Time is of the essence: Age at autism diagnosis, sex assigned at birth, and psychopathology.

LAY ABSTRACT: Previous research has shown that girls/women are diagnosed later than boys/men with autism. Individuals who are diagnosed later in life, especially girls/women, have greater anxious and depressive symptoms. Previous research has been limited due to narrow inclusionary criteria for enrollment in studies. The present study uses two samples-one clinic-based, large "real-world" sample and another research-based sample with strict criteria for autism diagnosis-to understand the relationships between diagnostic age, sex assigned at birth, and symptoms of anxiety/depression. In both samples, those who were diagnosed later had greater anxious/depressive symptoms, and anxiety was not predicted by sex. In the clinic-based but not research-based sample, those assigned female at birth were diagnosed later than those assigned male at birth. In the clinic-based sample only, individuals assigned female at birth and who were later diagnosed experienced greater symptoms of anxiety/depression compared to those assigned male who benefited from earlier diagnostic timing. Within the research-based sample, those assigned female at birth had greater depressive symptoms than those assigned male. These findings highlight the importance of timely identification of autism, especially for girls/women who are often diagnosed later. Community-based samples are needed to better understand real-world sex-based and diagnostic age-based disparities in mental health.

Gender, assigned sex at birth, and gender diversity: Windows into diagnostic timing disparities in autism.

LAY ABSTRACT: Later autism diagnosis is associated with risk for mental health problems. Understanding factors related to later autism diagnosis may help reduce mental health risks for autistic people. One characteristic associated with later autism diagnosis is female sex. However, studies often do not distinguish sex assigned at birth and gender identity. Gender diversity may be more common in autistic relative to neurotypical people, and autism is more common in gender-diverse populations. We studied age at autism diagnosis by sex assigned at birth, gender identity, and gender diversity (gender-diverse vs cisgender) status, separately. We studied three separate autistic samples, each of which differed in how they were diagnosed and how they were recruited. The samples included 193 persons (8.0-18.0 years) from a research-recruited academic medical center sample; 1,550 people (1.3-25.4 years) from a clinic-based sample; and 244 people (18.2-30.0 years) from a community-enriched sample. We found significant differences in the clinic-based and community-enriched samples. People assigned female sex at birth were diagnosed with autism significantly later than people assigned male at birth. People of female gender were diagnosed significantly later than people of male gender. Gender-diverse people were diagnosed significantly later than cisgender people. Sex assigned at birth, gender identity, and gender diversity may each show unique relationships with age of autism diagnosis. Differences in how autistic people are diagnosed and recruited are important to consider in studies that examine sex assigned at birth or gender identity. More research into autism diagnosis in adulthood is needed.

A randomized phase 2 trial of oral vitamin A for graft-versus-host disease in children and young adults.

ABSTRACT: Vitamin A plays a key role in the maintenance of gastrointestinal homeostasis and promotes a tolerogenic phenotype in tissue resident macrophages. We conducted a prospective randomized double-blinded placebo-controlled clinical trial in which 80 recipients of hematopoietic stem cell transplantation (HSCT) were randomized 1:1 to receive pretransplant high-dose vitamin A or placebo. A single oral dose of vitamin A of 4000 IU/kg, maximum 250 000 IU was given before conditioning. The primary end point was incidence of acute graft-versus-host disease (GVHD) at day +100. In an intent-to-treat analysis, incidence of acute GVHD was 12.5% in the vitamin A arm and 20% in the placebo arm (P = .5). Incidence of acute gastrointestinal (GI) GVHD was 2.5% in the vitamin A arm (P = .09) and 12.5% in the placebo arm at day +180. Incidence of chronic GVHD was 5% in the vitamin A arm and 15% in the placebo arm (P = .02) at 1 year. In an "as treated" analysis, cumulative incidence of acute GI GVHD at day +180 was 0% and 12.5% in recipients of vitamin A and placebo, respectively (P = .02), and cumulative incidence of chronic GVHD was 2.7% and 15% in recipients of vitamin A and placebo, respectively (P = .01). The only possibly attributable toxicity was asymptomatic grade 3 hyperbilirubinemia in 1 recipient of vitamin A at day +30, which self-resolved. Absolute CCR9+ CD8+ effector memory T cells, reflecting gut T-cell trafficking, were lower in the vitamin A arm at day +30 after HSCT (P = .01). Levels of serum amyloid A-1, a vitamin A transport protein with proinflammatory effects, were lower in the vitamin A arm. The vitamin A arm had lower interleukin-6 (IL-6), IL-8, and suppressor of tumorigenicity 2 levels and likely a more favorable gut microbiome and short chain fatty acids. Pre-HSCT oral vitamin A is inexpensive, has low toxicity, and reduces GVHD. This trial was registered at www.ClinicalTrials.gov as NCT03202849.

