Chronic Pain in Autistic Youth: Clinical Prevalence and Reflections on Tailoring Evidence-Based Interventions from an Interdisciplinary Treatment Team.

Though there is growing awareness of the overrepresentation of autistic patients in chronic pain clinics, potential adaptations for the assessment and treatment of chronic pain in this population have not yet been established. To address this gap, a retrospective review of electronic medical records and discussions by an interdisciplinary pain treatment team were summarized to inform potential biopsychosocial factors affecting the presentation, assessment, and treatment of chronic pain in autistic youth. Our sample included a record review of 95 patients receiving treatment in an interdisciplinary outpatient pediatric pain clinic. Results indicated that 9% (n = 9) of the patients presented to the clinic with a prior diagnosis of autism, but an additional 21% (n = 20) were identified as likely meeting criteria for autism based on the clinical assessment of the developmental history, behaviors observed during the clinical encounter(s), and expert clinical judgment, suggesting that the prevalence rate of autism may be closer to 30% in our outpatient pediatric pain clinic. Over half (52%) of the autistic youth presented to the clinic with widespread pain, 60% identified as female, and 6% identified as gender expansive or transgender. Qualitative insights revealed that most of the autistic patients had co-occurring sensory-processing challenges and difficulty in describing their pain, emotions, and somatic experiences and exhibited cognitive inflexibility and social challenges. We summarize our team's clinical reflections on how autism-relevant biopsychosocial vulnerability factors may contribute to the experience of pain in autistic youth and propose treatment targets and adaptations for the assessment and treatment of pain in this population. Finally, we recommend the need for interventions focused on sensorimotor integration, especially for autistic youth, and describe how pain clinics may be particularly helpful for identifying and supporting autistic females, for whom the potential role of autism in pain experiences had not been considered until receiving treatment in our clinic.

Modeling idiopathic autism in forebrain organoids reveals an imbalance of excitatory cortical neuron subtypes during early neurogenesis.

Idiopathic autism spectrum disorder (ASD) is highly heterogeneous, and it remains unclear how convergent biological processes in affected individuals may give rise to symptoms. Here, using cortical organoids and single-cell transcriptomics, we modeled alterations in the forebrain development between boys with idiopathic ASD and their unaffected fathers in 13 families. Transcriptomic changes suggest that ASD pathogenesis in macrocephalic and normocephalic probands involves an opposite disruption of the balance between excitatory neurons of the dorsal cortical plate and other lineages such as early-generated neurons from the putative preplate. The imbalance stemmed from divergent expression of transcription factors driving cell fate during early cortical development. While we did not find genomic variants in probands that explained the observed transcriptomic alterations, a significant overlap between altered transcripts and reported ASD risk genes affected by rare variants suggests a degree of gene convergence between rare forms of ASD and the developmental transcriptome in idiopathic ASD.

Development of peak alpha frequency reflects a distinct trajectory of neural maturation in autistic children.

Electroencephalographic peak alpha frequency (PAF) is a marker of neural maturation that increases with age throughout childhood. Distinct maturation of PAF is observed in children with autism spectrum disorder such that PAF does not increase with age and is instead positively associated with cognitive ability. The current study clarifies and extends previous findings by characterizing the effects of age and cognitive ability on PAF between diagnostic groups in a sample of children and adolescents with and without autism spectrum disorder. Resting EEG data and behavioral measures were collected from 45 autistic children and 34 neurotypical controls aged 8 to 18 years. Utilizing generalized additive models to account for nonlinear relations, we examined differences in the joint effect of age and nonverbal IQ by diagnosis as well as bivariate relations between age, nonverbal IQ, and PAF across diagnostic groups. Age was positively associated with PAF among neurotypical children but not among autistic children. In contrast, nonverbal IQ but not age was positively associated with PAF among autistic children. Models accounting for nonlinear relations revealed different developmental trajectories as a function of age and cognitive ability based on diagnostic status. Results align with prior evidence indicating that typical age-related increases in PAF are absent in autistic children and that PAF instead increases with cognitive ability in these children. Findings suggest the potential of PAF to index distinct trajectories of neural maturation in autistic children.

Early pregnancy loss medical management in clinical practice.

