Efficacy of spironolactone in treating hidradenitis suppurativa in women of childbearing age: a single-center retrospective analysis.

Background: Hidradenitis suppurativa (HS) is a chronic skin disease characterized by recurrent nodules that affect areas with a high density of apocrine sweat glands, such as the axillae and groin. Androgens are implicated in the pathophysiology of HS. Therefore, spironolactone, an antiandrogen therapy, is recommended. However, data on its use in women of childbearing age are limited, especially since its antiandrogenic effects may affect menstruation, fertility, and pubertal development. Objective: To evaluate the efficacy and safety of spironolactone in the treatment of hidradenitis suppurativa in women of childbearing age and to identify factors associated with treatment response. Methods: A retrospective analysis was conducted on female patients aged 12 to 50 with HS treated with spironolactone at Michigan Medicine dermatology clinics from 2000 to 2021. The patients' demographic data, HS characteristics, and spironolactone responses were examined. Statistical assessments were performed to determine the efficacy indicators. Results: Of the 157 patients reviewed, 31 showed an improvement in treatment. Variables such as axillary involvement, previous treatment failures, and use of intralesional steroids were linked to a lack of improvement in spironolactone. Through adjusted multiple logistic regression analysis, a significant association was observed between improvement status and Hurley stage 3 (odds ratio = 0.15 [95% CI: 0.02-0.79], P = .036), suggesting that patients with Hurley stage 3 were 85% less likely to exhibit improvement in spironolactone therapy. Limitations: The study's retrospective nature and reliance on single-center data can limit generalizability. The sample size is limited and therefore affects the study's statistical power. Conclusion: Thus, spironolactone may offer therapeutic benefits for HS in women of childbearing age. However, patients with severe disease (Hurley stage 3) had reduced response rates. Further prospective studies are recommended to validate these findings and determine the most suitable patient profile for spironolactone therapy for HS.

Bilingualism Predicts Affective Theory of Mind in Autistic Adults.

PURPOSE: This study examined the impact of bilingualism on affective theory of mind (ToM) and social prioritization (SP) among autistic adults compared to neurotypical comparison participants. METHOD: Fifty-two (25 autistic, 27 neurotypical) adult participants (ages 21-35 years) with varying second language (L2) experience, ranging from monolingual to bilingual, completed an affective ToM task. A subset of this sample also completed a dynamic eye-tracking task designed to capture differences in time spent looking at social aspects of a scene (SP). Four language groups were compared on task performance (monolingual autism and neurotypical, bilingual autism and neurotypical), followed by analyses examining the contribution of L2 experience, autism characteristics, and social face prioritization on affective ToM, controlling for verbal IQ. Finally, we conducted an analysis to identify the contribution of SP on affective ToM when moderated by autism status and L2 experience, controlling for verbal IQ. RESULTS: The monolingual autism group performed significantly worse than the other three groups (bilingual autism, monolingual neurotypical, and bilingual neurotypical) on the affective ToM task; however, there were no significant differences between the bilingual autism group compared to the monolingual and bilingual neurotypical groups. For autistic individuals, affective ToM capabilities were positively associated with both verbal IQ and L2 experience but did not relate to autism characteristics or SP during eye tracking. Neurotypical participants showed greater SP during the eye-tracking task, and SP did not relate to L2 or autism characteristics for autistic individuals. SP and verbal IQ predicted affective ToM performance across autism and neurotypical groups, but this relationship was moderated by L2 experience; SP more strongly predicted affective ToM performance among participants with lower L2 experience (e.g., monolingual) and had less of an impact for those with higher L2 experience. CONCLUSION: This study provides support for a bilingual advantage in affective ToM for autistic individuals. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25696083.

Factors Associated with Confirmed and Unconfirmed Autism Spectrum Disorder Diagnosis in Children Volunteering for Research.

