Aberrant Behavior Checklist Research Articles

Using Telehealth to Deliver Family-Based Cognitive Behavioral Treatment of Insomnia in a School-Aged Child With Autism Spectrum Disorder.

Chronic insomnia (>3 months) is common in children with autism. Cognitive behavioral treatment for insomnia in children (CBT-CI) holds promise for improving sleep and daytime functioning in school-aged children with autism and their parents, but typical delivery involving multiple in-person office visits limits accessibility. This case study describes telehealth delivery of CBT-CI (teleCBT-CI) with a 7-year 4-month-old biracial boy with autism spectrum disorder (ASD) and insomnia and his parents. He and his mother wore actigraphs and completed electronic sleep diaries for 2 weeks, and his mother completed the Aberrant Behavior Checklist at pre/post/1-month follow-up. He and both of his parents completed eight telehealth treatment sessions. TeleCBT-CI improved the boy's sleep (objective, subjective) and decreased irritability, lethargy, stereotypy, and hyperactivity. This case study shows that teleCBT-CI is feasible and can improve child sleep and functioning.

Adaptation Process and Psychometric Properties of the French Version of the Health of the Nation Outcome Scales for People with Learning Disabilities

ABSTRACT Introduction The aim of this study was to adapt the Health of the Nation Outcome Scales for people with Learning Disabilities into French (F-HoNOS-LD) and to examine its validity and reliability. Method Sixty-six adults with intellectual disabilities (ID) admitted to a psychiatric hospital took part in the study. Clinicians used the F-HoNOS-LD and the Aberrant Behavior Checklist (ABC) to test all of them at hospital admission. A subsample (n = 34) was tested with the F-HoNOS-LD a second time at the end of the hospital stay. Results The French version of the instrument showed evidence of convergent validity with the ABC and very good internal consistency. Repeated measures analyses revealed – as expected – a systematic decrease in F-HoNOS-LD scores. Conclusion Results of this study suggest that the F-HoNOS-LD is a reliable and valid instrument to measure clinical outcomes among French-speaking adults with ID.

Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder

BackgroundExperimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder.MethodsWe conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder. Participants were randomly assigned in a 1:1 ratio, with stratification according to age and verbal fluency, to receive oxytocin or placebo, administered intranasally, with a total target dose of 48 international units daily. The primary outcome was the least-squares mean change from baseline on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW), which includes 13 items (scores range from 0 to 39, with higher scores indicating less social interaction). Secondary outcomes included two additional measures of social function and an abbreviated measure of IQ.ResultsOf the 355 children and adolescents who underwent screening, 290 were enrolled. A total of 146 participants were assigned to the oxytocin group and 144 to the placebo group; 139 and 138 participants, respectively, completed both the baseline and at least one postbaseline ABC-mSW assessments and were included in the modified intention-to-treat analyses. The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was −3.7 in the oxytocin group and −3.5 in the placebo group (least-squares mean difference, −0.2; 95% confidence interval, −1.5 to 1.0; P=0.61). Secondary outcomes generally did not differ between the trial groups. The incidence and severity of adverse events were similar in the two groups.ConclusionsThis placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks. (Funded by the National Institute of Child Health and Human Development; SOARS-B ClinicalTrials.gov number, NCT01944046.)

Mitochondrial morphology is associated with respiratory chain uncoupling in autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is associated with unique changes in mitochondrial metabolism, including elevated respiration rates and morphological alterations. We examined electron transport chain (ETC) complex activity in fibroblasts derived from 18 children with ASD as well as mitochondrial morphology measurements in fibroblasts derived from the ASD participants and four typically developing controls. In ASD participants, symptoms severity was measured by the Social Responsiveness Scale and Aberrant Behavior Checklist. Mixed-model regression demonstrated that alterations in mitochondrial morphology were associated with both ETC Complex I+III and IV activity as well as the difference between ETC Complex I+III and IV activity. The subgroup of ASD participants with relative elevation in Complex IV activity demonstrated more typical mitochondrial morphology and milder ASD related symptoms. This study is limited by sample size given the invasive nature of obtaining fibroblasts from children. Furthermore, since mitochondrial function is heterogenous across tissues, the result may be specific to fibroblast respiration. Previous studies have separately described elevated ETC Complex IV activity and changes in mitochondrial morphology in cells derived from children with ASD but this is the first study to link these two findings in mitochondrial metabolism. The association between a difference in ETC complex I+III and IV activity and normal morphology suggests that mitochondrial in individuals with ASD may require ETC uncoupling to function optimally. Further studies should assess the molecular mechanisms behind these unique metabolic changes.Trial registration: Protocols used in this study were registered in clinicaltrials.gov as NCT02000284 and NCT02003170.

