Reading comprehension improvement in autism.

Introduction: A subset of autistic children excel at word decoding but have difficulty with reading comprehension (i.e., the discrepant poor comprehender reading profile). Prior research suggests the Visualizing and Verbalizing (V/V) for language comprehension and thinking intervention helps improve reading comprehension in autistic children with this reading profile. Previous studies have demonstrated the role of vocabulary, memory, and social functioning in reading comprehension; however, predictors and moderators of reading comprehension within this specific profile of autistic readers have not been thoroughly explored. Methods: In this study, we examined the effectiveness of the V/V intervention by comparing reading comprehension scores between groups and across time. Participants included a sample of autistic children (AUT-EXP; n=22) and a waitlist control group of autistic children (AUT-WLC; n=17) with reading comprehension difficulties, as well as a sample of non-autistic children (Non-AUT; n=26) (all age 8-13 years). AUT-EXP and AUT-WLC groups completed a battery of cognitive assessments during pre and post tests. We also analyzed whether cognitive assessment scores predicted reading comprehension, and examined the moderating effects of group (AUT-EXP vs. AUT-WLC) on these relationships. Results: The AUT-EXP group significantly improved in their pre to post reading comprehension scores (t(21)=4.19, p<.001, d=.89), whereas the AUT-WLC group did not. Verbal memory significantly predicted reading comprehension, though group did not moderate relationships between cognitive test performance and reading comprehension. Discussion: Results suggest that the V/V intervention may help improve reading comprehension for autistic children with the discrepant poor comprehender reading profile. Additionally, strategies for improving verbal memory may indirectly enhance reading comprehension in autistic children with this reading profile.

Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial.

OBJECTIVE: This study was undertaken to test the hypothesis that early vigabatrin treatment in tuberous sclerosis complex (TSC) infants improves neurocognitive outcome at 24 months of age. METHODS: A phase IIb multicenter randomized double-blind placebo-controlled trial was conducted of vigabatrin at first epileptiform electroencephalogram (EEG) versus vigabatrin at seizure onset in infants with TSC. Primary outcome was Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive assessment score at 24 months. Secondary outcomes were prevalence of drug-resistant epilepsy, additional developmental outcomes, and safety of vigabatrin. RESULTS: Of 84 infants enrolled, 12 were screen failures, 4 went straight to open label vigabatrin, and 12 were not randomized (normal EEG throughout). Fifty-six were randomized to early vigabatrin (n = 29) or placebo (n = 27). Nineteen of 27 in the placebo arm transitioned to open label vigabatrin, with a median delay of 44 days after randomization. Bayley-III cognitive composite scores at 24 months were similar for participants randomized to vigabatrin or placebo. Additionally, no significant differences were found between groups in overall epilepsy incidence and drug-resistant epilepsy at 24 months, time to first seizure after randomization, and secondary developmental outcomes. Incidence of infantile spasms was lower and time to spasms after randomization was later in the vigabatrin group. Adverse events were similar across groups. INTERPRETATION: Preventative treatment with vigabatrin based on EEG epileptiform activity prior to seizure onset does not improve neurocognitive outcome at 24 months in TSC children, nor does it delay onset or lower the incidence of focal seizures and drug-resistant epilepsy at 24 months. Preventative vigabatrin was associated with later time to onset and lower incidence of infantile spasms. ANN NEUROL 2023.

Effect of Co-occurring Psychiatric Disorders on Treatment of Children with Autism Spectrum Disorder and Anxiety.

Co-occurring psychiatric diagnoses are very common in individuals with ASD. Little is known about the effect that co-occurring psychiatric conditions may have on treatment response to CBT for children with ASD and anxiety. The present study examined the relationship between co-occurring psychiatric diagnoses and response to CBT for anxiety in ninety youth with ASD. Psychiatric complexity did not appear to differentially impact treatment response. A notable portion of youth with anxiety and externalizing disorders such as ADHD, no longer met criteria for those externalizing diagnoses following intervention. Results indicate that youth with ASD and anxiety present with complex psychiatric profiles and CBT for anxiety may positively affect co-occurring diagnoses. In addition, thorough and nuanced assessment of psychiatric symptoms in youth with ASD is needed to ensure the differentiation between diagnoses of anxiety and other co-occurring psychiatric symptoms.

