Emotion Regulation and Executive Function: Associations with Depression and Anxiety in Autism.

Background: Adolescents and young adults with autism spectrum disorder (ASD) are prone to experience co-occurring mental health conditions such as mood or anxiety disorders, as well as impairments in emotion regulation and executive functioning. However, little research has examined inter-relationships among these constructs, despite evidence of additional stressors and increased risk of internalizing disorders at this age, relative to non-autistic individuals. If either emotion regulation or executive functioning are shown to have patterns of association with mental health, this can inform mechanism-based intervention. Method: Fifty-seven autistic adolescents and adults (16-25 years) with ASD in a transition intervention completed questionnaires and clinician-administered measures at baseline. Analyses assessed whether executive functioning impairment, above and beyond emotion regulation impairment, were associated with depression and anxiety symptoms. Results: ASD characteristics, emotion regulation, anxiety, and depression were significantly correlated. ASD characteristics was a significant contributor to depression and emotion regulation impairments were significant contributors to anxiety and depression. Findings indicated that inhibition difficulties did not uniquely contribute to depression or anxiety above emotion regulation impairment. Difficulties in cognitive flexibility were associated with depression above and beyond ASD characteristics, IQ, and emotion regulation, but not associated with anxiety. Conclusions: Although preliminary, findings suggest that inflexibility and regulatory impairment should be considered in depression remediation approaches. Improving ER, on the other hand, may have broader transdiagnostic impact across both mood and anxiety symptoms in ASD.

Novel Virtual Vision Screening Program: Give Kids Sight Day 2020.

PURPOSE: To determine whether a low-technology novel virtual vision screening protocol can reliably screen pediatric visual acuity. METHODS: Give Kids Sight Day (GKSD), an annual out-reach program, aims to provide free vision screening and ophthalmic care to underserved children in Philadelphia, Pennsylvania. Children were screened virtually through the low-technology protocol. Based on screening results, 152 children were provided in-person eye examinations. Data from in-person examinations were compared to data from virtual screenings for 151 children who were seen in-person. RESULTS: Of 475 children screened virtually, 152 children were seen in-person for examination, and 151 children were included in the analysis. Results from 151 children (mean age: 10.7 years, age range: 5 to 18 years, 43% female, 28% speaking a non-English language) were reviewed. There was a moderate correlation (R = .64, P < .0001; n = 100 children) between screening and in-person visual acuity without refractive correction and a strong correlation (R = 0.82, P < .0001; n = 18 children) between screening and in-person visual acuity with refractive correction. Of the 140 children who were seen in-person, 133 children were provided glasses prescriptions. Seventeen children required a referral to a pediatric ophthalmologist for evaluation of ophthalmic conditions, most commonly strabismus (5.3%) and amblyopia (4%). CONCLUSIONS: The GKSD virtual visual acuity testing demonstrated good correlation with in-person visual acuity testing, supporting the virtual screening approach as a useful tool for future applications in widespread community vision outreach programs. Further studies are needed to refine virtual ophthalmic screening to optimize its applications in bridging the gaps in ophthalmic care. [J Pediatr Ophthalmol Strabismus. 2023;60(6):390-395.].

Brief Report: Creation of a Transition Readiness Scale for Adolescents with ASD.

The transition to postsecondary education is characterized by many changes for adolescents with autism spectrum disorder (ASD). A data-based understanding of a student's readiness for postsecondary education could help students, and their parents, better prepare for this life transition. The Transition Readiness Scale (TRS) was created to address this need. The TRS is a self/other-report questionnaire used to assess postsecondary readiness across behavioral, cognitive, and emotional domains among adolescents 15-18 years of age. The present study details measure development and provides preliminary psychometric properties in a sample of transition-aged youth with ASD. Results indicate strong internal consistency, adequate item-level analyses, and discriminant and concurrent validity. Future validation of the TRS in large-scale field testing is merited to inform clinical interpretation.

Cationic, Steroid-Based Imidazolium Amphiphiles Show Tunable Backbone-Dependent Membrane Selectivity in Fungi.