OBJECTIVES: This study aimed to review clinical practice outcomes of early pregnancy loss (EPL) medical management using mifepristone and misoprostol outside of a clinical trial setting. STUDY DESIGN: In this retrospective cohort study, we reviewed a deidentified database of patients who received mifepristone-misoprostol for EPL from May 2018 to May 2021 at our academic center-based clinic, which was a study site for a multicenter mifepristone-misoprostol EPL trial completed in March 2018. All patients received mifepristone 200 mg orally and misoprostol 800 mcg vaginally or buccally, with clinic follow-up typically scheduled within 1 week. The primary outcome was successful medical management, defined as management without the need for aspiration, and the secondary outcomes included additional interventions and indications, follow-up ultrasonography findings, and adverse events requiring treatment. RESULTS: We treated 90 patients with a median ultrasound-measured gestational size of 49 (range 30-80) days and median time from mifepristone to misoprostol of 24 (range 8-66) hours. Follow-up was completed in clinic by 80 (88.9%), completed remotely by five (5.6%), and not completed by five (5.6%) patients. Overall, 76 (95% CI 82.9%-96.0%) of 85 patients (89.4%) with follow-up were successfully managed without uterine aspiration. Eighty patients had initial follow-up ultrasonography interpreted as gestational sac expulsion; seven (8.8%) of these ultimately underwent aspiration, including one patient who had a previously undiagnosed cesarean scar ectopic pregnancy. Two patients had significant safety outcomes: one pelvic infection and one blood transfusion during aspiration in the patient with a cesarean scar ectopic pregnancy. CONCLUSIONS: Outside of a clinical trial setting, medical management of EPL with mifepristone and misoprostol remains effective and safe. IMPLICATIONS: Medical management of EPL with mifepristone and misoprostol is effective and safe outside of a clinical trial setting. A standardized protocol based on the best available clinical trial evidence can be used in clinical practice for the medical management of EPL.

Distinct Symptom Network Structure and Shared Central Social Communication Symptomatology in Autism and Schizophrenia: A Bayesian Network Analysis.

Autism (ASD) and schizophrenia spectrum disorders (SCZ) are neurodevelopmental conditions with overlapping and interrelated symptoms. A network analysis approach that represents clinical conditions as a set of "nodes" (symptoms) connected by "edges" (relations among symptoms) was used to compare symptom organization in the two conditions. Gaussian graphical models were estimated using Bayesian methods to model separate symptom networks for adults with confirmed ASD or SCZ diagnoses. Though overall symptom organization differed by diagnostic group, both symptom networks demonstrated high centrality of social communication difficulties. Autism-relevant restricted and repetitive behaviors and schizophrenia-related cognitive-perceptual symptoms were uniquely central to the ASD and SCZ networks, respectively. Results offer recommendations to improve differential diagnosis and highlight potential treatment targets in ASD and SCZ.

Sleep Problems and Autism Impairments in a Large Community Sample of Children and Adolescents.

Sleep problems are common in individuals with autism spectrum disorder (ASD). How sleep problems reflect specific ASD phenotypes is unclear. We studied whether sleep problems indexed functional impairment in a heterogeneous community sample of individuals with ASD. We analyzed 977 probands (233 females; age = 11.27 ± 4.13 years) from the Rhode Island Consortium for Autism Research and Treatment dataset, a unique public-private-academic collaboration involving all major points of service for families in Rhode Island. We found that individuals with a confirmed diagnosis of ASD were more likely to have sleep problems. However, across the whole sample and above and beyond a formal diagnosis, sleep problems were dimensionally associated with worse social impairment and poorer adaptive functioning. By using a large dataset reflective of the diversity of presentations in the community, this study underscores the importance of considering sleep problems in clinical practice to improve adaptive functioning in individuals with ASD.

Associations between sleep problems and domains relevant to daytime functioning and clinical symptomatology in autism: A meta-analysis.

