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Item 143 Training & Sustaining: Training and learning collaborative outcomes across a statewide network for early diagnosis of children with autism(Cambridge University Press, 2024-04-03) McNally Keehn, Rebecca; Paxton, Angela; Delaney, Mary; Ciccarelli, Mary; Pediatrics, School of MedicineOBJECTIVES/GOALS: Community-based primary care autism diagnostic models are one promising solution to delays in autism diagnosis. Our objective is to describe the development and report on outcomes related to primary care professional (PCP) training and sustained engagement in a longitudinal learning collaborative across a statewide network for autism diagnosis. METHODS/STUDY POPULATION: We developed ADAPT (i.e., Accelerating the Diagnosis of Autism with Primary care Training), a training program to prepare PCPs to develop independent competency in evaluation of autism in children ages 14-48 months. ADAPT includes didactic and case-based modules and expert practice-based coaching delivered by a diagnostic specialist; following training PCPs participate in a longitudinal learning collaborative. Aligned with competency-based medical education standards, measures of autism evaluation knowledge and diagnostic competency are collected. RESULTS/ANTICIPATED RESULTS: To date, 13 PCPs have completed ADAPT didactic and practicum training reaching competency in independent autism evaluation. Clinicians demonstrated significant improvement in total autism knowledge following didactic training (p=.02). There was an overall trend toward increased scoring agreement on an autism observational assessment over case observations and practicum evaluations. Similarly, PCPs demonstrated improved evaluation competence, moving on average from Advanced Beginner to Competent Performer as rated by expert trainers. Following training, PCPs attended 57% of monthly learning collaborative sessions. DISCUSSION/SIGNIFICANCE: Training PCPs to deliver autism evaluations as part of community-based models of care is a promising solution to address access and waitlist challenges. ADAPT is an intensive, standard PCP training model which results in achievement of independent competency and sustained engagement in in autism evaluation.Item A Literature Review of Similarities Between and Among Patients With Autism Spectrum Disorder and Epilepsy(Springer Nature, 2023-01-18) Assuah, Freda B.; Emanuel, Bryce; Lacasse, Brianna M.; Beggs, John; Lou, Jennie; Motta, Francis C.; Nemzer, Louis R.; Worth, Robert; Cravens, Gary D.; Mathematical Sciences, School of ScienceAutism spectrum disorder (ASD) has been shown to be associated with various other conditions, and most commonly, ASD has been demonstrated to be linked to epilepsy. ASD and epilepsy have been observed to exhibit high rates of comorbidity, even when compared to the co-occurrence of other disorders with similar pathologies. At present, nearly one-half of the individuals diagnosed with ASD also have been diagnosed with comorbid epilepsy. Research suggests that both conditions likely share similarities in their underlying disease pathophysiology, possibly associated with disturbances in the central nervous system (CNS), and may be linked to an imbalance between excitation and inhibition in the brain. Meanwhile, it remains unclear whether one condition is the consequence of the other, as the pathologies of both disorders are commonly linked to many different underlying signal transduction mechanisms. In this review, we aim to investigate the co-occurrence of ASD and epilepsy, with the intent of gaining insights into the similarities in pathophysiology that both conditions present with. Elucidating the underlying disease pathophysiology as a result of both disorders could lead to a better understanding of the underlying mechanism of disease activity that drives co-occurrence, as well as provide insight into the underlying mechanisms of each condition individually.Item A Biomarker Characterizing Neurodevelopment with applications in Autism(Nature Publishing Group, 2018-01-12) Wu, Di; José, Jorge V.; Nurnberger, John I., Jr.; Torres, Elizabeth B.; Medicine, School of MedicineDespite great advances in neuroscience and genetic studies, our understanding of neurodevelopmental disorders is still quite limited. An important reason is not having objective psychiatric clinical tests. Here we propose a quantitative neurodevelopment assessment by studying natural movement outputs. Movement is central to behaviors: It involves complex coordination, temporal alterations, and precise dynamic controls. We carefully analyzed the continuous movement output data, collected with high definition electromagnetic sensors at millisecond time scales. We unraveled new metrics containing striking physiological information that was unseen neither by using traditional motion assessments nor by naked eye observations. Our putative biomarker leads to precise individualized classifications. It illustrates clear differences between Autism Spectrum Disorder (ASD) subjects from mature typical developing (TD) individuals. It provides an ASD complementary quantitative classification, which closely agrees with the clinicaly assessed functioning levels in the spectrum. It also illustrates