Hepatocyte X-box binding protein 1 deficiency increases liver injury in mice fed a high-fat/sugar diet.

Fatty liver is associated with endoplasmic reticulum stress and activation of the hepatic unfolded protein response (UPR). Reduced hepatic expression of the UPR regulator X-box binding protein 1 spliced (XBP1s) is associated with human nonalcoholic steatohepatitis (NASH), and feeding mice a high-fat diet with fructose/sucrose causes progressive, fibrosing steatohepatitis. This study examines the role of XBP1 in nonalcoholic fatty liver injury and fatty acid-induced cell injury. Hepatocyte-specific Xbp1-deficient (Xbp1(-/-)) mice were fed a high-fat/sugar (HFS) diet for up to 16 wk. HFS-fed Xbp1(-/-) mice exhibited higher serum alanine aminotransferase levels compared with Xbp1(fl/fl) controls. RNA sequencing and Gene Ontogeny pathway analysis of hepatic mRNA revealed that apoptotic process, inflammatory response, and extracellular matrix structural constituent pathways had enhanced activation in HFS-fed Xbp1(-/-) mice. Liver histology demonstrated enhanced injury and fibrosis but less steatosis in the HFS-fed Xbp1(-/-) mice. Hepatic Col1a1 and Tgfß1 gene expression, as well as Chop and phosphorylated JNK (p-JNK), were increased in Xbp1(-/-) compared with Xbp1(fl/fl) mice after HFS feeding. In vitro, stable XBP1-knockdown Huh7 cells (Huh7-KD) and scramble control cells (Huh7-SCR) were generated and treated with palmitic acid (PA) for 24 h. PA-treated Huh7-KD cells had increased cytotoxicity measured by lactate dehydrogenase release, apoptotic nuclei, and caspase3/7 activity assays compared with Huh7-SCR cells. CHOP and p-JNK expression was also increased in Huh7-KD cells following PA treatment. In conclusion, loss of XBP1 enhances injury in both in vivo and in vitro models of fatty liver injury. We speculate that hepatic XBP1 plays an important protective role in pathogenesis of NASH.

The Roles and Needs of Families of Adolescents with ASD.

The transition of a student out of high school and into the adult world can be a stressful time for many families of high school students. This major life transition can be particularly challenging for students with ASD and their families. In this paper we first discuss the roles of families in the transition process for their son or daughter with ASD. Next, we present literature on the unique needs of families of adolescents with ASD during the transition to adulthood. Finally, we highlight current research on best practices for supporting transition-aged students and their families as well as discuss future directions for research and practice.

Low-Income Households of Children With Autism and the Economic Safety Net.

OBJECTIVE: This paper examines the distribution, parameters, and determinants of safety net program use among a nationally representative sample of low-income children with autism spectrum disorder (ASD). METHODS: We used data from the 2021 National Survey of Children's Health to produce population estimates of material hardship and safety net program use among 554 low-income households of children with ASD, ages 3 to 17 years, relative to 2831 children with other special health care needs (SHCN) and 8758 children with no SHCN of the same age. Design-adjusted multivariate logistic regression models identified predictors of cash assistance, Supplemental Nutrition Assistance Program, and disconnection from both. RESULTS: There were few significant differences in material hardship between children with ASD and those with other SHCN, although children with ASD experienced significantly higher levels of hardships compared to children with no SHCN. Having a child with ASD did not significantly increase the odds of safety net use. Health insurance and household income were stronger predictors of use than disability. Nine percent of disconnected children lived in households under 100% federal poverty level and experienced some type of material hardship. CONCLUSIONS: Future research about the economic security of children with ASD and their families could focus on the following 3 areas of inquiry: assess how race, ethnicity, or socioeconomic position interact with disability to influence safety net program use; examine the intersection between Medicaid and safety net programs at the state and national levels; and identify specific subgroups of children at risk for disconnection and understand why they are not accessing benefits.

The Economic Impacts of COVID-19 on Autistic Children and Their Families.