6.14 Randomized, Placebo-Controlled Trial With Open-Label Extension of Intranasal Oxytocin for Autism Spectrum Disorder

The neuropeptide oxytocin (OXT) plays an important role in human social behaviors. There is growing interest in the use of OXT for mental health conditions characterized by social impairment. Studies of adult populations with autism spectrum disorder (ASD) have shown promising responses in social cognition, quality of life, and repetitive behaviors. To date, few studies have examined the safety and tolerability of the sustained use of OXT in a pediatric population with ASD. None have comprehensively elicited adverse events, monitored cardiac function, or collected routine blood chemistries in a systematic way to evaluate the safety of intranasal OXT. In order to investigate the safety, tolerability, and potential efficacy of sustained, daily administration of OXT in children with ASD, we conducted a randomized, double-blind, placebo-controlled crossover pilot study in 25 youths aged 3 to 17 years. Intranasal administration of flexibly dosed oxytocin or placebo was provided for 8 weeks; then an additional 8 weeks of open-label oxytocin was given to all participants. All screened participants (n = 27) were recruited through the University of North Carolina at Chapel Hill. OXT treatment was well tolerated with the exception of a single subject. One in 12 subjects randomized to OXT discontinued during blind treatment, and 2 in 24 discontinued during open treatment. Adverse events were comparable between the oxytocin and placebo groups. All safety assessments including EEG and blood chemistry revealed no clinically significant differences between OXT and placebo. Secondary efficacy assessments indicated that significant within-group changes were observed after 8 weeks on the Aberrant Behavior Checklist (ABC)-Social Withdrawal, ABC-Irritability, and ABC-Stereotypy subscales (3 variables: all p < 0.05) in the OXT group. Findings in this study must be interpreted in the context of several limitations. Most prominent are the small sample size and multiple assessments. The primary goal of this study was to evaluate the safety and tolerability of a treatment that may be used for months if not years in a pediatric population. Our small pilot sample would likely miss uncommon but serious adverse events. Future studies must be powered and of sufficient duration to explore the long-term safety and tolerability of OXT.

SURAMIN INTRAVENOUS INFUSION FOR TREATING BOYS WITH AUTISM SPECTRUM DISORDER: RESULTS OF A 14-WEEK, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTIDOSE, PHASE 2 STUDY

Objectives: The objective of this presentation is to test the efficacy and safety of 2 doses of suramin vs placebo in children aged 4 to 17 years with autism spectrum disorder (ASD). The hypotheses are that at least 1 of 2 suramin doses would show improvement in the Aberrant Behavior Checklist (ABC) Core score and that treatment would be safe and tolerable. Methods: Fifty-two boys were enrolled in 3 treatment arms: 10 mg/kg and 20 mg/kg, and placebo dosed at baseline, at weeks 4 and 8. Subjects were diagnosed by DSM-5 criteria and severity measured by the Autism Diagnostic Observation Schedule. The main efficacy analyses were ABC Core (subscales 2, 3, and 5) and Clinical Global Impression–Improvement (CGI-I) scale. Question 1 was assessed using intent-to-treat sample change scores from baseline to endpoint using ANOVA. Although the study was not designed for formal statistical comparison, ABC Core and CGI-I were tested at a family-wise Type I level of 0.05 using Dunnett’s p value for multiple comparisons. The study was approved by the South Africa Health Products Regulatory Authority and each site’s IRB. Results: The study was conducted at 6 sites in South Africa. The sample was multiracial with a mean age of approximately 8 years and a range of 4 to 15 years. There was a wide variability in the severity of ASD symptoms at baseline. Forty-four subjects completed the study, and there were 8 early withdrawals (COVID-19: 5;serious adverse event [SAE]: 1;other reason: 2). The 10 mg arm showed a sustained benefit across time points. The ABC Core modeling mean ± standard error (SE) of 10 mg showed a greater numeric improvement (–12.5 ± 3.18) vs placebo (–8.9 ± 2.86) (nonsignificant) at Week 14. The 20 mg arm did not show improvement vs placebo at Week 14. In exploratory analyses, the 10 mg arm showed greater differences from placebo in ABC Core in younger and less severe subjects. CGI-I modeled mean ± SE changes from baseline were 2.8 ± 0.30 (p = 0.016) in the 10 mg arm and 2.0 ± 0.28 (p = 0.65) in the 20 mg arm vs 1.7 ± 0.27 in the placebo. Suramin was generally safe and well tolerated over 14 weeks. There was 1 SAE, status epilepticus, in a subject (20-mg arm) with multiple risk factors for seizure;it resolved without sequelae. Conclusions: This dose-ranging proof-of-concept study showed some positive results from a treatment with a novel mechanism of action. Limitations include the small sample size and exploratory analyses that require confirmation in a larger study. Suramin was safe and tolerable over 14 weeks.