TD potential age-related neurodevelopmental trajectories. Applying our movement biomarker to the parents of the ASD individuals studied in the cohort also shows a novel potential familial signature ASD tie. This paper proposes a putative behavioral biomarker to characterize the level of neurodevelopment with high predicting power, as illustrated in ASD subjects as an example.Item Caregiver Adaptation among Black and White Families of Individuals with Autism Spectrum Disorder and the Comparison of the Two Racial Groups(2020-08) Yu, Yue; McGrew, John; Mosher, Catherine; Zapolski, Tamika; Wu, Wei; Ruble, LisaTo date, only two studies, both using the same sample at two different time points, have quantitatively examined outcomes in Black caregivers of individuals with autism spectrum disorder (ASD). This study examined family adaptational outcomes in Black and White caregivers of individuals with ASD using the double ABCX model of family adaptation to examine the impacts of stressors, the A in the model (e.g., autism symptom severity, general life demands), resources/supports, the B in the model (e.g., social support), and individual coping/stress appraisal styles, the C in the model (e.g., cognitive appraisal, religious coping) on caregiver positive and negative adaptation outcomes, the X in the model, (e.g., caregiver strain, benefit finding, family quality of life). Black and White caregivers were compared on adaptation outcomes at the family, dyadic, and individual level, including both positively valenced (e.g., benefit finding) and negatively valenced outcomes (e.g., depression, caregiver strain). Participants were Black (N = 24) and White (N = 32) primary caregivers of individuals with ASD. Racial differences were found for both the general and racial-specific factors in the ABCX model. White and Black caregivers reported moderate and equal levels of caregiver strain. However, Black caregivers reported greater levels of anxiety and depression and lower levels of life satisfaction. When adjusting for potential ABC covariates, racial differences in outcomes were no longer significant. That is, racial differences in outcomes could be explained by differences in the proximal elements represented by the ABC variables of the model (e.g., passive-avoidance coping, religious coping). Black caregivers reported higher levels of pile-up of demands, formal social support, threat appraisal, passive-avoidance coping, and positive and negative religious coping than White caregivers. Different factors were related to caregiver strain in the two racial groups. Conscientiousness was a protective factor against caregiver strain for Black caregivers, whereas greater use of passive-avoidance coping and threat appraisal, higher levels of neuroticism and barriers to care, and lower levels of satisfaction with services, parenting self-efficacy, and formal social support were explanatory factors for increased caregiver strain among White caregivers. These results are helpful in informing interventions and support the cultural adaptation of care as provided to Black caregivers of individuals with ASD.Item Characterizing executive functioning and associated behaviors in individuals with dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) syndrome(Frontiers Media, 2025-01-07) Rea, Hannah M.; Webb, Sara Jane; Kurtz-Nelson, Evangeline C.; Hudac, Caitlin M.; Bernier, Raphael A.; Miles, Conor; Earl, Rachel; Whiting, Alana; Eayrs, Curtis; Johansson, Margaret; Wang, Tianyun; Eichler, Evan E.; Neuhaus, Emily; Pediatrics, School of MedicineIntroduction: DYRK1A, a protein kinase located on human chromosome 21, plays a role in postembryonic neuronal development and degeneration. Alterations to DYRK1A have been consistently associated with cognitive functioning and neurodevelopmental disorders (e.g., autism, intellectual disability). However, the broader cognitive and behavioral phenotype of DYRK1A syndrome requires further characterization. Specifically, executive functioning, or cognitive processes that are necessary for goal-directed behavior, has not yet been characterized in this population. Methods: Individuals with DYRK1A variants (n = 29; ages 4 to 21 years) were assessed with a standardized protocol with multiple measures of executive functioning: Delis-Kaplan Executive Function Schedule, and chronologically age-appropriate caregiver-report forms of the Behavior Rating Inventory of Executive Function (BRIEF) and Achenbach System of Empirically Based Assessment (ASEBA). We first examined the feasibility and appropriateness of established executive functioning measures among participants with DYRK1A syndrome to inform selection of executive functioning tools in future research. We then characterized executive functioning among the group, including associations with other phenotypic features. Results: Neurocognitive assessments of executive functioning were deemed infeasible due to cognitive and verbal functioning. Caregiver-report revealed elevated executive functioning concerns related to self-monitoring, working memory, and planning/organization on the BRIEF, and attention and ADHD on the CBCL. Only two participants had existing ADHD diagnoses; however, 5 participants (out of 10 participants with data) exceeded