are significantly associate with sensory sensitivities. Rather than repetitive behaviours being viewed as negative, stimming was associated with increased self-efficacy. Results suggest that stimming may have beneficial effects. Further work is needed to better understand how repetitive behaviours and stimming manifest in adulthood, how they change over time and their effects for autistic adults.

Self-reported Prospective and Retrospective Memory Among Middle Aged and Older Autistic and Non-autistic People.

OBJECTIVE: Self-reported memory difficulties are common among older adults, but few studies have examined memory problems among autistic middle-aged and older people. The current study examines self-rated prospective (PM) and retrospective (RM) memory difficulties and their associations with age in middle-aged and older autistic and non-autistic people. METHODS: 350 autistic people (58% assigned-female-at-birth; age-range: 40-83 years) and 350 non-autistic adults matched on age, birth-sex and education level were included in the analysis. Participants completed the Prospective and Retrospective Memory Questionnaire (PRMQ) which includes questions about PM vs. RM (memory type), environment-cued vs. self-cued (cue), and short vs. long delay (delay). RESULTS: Autistic people reported significantly more PM and RM difficulties than the comparison group. Both groups reported more difficulties with PM (vs. RM), self-cued (vs. environment-cued), and short (vs. long) delay. No significant interactions were observed. Among autistic people, younger age was associated with reporting more PM and RM difficulties, but this pattern was not observed among non-autistic people. CONCLUSIONS: Autistic people may be at reduced risk for memory problems as they age, compared to their same-age non-autistic peers. Further studies are required to explore the association between self-reported memory challenges and memory task performance among autistic older people.

Autism in England: assessing underdiagnosis in a population-based cohort study of prospectively collected primary care data.

Background: Autism has long been viewed as a paediatric condition, meaning that many autistic adults missed out on a diagnosis as children when autism was little known. We estimated numbers of diagnosed and undiagnosed autistic people in England, and examined how diagnostic rates differed by socio-demographic factors. Methods: This population-based cohort study of prospectively collected primary care data from IQVIA Medical Research Data (IMRD) compared the prevalence of diagnosed autism to community prevalence to estimate underdiagnosis. 602,433 individuals registered at an English primary care practice in 2018 and 5,586,100 individuals registered between 2000 and 2018 were included. Findings: Rates of diagnosed autism in children/young people were much higher than in adults/older adults. As of 2018, 2.94% of 10- to 14-year-olds had a diagnosis (1 in 34), vs. 0.02% aged 70+ (1 in 6000). Exploratory projections based on these data suggest that, as of 2018, 463,500 people (0.82% of the English population) may have been diagnosed autistic, and between 435,700 and 1,197,300 may be autistic and undiagnosed (59-72% of autistic people, 0.77%-2.12% of the English population). Age-related inequalities were also evident in new diagnoses (incidence): c.1 in 250 5- to 9-year-olds had a newly-recorded autism diagnosis in 2018, vs. c.1 in 4000 20- to 49-year-olds, and c.1 in 18,000 people aged 50+. Interpretation: Substantial age-related differences in the proportions of people diagnosed suggest an urgent need to improve access to adult autism diagnostic services. Funding: Dunhill Medical Trust, Economic and Social Research Council, Medical Research Council, National Institute for Health Research, the Wellcome Trust, and the Royal College of Psychiatrists.

Predictors of sleep quality for autistic people across adulthood.

Poor sleep can have a significant impact on physical health and well-being. Sleep problems are common among autistic children, but less is known about sleep across the autistic adult lifespan. Autistic adults (n = 730, aged 18-78 years) were recruited via Simons Powering Autism Research for Knowledge Research Match. Participants completed online surveys asking about demographics, health problems, social support, symptoms of anxiety and depression, and overall and specific aspects of sleep quality. Regression analyses explored the variables associated with sleep quality. Physical health, assigned female sex at birth and self-reported anxiety symptoms significantly contributed to models for all aspects of sleep. Perceived stress contributed to models of overall and subjective sleep quality, and daytime dysfunction. Depression symptoms did not contribute significantly to any of the models of sleep quality. However, utilizing government support mechanisms (such as social security) contributed to the model of sleep efficiency. Age contributed little to models of sleep quality, whereas perceived stress and psychotropic medication use contributed to some but not all aspects of sleep. Sleep quality is poor for autistic people across the adult lifespan. Given known impacts of poor sleep on health, cognition and quality of life, attention should be paid to sleep and its possible everyday effects for autistic people of all ages.