Autistic individuals experience significantly higher rates of sleep problems compared to the general population, which negatively impacts various aspects of daytime functioning. The strength of associations across domains of functioning has not yet been summarized across studies. The present meta-analysis examined the strength of associations between sleep problems and various domains of daytime functioning in autistic individuals. Searches were conducted in EMBASE, PubMed, Web of Science, and Google Scholar through May 2020. Inclusion criteria were: an index of sleep disturbance in individuals diagnosed with autism spectrum disorder (ASD); data collected prior to any sleep-related intervention; statistical data indicating relations between sleep problems and outcomes relevant to behavior, cognition, and physical or mental health. Exclusion criteria were: statistics characterizing the relationship between sleep disturbance and outcome variables that partialled out covariates; studies examining correlations between different measures of sleep disturbance. Participants totaled 15,074 from 49 published articles and 51 samples, yielding 209 effect sizes. Sleep problems were significantly associated with more clinical symptomatology and worse daytime functioning. Subgroup analyses demonstrated that sleep problems were most strongly associated with internalizing and externalizing symptoms and executive functioning, followed by core autism symptoms, family factors, and adaptive functioning. Findings highlight the far-reaching consequences of sleep problems on daytime functioning for autistic individuals and support the continued prioritization of sleep as a target for intervention through integrated care models to improve wellbeing. LAY SUMMARY: Autistic individuals experience higher rates of sleep problems, such as difficulty falling asleep and staying asleep, compared to the general population. We quantitatively summarized the literature about how sleep problems are related to different aspects of daytime functioning to identify areas that may be most affected by sleep. Sleep problems were related to all areas assessed, with the strongest associations for mood and anxiety symptoms. We recommend prioritizing sleep health in autistic individuals to improve wellbeing and quality of life.

Final 24-hour Drain Output and Postoperative Day Are Poor Indicators for Appropriate Drain Removal.

Drains are used in plastic surgery to remove excess fluid while ameliorating complications. However, there is a paucity of evidence supporting guiding parameters on when to discontinue a drain. The aim of our study was to determine whether two of the most common parameters, drain volume 24 hours before removal or postoperative day, are valid indicators for drain removal. Methods: A retrospective chart review was conducted for surgical operations performed by our division between July 2014 and May 2019. Of the 1308 patients, 616 had a drain and a complete record. Demographics, medical history, operative time, antibiotic use, anatomic site, donor/recipient, and complication type were recorded. Complications were defined as events that deviated from expected postoperative course or required pharmacological/procedural intervention. T-test and Chi square were used to analyze data. Results: In total, 544 patients were in the no complication group, and 72 were in the complication group. The complication group patients had drains removed later than patients in the no complication group (15.7 days versus 12.5 days, P = 0.0003) and had similar final 24-hour drain volumes versus patients in the no complication group (16.7 mL versus 18.8 mL, P = 0.2548). The complication group had more operations on the pelvis (11% versus 2.1%; P = 0.000017) or thigh (8.5% versus 3.4%; P = 0.029). Conclusions: Our data suggest neither postoperative day nor 24-hour volume before drain removal are valid indicators for removal. Late removal correlates with more complications; however, persisting output leading to later removal may be predictive of an impending complication rather than delays in drain removal causing the complication.

Patient Characteristics, Injury Types, and Costs Associated with Secondary Over-Triage of Isolated Cervical Spine Fractures.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: To aim of this study was to identify patient variables, injury characteristics, and costs associated with operative and non-operative treatment following inter-facility transfer of patients with isolated cervical spine fractures. SUMMARY OF BACKGROUND DATA: Patients with isolated cervical spine fractures are subject to inter-facility transfer for surgical assessment, yet are often treated nonoperatively. The American College of Surgeons' benchmark rate of "secondary over-triage" is <50%. Identifying patient and injury characteristics as well as costs associated with treatment following transfer of patients with isolated cervical spine fractures may help reduce rates of secondary over-triage and healthcare expenditures. METHODS: Patients transferred to a Level-1 trauma center with isolated cervical spine fractures between January 2015 and September 2020 were identified. Patient demographics, comorbidities, insurance data, injury characteristics, imaging workup, treatment, and financial data were collected for all patients. Multivariable logistic regression models were constructed to identify patient and injury characteristics associated with surgical treatment. RESULTS: Nearly 75% of patients were treated non-operatively. Over 97% of transfers were accepted by the general surgery trauma service. Multivariable modeling found that higher BMI, presence of any neurologic deficit including spinal cord or isolated spinal nerve root injuries, present smoking status, or cervical spine magnetic resonance imaging obtained post-transfer, were associated with surgical treatment for isolated cervical spine fractures. Among patients with type II dens fractures, increased fracture displacement was associated with surgical treatment. Median charges to patients treated operatively and nonoperatively were $380,890 and $90,734, respectively. Median hospital expenditures for patients treated operatively and nonoperatively were $55,115 and $12,131, respectively. CONCLUSION: A large proportion of patients with isolated cervical spine fractures are subject to over-triage. Injury characteristics are important for determining need for surgical treatment, and therefore interfacility transfer. Improving communication with spine surgeons when deciding to transfer patients may significantly reduce health care costs and resource use.Level of Evidence: 4.