Cationic amphiphiles have been reported to show broad antimicrobial activity. The potential for antimicrobial resistance to these molecules is low owing to their general cell membrane permeabilizing mode of action. However, their applications are often limited by toxicity resulting from their low selectivity for microbial cell membranes. Herein, we report a library of cationic, steroid-based imidazolium amphiphiles that show tunable antifungal activity in a variety of fungal pathogens of the genus Candida. We show that adoption of an ergosterol-derived backbone increases antifungal activity while modestly affecting hemolytic activity, thereby increasing overall selectivity by more than 8-fold in comparison to cholesterol-derived imidazolium salts. We hypothesize that this effect is caused by a privileged integration of the ergosterol-derived salts into fungal membranes leading to increased membrane disorder. We propose that these findings offer a useful platform for the development of improved amphiphilic fungicides.

Fluconazole-COX Inhibitor Hybrids: A Dual-Acting Class of Antifungal Azoles.

When used in combination with azole antifungal drugs, cyclooxygenase (COX) inhibitors such as ibuprofen improve antifungal efficacy. We report the conjugation of a chiral antifungal azole pharmacophore to COX inhibitors and the evaluation of activity of 24 hybrids. Hybrids derived from ibuprofen and flurbiprofen were considerably more potent than fluconazole and comparable to voriconazole against a panel of Candida species. The potencies of hybrids composed of an S-configured azole pharmacophore were higher than those with an R-configured pharmacophore. Tolerance, defined as the ability of a subpopulation of cells to grow in the presence of the drug, to the hybrids was lower than to fluconazole and voriconazole. The hybrids were active against a mutant lacking CYP51, the target of azole drugs, indicating that these agents act via a dual mode of action. This study established that azole-COX inhibitor hybrids are a novel class of potent antifungals with clinical potential.

Trajectories of Seizures, Medication Use, and Obesity Status into Early Adulthood in Autistic Individuals and Those with Other Neurodevelopmental Conditions.

Background: Physical and psychiatric health conditions affect the lives of many autistic adults. However, relatively little is known about individual trajectories in autistic individuals' physical and mental health from adolescence to adulthood. Methods: This study uses a well-characterized longitudinal sample (n = 253) to investigate rates of seizures, medication use, and obesity, from early adolescence (age 10 years) into adulthood (age 30 years). Within this sample, 196 participants were diagnosed with autism spectrum disorder (ASD), whereas the remaining 57 participants never received an ASD diagnosis, but, rather, were diagnosed with other neurodevelopmental conditions. Data were collected through parent report questionnaires and in-person interviews and assessments. Results: Seizure onset continued well into adulthood, with two individuals experiencing their first seizure at the age of 25 years. Seizures and neuropsychiatric medication use were both higher for those with lower intelligence quotient (IQs). In addition, medication use increased over time for these individuals, whereas those with higher IQs saw a reduction in medication use with age. Between the ages of 15 to 30 years, the predicted probability of medication use increased from 82% to 88% for those with lower IQs and decreased from 37% to 13% for those with higher IQs. Collectively, almost 70% of all participants in this study were classified as either overweight or obese. Body mass index (BMI) increased throughout adulthood, especially for those with higher IQs. The steepest increase in BMI over time occurred for those with higher IQs who also took antipsychotic medications. Conclusion: Overall, continued risk for developing seizures, high rates of neuropsychiatric medication use, and significant and increasing rates of obesity from adolescence to adulthood underscore the importance of monitoring health issues in autistic individuals and those diagnosed with other neurodevelopmental conditions throughout the lifespan.