the cutoff on the BRIEF, 13 individuals (out of 27 with data) exceeded the cutoff on the ASEBA ADHD subscale, and 18 exceeded the cutoff on the ASEBA attention subscale. There was concordance between ADHD diagnosis and the ASEBA, but not BRIEF. Executive functioning was correlated with nonverbal IQ and autism traits. Discussion: Objective measures of executive functioning are needed for individuals with intellectual disability who are nonverbal and/or have motor limitations. Diagnostic overshadowing, or the tendency to attribute all problems to intellectual disability and to leave other co-existing conditions, such as executive functioning challenges or ADHD, undiagnosed, is common. Phenotypic characterization of executive functioning is therefore important for our understanding of DYRK1A syndrome and for ensuring that caregivers' concerns are addressed, and individuals receive the clinical services that best meet their needs.Item A Double-Blind, Placebo-Controlled Trial of Oral Human Immunoglobulin for Gastrointestinal Dysfunction in Children with Autistic Disorder(Springer, 2009-01-16) Handen, Benjamin L.; Melmed, Raun D.; Hansen, Robin L.; Aman, Michael G.; Burnham, David L.; Bruss, Jon B.; McDougle, Christopher J.; Psychiatry, School of MedicineControversy exists regarding the extent and possible causal relationship between gastrointestinal symptoms and autism. A randomized, double-blind, placebo-controlled, parallel groups, dose-ranging study of oral, human immunoglobulin (IGOH 140, 420, or 840 mg/day) was utilized with 125 children (ages 2–17 years) with autism and persistent GI symptoms. Endpoint analysis revealed no significant differences across treatment groups on a modified global improvement scale (validated in irritable bowel syndrome studies), number of daily bowel movements, days of constipation, or severity of problem behaviors. IGOH was well-tolerated; there were no serious adverse events. This study demonstrates the importance of conducting rigorous trials in children with autism and casts doubt on one GI mechanism presumed to exert etiological and/or symptomatic effects in this population.Item Electrophysiological Measures of Tactile and Auditory Processing in Children With Autism Spectrum Disorder(Frontiers Media, 2021-12-23) Kadlaskar, Girija; Bergmann, Sophia; McNally Keehn, Rebecca; Seidl, Amanda; Keehn, Brandon; Pediatrics, School of MedicineBehavioral differences in responding to tactile and auditory stimuli are widely reported in individuals with autism spectrum disorder (ASD). However, the neural mechanisms underlying distinct tactile and auditory reactivity patterns in ASD remain unclear with theories implicating differences in both perceptual and attentional processes. The current study sought to investigate (1) the neural indices of early perceptual and later attentional factors underlying tactile and auditory processing in children with and without ASD, and (2) the relationship between neural indices of tactile and auditory processing and ASD symptomatology. Participants included 14, 6-12-year-olds with ASD and 14 age- and non-verbal IQ matched typically developing (TD) children. Children participated in an event-related potential (ERP) oddball paradigm during which they watched a silent video while being presented with tactile and auditory stimuli (i.e., 80% standard speech sound/a/; 10% oddball speech sound/i/; 10% novel vibrotactile stimuli on the fingertip with standard speech sound/a/). Children's early and later ERP responses to tactile (P1 and N2) and auditory stimuli (P1, P3a, and P3b) were examined. Non-parametric analyses showed that children with ASD displayed differences in early perceptual processing of auditory (i.e., lower amplitudes at central region of interest), but not tactile, stimuli. Analysis of later attentional components did not show differences in response to tactile and auditory stimuli in the ASD and TD groups. Together, these results suggest that differences in auditory responsivity patterns could be related to perceptual factors in children with ASD. However, despite differences in caregiver-reported sensory measures, children with ASD did not differ in their neural reactivity to infrequent touch-speech stimuli compared to TD children. Nevertheless, correlational analyses confirmed that inter-individual differences in neural responsivity to tactile and auditory stimuli were related to social skills in all children. Finally, we discuss how the paradigm and stimulus type used in the current study may have impacted our results. These findings have implications for everyday life, where individual differences in responding to tactile and auditory stimuli may impact social functioning.Item Elevated and Accelerated: Locus Coeruleus Activity and Visual Search Abilities in Autistic Children(Elsevier, 2023) Keehn, Brandon; Kadlaskar, Girija; McNally Keehn, Rebecca; Pediatrics, School of MedicineBackground: Autistic individuals excel at visual search, however, the neural mechanism(s) underlying this advantage remain unclear. The locus coeruleus-norepinephrine (LC-NE) system, which plays a critical role in sensory perception and selective attention, has been shown to function in a persistently elevated state in individuals on the spectrum. However, the