PURPOSE: Diagnostic accuracy of autism spectrum disorder (ASD) is crucial to track and characterize ASD, as well as to guide appropriate interventions at the individual level. However, under-diagnosis, over-diagnosis, and misdiagnosis of ASD are still prevalent. METHODS: We describe 232 children (MAge = 10.71 years; 19% female) with community-based diagnoses of ASD referred for research participation. Extensive assessment procedures were employed to confirm ASD diagnosis before study inclusion. The sample was subsequently divided into two groups with either confirmed ASD diagnoses (ASD+) or unconfirmed/inaccurate diagnoses (ASD-). Clinical characteristics differentiating the groups were further analyzed. RESULTS: 47% of children with community-based ASD diagnoses did not meet ASD criteria by expert consensus. ASD + and ASD- groups did not differ in age, gender, ethnicity, or racial make-up. The ASD + group was more likely to have a history of early language delays compared to the ASD- group; however, no group differences in current functional language use were reported by caregivers. The ASD + group scored significantly higher on ADI-R scores and on the ADOS-2 algorithm composite scores and calibrated severity scores (CSSs). The ASD- group attained higher estimated IQ scores and higher rates of psychiatric disorders, including anxiety disorder, disruptive behavior, and mood disorder diagnoses. Broadly, caregiver questionnaires (SRS-2, CCC-2) did not differentiate groups. CONCLUSION: Increased reported psychiatric disorders in the ASD- group suggests psychiatric complexity may contribute to community misdiagnosis and possible overdiagnosis of ASD. Clinician-mediated tools (ADI-R, ADOS-2) differentiated ASD + versus ASD- groups, whereas caregiver-reported questionnaires did not.

The relationship between acrochordons, obesity, and metabolic syndrome in the pediatric population: A retrospective cohort study.

BACKGROUND: Acrochordons or skin tags are common benign skin growths. Several studies explored the relationship between obesity and metabolic syndrome in adults but remains unexplored in children. METHODS: This was a single-center retrospective cohort study of outpatient dermatology patients between 1 January 2000 to 1 January 2021. Children under 18 years old diagnosed with acrochordons using diagnostic codes International Classification of Diseases, 10th Revision (ICD-10) L91.8 and 9th Revision (ICD-9) 701.8 were included. We collected patient demographics, past medical history, laboratory values, vital signs, and physical exam. Body mass index (BMI) was calculated and stratified into categories based on the Center for Disease Control's BMI-for-Age Growth Charts. Metabolic syndrome was diagnosed when three of the five criteria were met. Data were propensity-matched and compared with NHANES (National Health and Nutrition Examination Survey), which offered a generalizable sample to the US population. RESULTS: Fifty-five patients under 18 years old with a diagnosis of acrochordons were mostly Caucasian (76%) and female (64%). The mean BMI was 27.3, with 49.5% categorized as obese and 20% as overweight. The mean age of diagnosis was 10.1 years. Acrochordon predominantly appeared in the axilla. In our cohort, three patients (5.5%) met the criteria for metabolic syndrome. The prevalence of obesity (42% vs. 21%), type 2 diabetes mellitus (4.8% vs. 0.6%), hyperlipidemia (8.1% vs. 0%), and hypertension (1.6% vs. 0%) was greater in our cohort compared with NHANES. CONCLUSIONS: Like the adult population, acrochordons may serve as marker for metabolic disease in the pediatric population.

Diagnostic assessment of autism spectrum disorder in transgender and gender diverse youth.

Objective: Higher prevalence of autism spectrum disorder (ASD) diagnosis and associated traits has been observed among transgender and gender diverse (TGD) youth, and the number of TGD youth requesting evaluation for autism is growing. This study explored the demographic and clinical profiles of TGD youth evaluated in a specialty autism clinic. Method: Retrospective autism evaluation results for 41 TGD youth aged 5-18 years and 67 cisgender-matched controls were included in the study. Results: Approximately, half of TGD youth were diagnosed with autism (TGDASD+; n = 19 vs. TGDASD-; n = 22). There were no group differences in sex assigned at birth, gender identity, FSIQ, race, or ethnicity. Compared to TGDASD- (allistic) youth, TGD autistics had significantly lower adaptive functioning and were more likely to have an IEP eligibility of ASD. Anxiety and mood disorders were more common in TGD youth, whereas language disorders were more prevalent in cisgender controls. Attention-Deficit/Hyperactivity Disorder (ADHD) was more common among TGDASD- youth (72%) than TGDASD+ youth (47%), though not significantly. Conclusions: TGD youth with school-based IEP eligibilities of ASD and lower adaptive functioning are more likely to be diagnosed with ASD upon medical evaluation. The combination of identifying as TGD and having ADHD may heighten suspicion for ASD. Asking about gender identity during autism evaluations for children middle school-aged and older is recommended.