Why was this study done?: Autistic individuals and those diagnosed with other neurodevelopmental conditions are at risk for many physical health issues from adolescence to adulthood. This includes, but is not limited to, seizure disorders, high rates of medication use, and obesity. Yet, not much longitudinal research exists measuring these health issues throughout the lifespan and, especially, in adulthood. What did the researchers do?: The researchers analyzed data from a sample of 253 individuals who lived in North Carolina, Michigan, and Illinois. This sample was recruited almost 30 years ago, beginning the study when they were roughly 2 years old. Some participants had an autism spectrum disorder diagnosis, and some did not, but instead had other neurodevelopmental conditions. The researchers measured changes in medication use, height, and weight beginning in early adolescence (age 10 years) into adulthood (age 30 years). The researchers also tracked seizure occurrences across the life span (beginning at age 2 years up until age 30 years). What were the results of the study?: In adulthood, this sample showed high rates of obesity and medication use. For example, almost 70% of this sample was classified as either overweight or obese. In addition, 55% of this sample was taking at least one neuropsychiatric medication in adulthood, and 22% of this sample was taking three different types of medication at the same time. Individuals with higher and lower intelligence quotient (IQs) had different findings over time: obesity increased throughout adulthood for those with higher IQs and medication use increased throughout adulthood for those with lower IQs. Seizures first developed for a group of individuals in adolescence and adulthood. Two individuals experienced their first seizure as late as 25 years of age. What do these findings add to what is already known?: Research, and especially longitudinal research, on physical health in autistic adults is limited. Although we know that autistic individuals generally experience high rates of obesity, seizure disorders, and medication use, less is known about how these physical health issues change over the lifespan. This study has provided useful information regarding how certain physical health issues change over time, and who these physical health issues impact the most in adulthood. How will these findings help autistic adults now or in the future?: The findings in this study identified that, in adulthood, autistic adults experience high rates of physical health issues, including increasing rates of obesity and medication use for certain populations. These findings confirm how important it is for autistic adults to have access to quality health care across the lifespan. We hope that, with these findings in mind, caregivers and health professionals will work to ensure that autistic individuals, from childhood through adolescence and adulthood, will have access and assistance in monitoring these ongoing and persistent health problems.

Diagnostic stability in individuals with autism spectrum disorder: insights from a longitudinal follow-up study.

BACKGROUND: This longitudinal study of autism symptom trajectories provides unique information that can characterize autism features and diagnostic patterns from childhood to adulthood. METHODS: Participants (n = 155) were part of a longitudinal cohort referred for possible autism where in-person assessments were completed at ages 2, 3, 5, 9, 19, and 25. Assessors were blinded to previous diagnoses. Based on adult best estimate diagnoses, participants were categorized into one of the four groups: Retained ASD, Lost ASD, Never Had ASD, or Gained ASD Diagnosis. To examine developmental changes in autism symptoms, mixed models indicated the rate of change in ADOS CSS and ADI-R scores in each diagnostic group. RESULTS: A subset of participants with VIQ> and <70 were assigned a diagnosis in adulthood that differed from diagnoses earlier in development. Across cognitive levels, the majority of novel diagnoses emerged in adulthood. For those with VIQ > 70, improvements in ADOS CSS over time for the Lost Diagnosis group and worsening in CSS in the Gained Diagnosis group were gradual. Individuals with VIQ > 70 who lost a diagnosis even in adulthood could be distinguished on CSS and ADI-R scores by age 5 from those who retained their ASD diagnosis. Although most participants with VIQ < 70 saw decreases in autistic symptoms as a whole, changes in autism diagnoses were confounded by disentangling profound intellectual disability as a differential diagnosis or co-occurrence. Only the Never Had Diagnosis group revealed significant changes in ADOS scores over time, with autism symptoms increasing. CONCLUSIONS: Associated with gradual changes in core features of autism beginning in childhood, diagnoses of autism can shift across development.

Predicting Uncertain Multi-Dimensional Adulthood Outcomes From Childhood and Adolescent Data in People Referred to Autism Services.