CLINICAL UTILITY OF OPTIMIZED FRAGILE X PROTEIN ANALYSIS

The fragile X mental retardation 1 (FMR1) gene-specific protein product, fragile X protein (FXP), is critical for brain development. An unstable trinucleotide repeat expansion (cytosine-guanine-guanine [CGG] repeats >200) and subsequent abnormal methylation of FMR1 located on the X chromosome results in fragile X syndrome (FXS) and markedly reduced FXP levels. There are few studies demonstrating relationships between FXP levels and phenotypic expression. Identifying these relationships may be critical to planning clinical care and understanding development over time. Here, we optimized a method to reliably and reproducibly detect FXP at extremely low values in whole blood samples to examine the relationship between FXP levels and relevant clinical features in FXS. Fifty-two individuals with full-mutation FXS (28 males [FXS(M)] and 24 females [FXS(F)]) aged 11 to 45 years completed a battery of psychosocial, neurocognitive, and electrophysiological measures. Participant whole blood samples, obtained via venipuncture, were spotted onto Whatman Bloodstain cards. Dried blood spots were hole-punched from the cards, and proteins were eluted. The eluate was analyzed in triplicate against a 9-point standard curve generated from a recombinant protein, via a Luminex-based immunoassay, to determine participants’ FXP concentration. Higher FXP levels related to higher IQ scores, less severe stereotyped behaviors, hyperactivity, speech abnormalities, and lower resting-state gamma power across sexes. Unexpectedly, higher FXP levels were associated with more severe social anxiety in FXS(M) and more severe depressive symptoms in FXS(F). In a subset of individuals who completed an investigational drug study (n = 12), only FXS(M) with complete absence of FMRP demonstrated increased Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) verbal memory and reduced Aberrant Behavior Checklist (ABC) irritability. Our optimized FXP analysis, which allowed us to reproducibly identify FXP at extremely low values, provides new evidence of the link between FXP production and clinical phenotypic expression in FXS. Of note, we identify a subset of patients—males without any FXP—who demonstrated significant improvement on verbal memory and irritability following a 2-week course of an investigational drug, suggesting that optimized FXP analysis may be a highly useful tool in treatment planning and trial stratification.

RECONNECT (ZYN2-CL-033): DESIGN OF A PHASE 3 TRIAL OF ZYN002 CANNABIDIOL TRANSDERMAL GEL IN CHILDREN AND ADOLESCENTS WITH FRAGILE X SYNDROME BASED UPON LEARNINGS FROM CONNECT-FX (ZYN2-CL-016)

ZYN002 is a pharmaceutically manufactured transdermal cannabidiol gel in development for the treatment of behavioral symptoms in Fragile X syndrome (FXS). RECONNECT is a pivotal, randomized, double-blind, Phase 3 trial to assess the efficacy and safety of ZYN002 in children/adolescents aged 3 to 17 years with a full FMR1 gene mutation. RECONNECT is designed based on learnings from CONNECT-FX which was completed during the SARS-COV-2 (COVID-19) pandemic in patients with FXS dependent upon caregivers for assessments and support. The results and conduct of CONNECT-FX were reviewed to identify key learnings to design RECONNECT. Lessons learned: 1) treatment response for ZYN002 was greatest in patients with ≥90% methylation of the FMR1 gene; 2) the Aberrant Behavior Checklist–Community FXS Specific (ABC‒CFXS) was determined fit-for-purpose and meaningful within-patient change was determined for the Social Avoidance, Irritability and Socially Unresponsive/Lethargic subscales; 3) the Caregiver Global Impression of Severity/Change (CaGI-S/C) were highly responsive to change, with greatest change on the Social Interactions; 4) a FXS-specific Clinical Global Impression of Severity/Improvement (CGI-S/I) assessment was developed based upon outcomes in response to FDA guidance to use a disease-specific CGI; and 5) virtual visits were successfully incorporated as a result of COVID-19. RECONNECT will randomly assign approximately 200 patients 1:1 to receive 18-weeks of treatment with ZYN002 or placebo. The primary endpoint is change from baseline in the ABC‒CFXS Social Avoidance subscale at week 18 in patients with complete methylation of the FMR1 gene (100% by methylation PCR). Key secondary endpoints include change from baseline in ABC-CFXS Irritability, improvement in CaGI-C Social Interactions and FXS-specific CGI-I, and change from baseline in ABC-CFXS Social Avoidance in the full population (complete and partial methylation). Four of 8 visits will be virtual to reduce family burden. Results from RECONNECT may provide the data needed to support the potential approval of ZYN002 as the first treatment of the behavioral symptoms associated with FXS.