relationship between elevated tonic LC-NE activity and accelerated search in autism has not been explored. Objective: To examine the relationship between visual search abilities and resting pupil diameter (an indirect measure of tonic LC-NE activation) in autistic and neurotypical children. Methods: Participants were 24 school-aged autistic children and 24 age- and IQ-matched neurotypical children aged 8-15 years. Children completed two tasks: a resting eye-tracking task and a visual search paradigm. For the resting eye-tracking task, pupil diameter was monitored while participants fixated a central crosshair. For the visual search paradigm, participants were instructed to find the target (vertical line) embedded within an array of tilted (10°) distractor lines. The target was present on 50% of trials, and displayed within set sizes of 18, 24, and 36 items. Results: Consistent with previous studies, autistic children had significantly larger resting pupil size and searched faster and more efficiently compared to their neurotypical peers. Eye-tracking findings revealed that accelerated search was associated with fewer, not shorter, fixations in the autism group. Autistic children also showed reduced leftward search bias. Larger resting pupil size, indicative of increased tonic activation of the LC-NE system, was associated with greater search efficiency, longer fixation durations, and reduced leftward bias. Finally, within both groups reduced leftward bias was associated with increased autism symptomatology. Discussion: Together, these findings add to the existing body of research highlighting superior search in autism, suggest that elevated tonic LC-NE activity may contribute to more efficient search, and link non-social visual-spatial processing strengths to autism symptoms.Item Equivalent Behavioral Facilitation to Tactile Cues in Children with Autism Spectrum Disorder(MDPI, 2021-05-13) Kadlaskar, Girija; Bergmann, Sophia; McNally Keehn, Rebecca; Seidl, Amanda; Keehn, Brandon; Pediatrics, School of MedicineThe alerting network, a subcomponent of attention, enables humans to respond to novel information. Children with ASD have shown equivalent alerting in response to visual and/or auditory stimuli compared to typically developing (TD) children. However, it is unclear whether children with ASD and TD show equivalent alerting to tactile stimuli. We examined (1) whether tactile cues affect accuracy and reaction times in children with ASD and TD, (2) whether the duration between touch-cues and auditory targets impacts performance, and (3) whether behavioral responses in the tactile cueing task are associated with ASD symptomatology. Six- to 12-year-olds with ASD and TD participated in a tactile-cueing task and were instructed to respond with a button press to a target sound /a/. Tactile cues were presented at 200, 400, and 800 ms (25% each) prior to the auditory target. The remaining trials (25%) were presented without tactile cues. Findings suggested that both groups showed equivalent alerting responses to tactile cues. Additionally, all children were faster to respond to auditory targets at longer cue-target intervals. Finally, there was an association between rate of facilitation and RRB scores in all children, suggesting that patterns of responding to transient phasic cues may be related to ASD symptomatology.Item The Exchange of Social Support via Social Networks of Maternal Caregivers for Children with Autism Spectrum Disorders(2011-08-19) Coates, Heather L.; Jones, Josette; Kharazzi, Hadi; Schilling, KatherineThe role of social support in the lives of the 16.8 million caregivers for children with special needs in the U.S. is not adequately understood. Many studies have explored seeking health information online, but failed to consider information exchanged through social networks (i.e., family, friends, colleagues, neighbors, etc.). Caregivers of children with special needs spend on average 30 hours per week providing such care. The burden of caregiving can negatively affect caregivers physically, mentally and emotionally, socially, and financially. Social support is one potential mediator for the effects of caregiver burden. The objective of this study was to explore the flow of four dimensions of social support within the social networks of maternal caregivers for children diagnosed with an autism spectrum disorder (ASD). A convenience sample was gathered via electronic distribution lists for Indiana parents of children with special needs. Participants could elect to complete a face-to-face interview or an anonymous online survey. The typical participant was Caucasian, married, college-educated, and located in Central Indiana. Respondent social networks are composed of multiplex relations, indicating strong ties. Significant correlations were found for participant age, child age, and the age of diagnosis, and network members for various networks. Specifically, a later age of child diagnosis is associated with fewer network members for the caregiver. Correlational analyses between dimensions of social support and network characteristics suggest options for further study. Overall, the results of this exploratory study are inconclusive, but can provide direction for future research.