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.

Plasmonic and Photothermal Properties of Silica-Capped Gold Nanoparticle Aggregates.

Owing to their biocompatibility, gold nanoparticles have many applications in healthcare, notably for targeted drug delivery and the photothermal therapy of tumors. The addition of a silica shell to the nanoparticles can help to minimize the aggregation of the nanoparticles upon exposure to harsh environments and protect any Raman reporters adsorbed onto the metal surface. Here, we report the effects of the addition of a silica shell on the photothermal properties of a series of gold nanostructures, including gold nanoparticle aggregates. The presence of a Raman reporter at the surface of the gold nanoparticles also allows the structures to be evaluated by surface-enhanced Raman scattering (SERS). In this work, we explore the relationship between the degree of aggregation and the position and the extinction of the near-infrared plasmon on the observed SERS intensity and in the increase in bulk temperature upon near-infrared excitation. By tailoring the concentration of the silane and the thickness of the silica shell, it is possible to improve the photothermal heating capabilities of the structures without sacrificing the SERS intensity or changing the optical properties of the gold nanoparticle aggregates.

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.

Optoplasmonic Effects in Highly Curved Surfaces for Catalysis, Photothermal Heating, and SERS.

Surface curvature can be used to focus light and alter optical processes. Here, we show that curved surfaces (spheres, cylinders, and cones) with a radius of around 5 µm lead to maximal optoplasmonic properties including surface-enhanced Raman scattering (SERS), photocatalysis, and photothermal processes. Glass microspheres, microfibers, pulled fibers, and control flat substrates were functionalized with well-dispersed and dense arrays of 45 nm Au NP using polystyrene-block-poly-4-vinylpyridine (PS-b-P4VP) and chemically modified with 4-mercaptobenzoic acid (4-MBA, SERS reporter), 4-nitrobenzenethiol (4-NBT, reactive to plasmonic catalysis), or 4-fluorophenyl isocyanide (FPIC, photothermal reporter). The various curved substrates enhanced the plasmonic properties by focusing the light in a photonic nanojet and providing a directional antenna to increase the collection efficacy of SERS photons. The optoplasmonic effects led to an increase of up to 1 order of magnitude of the SERS response, up to 5 times the photocatalytic conversion of 4-NBT to 4,4'-dimercaptoazobenzene when the diameter of the curved surfaces was about 5 µm and a small increase in photothermal effects. Taken together, the results provide evidence that curvature enhances plasmonic properties and that its effect is maximal for spherical objects around a few micrometers in diameter, in agreement with a theoretical framework based on geometrical optics. These enhanced plasmonic effects and the stationary-phase-like plasmonic substrates pave the way to the next generation of sensors, plasmonic photocatalysts, and photothermal devices.

Measuring flexibility in autistic adults: Exploring the factor structure of the flexibility scale self report.