Classifying children with ASD by service utilization and treatment type: A cluster analysis of a nationally representative United States survey.

BACKGROUND: If there are patterns of the distribution of services and treatments across the population of people with ASD, these patterns should be based along clinical characteristics or other service needs and not sociodemographic characteristics unrelated to evidence-based care. We examined how individuals in a broad, nationally representative sample "grouped together" based on service utilization and services needed but not covered by insurance. By understanding various treatment patterns, clinicians, researchers, policymakers, and self-advocates and their families can better advocate for high-quality, evidence-based services to be provided equitably. METHODS: Using the 2011 Survey of Pathways to Diagnosis and Services, a cluster analysis was performed to explore patterns in this population based on medication use, private services use, school-based service use, and services not covered by insurance. Differences in clusters were then explored through multinomial logistic regression. RESULTS: Six clusters emerged, showing differences in the level of service/medication usage and insurance coverage. Differences across clusters were associated with the level of functional limitation and age at ASD diagnosis. Disparities by insurance type, functional limitation, and age at diagnosis exist among patterns of ASD service provision. CONCLUSIONS: Our analysis showed that intervention for children with ASD can be across several scales - high and low users of services (both private and school-based), high and low users of medications, and high and low levels of reported non-covered services. The differences were clustered in multiple ways. Further research should incorporate longitudinal and nationally representative data to explore these relationships further.

Pathways to Suicidal Behavior in Children and Adolescents: Examination of Child Maltreatment and Post-Traumatic Symptoms.

Suicide in youth exacts significant personal and community costs. Thus, it is important to understand predisposing risk factors. Experiencing adverse childhood experiences (ACEs), such as child maltreatment (CM-ACE), and the presence of post-traumatic stress disorder has been identified as a risk factor of suicidal behaviors among adults. Theoretical models of suicide suggest that the presence of painful experiences such as CM-ACEs increase the risk of suicidal behaviors. The relation between child maltreatment, post-traumatic stress symptom clusters (PTSS) and suicidal behaviors has not been explicitly examined among youth. The present study examined the relations between CM-ACEs, PTSS clusters, and suicidal behaviors in a clinical population of children. Children, male, ages 6 to 14, enrolled in a residential treatment program completed self-report measures to evaluate variables of interest. Path analyses revealed statistically significant direct effects of CM-ACEs and PTSS clusters on suicidal behaviors. Significant total indirect effects and marginally significant individual indirect effects of intrusion and avoidance symptoms were observed for the relation between CM-ACEs and suicidal behavior. Findings suggest that symptoms associated with specific PTSS clusters might help explain the relation between CM-ACEs and suicidal behavior, and therefore, present important implications for clinical practice and future research.

Pathways from child maltreatment to proactive and reactive aggression: The role of posttraumatic stress symptom clusters.

OBJECTIVE: Childhood aggression is related to a myriad of negative concurrent and long-term outcomes. To mitigate the risks associated with childhood aggression, it is important to understand risk factors that might predispose 1 to aggressive behaviors. One risk factor commonly associated with aggression is the experience of child maltreatment. A common outcome associated with child maltreatment is the development of posttraumatic stress symptoms (PTSS). Several prevailing theoretical models of both posttraumatic stress and aggression indicate that these constructs have similar underlying cognitive, behavioral, and emotional mechanisms. Therefore, the present study examined the relations between and among child maltreatment, PTSS clusters, and proactive and reactive aggression in children. METHOD: Children between the ages of 6 and 14 who were enrolled in a residential treatment program completed self-report measures to evaluate variables of interest. These variables were included as multiple outcomes in a path analysis model in which individual PTSS clusters were examined as potential multiple mediators of the relations between child maltreatment and proactive and reactive aggression. RESULTS: Direct effects of child maltreatment and PTSS clusters on aggression were observed. Significant indirect effects of the intrusion PTSS cluster on the relation between child maltreatment and reactive aggression was found. CONCLUSIONS: Findings suggest that symptoms associated with these specific PTSS clusters might help explain the relation between child maltreatment and reactive aggression and therefore present important implications for clinical practice and future research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Systematic Review and Meta-Analysis of the Clinical Utility of the ADOS-2 and the ADI-R in Diagnosing Autism Spectrum Disorders in Children.

The Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) and the Autism Diagnostic Interview, Revised (ADI-R) have high accuracy as diagnostic instruments in research settings, while evidence of accuracy in clinical settings is less robust. This meta-analysis focused on efficacy of these measures in research versus clinical settings. Articles (n = 22) were analyzed using a hierarchical summary receiver operating characteristics (HSROC) model. ADOS-2 performance was stronger than the ADI-R. ADOS-2 sensitivity and specificity ranged from .89-.92 and .81-.85, respectively. ADOS-2 accuracy in research compared with clinical settings was mixed. ADI-R sensitivity and specificity were .75 and .82, respectively, with higher specificity in research samples (Research = .85, Clinical = .72). A small number of clinical studies were identified, indicating ongoing need for investigation outside research settings.

Testing a Tailored Social-Ecological Model for Autism Spectrum Disorders.

OBJECTIVE: To propose a tailored social ecological model for Autism Spectrum Disorders and explore relationships between variables in a large nationally-representative dataset. METHODS: A tailored social-ecological model was developed and examined across variables in the 2016/2017 National Survey of Children's Health. A series of iterative multivariable logistic regressions were performed including individual, family, and community/neighborhood variables. A multivariable logistic regression using state-level fixed effects was performed to understand dynamics related to macro-level policies. RESULTS: In the full model, gender, disability severity, certain types of insurance coverage and household income were significantly related to ASD diagnosis. Females had lower odds of a diagnosis compared to males (aOR: 0.27; CI:0.18-0.41). Children with at least one other moderate/severe disability had odds 7.61 higher (CI:5.36-10.82) of a diagnosis than children without moderate/severe disabilities. Children with public insurance only (aOR:1.66; CI:1.14-2.41) or both private and public insurance coverage (aOR: 2.62; CI:1.6-4.16) had higher odds of a diagnosis compared to children with private insurance only. For those who reported it was "somewhat" or "very often" hard to cover basics with their income, odds of a diagnosis were higher compared to those who reported it was "never" or "hardly ever" hard to cover basics (aOR: 1.676; CI:0.21-2.56). CONCLUSIONS FOR PRACTICE: Patterns of ASD diagnosis are related to individual and family characteristics. There is some evidence that a child's environment has some relationship to reported ASD diagnosis. Professionals should be aware of an individual's environmental factors or context when assessing for ASD.

Comorbid Internalizing and Externalizing Symptoms Among Children with ADHD: The Influence of Parental Distress, Parenting Practices, and Child Routines.

Emotional/behavioral concerns are common among children with ADHD. Familial factors (e.g., parental adjustment, parenting behaviors) are linked to the presence of comorbid internalizing/externalizing symptoms among children with ADHD. The purpose of the present study was to evaluate a model that includes multiple familial variables and their direct and indirect effects on child emotional and behavioral problems among children with ADHD. Participants included parents of children (6-12 years of age; M = 8.87, SD = 1.92) with a diagnosis of ADHD (N = 300). Participants completed measures of child emotional/behavioral concerns, parental distress, routines, and parenting behaviors. Path analyses revealed direct effects for parental distress, parent behavior and routines on child adjustment, after controlling for the other variables. A significant indirect relation between parental distress, routines, and externalizing behavior was observed. These findings highlight one specific path through which parental distress appears to influence specific behavioral concerns that are commonly observed in children with ADHD.

Pilot Study of Neurodevelopmental Impact of Early Epilepsy Surgery in Tuberous Sclerosis Complex.