Females evaluated for autism: characteristics and co-occurring and differential DSM-5 diagnoses.

Objective: While sex differences in autism spectrum disorder (ASD) have been identified in areas such as neurocognitive functioning, behavior patterns, and diagnostic criteria, less work has focused on differences within females referred for ASD evaluation, including those who did not go on to receive a diagnosis. This study examined psychological and behavioral characteristics and co-occurring and differential DSM-5 diagnoses between pediatric female participants who received an ASD diagnosis (ASD+) and those who did not (ASD-). Method: Data on cognitive functioning, adaptive functioning, internalizing symptoms, externalizing symptoms, and ADOS-2 scores were analyzed among 137 3- to 20-year-old patients. The sample was divided into two age groups (ages 3-8 and ages 9-20) for analyses of between-group differences (ASD+ vs. ASD-) and predictors of group membership. Results: Females in the ASD+ group were significantly younger, had lower cognitive scores, lower internalizing and externalizing symptoms, and had higher Autism Diagnostic Observation Schedule-2 (ADOS-2) scores than those in the ASD- group. ADOS-2 scores were also the only significant predictor of ASD group membership across age groups. The ASD+ group had a higher percentage of intellectual disability while the ASD- group had higher percentages of anxiety disorder, attention-deficit/hyperactivity disorder, and disruptive behavior disorders. Conclusions: Psychological and behavioral presentations among females referred for ASD evaluation varied with age and ASD diagnostic groups. These results highlight potential female differences in ASD referrals and identification of ASD and the need to improve care for females in consideration of demographic factors.

Social Functioning and Autistic Behaviors in Youth Following Acquired Brain Injury.

Children and adolescents who survive the pediatric intensive care unit (PICU) with an acquired brain injury (ABI) often demonstrate a variety of physical, cognitive, emotional/behavioral, and social sequelae termed post-intensive care syndrome (PICS). Social communication and interaction challenges have also been observed clinically, and there is growing literature documenting these occurrences in youth following ABI. The extent of these social changes varies among patients, and a subset of patients go on to exhibit social and behavioral profiles closely resembling those of autistic youth. We reviewed empirical research regarding social functioning in youth following ABI, as well as the overlap between individuals with ABI and autistic youth, published from January 2009 to August 2022 on PubMed and Scopus databases. Clinical case examples from a well-established post-PICU follow-up program are also provided to exemplify the complexity of this phenomenon.

Identifying Patient Characteristics to Understand Which Children May Receive Diagnostic Clarity in a Virtual Autism Spectrum Disorder Evaluation.

Given long waitlists for autism spectrum disorder (ASD) evaluation coupled with the COVID-19 pandemic, it is crucial to triage patients to services they are likely to receive diagnostic clarity (i.e., virtual, in-person evaluation). Participants attended a virtual ASD assessment. A subset also attended in-person evaluation. Results suggest younger children with educational services for ASD may benefit from virtual assessment while older patients with a history of psychiatric conditions may benefit from in-person evaluation. An ASD symptom severity tool related to virtual and in-person diagnostic clarity. Family history of ASD related to in-person diagnosis while other variables (e.g., age, educational services) did not. The study suggests patient characteristics may be used to determine for whom virtual ASD assessment may be appropriate.

Co-occurring Down Syndrome and Autism Spectrum Disorder: Cognitive, Adaptive, and Behavioral Characteristics.

The current study explores functioning in individuals with co-occurring Autism Spectrum Disorder and Down Syndrome (ASD+DS; n = 23), individuals with ASD and cognitive impairment (ASD+ID; n = 99) and individuals with idiopathic ID (n = 38). ANCOVA results revealed that individuals with ASD+DS showed strengths in behavioral functioning compared to individuals with ID and more similar behavioral functioning to those with ASD+ID (η2 = 0.12), with the exception of disruptive behaviors. Cognitive functioning (ɸc = 0.41) and ASD symptomatology (η2 = 0.11) were more comparable for children with ASD+DS and ASD + ID than for individuals with ID. Individuals with ASD+DS had the lowest overall adaptive skills (η2 = 0.11). Findings highlight similarities between ASD+DS and ASD+ID groups, emphasizing the importance of ASD identification within the DS population to provide access to specific interventions.