PURPOSE: We used data from the National Survey of Children's Health to (1) examine differences in economic hardship and safety net program use after the implementation of federal relief efforts, and (2) assess whether the COVID-19 pandemic exacerbated autism-based disparities in hardship and program use. METHODS: We examined five dimensions of economic hardship (poverty, food insecurity, medical hardship, medical costs, and foregone work) and four safety net programs (cash assistance, Supplemental Nutrition Assistance Program (SNAP), Special Supplemental Nutrition Program for Women, Infants and Children (WIC), and free or reduced-cost meals). First, we calculated adjusted prevalence and odds ratios to compare pre-COVID (2018-2019) and during COVID (2021) outcomes by autism status. Next, we calculated the adjusted odds of each outcome among autistic children compared to those of children with and without other special healthcare needs at both time points. RESULTS: COVID-19 exacerbated autism-based disparities in food insecurity, SNAP, and public health insurance, but alleviated inequities in medical hardship, foregone work, and cash assistance. Autistic children did not experience declines in food insecurity or increases in SNAP like other children; medical hardship and foregone work decreased more for autistic children; and the magnitude of autism-based differences in public coverage significantly increased during the pandemic. CONCLUSION: Federal relief efforts likely improved economic outcomes of children; however, these effects varied according to type of hardship and by disability group. Efforts to promote economic well-being among autistic populations should be tailored to the financial challenges most salient to low-income autistic children, like food insecurity.

More Than Just a Variable: The Need to Explicitly Focus on Black Youth Within Autism Transitions Research.

Little evidence is available to provide context for understanding the experiences of parents and youth from historically marginalized groups as they age into adulthood, especially in regard to the transition experiences of Black autistic transition-age youth and their family members. This commentary builds upon recent publications that inform intersectional understandings of Black autistic experiences in America, and outlines research recommendations to better address the specific needs of Black autistic transition-age youth. Given the noted deficits in transition research and the transition process in regard to the experiences of Black autistic youth, we provide recommendations for improving autism transition research. We propose changes that are necessary to achieve equitable research processes, which could inform the design of targeted interventions to improve transition experiences for Black autistic youth.

Why is this topic important? There is little research on the experiences of Black autistic youth and young adults during the transition to adulthood. It is important to study this group of people, because they may have more unmet needs for services and supports during the transition years. They may have a harder time achieving employment or continuing their education because of the long-term effects of racism in communities. What is the purpose of this article? To add to what is known on this topic, we report on recent studies about Black autistic youth during the transition to adulthood. We provide research and practice recommendations. What personal or professional perspectives do the authors bring to this topic? The authors of this study are allistic researchers and research assistants who are members of a research team working on, or advising, autism transition research. A.M.R. is a White researcher, and a family member of autistic individuals, who studies the transition experiences of autistic youth. S.V. is a Black, nonbinary, public health social worker with experience in Black LGBTQIA+ mental health. E.-D.W. is a Black researcher who studies the mental health of Black autistic youth. H.S. is a White qualitative sociologist with experience studying the transition to young adulthood from the critical disability lens. K.A.A. is a mixed-race researcher who is White-presenting and who studies the intersectionality of autism, race, and poverty. T.M.H. is a Black researcher whose work focuses on intersecting identities, with a special focus on race and autism, and the way those intersections impact the lived experiences of individuals. L.L.S. is a White researcher with experience in studying health services disparities. The positionality of this team is that we identify as nonautistic researchers who seek to support increased focus on Black autistic youth and adults within autism research. What is already known about this topic? We know that there has been little attention given to studying how Black autistic youth and their families experience the transition to adulthood. We also know they are less likely to receive information about the transition in a timely manner. These disparities are unacceptable. What do the authors recommend? We need to find better ways to learn about the barriers that Black autistic youth face as they become adults. We also need to learn about the strengths they use to overcome these barriers. That information will help us to design ways to improve transitions. This work should be done with Black autistic youth and their families as partners. Researchers should use different approaches to invite Black youth into their studies. When researchers are designing studies they should think about the connections between people's identities such as being autistic, Black, or poor, because these identities combine to make discrimination worse. It would be helpful if the leaders of academic departments placed value on hiring Black and autistic scholars and encouraged more diversity within research. How will these recommendations help autistic adults now or in the future? It is possible to make changes in how Black autistic transition-age youth move through transition. However, the same solutions will not work for all communities. This is because different communities experience different barriers to receiving information and services during the transition years. We hope these recommendations will help researchers to think about how they can improve the participation of Black autistic youth and their family members.