BACKGROUND: To determine if early epilepsy surgery mitigates detrimental effects of refractory epilepsy on development, we investigated surgical and neurodevelopmental outcomes in children with tuberous sclerosis complex who underwent surgery before age two years. METHODS: Prospective multicenter observational study of 160 children with tuberous sclerosis complex. Surgical outcome was determined for the seizure type targeted by surgery. We obtained Vineland Adaptive Behavior Scales, Second Edition (Vineland-II); Mullen Scales of Early Learning; and Preschool Language Scales, Fifth Edition, at age three, six, nine, 12, 18, 24, and 36 months. Surgical cases were compared with children without seizures, with controlled seizures, and with medically refractory seizures. RESULTS: Nineteen children underwent surgery (median age 17 months, range 3.7 to 21.3), and mean follow-up was 22.8 months (range 12 to 48). Surgical outcomes were favorable in 12 (63%, Engel I-II) and poor in seven (37%, Engel III-IV). Nine (47%) had new or ongoing seizures distinct from those surgically targeted. All children with seizures demonstrated longitudinal decline or attenuated gains in neurodevelopment, the surgical group scoring the lowest. Favorable surgical outcome was associated with increased Mullen Scales of Early Learning receptive and expressive language subscores compared with the medically refractory seizure group. A nonsignificant but consistent pattern of improvement with surgery was seen in all tested domains. CONCLUSIONS: These pilot data show neurodevelopmental gains in some domains following epilepsy surgery. A properly powered, prospective multicenter observational study of early epilepsy surgery is needed, using both surgical and developmental outcome metrics.

Scalp EEG spikes predict impending epilepsy in TSC infants: A longitudinal observational study.

OBJECTIVE: To determine if routine electroencephalography (EEG) in seizure-naive infants with tuberous sclerosis complex (TSC) can predict epilepsy and subsequent neurocognitive outcomes. METHODS: Forty infants 7 months of age or younger and meeting the genetic or clinical diagnostic criteria for tuberous sclerosis were enrolled. Exclusion criteria included prior history of seizures or treatment with antiseizure medications. At each visit, seizure history and 1-hour awake and asleep video-EEG, standardized across all sites, were obtained until 2 years of age. Developmental assessments (Mullen and Vineland-II) were completed at 6, 12, and 24 months of age. RESULTS: Of 40 infants enrolled (mean age of 82.4 days), 32 completed the study. Two were lost to follow-up and six were treated with antiepileptic drugs (AEDs) due to electrographic seizures and/or interictal epileptiform discharges (IEDs) on their EEG studies prior to the onset of clinical seizures. Seventeen of the 32 remaining children developed epilepsy at a mean age of 7.5 months (standard deviation [SD] = 4.4). Generalized/focal slowing, hypsarrhythmia, and generalized/focal attenuation were not predictive for the development of clinical seizures. Presence of IEDs had a 77.3% positive predictive value and absence a 70% negative predictive value for developing seizures by 2 years of age. IEDs preceded clinical seizure onset by 3.6 months (mean). Developmental testing showed significant decline, only in infants with ongoing seizures, but not infants who never developed seizures or whose seizures came under control. SIGNIFICANCE: IEDs identify impending epilepsy in the majority (77%) of seizure-naive infants with TSC. The use of a 1-hour awake and asleep EEG can be used as a biomarker for ongoing epileptogenesis in most, but not all, infants with TSC. Persistent seizures, but not history of interictal epileptiform activity or history of well-controlled seizures, correlated with low scores on the Vineland and Mullen tests at 2 years of age.

Impacting development in infants with tuberous sclerosis complex: Multidisciplinary research collaboration.

The Tuberous Sclerosis Complex Autism Center of Excellence Network (TACERN) is a 6-site collaborative conducting longitudinal research on infants with tuberous sclerosis complex (TSC), focused on identifying early biomarkers for autism spectrum disorder (ASD). A multidisciplinary research team that includes the specialties of psychology, neurology, pediatrics, medical genetics, and speech-language pathology, its members work together to conduct studies on neurological status, brain structure and function, neurodevelopmental phenotype, and behavioral challenges in this population. This article provides insights into the roles of the multidisciplinary multisite team and lessons learned from the collaboration, in terms of research as well as training of future researchers and clinicians. In addition, the authors detail the major findings to date, including those related to the identification and measurement of early symptoms of ASD, relationship between seizures and early development, and early biomarkers for epilepsy and developmental delay in infants and young children with TSC. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Training clinicians to deliver group CBT to manage anxiety in youth with ASD: Results of a multisite trial.