Autism Diagnostic Observation Schedule (ADOS-2) elevations in a clinical sample of children and adolescents who do not have autism: Phenotypic profiles of false positives.

OBJECTIVE: While the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) shows high sensitivity for detecting autism spectrum disorder (ASD) when present (i.e. true positives), scores on the ADOS-2 may be falsely elevated for individuals with cognitive impairments or psychological concerns other than ASD (i.e. false positives). This study examined whether demographic, psychological, cognitive, and/or adaptive factors predict ADOS-2 false positives and which psychiatric diagnoses most often result in false positives. METHOD: Sensitivity, specificity, false positive, and false negative rates were calculated among 214 5- to 16-year-old patients who completed an ADOS-2 (module 3) as part of an ASD diagnostic evaluation. Additional analyses were conducted with the 101 patients who received clinically elevated ADOS-2 scores (i.e. 56 true positives and 45 false positives). RESULTS: Results revealed a 34% false positive rate and a 1% false negative rate. False positives were slightly more likely to be male, have lower restricted and repetitive behavior (RRB) severity scores on the ADOS-2, and demonstrate elevated anxiety during the ADOS-2. Neither IQ, adaptive functioning, nor caregiver-reported emotional functioning was predictive of false positive status. Trauma-related psychiatric diagnoses were more common among false positives. CONCLUSIONS: The ADOS-2 should not be used in isolation to assess for ASD, and, in psychiatrically-complex cases, RRB symptom severity may be particularly helpful in differentiating ASD from other psychiatric conditions. Additionally, heightened levels of anxiety, more so than overactivity or disruptive behavior, may lead to non-ASD specific elevations in ADOS-2 scores.

A simultaneous [11C]raclopride positron emission tomography and functional magnetic resonance imaging investigation of striatal dopamine binding in autism.

The social motivation hypothesis of autism posits that autism spectrum disorder (ASD) is characterized by impaired motivation to seek out social experience early in life that interferes with the development of social functioning. This framework suggests that impaired mesolimbic dopamine function underlies compromised responses to social rewards in ASD. Although this hypothesis is supported by functional magnetic resonance imaging (fMRI) studies, no molecular imaging study has evaluated striatal dopamine functioning in response to rewards in ASD. Here, we examined striatal functioning during monetary incentive processing in ASD and controls using simultaneous positron emission tomography (PET) and fMRI. Using a bolus + infusion protocol with the D2/D3 dopamine receptor antagonist [11C]raclopride, voxel-wise binding potential (BPND) was compared between groups (controls = 12, ASD = 10) in the striatum. Striatal clusters showing significant between-group BPND differences were used as seeds in whole-brain fMRI general functional connectivity analyses. Relative to controls, the ASD group demonstrated decreased phasic dopamine release to incentives in the bilateral putamen and left caudate, as well as increased functional connectivity between a PET-derived right putamen seed and the precuneus and insula. Within the ASD group, decreased phasic dopamine release in the putamen was related to poorer theory-of-mind skills. Our findings that ASD is characterized by impaired striatal phasic dopamine release to incentives provide support for the social motivation hypothesis of autism. PET-fMRI may be a suitable tool to evaluate novel ASD therapeutics targeting the striatal dopamine system.

Dynamic Eye Tracking as a Predictor and Outcome Measure of Social Skills Intervention in Adolescents and Adults with Autism Spectrum Disorder.

To evaluate an eye tracking task as a predictor and outcome measure of treatment response for autism spectrum disorder (ASD) social skills interventions, adolescents and young adults with ASD completed the eye tracking task before, immediately after, and two months after completing Social Cognition and Interaction Training for Autism (SCIT-A). The study compared SCIT-A participants (n = 20) to participants with ASD who received treatment as usual (TAU; n = 21). Overall, increased visual attention to faces and background objects and decreased attention to hands playing with toys at baseline were associated with improved social functioning immediately following intervention, suggesting this eye tracking task may reliably predict ASD social intervention outcomes.

Neural Mechanisms of Vicarious Reward Processing in Adults with Autism Spectrum Disorder.