Seizure frequency, quality of life, behavior, cognition, and sleep in pediatric patients enrolled in a prospective, open-label clinical study with cannabidiol

ObjectiveTo evaluate the effects of oral pharmacological cannabidiol (CBD) on seizures, side effects, quality of life, behavior, mood, and sleep in children with drug-resistant epilepsy (DRE) during a phase II, prospective, open-label clinical study. MethodsDuring a phase II expanded access program (EAP) study to evaluate the safety and efficacy of using cannabidiol (CBD) for the long-term treatment of children with drug-resistant epilepsy, secondary outcome measures were also performed, including quality of life (QOLCE), behavior (aberrant behavior checklist ABC), and sleep (children’s sleep habit questionnaire, CSHQ). Participants between the ages of 2 and 16 years of age with drug-resistant epilepsy (n = 35) were included in this EAP. Primary outcomes included change in parent-recorded seizure frequency relative to baseline, as well as the safety and tolerability over the course of 24 months of CBD treatment. Secondary outcomes observed in the first 12 months included changes in child behavior, and cognitive function, and sleep quality. ResultsThe median change in overall seizure frequency decreased from baseline (n = 33) by −61.3% ([n = 33], Inter Quartile Range (IQR): 43–88%) at month 3, −62.9% at month 6 ([n = 29], IQR: 48–92%), −74.7% at month 12 ([n = 29], IQR: 64–96%), and finally −83.7% ([n = 28], IQR: 68–100%) at the conclusion of 24 months of treatment. Seven (20%) of the 35 patients enrolled withdrew from treatment and observation by month 24: 2 failed inclusion criteria at baseline, 4 due to lack of treatment efficacy, and 1 was lost to follow-up. The 12-month recording of secondary measures revealed a significant improvement in Irritability (-39.4%, [n = 28], ABC), Hyperactivity (-45.4%, [n = 28], ABC), Cognition in Quality of Life (+14.2%, [n = 28], QOLCE), Behavioral function (+14.7%, [n = 28], QOLCE), General Health (+14.7%, [n = 28], QOLCE), Sleep duration (–33.9%, [n = 28], CSHQ), Daytime sleepiness (–23.8%, [n = 28], CSHQ), and nocturnal arousals (-36.2%, [n = 28], CSHQ). SignificanceThe results of this phase II open-label study demonstrate that pharmacological CBD significantly reduces seizure frequency, and improves QOL, behavior deficits, and sleep disruption, in children with drug-resistant epilepsy. The results also suggest that CBD is efficacious in controlled seizures over a 2-year period in childhood DRE.

Urinary and Plasma Antioxidants in Behavioral Symptoms of Individuals With Autism Spectrum Disorder