Evidence from the Autism Transitions Research Project (2017-2022): Capstone review and services research recommendations.

Few funding sources have explicitly supported systems-wide research to identify mechanisms for improving access, service delivery, outcomes and wellbeing for autistic transition-age youth and young adults. We aimed to integrate findings from research produced through a five-year federal Autism Transition Research Project (ATRP) cooperative agreement. This capstone review sought to: (1) map the body of scientific evidence that emerged from this federal award, and (2) identify remaining evidence gaps to inform future autism transition services research. We used scoping review methods to assess 31 ATRP-funded published scientific studies. We charted study characteristics, topical domains, socio-ecological levels of variables, focus on equity, and inclusion of autistic participants. We evaluated how these topics were addressed across studies to identify continued gaps in the evidence base. Compared to prior published reviews and research agendas, we found improvements in characterization of study participants, broader examination of socio-ecological correlates, and examination of multiple outcome domains. However, we also identified continued deficits in inclusion of autistic study participants, use of multisectoral data, and research with a strong focus on equity. Our recommended priorities for autism transition services research to facilitate healthy life outcomes and wellbeing included: continued analysis of population-level data and improved data infrastructure; development of service delivery methods and interventions that target marginalized groups; expanded research to inform improvements in the performance and coordination of complex service ecosystems that interface with autistic youth; and bolstering the roles of autistic research participants.

Reducing endoplasmic reticulum stress does not improve steatohepatitis in mice fed a methionine- and choline-deficient diet.

Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of nonalcoholic steatohepatitis. The ER stress response is activated in the livers of mice fed a methionine- and choline-deficient (MCD) diet, yet the role of ER stress in the pathogenesis of MCD diet-induced steatohepatitis is unknown. Using chemical chaperones on hepatic steatosis and markers of inflammation and fibrosis in mice fed a MCD diet, we aim to determine the effects of reducing ER stress. C57BL/6J mice were fed a MCD diet with or without the ER chemical chaperones 4-phenylbutyric acid (PBA) and tauroursodeoxycholic acid (TUDCA) for 2 wk. TUDCA and PBA effectively attenuated the ER stress response in MCD diet-fed mice, as evidenced by reduced protein levels of phosphorylated eukaryotic initiation factor 2α and phosphorylated JNK and suppression of mRNA levels of CCAAT/enhancer binding protein homologous protein, glucose-regulated protein 78 kDa, and X-box binding protein 1. However, PBA and TUDCA did not decrease MCD diet-induced hepatic steatosis. MCD diet-induced hepatic inflammation, as evidenced by increased plasma alanine aminotransferase and induction of hepatic TNFα expression, was also not reduced by PBA or TUDCA. PBA and TUDCA did not attenuate MCD diet-induced upregulation of the fibrosis-associated genes tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9. ER chemical chaperones reduce MCD diet-induced ER stress, yet they do not improve MCD diet-induced hepatic steatosis, inflammation, or activation of genes associated with fibrosis. These data suggest that although the ER stress response is activated by the MCD diet, it does not have a primary role in the pathogenesis of MCD diet-induced steatohepatitis.

National and State Trends in autistic Adult Supplemental Security Income Awardees: 2005-2019.

This paper used Social Security Administration program data from 2005 to 2019 to examine national- and state-level changes in the number of new adult supplemental security income (SSI) awardees on the autism spectrum relative to awardees with intellectual disability and other mental health disorders. We identified three main findings: the number of autistic awards increased between 2005 and 2019 when awards for all other mental health disorders declined; roughly nine out of every 10 autistic adult awardees were between ages 18-25 years; there was variation in the growth of autistic awards across states. These findings support the need to consider geographic and age differences in SSI program participation among autistic adults and determine the underlying causes.