Cognitive flexibility differences are common for autistic individuals and have an impact on a range of clinical outcomes. However, there is currently a lack of well validated measurement tools to assess flexibility in adulthood. The Flexibility Scale was originally designed as a parent-report measure of real-world flexibility challenges in youth. The original Flexibility Scale provides a total score and five subscales: Routines and Rituals, Transitions and Change, Special Interests, Social Flexibility, and Generativity. In this study, we evaluate the factorial validity of the Flexibility Scale as a self-report (Flexibility Scale Self Report) measure of cognitive flexibility, adapted from the original Flexibility Scale, for use by autistic adults. This study includes both a primary sample (n = 813; mean age = 40.3; 59% female) and an independently recruited replication sample (n = 120; mean age = 32.8; 74% female) of individuals who completed the Flexibility Scale Self Report. The analysis consisted of an initial confirmatory factor analysis (CFA) of the original Flexibility Scale structure, followed by exploratory factor analysis (EFA) and factor optimization within a structural equation modeling framework to identify the optimal structure for the questionnaire in adults. The identified structure was then replicated through CFA in the replication sample. Our results indicate an alternative optimal scale structure from the original Flexibility Scale, which includes fewer items, and only three (Routines/Rituals, Transitions and Change, Special Interests) of the five subscales contributing to the flexibility total score. Comparisons revealed no structural differences within the scale based on sex assigned at birth. Here the Generativity and Social Flexibility scales are treated as independent but related scales. The implications for measurement of cognitive flexibility in clinical and research settings, as well as theoretical underpinnings are discussed.

Optimized vitamin D repletion with oral thin film cholecalciferol in patients undergoing stem cell transplant.

Vitamin D deficiency is common in childhood, pervasive before and after bone marrow transplant, and is associated with increased incidence of graft-versus-host disease (GVHD) and decreased survival in patients undergoing hematopoietic stem cell transplant (HSCT). Numerous barriers impede replacement, including malabsorption secondary to gut GVHD, mucositis, inability to take capsules, kidney disease, liver disease, and infection; many patients remain refractory despite vitamin D therapy. We hypothesized that a different formulation of cholecalciferol, administered on the tongue as a readily dissolving oral thin film (OTF), would ease administration and facilitate therapeutic vitamin D levels (>35 ng/mL) in patients who are refractory. In this prospective pilot study, we evaluated 20 patients after HSCT (range, day +21 - day +428 at enrollment) with serum vitamin D levels ≤35 ng/mL. Cholecalciferol OTF strips were administered for 12 weeks. Dosing was based on patient body weight and titrated per individual pharmacokinetics. Wilcoxon matched-pairs signed-rank test demonstrated marked improvement in all 20 patients who were formerly refractory, increasing from a median baseline vitamin D level of 29.2 ng/mL to 58 ng/mL at end of study (P < .0001). All patients demonstrated improvement in serum vitamin D level by week 4 on study, some of whom had been refractory for years prior. Median dose was 1 OTF strip (40 000 IU) per week. No toxicity was observed. This formulation proved to be safe, effective, efficient, and well received. We are eager to explore other patient populations, which might benefit from this promising development, and other therapeutics that might be optimized using this mode of delivery. This trial was registered at www.clinicaltrials.gov as #NCT04818957.

Evaluating nanoparticle localisation in glioblastoma multicellular tumour spheroids by surface enhanced Raman scattering.

Glioblastoma multiforme (GBM) is a particularly aggressive and high-grade brain cancer, with poor prognosis and life expectancy, in urgent need of novel therapies. These severe outcomes are compounded by the difficulty in distinguishing between cancerous and non-cancerous tissues using conventional imaging techniques. Metallic nanoparticles (NPs) are advantageous due to their diverse optical and physical properties, such as their targeting and imaging potential. In this work, the uptake, distribution, and location of silica coated gold nanoparticles (AuNP-SHINs) within multicellular tumour spheroids (MTS) derived from U87-MG glioblastoma cells was investigated by surface enhanced Raman scattering (SERS) optical mapping. MTS are three-dimensional in vitro tumour mimics that represent a tumour in vivo much more closely than that of a two-dimensional cell culture. By using AuNP-SHIN nanotags, it is possible to readily functionalise the inner gold surface with a Raman reporter, and the outer silica surface with an antibody for tumour specific targeting. The nanotags were designed to target the biomarker tenascin-C overexpressed in U87-MG glioblastoma cells. Immunochemistry indicated that tenascin-C was upregulated within the core of the MTS, however limitations such as NP size, quiescence, and hypoxia, restricted the penetration of the nanotags to the core and they remained in the outer proliferating cells of the spheroids. Previous examples of MTS studies using SERS demonstrated the incubation of NPs on a 2D monolayer of cells, with the subsequent formation of the MTS from these pre-incubated cells. Here, we focus on the localisation of the NPs after incubation into pre-formed MTS to establish a better understanding of targeting and NP uptake. Therefore, this work highlights the importance for the investigation and translation of NP uptake into these 3D in vitro models.