INTRODUCTION: Autism spectrum disorder is a highly heterogeneous diagnosis. When a child is referred to autism services or receives a diagnosis of autism spectrum disorder it is not known what their potential adult outcomes could be. We consider the challenge of making predictions of an individual child's long-term multi-facetted adult outcome, focussing on which aspects are predictable and which are not. METHODS: We used data from 123 adults participating in the Autism Early Diagnosis Cohort. Participants were recruited from age 2 and followed up repeatedly through childhood and adolescence to adulthood. We predicted 14 adult outcome measures including cognitive, behavioral and well-being measures. Continuous outcomes were modeled using lasso regression and ordinal outcomes were modeled using proportional odds regression. Optimism corrected predictive performance was calculated using cross-validation or bootstrap. We also illustrated the prediction of an overall composite formed by weighting outcome measures by priorities elicited from parents. RESULTS: We found good predictive performance from age 9 for verbal and non-verbal IQ, and daily living skills. Predictions for symptom severity, hyperactivity and irritability improved with inclusion of behavioral data collected in adolescence but remained modest. For other outcomes covering well-being, depression, and positive and negative affect we found no ability to predict adult outcomes at any age. Predictions of composites based on parental priorities differed in magnitude and precision depending on which parts of the adult outcome were given more weight. CONCLUSION: Verbal and non-verbal IQ, and daily living skills can be predicted well from assessments made in childhood. For other adult outcomes, it is challenging to make meaningful predictions from assessments made in childhood and adolescence using the measures employed in this study. Future work should replicate and validate the present findings in different samples, investigate whether the availability of different measures in childhood and adolescence can improve predictions, and consider systematic differences in priorities.

Improving Transition to Adulthood for Students with Autism: A Randomized Controlled Trial of STEPS.

Emerging adulthood is a period of heightened risk for young people with autism spectrum disorder (ASD). Due in part to a lack of evidence-based services and supports during the transition to adulthood, many emerging adults fail to matriculate into postsecondary education or thrive in productive employment. The Stepped Transition in Education Program for Students with ASD (STEPS) was developed to address the psychosocial, transition-related needs of emerging adults with ASD. Adolescents and emerging adults (n = 59) with ASD were randomly assigned to either STEPS or transition as usual (TAU). Results indicate that STEPS is acceptable to young people with ASD and their parents and that it can be implemented with high fidelity. Among secondary school students, those who completed STEPS exhibited significantly greater gains in transition readiness from high school, and these gains were largely sustained after program completion. Among students enrolled in postsecondary education, STEPS resulted in increased levels of student adaptation to college relative to those in TAU. Programming to address ASD-related challenges can promote successful educational transitions.

Trajectories of co-occurring psychopathology symptoms in autism from late childhood to adulthood.

Given high rates of co-occurring conditions in youth and adults with autism spectrum disorder (ASD), it is critical to examine the developmental trajectories of these symptoms of psychopathology. Using data from a cohort of participants (n = 194), most of whom were first assessed for ASD in very early childhood, we investigated the trajectories of co-occurring depressive, anxiety, and attention-deficit hyperactivity disorder (ADHD) symptoms from late childhood to adulthood. Additionally, childhood predictors and adult outcomes associated with these symptom trajectories were examined. Using group-based trajectory modeling, we found two distinct classes of individuals exhibiting each of these co-occurring symptom patterns: one class exhibited fairly low symptoms across time, and one class with elevated symptoms with varied fluctuation across time (ADHD symptoms starting high but decreasing, anxiety symptoms high and stable, and depressive symptoms fluctuating but peaking at clinically significant levels in young adulthood). All high trajectory classes were associated with age 9 adaptive skills; verbal IQ predicted higher anxiety and depressive symptom classes. After accounting for verbal IQ, all high symptom trajectory classes were negative predictors of objective adult outcomes. These findings call for wide-ranging considerations of the needs of individuals across ability levels, autism symptoms, and behavioral and emotional challenges.

Measuring Social Motivation in Autism Spectrum Disorder: Development of the Social Motivation Interview.

Social motivation in individuals with ASD is inferred from the observation of overt behaviors and neurological correlates. Motivation, however, can be distinguishable from overt behavior and neurologic reactivity. Nevertheless, few studies have examined the cognitive processes that may influence goal-directed tasks involved in social interaction. This study addressed this conceptual need by developing a novel interview. The social motivation interview (SMI) assesses for internal cognitions as they relate to social motivation by evaluating social desire, interest, and behaviors in eighteen children with ASD (M years = 12.84). Pilot testing suggested feasibility of administration, user satisfaction, and promising psychometric properties. Future examination of the SMI in large-scale field testing is warranted.

Antifungal activity, mode of action variability, and subcellular distribution of coumarin-based antifungal azoles.