A chronic high-cholesterol diet paradoxically suppresses hepatic CYP7A1 expression in FVB/NJ mice.

Cholesterol 7α-hydroxylase (CYP7A1) encodes for the rate-limiting step in the conversion of cholesterol to bile acids in the liver. In response to acute cholesterol feeding, mice upregulate CYP7A1 via stimulation of the liver X receptor (LXR) α. However, the effect of a chronic high-cholesterol diet on hepatic CYP7A1 expression in mice is unknown. We demonstrate that chronic cholesterol feeding (0.2% or 1.25% w/w cholesterol for 12 weeks) in FVB/NJ mice results in a >60% suppression of hepatic CYP7A1 expression associated with a >2-fold increase in hepatic cholesterol content. In contrast, acute cholesterol feeding induces a >3-fold upregulation of hepatic CYP7A1 expression. We show that chronic, but not acute, cholesterol feeding increases the expression of hepatic inflammatory cytokines, tumor necrosis factor (TNF)α, and interleukin (IL)-1ß, which are known to suppress hepatic CYP7A1 expression. Chronic cholesterol feeding also results in activation of the mitogen activated protein (MAP) kinases, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). Furthermore, we demonstrate in vitro that suppression of CYP7A1 by TNFα and IL-1ß is dependent on JNK and ERK signaling. We conclude that chronic high-cholesterol feeding suppresses CYP7A1 expression in mice. We propose that chronic cholesterol feeding induces inflammatory cytokine activation and liver damage, which leads to suppression of CYP7A1 via activation of JNK and ERK signaling pathways.

Medication Use in Youth With Autism and Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Children with autism spectrum disorder (ASD) may benefit from medication to treat a diverse array of behaviors and health conditions common in this population including co-occurring conditions associated with ASD, such as attention-deficit/hyperactivity disorder (ADHD) and anxiety. However, prescribing guidelines are lacking and research providing national estimates of medication use in youth with ASD is scant. We examined a nationally representative sample of children and youth ages 6 to 17 with a current diagnosis of ASD to estimate the prevalence and correlates of psychotropic medication. METHODS: This study used data from the 2016 and 2017 National Survey of Children's Health. We estimated unadjusted prevalence rates and used multivariable logistic regression to estimate the odds of medication use in children and youth across 3 groups: those with ASD-only, those with ASD and ADHD, and those with ADHD-only. RESULTS: Two thirds of children ages 6 to 11 and three quarters of youth ages 12 to 17 with ASD and ADHD were taking medication, similar to children (73%) and youth with ADHD-only (70%) and more than children (13%) and youth with ASD-only (22%). There were no correlates of medication use that were consistent across group and medication type. Youth with ASD and ADHD were more likely to be taking medication for emotion, concentration, or behavior than youth with ADHD-only, and nearly half took ASD-specific medication. CONCLUSIONS: This study adds to the literature on medication use in children and youth with ASD, presenting recent, nationally representative estimates of high prevalence of psychotropic drug use among children with ASD and ADHD.

Vocational Rehabilitation Service Utilization and Employment Outcomes Among Secondary Students on the Autism Spectrum.

U.S. policy interventions encourage earlier provision of Vocational Rehabilitation (VR) services to support students and youth with disabilities such as autism spectrum disorder (ASD) during the transition from school to work. We analyzed Rehabilitation Services Administration (RSA-911) data using multivariable logistic regression to determine the association of VR services receipt with employment outcomes for students ages 16-21, same-age non-student youth and young adults with ASD. Students with autism received job-related services (job search, job placement, and on-the-job supports) at rates significantly below comparison groups, even though odds of successful employment at VR exit were significantly higher if they received these services. Findings suggest that rates of employment among students with autism might be improved with intentional delivery of job-related services.

Trends in Supplemental Security Income Payments to Adults With Autism.