OBJECTIVE: Few guidelines are available regarding optimal training models for practitioners delivering cognitive-behavioral therapy (CBT) for anxiety in youth with autism spectrum disorder (ASD). The present study systematically compared 3 instructional conditions for delivering the Facing Your Fears program (FYF) to children with ASD and anxiety. METHOD: Thirty-four clinicians (Mage = 34 years; 94% women, 88% Caucasian) and an intent-to-treat sample of 91 children with ASD and anxiety (Mage = 11; 84% male 53% Caucasian) met eligibility criteria across 4 sites. A 3-group parallel design via a Latin square procedure was used to randomize 9 teams of clinicians to 1 of 3 training conditions: Manual, Workshop, Workshop-Plus. The effectiveness of instructional condition was assessed via implementation (CBT knowledge, treatment fidelity) and treatment outcomes (reductions in anxiety as measured by the Anxiety Disorders Interview Schedule-Parent (ADIS-P). RESULTS: Clinicians in both Workshop conditions significantly increased CBT knowledge postworkshop, F(1, 18) = 19.8, p < .001. Excellent treatment fidelity was obtained across conditions (above 89%), although clinicians in the Workshop conditions obtained significantly higher fidelity ratings and delivered FYF with greater quality than the Manual condition. Children with ASD demonstrated significant reductions in anxiety symptoms for three of the four anxiety diagnoses, with no differences noted across instructional condition. Rates of improvement were lower than those obtained in a previous controlled trial. CONCLUSIONS: Results suggest that although there may be some advantage to participating in a Workshop, clinicians in all conditions could deliver FYF with excellent fidelity and yield positive treatment outcomes. Lack of a no-treatment comparison group limits interpretation of findings. (PsycINFO Database Record

Predicting Internalizing and Externalizing Symptoms in Children with ASD: Evaluation of a Contextual Model of Parental Factors.

Parental adjustment, parenting behaviors, and child routines have been linked to internalizing and externalizing child behavior. The purpose of the present study was to evaluate a comprehensive model examining relations among these variables in children with ASD and their parents. Based on Sameroff's Transactional Model of Development (Sameroff in: The transactional model of development: How children and contexts shape each other, American Psychological Association, Washington, DC, 2009), researchers hypothesized that these factors would collectively predict child behavior. Parents (n = 67) completed measures of parental adjustment, parenting behaviors, child routines, and child behavior using the Hopkins Symptom Checklist, Alabama Parenting Questionnaire, Child Routines Inventory, and Child Behavior Checklist, respectively. Results indicated that parental adjustment predicted harsh/disengaged parenting (B = 0.17, p < .01) and internalizing behavior (B = 0.32, p < .01). Harsh/disengaged parenting and warm/supportive parenting predicted externalizing behavior (B = 0.59, p < .01) and internalizing behavior (B = - 0.49 p < .01), respectively.

Changes in intrinsic local connectivity after reading intervention in children with autism.

Most of the existing behavioral and cognitive intervention programs in autism spectrum disorders (ASD) have not been tested at the neurobiological level, thus falling short of finding quantifiable neurobiological changes underlying behavioral improvement. The current study takes a translational neuroimaging approach to test the impact of a structured visual imagery-based reading intervention on improving reading comprehension and assessing its underlying local neural circuitry. Behavioral and resting state functional MRI (rs-fMRI) data were collected from children with ASD who were randomly assigned to an Experimental group (ASD-EXP; n=14) and a Wait-list control group (ASD-WLC; n=14). Participants went through an established reading intervention training program (Visualizing and Verbalizing for language comprehension and thinking or V/V; 4-h per day, 10-weeks, 200h of face-to-face instruction). Local functional connectivity was examined using a connection density approach from graph theory focusing on brain areas considered part of the Reading Network. The main results are as follows: (I) the ASD-EXP group showed significant improvement, compared to the ASD-WLC group, in their reading comprehension ability evidenced from change in comprehension scores; (II) the ASD-EXP group showed increased local brain connectivity in Reading Network regions compared to the ASD-WLC group post-intervention; (III) intervention-related changes in local brain connectivity were observed in the ASD-EXP from pre to post-intervention; and (IV) improvement in language comprehension significantly predicted changes in local connectivity. The findings of this study provide novel insights into brain plasticity in children with developmental disorders using targeted intervention programs.