Self-harm and Suicidality Experiences of Middle-Age and Older Adults With vs. Without High Autistic Traits.

Suicide has been identified as a leading cause of premature death in autistic populations. Elevated autistic traits have also been associated with higher rates of self-harm, suicidal ideation, and suicidal self-harm in the general population, but this has yet to be examined in older age. Using baseline cross-sectional data from the PROTECT study, middle-age and older adults with high autistic traits (n = 276) had significantly higher rates of suicidal ideation, deliberate self-harm, and suicidal self-harm than an age/sex-matched comparison group (n = 10,495). These differences represented a 5- to 6-fold increase in likelihood for self-harming and suicidality. These findings, which remained when controlling for depression symptoms, suggest that middle-age and older adults with high autistic traits may be particularly at risk of self-harm and suicidal behaviours.

The cognitive profile of middle-aged and older adults with high vs. low autistic traits.

Cognitive differences in memory, information processing speed (IPS), and executive functions (EF), are common in autistic and high autistic trait populations. Despite memory, IPS and EF being sensitive to age-related change, little is known about the cognitive profile of older adults with high autistic traits. This study explores cross-sectional memory, IPS and EF task performance in a large sample of older adults in the online PROTECT cohort (n = 22,285, aged 50-80 years), grouped by high vs. low autistic traits. Approximately 1% of PROTECT participants (n = 325) endorsed high autistic traits [henceforth Autism Spectrum Trait (AST) group]. Differences between AST and age-, gender-, and education-matched comparison older adults (COA; n = 11,744) were explored on memory, IPS and EF tasks and questionnaires administered online. AST had lower performance than COA on tasks measuring memory, working memory, sustained attention, and information processing. No group differences were observed in simple attention or verbal reasoning. A similar pattern of results was observed when controlling for age, and current depression and anxiety symptoms. In addition, AST self-reported more cognitive decline than COA, but this difference was not significant when controlling for current depression symptoms, or when using informant-report. These findings suggest that autistic traits are associated with cognitive function in middle-aged and later life. Older adults with high autistic traits experienced more performance difficulties in a range of memory, IPS and EF tasks compared with the low autistic traits comparison group. Further longitudinal work is needed to examine age-related change in both older autistic and autistic trait populations.

Cardiovascular disease risk factors in autistic adults: The impact of sleep quality and antipsychotic medication use.

Approximately 40% of American adults are affected by cardiovascular disease (CVD) risk factors (e.g., high blood pressure, high cholesterol, diabetes, and overweight or obesity), and risk among autistic adults may be even higher. Mechanisms underlying the high prevalence of CVD risk factors in autistic people may include known correlates of CVD risk factors in other groups, including high levels of perceived stress, poor sleep quality, and antipsychotic medication use. A sample of 545 autistic adults without intellectual disability aged 18+ were recruited through the Simons Foundation Powering Autism Research, Research Match. Multiple linear regression models examined the association between key independent variables (self-reported perceived stress, sleep quality, and antipsychotic medication use) and CVD risk factors, controlling for demographic variables (age, sex assigned at birth, race, low-income status, autistic traits). Overall, 73.2% of autistic adults in our sample had an overweight/obesity classification, 45.3% had high cholesterol, 39.4% had high blood pressure, and 10.3% had diabetes. Older age, male sex assigned at birth, and poorer sleep quality were associated with a higher number of CVD risk factors. Using antipsychotic medications was associated with an increased likelihood of having diabetes. Poorer sleep quality was associated with an increased likelihood of having an overweight/obesity classification. Self-reported CVD risk factors are highly prevalent among autistic adults. Both improving sleep quality and closely monitoring CVD risk factors among autistic adults who use antipsychotic medications have the potential to reduce risk for CVD.