OBJECTIVE: This study used Social Security Administration program data to identify population-level trends in Supplemental Security Income (SSI) program participation and payments to adult recipients with autism spectrum disorder (ASD) relative to recipients with intellectual disability and other mental disorders. METHODS: The authors examined SSI program data from 2005 to 2015. Variables included caseload size, number of new adult awardees per year, total annual SSI payments per disability group, and average annual SSI payment per recipient. RESULTS: Adults with ASD represented a growing share of the total first-time SSI awards given to adults with mental disorders, with percentages increasing from 1.3% in 2005 to 5.0% in 2015. In 2015, 158,105 adults with ASD received SSI benefits, a 326.8% increase since 2005. Federal SSI payments to adults with ASD increased by 383.2% during the same period (totaling roughly $1.0 billion in 2015). The annual average payment for adults with ASD was $6,527.40 in 2015. CONCLUSIONS: The purpose of the SSI program is to reduce the extent of poverty by providing monthly payments to eligible individuals with disabilities. The authors found that a large and growing number of adults with autism receive SSI benefits. This finding underscores the importance of future research related to the economic security of adults on the autism spectrum.

Prevalence and Correlates of Work Experiences Among High School Students on the Autism Spectrum.

This study used nationally representative data to describe the prevalence and correlates of work experiences among high school students with autism who received special education. Four in tenstudents with autism experienced any type of work (community-based, school-sponsored, paid or unpaid) within a given year-significantly fewer than peers with and without disabilities. Rates of paid work among students with autism were comparable to students with intellectual disability (ID)but half the rate of non-special education peers. Among youth with autism, significant correlates of having work experiences included being white, parent participation in transition planning, and functional skills including navigation. Fostering a variety of early work experiences should be a key goal of disability employment policy at federal and state levels.

Social-Ecological Correlates in Adult Autism Outcome Studies: A Scoping Review.

The transition into adulthood is a critical period in the life course that shapes later outcomes. Many adults on the autism spectrum fare poorly across a wide range of quality of life indicators. Understanding the multilevel factors that influence transition outcomes is necessary to develop strategies that promote better outcomes. In this scoping review, we characterize the use of social-ecological factors in adult autism outcome studies, identify understudied areas of research, and provide recommendations for future research. We conducted a literature search for studies in which the relationship between social-ecological factors and transition outcomes among transition-age youth with autism was assessed. We organized variables used in studies across 5 levels of influence: family-, interpersonal-, institutional-, community-, and policy-level factors. Our findings reveal that both breadth and depth of social-ecological factors usage in autism outcomes studies is limited because of the narrow inclusion of variables across social-ecological levels, the overreliance on a limited number of national data sets, and the overall lack of variation in research design. We propose 9 recommendations to inform the development of multilevel studies.

Transition of Individuals With Autism to Adulthood: A Review of Qualitative Studies.

Many young adults with autism spectrum disorder experience poor transition outcomes in key areas, including postsecondary employment, higher education, health care, social connectedness, and independent living, yet we lack a clear understanding of the specific factors that impact these outcomes. We reviewed qualitative research in which the perspectives of youth and young adults with autism spectrum disorder, parents, services providers, and other stakeholders were gathered to identify barriers and facilitators to optimal outcomes. Findings revealed that poor transition outcomes are influenced by several factors, including poor person-environment fit, uncertainty about the roles of parents, and the lack of comprehensive or integrated services. These findings also revealed the aspects of familial, organizational, and policy contexts that may be targeted for interventions. Finally, stakeholders emphasized that supports should be individualized and focused on the changing aspects of the young adult's social and physical environment rather than behavior change. We discuss implications for policy and practice and provide recommendations for further research.

A National Research Agenda for the Transition of Youth With Autism.