From word reading to multisentence comprehension: Improvements in brain activity in children with autism after reading intervention.

BACKGROUND: Children with ASD show a unique reading profile characterized by decoding abilities equivalent to verbal abilities, but with lower comprehension skills. Neuroimaging studies have found recruitment of regions primarily associated with visual processing (e.g., fusiform gyrus and medial parietal cortex), but reduced activation in frontal and temporal regions, when reading in adults with ASD. The purpose of this study was to assess neural changes associated with an intense reading intervention program in children with ASD using three fMRI tasks of reading. METHODS: 25 children with ASD were randomly assigned to a treatment (ASD-EXP) or waitlist group (ASD-WLC). Children participated in a reading intervention program (4-hour sessions per day, 5 days a week for 10 weeks). We utilized three tasks: word, sentence, and multisentence processing, each with differential demands of reading comprehension. fMRI data were acquired at each of two scanning sessions 10-weeks apart. RESULTS: Across tasks, post-intervention results revealed that the ASD-EXP group showed greater activation in bilateral precentral gyrus and the postcentral gyrus, visual processing regions (e.g., occipital cortex, fusiform gyrus), and frontal regions. In the word task, left thalamus and the right angular gyrus (AG) activation was unique to the ASD-EXP group post-intervention. Sentence tasks showed differential activation of core language areas (e.g., IFG, IPL) post-intervention. CONCLUSIONS: Our results provide evidence for differential recruitment of brain regions based on task demands in children with ASD, and support the potential of targeted interventions to alter brain activation in response to positive gains in treatment. Children with ASD have a different reading profile from other reading disorders that needs to be specifically targeted in interventions.

Utility of the Autism Observation Scale for Infants in Early Identification of Autism in Tuberous Sclerosis Complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder with high prevalence of associated autism spectrum disorder (ASD). Our primary objectives were to determine early predictors of autism risk to identify children with TSC in most need of early interventions. The Autism Observation Scale for Infants (AOSI) was evaluated as a measure of ASD-associated behaviors in infants with TSC at age 12 months and its ability to predict ASD at 24 months. METHODS: Children ages 0 to 36 months with TSC were enrolled in the TSC Autism Center of Excellence Research Network (TACERN), a multicenter, prospective observational study to identify biomarkers of ASD. The AOSI was administered at age 12 months and the Autism Diagnostic Observation Schedule-2 (ADOS-2) and Autism Diagnostic Interview-Revised (ADI-R) at 24 months. Developmental functioning was assessed using the Mullen Scales of Early Learning. Children were classified as ASD or non-ASD according to the ADOS-2. RESULTS: Analysis included 79 children who had been administered the AOSI at 12 months and ADOS-2 and ADI-R at 24 months. The ASD group had a mean AOSI total score at 12 months significantly higher than the non-ASD group (11.8 ± 7.4 vs 6.3 ± 4.7; P < 0.001). An AOSI total score cutoff of 13 provided a specificity of 0.89 to detect ASD with the ADOS-2. AOSI total score at 12 months was similarly associated with exceeding cutoff scores on the ADI-R. CONCLUSIONS: The AOSI is a useful clinical tool in determining which infants with TSC are at increased risk for developing ASD.

"Decoding versus comprehension": Brain responses underlying reading comprehension in children with autism.

Despite intact decoding ability, deficits in reading comprehension are relatively common in children with autism spectrum disorders (ASD). However, few neuroimaging studies have tested the neural bases of this specific profile of reading deficit in ASD. This fMRI study examined activation and synchronization of the brain's reading network in children with ASD with specific reading comprehension deficits during a word similarities task. Thirteen typically developing children and 18 children with ASD performed the task in the MRI scanner. No statistically significant group differences in functional activation were observed; however, children with ASD showed decreased functional connectivity between the left inferior frontal gyrus (LIFG) and the left inferior occipital gyrus (LIOG). In addition, reading comprehension ability significantly positively predicted functional connectivity between the LIFG and left thalamus (LTHAL) among all subjects. The results of this study provide evidence for altered recruitment of reading-related neural resources in ASD children and suggest specific weaknesses in top-down modulation of semantic processing.