Social support and links to quality of life among middle-aged and older autistic adults.

LAY ABSTRACT: Social support can take many forms, such as practical help, time spent socially with others, or the satisfaction with personal relationships. Social support is known to affect quality of life (QoL) in both non-autistic older and autistic young adults. QoL reflects how satisfied an individual is with their life either overall or in a certain area. We know little about middle-aged and older autistic adults' experiences of social support or QoL. In this study, 388 adults aged 40-83 years old, completed online questionnaires asking about background such as age and sex, depression and anxiety symptoms, QoL (physical, psychological, social, environmental, and autism-specific), and different types of social support. Even after taking into account background, depression, and anxiety, social support was important for individuals' QoL. To our knowledge this is the first paper to examine the relationship between social support and QoL in middle-aged and older autistic adults. Improving social support may have a significant impact on the QoL of older autistic adults. Future studies should examine whether age-related changes in social support (size, content, and arrangement of social networks) that are common in non-autistic aging, also occur among older autistic adults.

Self-reported cognitive decline among middle and older age autistic adults.

Very little is known about autistic adults as they age. Early evidence suggests a potentially high risk for dementia and atypical cognitive decline in autistic middle and older age adults. Research in the general population indicates that self-reported cognitive decline may predict future dementia earlier than performance-based measures. Nevertheless, self-report dementia screeners have not been used to date in autism research. In a sample of middle and older age autistic adults (N = 210), participants completed a self-rated dementia screener, the AD8, to describe the rate of cognitive decline, examine associations of cognitive decline with age, educational level, sex designated at birth, and autistic traits, and document the psychometrics of a dementia screener in autistic adults. We found high rates of cognitive decline with 30% of the sample screening positive. The most common symptoms were declining interest in leisure activities, and increases in everyday problems with thinking, memory, and judgment. There was evidence that autistic individuals designated female at birth may be more vulnerable to cognitive decline than autistic individuals designated male at birth. Notably, reports of cognitive decline did not vary by age or educational level. Modestly elevated autistic traits were found in those screening positive versus negative for cognitive decline. Finally, the dementia screener showed good psychometrics, including convergent validity with an independent measure of current memory problems. These results could signal an emerging public health crisis in autistic adults as they age, and support the potential utility of self-report measures for early screening for cognitive decline in this population.

Aging and autism: Do measures of autism symptoms, co-occurring mental health conditions, or quality of life differ between younger and older autistic adults?

Previous research has indicated that autistic adults experience higher rates of co-occurring mental health difficulties and poorer quality of life (QoL) than their non-autistic peers. Little is known, however, about these aspects in older age or whether younger and older autistic adults experience similar patterns This cross-sectional study investigated potential age-related effects on autism symptoms, self-reported mental health, and QoL in younger and older autistic adults (n = 79, aged 19-71 years) compared to a non-autistic control group (n = 57) matched for gender, age and IQ. Results showed that autistic adults had higher levels of self-reported autism symptoms and poorer QoL than controls. There were no significant age effects on autism symptoms or on most self-rated mental health symptoms. However, significantly more autistic adults in the younger versus older group scored above the clinical threshold for anxiety, somatoform disorders and eating disorders. Older autistic adults rated social QoL as significantly better than younger autistic adults; there was no significant age difference in the control group. Self-reported QoL was best predicted by self-ratings of severity of depressive symptoms in both groups. Further research is needed to track autism and co-occurring mental health symptomatology across the lifespan, so that service provision can be tailored accordingly. LAY SUMMARY: Young autistic adults have reported more psychological difficulties and poorer quality of life (QoL) than the general population. We investigated whether these difficulties continue into older age. Autism symptoms and mental health problems were common in autistic adults, with no difference between age groups, except for anxiety, physical and eating problems. Although QoL was poorer in both younger and older autistic compared to non-autistic adults, older autistic adults reported better social QoL than those who were younger.