Previous studies examining the neural substrates of reward processing in ASD have explored responses to rewards for oneself but not rewards earned for others (i.e., vicarious reward). This omission is notable given that vicarious reward processing is a critical component of creating and maintaining social relationships. The current study examined the neural mechanisms of vicarious reward processing in 15 adults with ASD and 15 age- and gender-matched typically developing controls. Individuals with ASD demonstrated attenuated activation of reward-related regions during vicarious reward processing. Altered connectivity was also observed in individuals with ASD during reward receipt. These findings of altered neural sensitivity to vicarious reward processing may represent a mechanism that hinders the development of social abilities in ASD.

Neural Mechanisms of Reward Prediction Error in Autism Spectrum Disorder.

Few studies have explored neural mechanisms of reward learning in ASD despite evidence of behavioral impairments of predictive abilities in ASD. To investigate the neural correlates of reward prediction errors in ASD, 16 adults with ASD and 14 typically developing controls performed a prediction error task during fMRI scanning. Results revealed greater activation in the ASD group in the left paracingulate gyrus during signed prediction errors and the left insula and right frontal pole during thresholded unsigned prediction errors. Findings support atypical neural processing of reward prediction errors in ASD in frontostriatal regions critical for prediction coding and reward learning. Results provide a neural basis for impairments in reward learning that may contribute to traits common in ASD (e.g., intolerance of unpredictability).

Rates of Co-occurring Psychiatric Disorders in Autism Spectrum Disorder Using the Mini International Neuropsychiatric Interview.

Individuals with autism spectrum disorder (ASD) often meet criteria for at least one additional psychiatric disorder. The present study evaluated the utility of the Mini International Neuropsychiatric Interview (MINI) in assessing co-occurring psychiatric disorders in children, adolescents, and young adults with ASD. Ninety-one percent of children/adolescents and thirty-one percent of young adults were diagnosed with one or more co-occurring diagnoses using the MINI. MINI diagnostic rates were comparable to those found in the literature on children/adolescents with ASD; however, in young adults, MINI diagnostic rates were lower relative to rates found in the literature on young adults with ASD. Implications for treatment, transitioning to adulthood, and the need for instruments developed specifically to diagnose co-occurring disorders in ASD are discussed.

Social and nonsocial visual prediction errors in autism spectrum disorder.

Impaired predictive coding has been proposed as a framework to explain discrepancies between expectations and outcomes in autism spectrum disorder (ASD) that may contribute to core symptoms of the disorder. However, no eye tracking study has directly addressed this framework in the context of visual predictions of social and nonsocial stimuli. The current study used eye tracking to examine violations of learned visual associations of both social and nonsocial stimuli. Twenty-six adolescents with ASD and 18 typically developing control (TDC) adolescents completed an outcome expectation eye tracking task in which predictive cues correctly (80% of trials) or incorrectly (20% of trials) indicated the location (left or right) of forthcoming social or nonsocial stimuli. During violation trials, individuals with ASD focused their gaze relatively more often on stimuli presented on locations that violated the learned association and less often on locations that corresponded with the learned association. This finding was not moderated by stimulus type (i.e., social vs. nonsocial). Additionally, participants who looked at incorrectly predicted locations more often had significantly greater ASD symptom severity. These results are consistent with theories that characterize ASD as a disorder of prediction and have potential implications for understanding symptoms related to prediction errors in individuals with ASD. Autism Res 2019, 12: 878-883. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Individuals with autism spectrum disorder (ASD) exhibit impairments making predictions that may impact learning. In this study, we used eye tracking methodology and found that individuals with ASD were less likely to look at the predicted location when a visual routine was violated. This pattern was evident for both social and nonsocial images and was associated with greater ASD symptom severity. These findings provide additional support for predictive challenges in ASD.

A potential mechanistic role for neuroinflammation in reward processing impairments in autism spectrum disorder.