Sexual Minority Identities in Autistic Adults: Diversity and Associations with Mental Health Symptoms and Subjective Quality of Life.

Background: Although disparities in mental health and subjective quality of life (QoL) have been reported for autistic adults, reasons for these disparities are poorly understood. A potential factor in these disparities is exposure to social stressors related to minority status (i.e., minority stress), including stigma and discrimination. Autistic individuals are more likely than nonautistic individuals to be from groups with other minority identities, including sexual minorities (i.e., sexual orientations such as asexual, bisexual, gay). However, to date, few studies have examined whether sexual minority autistic adults experience diminished mental health relative to heterosexual autistic adults, and no research has examined subjective QoL for sexual minority compared with heterosexual autistic adults. Methods: Participants were 651 autistic adults aged 18.5 to 83.3 years recruited through Simons Powering Autism Research's Research Match. All participants resided in the United States. Participants completed surveys online, including measures of anxious and depressive symptomatology, perceived stress, and subjective QoL. Participants reported their sexual orientation and other sociodemographic variables. Results: A large proportion of autistic adults reported a sexual minority identity (41.2%), and a diversity of sexual identities was reported. Sexual minority autistic adults reported poorer mental health and lower subjective QoL across all assessed domains relative to heterosexual autistic adults. Conclusion: Understanding factors that may be associated with poorer mental health and decreased subjective QoL in autistic adults is critical and has been identified as a research priority by autistic stakeholders. The findings reported here underscore the need to examine mental health and subjective QoL disparities among autistic individuals within a societal context, taking into consideration the potential of intersecting minority identities and increased social stressors, as these added stressors may increase risks for poorer outcomes.

Why is this an important issue?: Autistic people are at risk for mental health problems, such as depression and anxiety, and report lower quality of life. Autistic people are more likely than nonautistic people to identify as a sexual minority. Sexual minority identities are sexual orientations other than heterosexual, such as asexual, bisexual, or gay. Sexual minority persons are also at risk for mental health problems and lower quality of life. Autistic people who are sexual minorities may have even higher risk of mental health problems and lower quality of life. What was the purpose of this study?: There is little research on mental health and quality of life in persons who are both autistic and identify as a sexual minority. Sexual minority autistic adults may be exposed to more minority-related stress than heterosexual autistic adults. People who belong to minority groups face added stress created by society. This added stress is referred to as minority stress, which includes things such as discrimination, rejection, or violence. Minority stress could increase risk for poor outcomes. We compared heterosexual and sexual minority autistic adults to see if having more than one minority identity (an autistic identity and a sexual minority identity) was associated with mental health or subjective quality of life. Subjective quality of life refers to how a person feels about parts of their life, such as their physical and psychological health or their living arrangements. What did the researchers do?: We asked 651 autistic adults living in the United States to complete surveys online. Participants rated their anxiety, depression, and everyday stress; answered questions about their subjective quality of life; and reported their sexual orientation, sex assigned at birth, and gender identity. We compared sexual minority with heterosexual autistic adults to see if they differed for mental health or subjective quality-of-life ratings. What were the results of the study?: A total of 41.2% of autistic adults reported a sexual minority identity. Autistic adults reported a diversity of sexual orientations, including asexual, bisexual, gay, and pansexual. Sexual minority autistic adults reported more depression, anxiety, and stress compared with heterosexual autistic adults. Sexual minority autistic adults reported poorer subjective quality of life across different areas of their lives compared with heterosexual autistic adults. Sexual minority autistic adults reported having less energy and more physical pain than heterosexual autistic adults. Sexual minority autistic adults also reported feeling more negative emotions and having problems with thinking/concentration. Sexual minority autistic adults reported more concerns about things such as having health care and transportation and greater worries about feeling safe in their homes and neighborhoods. Finally, sexual minority autistic adults were more likely to report that they faced barriers in their everyday lives (such as sensory sensitivities making it hard to grocery shop). What are the potential weaknesses in the study?: Although we found significant differences between sexual minority and heterosexual autistic groups, other factors likely play a role in these results. For example, we know that not having enough social support can contribute to worse mental health and quality of life. Measuring other such factors is needed in future studies. How will these findings help autistic adults now or in the future?: These findings highlight the need for more awareness of sexual minority identities in autistic adults. Understanding factors that may contribute to worse mental health and quality of life for autistic adults can help us improve well-being for all autistic people.