Traumatic life experiences and post-traumatic stress symptoms in middle-aged and older adults with and without autistic traits.

OBJECTIVES: Research with younger adults has begun to explore associations between autism/autistic traits and vulnerability to Post Traumatic Stress Disorder (PTSD). Large scale studies and/or examination of age-effects have not been conducted. METHODS: Adults aged 50 years+ from the PROTECT study (n = 20,220) completed items about current and childhood socio-communicative difficulties characteristic of autism. Approximately 1% (n = 251) endorsed high autistic traits, henceforth the Autism Spectrum Traits (AST) group. Differences between the AST and an age-and sex-matched "Comparison Older Adults" (COA; n = 9179) group were explored for lifetime traumatic experiences and current symptoms of PTSD, depression, and anxiety. RESULTS: Almost 30% of the AST group, compared to less than 8% of the COA, reported severe trauma in childhood/adulthood, including emotional, physical or sexual abuse. Elevated current PTSD symptoms were reported by AST compared to COA. An interaction was observed between autistic traits and trauma severity; the effect of level of trauma on PTSD symptoms was significantly greater for AST versus COA participants. This interaction remained significant when controlling for current depression and anxiety symptoms. CONCLUSIONS: The findings suggest that high autistic traits may increase the likelihood of experiencing trauma across the lifespan, and the impact of severe trauma on PTSD symptoms. Older adults with high (vs. low) autistic traits may be at greater risk of experiencing PTSD symptoms in latter life. Future research should test whether the pattern of results is similar for diagnosed autistic adults.

Chalcones identify cTXNPx as a potential antileishmanial drug target.

With current drug treatments failing due to toxicity, low efficacy and resistance; leishmaniasis is a major global health challenge that desperately needs new validated drug targets. Inspired by activity of the natural chalcone 2',6'-dihydroxy-4'-methoxychalcone (DMC), the nitro-analogue, 3-nitro-2',4',6'- trimethoxychalcone (NAT22, 1c) was identified as potent broad spectrum antileishmanial drug lead. Structural modification provided an alkyne containing chemical probe that labelled a protein within the parasite that was confirmed as cytosolic tryparedoxin peroxidase (cTXNPx). Crucially, labelling is observed in both promastigote and intramacrophage amastigote life forms, with no evidence of host macrophage toxicity. Incubation of the chalcone in the parasite leads to ROS accumulation and parasite death. Deletion of cTXNPx, by CRISPR-Cas9, dramatically impacts upon the parasite phenotype and reduces the antileishmanial activity of the chalcone analogue. Molecular docking studies with a homology model of in-silico cTXNPx suggest that the chalcone is able to bind in the putative active site hindering access to the crucial cysteine residue. Collectively, this work identifies cTXNPx as an important target for antileishmanial chalcones.

The Mental and Physical Health Profiles of Older Adults Who Endorse Elevated Autistic Traits.