Azole antifungals inhibit the biosynthesis of ergosterol, the fungal equivalent of cholesterol in mammalian cells. Here we report an investigation of the activity of coumarin-substituted azole antifungals. Screening against a panel of Candida pathogens, including a mutant lacking CYP51, the target of antifungal azoles, revealed that this enzyme is inhibited by triazole-based antifungals, whereas imidazole-based derivatives have more than one mode of action. The imidazole-bearing antifungals more effectively reduced trailing growth associated with persistence and/or recurrence of fungal infections than triazole-based derivatives. The imidazole derivatives were more toxic to mammalian cells and more potently inhibited the activity of CYP3A4, which is one of the main causes of azole toxicity. Using live cell imaging, we showed that regardless of the type of azole ring fluorescent 7-diethylaminocoumarin-based azoles localized to the endoplasmic reticulum, the organelle that harbors CYP51. This study suggests that the coumarin is a promising scaffold for development of novel azole-based antifungals that effectively localize to the fungal cell endoplasmic reticulum.

Attention Bias Modification Treatment for Adolescents With Social Anxiety Disorder.

Social anxiety disorder (SAD) tends to emerge during the early teenage years and is particularly refractory to change even when standard evidence-based CBT treatments are delivered. Efforts have been made to develop novel, mechanistic-driven interventions for this disorder. In the present study, we examined Attention Bias Modification Treatment (ABMT) for youth with SAD. Participants were 58 adolescents (mean age = 14.29 years) who met diagnostic criteria for SAD and who were randomized to ABMT or a placebo control condition, Attention Control Training (ACT). We predicted that ABMT would result in greater changes in both threat biases and social anxiety symptoms. We also explored potential moderators of change including the severity of social anxiety symptoms, the level of threat bias at pretreatment, and the degree of temperament-defined attention control. Contrary to our hypotheses, changes in attention bias were not observed in either condition, changes in social anxiety symptoms and diagnosis were small, and significant differences were not observed between the ABMT and ACT conditions. Little support for the proposed moderators was obtained. Reasons for our failure to find support for ABMT and its potential moderators are explored and recommendations for changes in the ABMT paradigm are suggested.

Variability of attention bias in socially anxious adolescents: differences in fixation duration toward adult and adolescent face stimuli.

Prior research on attention bias in anxious youth, often utilising a visual dot probe task, has yielded inconsistent findings, which may be due to how bias is assessed and/or variability in the phenomenon. The present study utilises eye gaze tracking to assess attention bias in socially anxious adolescents, and explores several methodological and within-subject factors that may contribute to variability in attention bias. Attention bias to threat was measured in forty-two treatment-seeking adolescents (age 12-16 years) diagnosed with Social Anxiety Disorder. Bias scores toward emotional stimuli (vigilant attention) and bias scores away from emotional stimuli (avoidant attention) were explored. Bias scores changed between vigilance and avoidance within individuals and over the course of stimulus presentation. These differences were not associated with participant characteristics nor with self-reported social anxiety symptoms. However, clinician rated severity of social anxiety, explained a significant proportion of variance in the bias scores for adult, but not the adolescent, stimuli. Variability in attention bias among socially anxious adolescents is common and varies as a function of stimulus duration and type. Results may inform stimulus selection for future research.

Feasibility and Preliminary Efficacy of an Adapted Transdiagnostic Treatment for Children With Executive Function Deficits.

Few psychological interventions exist to target executive function difficulties in children and adolescents. The current study modified the Unstuck and On Target! intervention protocol for use in an outpatient clinic setting with a diagnostically diverse group of participants. Participants engaged in a 10-week child and parent group treatment with assessment measurement at pre- and post-treatment. Assessments consisted of parent-report questionnaires, clinician-administered tasks, and treatment fidelity ratings. Results suggest that the modified intervention was delivered with high fidelity and is feasible and acceptable in a transdiagnostic sample. Although preliminary, efficacy appears promising and suggests that parent-rated executive function, as well as behavioral and emotional challenges, are amenable to change as a result of intervention participation. The results imply that the modified intervention has merit, and should be further explored within the context of larger studies.