Internet-delivered cognitive behavioral therapy for youth with functional abdominal pain: a randomized clinical trial testing differential efficacy by patient subgroup.

ABSTRACT: Inconsistent results of psychological treatments for pediatric functional abdominal pain (FAP) may be due to heterogeneity of patients' pain-related psychological characteristics. This randomized controlled trial tested whether statistically derived patient subgroups (high pain dysfunctional [HPD], high pain adaptive [HPA], and low pain adaptive [LPA]) moderated response to cognitive behavior therapy (CBT) for adolescents with FAP and their parents (n = 278 dyads; patients were 66% female, mean [SD] age was 14.62 [1.88] years, and parents were 95% female). Randomization to Internet-delivered CBT vs Internet-delivered pain education (EDU) was stratified by patient subgroup. Follow-up assessments of gastrointestinal (GI) symptoms (primary outcome), abdominal pain, and pain interference were at midtreatment, posttreatment, 6 months, and 12 months. Data were analysed using linear mixed effects models. Significant treatment × subgroup × time interaction effects showed that patient subgroup significantly moderated the effect of treatment on GI symptoms (t[853 = -2.93, P = 0.003) and abdominal pain (t(844) = -2.14, P = 0.03) across the treatment period. Among HPD youth, those in CBT had significantly greater GI symptom reduction than those in EDU through posttreatment. By contrast, among HPA and LPA youth, symptom improvement did not differ by treatment condition. Furthermore, among all patients assigned to CBT, HPD youth demonstrated significantly greater reductions in GI symptoms compared with HPA and LPA youth and greater reductions in abdominal pain compared with LPA youth. All subgroups maintained symptom reductions throughout the follow-up period. Results suggest that subgrouping FAP patients may inform treatment allocation and optimize treatment response.

Long-term Follow-up of Preoperative Infant Event-related Potentials in School-age Children with Craniosynostosis.

BACKGROUND: Previous studies demonstrated impaired auditory processing in children with sagittal and metopic craniosynostosis before surgical correction. This study investigated whether worse presurgical neural response as assessed by event-related potentials (ERP) was predictive of poorer school-age neurocognition. METHODS: Preoperative infant ERP was recorded in 15 sagittal and 18 metopic patients. Mismatch negativity and P150 paradigms were derived from ERP recordings, as previously published. Of those, 13 sagittal and 13 metopic patients returned for neurocognitive evaluation 6 or more years later. ERP was correlated to neurocognitive outcomes using Spearman's correlations controlling for age. Two-tailed t-tests were used to evaluate the influence of age at the time of surgery (6 months) and morphologic severity on neurocognitive outcomes. RESULTS: In the sagittal group, no significant correlations were found between preoperative mismatch negativity or P150 amplitudes and neurocognitive outcomes. Although no correlation was found between mismatch negativity and neurocognitive outcome in the metopic group, those with lower P150 amplitudes had higher scores in performance IQ (r = -0.877, P < 0.001) and full-scale IQ (r = -0.893, P < 0.001). Morphologic severity and neurocognitive outcomes showed no relationship in the sagittal or metopic groups. Patients who received surgery at less than 6 months had higher full-scale IQ (109.69 versus 95.92, P = 0.025), visuomotor integration (103.15 versus 90.46, P = 0.041), and visual perception scores (105.69 versus 96.08, P = 0.033). CONCLUSIONS: Preoperative infant ERP does not correlate with school-age neurocognitive outcomes. Earlier age at the time of surgery was associated with improved neurocognitive outcomes.

A Default Option to Improve Nutrition for Adults With Low Income Using a Prefilled Online Grocery Shopping Cart.