Synthesis, characterisation and multi-modal intracellular mapping of cisplatin nano-conjugates.

The synthesis of nanocarriers for the delivery of the antitumor drug cisplatin is reported. Multimodal-imaging consisting of surface enhanced Raman scattering and laser ablation inductively coupled plasma time of flight mass spectrometry was used to visualise the intracellular uptake of both the nanocarrier and drug.

Interrelated Roles of Multiple Key Structure-Directing Agents in Seed-Mediated Growth of Monodisperse and Multibranched Au Nanoparticles.

Detailed mechanistic investigations of the interrelated roles of multiple key structure-directing agents in the growth solution of Au nanoparticles (AuNPs) is required for the optimization of synthetic protocols. Here, we report a robust seed-mediated growth strategy for synthesizing multibranched NPs (MB-AuNPs) with monodispersed size distribution, and investigate the roles of Ag ions and 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid (HEPES) based on an overgrowth synthesis approach. The intertwining roles of Ag+ , surface-capping stabilizers, and reducing agents were elucidated, and used to control the morphology of MB-AuNPs. The overgrowth of MB-AuNPs involves two distinct underlying pathways, namely, directional and anisotropic growth of Au branches on specific facets of Au seeds as well as an aggregation and growth mechanism governed by HEPES. In addition to Ag ions and HEPES, morphology tunability can also be achieved by pre-modification of the Au seeds with molecular probes. Optimized probe-containing MB-AuNPs prove to be excellent surface-enhanced Raman scattering (SERS) substrates and nanozymes. Taken together, the results of this work reveal the mechanistic evolution of nanocrystal growth which should stimulate the development of new synthetic strategies, improve the capabilities of tuning the optical, catalytic, and electronic properties of NPs, and further advance their applications in biolabeling, imaging, biosensing, and therapy.

The autism spectrum among transgender youth: default mode functional connectivity.

The common intersection of autism and transgender identities has been described in clinical and community contexts. This study investigates autism-related neurophenotypes among transgender youth. Forty-five transgender youth, evenly balanced across non-autistic, slightly subclinically autistic, and full-criteria autistic subgroupings, completed resting-state functional magnetic resonance imaging to examine functional connectivity. Results confirmed hypothesized default mode network (DMN) hub hyperconnectivity with visual and motor networks in autism, partially replicating previous studies comparing cisgender autistic and non-autistic adolescents. The slightly subclinically autistic group differed from both non-autistic and full-criteria autistic groups in DMN hub connectivity to ventral attention and sensorimotor networks, falling between non-autistic and full-criteria autistic groups. Autism traits showed a similar pattern to autism-related group analytics, and also related to hyperconnectivity between DMN hub and dorsal attention network. Internalizing, gender dysphoria, and gender minority-related stigma did not show connectivity differences. Connectivity differences within DMN followed previously reported patterns by designated sex at birth (i.e. female birth designation showing greater within-DMN connectivity). Overall, findings suggest behavioral diagnostics and autism traits in transgender youth correspond to observable differences in DMN hub connectivity. Further, this study reveals novel neurophenotypic characteristics associated with slightly subthreshold autism, highlighting the importance of research attention to this group.

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.

The Gender Self-Report: A multidimensional gender characterization tool for gender-diverse and cisgender youth and adults.