OBJECTIVES: The mental and physical health profile of autistic people has been studied in adolescence and adulthood, with elevated rates of most conditions being reported. However, this has been little studied taking a dimensional approach to autistic traits and in older age. METHODS: A total of 20,220 adults aged 50-81 years from the PROTECT study reported whether they experienced persistent sociocommunicative traits characteristic of autism. Approximately 1%, 276 individuals, were identified as endorsing elevated autistic traits in childhood and currently, henceforth the "Autism Spectrum Trait" (AST) group. An age- and gender-matched comparison group was formed of 10,495 individuals who did not endorse any autistic behavioral traits, henceforth the "Control Older Adults" (COA) group. Differences between AST and COA groups were explored in self-reported psychiatric diagnoses, self-reported symptoms of current depression and anxiety, and self-reported physical health diagnoses. Associations were also examined between autistic traits and health across the whole sample. RESULTS: The AST group reported significantly elevated rates of psychiatric diagnoses compared to the COA group. Additionally, the AST group showed significantly higher self-reported symptoms of current depression and anxiety than the COA group. However, few differences were observed in individual physical health conditions, and no differences in total co-occurring physical diagnoses between groups. Similar associations between autistic traits and health were also found taking a dimensional approach across the whole sample. DISCUSSION: These findings suggest that older adults with elevated autistic traits may be at greater risk of poorer mental, but not physical, health in later life. Future studies should incorporate polygenic scores to elucidate the possible genetic links between the propensity to autism/high autistic traits and to psychiatric conditions, and to explore whether those with elevated autistic traits experience particular barriers to mental health care.

Age-Related Effects on Social Cognition in Adults with Autism Spectrum Disorder: A Possible Protective Effect on Theory of Mind.

Impaired social cognition has been suggested to underlie the social communication difficulties that define autism spectrum disorder (ASD). In typical development, social cognition may deteriorate in older age, but age effects in ASD adults have been little explored. In the present study, we compared groups of younger and older adults with and without ASD (n = 97), who completed a set of social cognition tasks assessing theory of mind (ToM), and self-report measures of empathy and alexithymia. While typically developing (TD) younger adults outperformed elderly TD and younger ASD participants, younger and older ASD adults did not differ in their ToM performance, and the elderly ASD and TD groups performed equivalently. By contrast, ASD adults reported lower empathy scores and higher levels of alexithymia symptoms compared to TD adults regardless of age. The difference between ASD and TD groups in self-reported empathy scores was no longer significant when alexithymia was covaried (with the exception of the Perspective Taking subscore). Results suggest a possible age-protective effect on ToM in the ASD group. In addition, empathy difficulties appear to be associated with alexithymia rather than ASD per se. Possible interpretations are discussed, and future directions for autism aging research are proposed. LAY SUMMARY: People with autism spectrum disorder (ASD) have difficulties with social understanding. Some age-related studies in typical development have shown a decline in social understanding in older age. We investigated whether a similar pattern is present in adults with ASD. We found that understanding what someone is thinking was not worse in older versus younger autistic adults. Also, we reported further evidence suggesting that emotional empathy difficulties were related to difficulties with understanding one's own emotions rather than with autism itself. Autism Res 2021, 14: 911-920. © 2020 International Society for Autism Research and Wiley Periodicals LLC.

Antileishmanial Chemotherapy through Clemastine Fumarate Mediated Inhibition of the Leishmania Inositol Phosphorylceramide Synthase.

Current chemotherapeutics for leishmaniasis have multiple deficiencies, and there is a need for new safe, efficacious, and affordable medicines. This study describes a successful drug repurposing approach that identifies the over-the-counter antihistamine, clemastine fumarate, as a potential antileishmanial drug candidate. The screening for inhibitors of the sphingolipid synthase (inositol phosphorylceramide synthase, IPCS) afforded, following secondary screening against Leishmania major (Lmj) promastigotes, 16 active compounds. Further refinement through the dose response against LmjIPCS and intramacrophage L. major amastigotes identified clemastine fumarate with good activity and selectivity with respect to the host macrophage. On target engagement was supported by diminished sensitivity in a sphingolipid-deficient L. major mutant (ΔLmjLCB2) and altered phospholipid and sphingolipid profiles upon treatment with clemastine fumarate. The drug also induced an enhanced host cell response to infection indicative of polypharmacology. The activity was sustained across a panel of Old and New World Leishmania species, displaying an in vivo activity equivalent to the currently used drug, glucantime, in a mouse model of L. amazonensis infection. Overall, these data validate IPCS as an antileishmanial drug target and indicate that clemastine fumarate is a candidate for repurposing for the treatment of leishmaniasis.