OBJECTIVE: To determine whether a prefilled online grocery shopping (default) cart improves the nutritional quality of groceries purchased compared with receiving nutrition education (NE). DESIGN: Longitudinal study. SETTING: Three food pantries in the US. PARTICIPANTS: Thirty-eight adults with low income. INTERVENTION: Groceries were purchased online for 5 consecutive weeks. After a baseline shopping trip, participants were randomized to receive NE or a nutritionally balanced prefilled online grocery shopping cart (ie, default cart) before shopping (from week 1 [T1] to week 4 [T4]). MAIN OUTCOME MEASURES: Diet quality (Healthy Eating Index [HEI-2015] scores), energy, and energy density of each online cart (ie, grocery purchases). ANALYSIS: Piecewise linear mixed-effects models. RESULTS: From baseline to T1, HEI-2015 scores in the default condition significantly increased (95% confidence interval [CI], 9.79-23.39), whereas total calories (95% CI, -10,942 to -1,663) and energy density (95% CI, -0.70 to -0.45) significantly decreased compared with NE. Improved HEI-2015 scores were maintained through T4. Calories and energy density increased from T1 to T4 in the default condition, but values remained lower (ie, more healthful) than the NE condition. In the NE condition, outcomes did not significantly change during the intervention. CONCLUSIONS AND IMPLICATIONS: Providing an online default cart may improve the nutritional quality of grocery purchases. However, future research is warranted to assess whether adding a second nudge later in the intervention or combining the NE and default cart further promotes healthy purchasing behavior.

Osteoporosis Is Undertreated After Low-energy Vertebral Compression Fractures.

INTRODUCTION: Despite guidelines recommending postfracture bone health workup, multiple studies have shown that evaluation and treatment of osteoporosis has not been consistently implemented after fragility fractures. The primary aim of this study was to evaluate rates of osteoporosis evaluation and treatment in adult patients after low-energy thoracolumbar vertebral compression fractures (VCFs). METHODS: We retrospectively reviewed all patients ≥60 years old presenting to a single academic trauma center with acute thoracolumbar VCFs after a ground-level fall from 2016 to 2020 . Rates of osteoporosis screening with dual-energy x-ray absorptiometry and initiation of pharmaceutical treatment were recorded at four time points: before the date of injury, during index hospitalization, at first primary care provider follow-up, and at final primary care provider follow-up. Rates of subsequent falls and secondary fragility fractures were recorded. One-year mortality and overall mortality were also calculated. RESULTS: Fifty-two patients with a mean age of 83 years presenting with thoracic and/or lumbar fractures after a ground-level fall were included. At a mean final follow-up of 502 days, only 10 patients (19.2%) received pharmacologic therapy for osteoporosis and only 6 (11.5%) underwent postinjury dual-energy x-ray absorptiometry evaluation. Twenty-five patients (48%) had at least one subsequent fall at a mean of 164 days from the initial date of injury. Eleven patients with subsequent falls sustained an additional fragility fracture because of the fall, including six operative injuries. One-year mortality among the 52 patients was 26.9%, and the overall mortality rate was 44.2% at the final follow-up. DISCUSSION: Osteoporosis remains a major public health issue that markedly affects quality of life and healthcare costs. Our study demonstrates the additional need for improved osteoporosis workup and intervention among patients who have sustained VCFs. We hope that our study helps raise awareness for improved osteoporosis evaluation and treatment among spine surgeons and all medical professionals treating patients with fragility fractures. LEVEL OF EVIDENCE: Retrospective Case Series, Level IV Evidence.

Comorbid Sleep Disturbance in Adolescents with Functional Abdominal Pain.

OBJECTIVE/BACKGROUND: Sleep disturbances have been commonly reported as comorbid in youth with pain conditions, but prior research specific to functional abdominal pain (FAP) is limited. This study describes individual factors associated with increased risk for sleep disturbance and characterizes the relationship between sleep disturbance and pain-related variables. PARTICIPANTS: Participants included 278 adolescents (age 11 to 17 years, M age = 15 years; 89% Caucasian; 65% female) with FAP. METHODS: Participants reported on sleep disturbances, abdominal pain severity, functional disability, somatic symptoms, and healthcare utilization. RESULTS: Female adolescents reported greater sleep disturbance than male adolescents (t(276) = 5.52, p < .001, Cohen's d = 0.70) and increased age was associated with greater sleep disturbance (r =.20, p =.001). In hierarchical regressions controlling for age, sex, and abdominal pain, greater sleep disturbance was significantly associated with greater functional disability (ß =.32), non-gastrointestinal somatic symptoms (ß =.35), and emergency department visits (ß =.29). CONCLUSIONS: Results suggest that sleep disturbance is common and should be assessed in youth presenting with FAP and may be a potential target for intervention.

Subgroups of Pediatric Patients With Functional Abdominal Pain: Replication, Parental Characteristics, and Health Service Use.