Accumulating evidence suggests that autism spectrum disorder (ASD) may be conceptualized within a framework of reward processing impairments. The Social Motivation Theory of Autism posits that reduced motivation to interact with people and decreased pleasure derived from social interactions may derail typical social development and contribute to the emergence of core social communication deficits in ASD. Neuroinflammation may disrupt the development of mesolimbic dopaminergic systems that are critical for optimal functioning of social reward processing systems. This neuroinflammation-induced disturbance of mesolimbic dopaminergic functioning has been substantiated using maternal immune activation rodent models whose offspring show aberrant dopaminergic corticostriatal function, as well as behavioral characteristics of ASD model systems. Preclinical findings are in turn supported by clinical evidence of increased mesolimbic neuroinflammatory responses in individuals with ASD. This review summarizes evidence for reward processing deficits and neuroinflammatory impairments in ASD and examines how immune inflammatory dysregulation may impair the development of dopaminergic mesolimbic circuitry in ASD. Finally, future research directions examining neuroinflammatory effects on reward processing in ASD are proposed.

Vicarious Effort-Based Decision-Making in Autism Spectrum Disorders.

This study investigated vicarious effort-based decision-making in 50 adolescents with autism spectrum disorders (ASD) compared to 32 controls using the Effort Expenditure for Rewards Task. Participants made choices to win money for themselves or for another person. When choosing for themselves, the ASD group exhibited relatively similar patterns of effort-based decision-making across reward parameters. However, when choosing for another person, the ASD group demonstrated relatively decreased sensitivity to reward magnitude, particularly in the high magnitude condition. Finally, patterns of responding in the ASD group were related to individual differences in consummatory pleasure capacity. These findings indicate atypical vicarious effort-based decision-making in ASD and more broadly add to the growing body of literature addressing social reward processing deficits in ASD.

Feedforward and feedback motor control abnormalities implicate cerebellar dysfunctions in autism spectrum disorder.

Sensorimotor abnormalities are common in autism spectrum disorder (ASD) and among the earliest manifestations of the disorder. They have been studied far less than the social-communication and cognitive deficits that define ASD, but a mechanistic understanding of sensorimotor abnormalities in ASD may provide key insights into the neural underpinnings of the disorder. In this human study, we examined rapid, precision grip force contractions to determine whether feedforward mechanisms supporting initial motor output before sensory feedback can be processed are disrupted in ASD. Sustained force contractions also were examined to determine whether reactive adjustments to ongoing motor behavior based on visual feedback are altered. Sustained force was studied across multiple force levels and visual gains to assess motor and visuomotor mechanisms, respectively. Primary force contractions of individuals with ASD showed greater peak rate of force increases and large transient overshoots. Individuals with ASD also showed increased sustained force variability that scaled with force level and was more severe when visual gain was highly amplified or highly degraded. When sustaining a constant force level, their reactive adjustments were more periodic than controls, and they showed increased reliance on slower feedback mechanisms. Feedforward and feedback mechanism alterations each were associated with more severe social-communication impairments in ASD. These findings implicate anterior cerebellar circuits involved in feedforward motor control and posterior cerebellar circuits involved in transforming visual feedback into precise motor adjustments in ASD.

Individuals with autism spectrum disorder show abnormalities during initial and subsequent phases of precision gripping.

Sensorimotor impairments are common in autism spectrum disorder (ASD), but they are not well understood. Here we examined force control during initial pulses and the subsequent rise, sustained, and relaxation phases of precision gripping in 34 individuals with ASD and 25 healthy control subjects. Participants pressed on opposing load cells with their thumb and index finger while receiving visual feedback regarding their performance. They completed 2- and 8-s trials during which they pressed at 15%, 45%, or 85% of their maximum force. Initial pulses guided by feedforward control mechanisms, sustained force output controlled by visual feedback processes, and force relaxation rates all were examined. Control subjects favored an initial pulse strategy characterized by a rapid increase in and then relaxation of force when the target force was low (Type 1). When the target force level or duration of trials was increased, control subjects transitioned to a strategy in which they more gradually increased their force, paused, and then increased their force again. Individuals with ASD showed a more persistent bias toward the Type 1 strategy at higher force levels and during longer trials, and their initial force output was less accurate than that of control subjects. Patients showed increased force variability compared with control subjects when attempting to sustain a constant force level. During the relaxation phase, they showed reduced rates of force decrease. These findings suggest that both feedforward and feedback motor control mechanisms are compromised in ASD and these deficits may contribute to the dyspraxia and sensorimotor abnormalities often seen in this disorder.