In this article, we outline a national research agenda to improve the transition to adulthood among youth with autism. We synthesized the results from 5 interconnected sets of activities: (1) a scoping review of published autism research and research priority statements, (2) a series of key informant interviews with stakeholders, (3) a 2-day National Research Agenda meeting, (4) a modified Delphi survey of stakeholders, and (5) 2 formal reviews of published literature on autism and transition. We identified 2 overarching priorities to advance research about autism and transition: (1) increased focus on community- and systems-level factors that influence outcomes with population-level approaches to measuring outcomes and (2) greater involvement of people with autism in establishing research priorities, designing research studies, and producing study findings and recommendations. We discuss how the life course framework can guide future inquiry that addresses gaps in extant research.

Introduction to Transitions in the Life Course of Autism and Other Developmental Disabilities.

The Health Care Transitions Research Network for Autism Spectrum Disorder and other Developmental Disabilities and the Life Course Research Network, both funded by the Maternal and Child Health Bureau, invited articles for this Supplement. Our goal in this Supplement is to highlight and explore developmental and transition-related challenges over the life course of individuals on the autism spectrum and other neurodevelopmental disabilities, discuss the clinical and practice implications of these issues, highlight gaps in knowledge, and identify directions for future research.

Stakeholder Perspectives on Research and Practice in Autism and Transition.

OBJECTIVES: Individuals with autism spectrum disorder (ASD) are reported to experience significant challenges during the transition to adulthood. Although recent evidence indicates that individuals with ASD experience poor outcomes in adulthood, little is understood about the contributing factors. In this qualitative study, we investigated the barriers to and needs in research and practice in the transition to adulthood among individuals with ASD. METHODS: Thirteen researchers, including service providers, family members, and an individual with ASD participated in 30- to 60-minute, semistructured, open-ended telephone interviews. Interviews were transcribed, and data were analyzed by using an inductive approach to identify themes related to barriers to and needs in the transition to adulthood for youth with ASD. RESULTS: Stakeholders identified the need for transition planning and preparation to begin earlier and for systems to better accommodate the interests and varying abilities of individuals with ASD. Stakeholders also felt that parent and service provider expectations and perceptions influence early opportunities and experiences offered throughout the transition process. CONCLUSIONS: This study reveals the multilevel barriers to and needs in the transition to adulthood and the need for interagency and multidisciplinary collaboration and research to address the varying levels of needs, abilities, and multisector challenges.

The Medical Home and Health Care Transition for Youth With Autism.

BACKGROUND: Our objective in this study was to describe the association between the receipt of health care transition services (HCTS) and having a medical home in youth with autism spectrum disorder (ASD). Youth with ASD receive HCTS less often than other youth with special health care needs but are in particular need of continuous, comprehensive health care. METHODS: We used the National Survey of Children with Special Health Care Needs to describe the receipt of HCTS in youth with ASD and its association with presence of a medical home. Descriptive statistics are presented, and logistic regression is used to assess the association between medical home and HCTS. RESULTS: Twenty-one percent of youth with ASD met the criteria for receiving HCTS. Youth with ASD and a medical home were almost 3 times as likely to receive HCTS as youth without a medical home, and youth who received family-centered care and have adequate care coordination within the medical home were more than twice as likely to receive HCTS as those who did not. CONCLUSIONS: Youth with ASD are not receiving HCTS at the same rate as their peers. Increasing provider awareness of autism, the components of a medical home, and of the importance of HCTS could greatly help increase the percentage of youth who receive effective HCTS.

Postsecondary Expectations of High-School Students With Autism Spectrum Disorders.

This study examined the perceptions of adulthood among 31 high school students with autism spectrum disorder (ASD). We had two research aims: (1) to report students' postsecondary expectations in terms of school, work, friendships and living arrangement and (2) to describe how our sample defined adulthood. To better compare our sample's criteria of adulthood to the criteria traditionally endorsed in secondary schools, we used a directed content analysis approach. Data were derived from a semi-structured interview that questioned students about friendships, activities and the transition to adulthood. The majority of students expected to attain traditional markers of adulthood after high school; however, for some the pathways to achieving these outcomes were narrowly defined and perceived as a rigid, linear process. Independence, maturity and personal responsibility were the most highly endorsed characteristics of adulthood, followed by chronological age and traditional markers. Implications for transition planning and adult services are discussed.