OBJECTIVES: Prior work in a cohort of youth with functional abdominal pain (FAP) identified patient subgroups (High Pain Dysfunctional, High Pain Adaptive, Low Pain Adaptive) that predicted differences in the course of FAP from childhood into young adulthood. We aimed to replicate these subgroups in a new sample of adolescents with FAP using the original classification algorithm and to extend subgroup characteristics to include parental characteristics and health service use. METHODS: Adolescents (n=278; ages 11 to 17 y, 66% females) presenting to a gastroenterology clinic for abdominal pain, and their parents (92% mothers) completed self-report measures; adolescents also completed a 7-day pain diary. RESULTS: The replicated patient subgroups exhibited distress and impairment similar to subgroups in the original sample. Moreover, in novel findings, the High Pain Dysfunctional subgroup differed from other subgroups by the predominance of mother-daughter dyads jointly characterized by high levels of anxiety, depressive symptoms, pain behavior, and pain catastrophizing. The High Pain Dysfunctional subgroup used more health care services than Low Pain Adaptive but did not differ from High Pain Adaptive. DISCUSSION: Findings replicate and extend the original FAP classification and suggest that the subgroups have unique patient and parent features that may reflect distinct illness mechanisms requiring different treatments.

Temporal and Reciprocal Relations Between ADHD symptoms and Emotional Problems in School-Age Children.

Objective: The study aimed to investigate the reciprocal and temporal relations between ADHD symptoms and emotional problems in school-age children. Method: This 1-year longitudinal study with a four-wave design included 1,253 children and adolescents (254 third graders, 281 fifth graders, and 718 eighth graders; 50.9% boys). ADHD symptoms and emotional problems were measured using parent report of the Swanson, Nolan, and Pelham, Version IV Scale and Strengths and Difficulties Questionnaire. Results: Cross-lagged panel analyses indicated that both inattention and hyperactivity/impulsivity symptoms were associated with emotional problems over the 1-year period. However, only inattention symptoms demonstrated a transactional relationship with emotional problems, such that inattention predicted future emotional problems, which in turn led to increases in inattention symptoms. Conclusion: Our findings highlight the transactional and dynamic interplay between inattention symptoms and emotional problems and support the mechanistic role of inattention symptoms in the development and persistence of emotional problems in school-age children.

Depression in Youth with Autism Spectrum Disorder.

Depression is both common and impactful in youth with autism spectrum disorder (ASD) and is swiftly growing in recognition as a major public health concern within the autism community. This article is intended to provide a brief overview of the prevalence, impact, presentation, and risk factors associated with cooccurring depression in children and adolescents with ASD. Clinical guidelines for the assessment and treatment of depression in the ASD population are offered in line with the small existing evidence base.

Social and nonsocial reward moderate the relation between autism symptoms and loneliness in adults with ASD, depression, and controls.

Individuals with autism spectrum disorder (ASD) report high levels of co-occurring mood disorders. Previous work suggests that people with ASD also experience aberrant responses to social reward compared to typically developing (TD) peers. In the TD population, aberrant reward processing has been linked to anhedonia (i.e., loss of pleasure), which is a hallmark feature of depression. This study examined the interplay between self-reported pleasure from social and nonsocial rewards, autism symptom severity, loneliness, and depressive symptoms across adults with autism spectrum disorder (ASD; N = 49), TD currently depressed adults (TD-dep; N = 30), and TD never depressed controls (TD-con; N = 28). The ASD cohort reported levels of social and nonsocial anhedonia that were greater than TD-con but not significantly different from TD-dep. Across cohorts, both social and nonsocial hedonic capacity moderated the relationship between autism symptoms and loneliness: individuals with low capacity for pleasure experienced elevated loneliness regardless of autism symptom severity, while those with intact capacity for pleasure (i.e., less anhedonia) experienced greater loneliness as a function of increased autism symptoms. Loneliness was the strongest predictor of depressive symptoms across clinical cohorts. Our findings suggest a putative pathway from trait-like anhedonia in ASD to depression via elevated loneliness and indicate that variability in hedonic capacity within the autism spectrum may differentially confer risk for depression in adults with ASD. Results underscore potential mental health benefits of social skills interventions and community inclusion programs for adults with ASD. Autism Res 2019, 12: 884-896. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The relationship between autism symptoms and loneliness depended on one's ability to experience both social and nonsocial pleasure. Adults who experienced less pleasure reported high levels of loneliness that did not depend autism severity, while adults with high capacity for pleasure were especially lonely if they also had many autism symptoms. Loneliness was the strongest predictor of depressive symptoms, compared to capacity for social and nonsocial pleasure and autism symptoms.