Educator perspectives on the postsecondary transition difficulties of students with autism.

Addressing the challenges of adolescents and emerging adults with autism spectrum disorder is crucial to improving the outcomes of these students in the postsecondary setting. Although secondary and postsecondary educators and staff are critical to helping these students access services, there has been little investigation into the perspectives of this stakeholder group, with respect to the needs of postsecondary students with autism spectrum disorder. A series of focus groups was conducted with secondary and postsecondary educators to understand educator perspectives related to the challenges faced by postsecondary students with autism spectrum disorder. Competence, autonomy and independence, and the development and sustainment of interpersonal relationships emerged as primary areas of difficulty and corresponding need. Results suggest that targeted interventions addressing these areas should be implemented, prior to and during enrollment in a postsecondary setting, to facilitate transition in a comprehensive manner.

Autism Goes to College: Understanding the Needs of a Student Population on the Rise.

Understanding the needs of adolescents and emerging adults with Autism Spectrum Disorder (ASD) with respect to transition to postsecondary education is critical to development of user-informed transition programming. Parents of adolescents and emerging adults with ASD (n = 52) and ADHD (n = 47) completed an online survey. Social interaction training and independent living training were services frequently requested by parents in the ASD group. Additionally, parents of postsecondary students with ASD endorsed distinct challenges with self-advocacy, managing emotions, and managing personal/adaptive skills relative to postsecondary students with ADHD. The profile of parent-reported difficulties and needed services compared to transition to postsecondary education for students with ASD is distinguishable from that for ADHD, suggesting individualized transition planning and in-college supports.

Development of a College Transition and Support Program for Students with Autism Spectrum Disorder.

Empirically based, consumer-informed programming to support students with Autism Spectrum Disorder (ASD) transitioning to college is needed. Informed by theory and research, the Stepped Transition in Education Program for Students with ASD (STEPS) was developed to address this need. The first level (Step 1) supports high school students and the second level (Step 2) is for postsecondary students with ASD. Herein, we review the extant research on transition supports for emerging adults with ASD and describe the development of STEPS, including its theoretical basis and how it was informed by consumer input. The impact of STEPS on promotion of successful transition into college and positive outcomes for students during higher education is currently being evaluated in a randomized controlled trial.

Students with autism spectrum disorder in college: Results from a preliminary mixed methods needs analysis.

BACKGROUND: There is a growing call for empirically based programming to support the success of students with autism spectrum disorder (ASD) as they transition to college. AIMS: The purpose of this study was to identify the needs and challenges faced by adolescents and young adults with ASD in postsecondary education. METHODS: A mixed methods approach was taken to explore the needs of college-bound and college-enrolled students with ASD. Primary stakeholders (i.e., parents, educators/support staff from secondary and postsecondary institutions, and students) participated in an online survey (n=67) and focus groups (n=15). RESULTS: Across the stakeholder groups, commonly identified areas of difficulty included limited interpersonal competence, managing competing demands in postsecondary education, and poor emotional regulation. There was a high degree of agreement across stakeholders in the identified needs and challenges. IMPLICATIONS: Findings from this preliminary needs analysis will inform the development of programming to support students with ASD.

Psychosocial and Computer-Assisted Intervention for College Students with Autism Spectrum Disorder: Preliminary Support for Feasibility.

The number of young adults with Autism Spectrum Disorders (ASD) enrolled in higher education institutions has steadily increased over the last decade. Despite this, there has been little research on how to most effectively support this growing population. The current study presents data from a pilot trial of two novel intervention programs developed for college students with ASD. In this small randomized controlled trial, college students with ASD (n = 8) were assigned to one of two new programs - either an intervention based on a virtual reality-Brain-Computer Interface for ASD (BCI-ASD) or a psychosocial intervention, the College and Living Success (CLS) program. Preliminary evidence supports the feasibility and acceptability of both programs, although behavioral outcomes were inconsistent across participants and interventions. Results indicate that expanded research on psychosocial and computer-assisted intervention approaches for this population is warranted, given the preliminary support found in this pilot study.