Gender identity is a core component of human experience, critical to account for in broad health, development, psychosocial research, and clinical practice. Yet, the psychometric characterization of gender has been impeded due to challenges in modeling the myriad gender self-descriptors, statistical power limitations related to multigroup analyses, and equity-related concerns regarding the accessibility of complex gender terminology. Therefore, this initiative employed an iterative multi-community-driven process to develop the Gender Self-Report (GSR), a multidimensional gender characterization tool, accessible to youth and adults, nonautistic and autistic people, and gender-diverse and cisgender individuals. In Study 1, the GSR was administered to 1,654 individuals, sampled through seven diversified recruitments to be representative across age (10-77 years), gender and sexuality diversity (∼33% each gender diverse, cisgender sexual minority, cisgender heterosexual), and autism status (> 33% autistic). A random half-split subsample was subjected to exploratory factor analytics, followed by confirmatory analytics in the full sample. Two stable factors emerged: Nonbinary Gender Diversity and Female-Male Continuum (FMC). FMC was transformed to Binary Gender Diversity based on designated sex at birth to reduce collinearity with designated sex at birth. Differential item functioning by age and autism status was employed to reduce item-response bias. Factors were internally reliable. Study 2 demonstrated the construct, convergent, and ecological validity of GSR factors. Of the 30 hypothesized validation comparisons, 26 were confirmed. The GSR provides a community-developed gender advocacy tool with 30 self-report items that avoid complex gender-related "insider" language and characterize diverse populations across continuous multidimensional binary and nonbinary gender traits. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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.

Reduced-Intensity Conditioning Mitigates Risk for Primary Ovarian Insufficiency but Does Not Decrease Risk for Infertility in Pediatric and Young Adult Survivors of Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for many pediatric malignant and nonmalignant conditions. Gonadal insufficiency or infertility is present in almost all HSCT survivors who received a myeloablative conditioning (MAC) regimen. Reduced-intensity conditioning (RIC) regimens are being increasingly used in medically fragile patients or in patients with nonmalignant diagnoses to limit the toxicities associated with HSCT; however, the short-term and long-term gonadal toxicity of RIC regimens in pediatric and young adult survivors remains unknown. In this study, we compared the prevalence of gonadal insufficiency and infertility among pubertal and postpubertal pediatric and young adult survivors of HSCT who received a RIC regimen versus those who received a MAC regimen. Twenty-three females (RIC, n = 8; MAC, n = 15) and 35 males (RIC, n = 19; MAC, n = 16) were included in this single-center, retrospective cross-sectional study. Eligible patients were those with available laboratory results who were ≥1 year post-HSCT, age <40 years, and pubertal or postpubertal as assessed by an endocrinologist. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and anti-Müllerian hormone (AMH) levels were measured in females, and FSH, LH, total testosterone, and inhibin B (InhB) levels were measured in males. Twenty-one males (RIC, n = 11; MAC, n = 10) underwent semen analysis through a separate consent. Parametric and nonparametric analyses were undertaken to compare the RIC and MAC groups. Female patients who received RIC were less likely than those who received MAC to develop primary ovarian insufficiency, as demonstrated by elevated FSH (P = .02) and low estradiol (P = .01) or elevated LH (P = .09). Most females in the RIC (75%) and MAC (93%) groups had low AMH levels, indicating low or absent ovarian reserve, with no significant difference between the groups (P = .53). In males, there were no significant differences between the 2 groups in the prevalence of abnormal FSH, LH, testosterone, or InhB levels. Ten of 11 RIC males (91%) and 10 of 10 MAC males (100%) had azoospermia or oligospermia, at a median time to semen analysis from HSCT of 3.7 years (range, 1.3 to 12.2 years). RIC may pose less risk than MAC for primary ovarian insufficiency among female survivors of HSCT; however, both female and male recipients of either RIC or MAC regimens are at high risk for infertility. In the largest reported series of semen analyses of pediatric and young adult male recipients of RIC, azoospermia or oligospermia was found in nearly all (91%) RIC survivors. All patients undergoing HSCT should receive counseling about the high risk of gonadal toxicity, and efforts should be made to preserve fertility in patients undergoing either RIC or MAC.

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.