The balance between antioxidant capacity and oxidative stress-induced free radicals may be crucial in the pathophysiological development factor of autism spectrum disorder (ASD). We measured the following urinary and plasma biomarker levels of oxidative stress and antioxidants. As urinary biomarkers, (1) hexanoyl-lysine (HEL), which is a new biomarker of oxidative stress, (2) the total antioxidant capacity (TAC), and (3) 8-hydroxy-2′-deoxyguanosine (8-OHdG), as a product of oxidative modifications to DNA; and the plasma levels of (4) the antioxidant protein superoxide dismutase (SOD), which is the crucial defense again oxygen reactive species, and (5) transferrin and (6) ceruloplasmin, which are biomarkers of iron and copper neurotransmission and oxidant-antioxidant systems. We examined the relationship between these urinary and plasma biomarkers and behavioral symptoms in 19 individuals with ASD (mean age, 10.8 ± 5.2 years) and 10 age-matched healthy controls (mean age, 14.2 ± 7.0 years). Behavioral symptoms were estimated using the Aberrant Behavior Checklist (ABC). Urinary TAC levels were significantly lower, whereas urinary HEL levels were significantly increased in the ASD group as compared with the control group. The five ABC subscale and total scores were significantly raised in the autism group than in the control group. The results of a linear regression analysis revealed that plasma SOD levels may be a more accurate predictor of differences in ABC scores between individuals with ASD and control individuals. The present study firstly revealed the important findings that the cooperation between the urinary antioxidant TAC and plasma SOD levels may contribute to the ABC subscale scores of stereotypy. Urinary TAC activity and antioxidant protein SOD may be associated with incomplete mineral body store and antioxidant-related transcription factor and browning reactions. Consequently, a critical imbalance between TAC urinary levels and plasma SOD levels may be an important contributor to autistic behavioral symptoms.

Neurocognitive Outcomes from Memantine: A Pilot, Double-Blind, Placebo-Controlled Trial in Children with Autism Spectrum Disorder.

Objective: Studies interrogating therapeutics which alter the excitation-inhibition balance in the treatment of autism spectrum disorder (ASD) have reported mixed results on social and behavioral outcomes. Methods: The aim of this randomized, double-blind placebo-controlled pilot trial was to evaluate neurocognitive effects of memantine over a 24-week trial. Twenty-three children ages 6-12 years old with ASD were randomized to memantine or placebo. Primary outcomes included measures of apraxia and expressive language with evaluations at midpoint (week 12) and endpoint (week 24). Secondary outcomes included memory and adaptive behavior measures. Exploratory outcomes included changes in overall cognitive functioning and behavior (e.g., Aberrant Behavior Checklist). Results: Results suggest that memantine was well-tolerated. Dropout rates were high across groups with only 14 participants completing the 6-month trial. Memantine was not associated with improvements in apraxia and expressive language. Treatment with memantine was associated with improvements in verbal recognition memory as measured by the Narrative Memory-Recognition (NEPSY-II) (F = 5.05, p = .03). In addition, exploratory analyses of changes in Intelligence quotient (IQ) suggest improvements on verbal IQ (d = 1.8). Conclusions: Results suggest future studies of memantine in ASD may benefit from shifting treatment targets from social and behavioral outcomes to exploration of effects of memantine on cognition, potentially as an adjunct to learning and educational interventions. ClinicalTrials.gov: NCT01372449.

Feeding difficulties in Asian children with autism spectrum disorder

To characterize the nature and severity of feeding difficulties in Asian young children with Autism Spectrum Disorders (ASD) and identify potential predictors of poorer feeding outcomes. Cross sectional study of children aged 1-7 years with ASD. Parents completed the following: demographic information, brief autism mealtime behavior inventory, aberrant behavior checklist (ABC), behavioral pediatrics feeding assessment scale (BPFAS) and caregiver feeding style questionnaire. Additional information (medical data, cognitive and developmental assessment results, e.g., Autism Diagnostic Observation Schedule Second Edition, Autism Diagnostic Interview, Revised, Vineland Adaptive Behaviour Scales, etc.) were subsequently obtained from electronic medical records retrospectively by one of the study team members. Of the 67 children, 28.4% had feeding difficulties (high BPFAS total frequency score). Caregiver feeding styles were authoritarian (34.8%) or indulgent (39.4%). Child characteristics did not significantly predict for the severity of feeding difficulties. Univariate analysis revealed that authoritarian feeding style (p=0.001) and ABC hyperactivity score (p=0.006) were significantly associated with BPFAS severity score. Multivariate analysis revealed that ABC hyperactivity score remained significantly associated with BPFAS severity score after controlling for all other ABC subscale scores. A final regression model including all child characteristics and ABC scores did not reveal any significant predictors of BPFAS total frequency score (R2=0.557). Our findings suggest an association between hyperactivity, authoritarian feeding style and feeding difficulties. Children with ASD who have significant hyperactivity behaviors in the context of parents with an authoritarian feeding style should be actively screened for problematic feeding behaviors.

Aberrant behavior prediction and severity analysis for autistic child through deep transfer learning to avoid adverse drug effect

Autism Spectrum Disorder (ASD), in child is identified through various parameters such as social skills, repetitive behaviors, speech and nonverbal communication. Among the above parameters repetitive behavior plays a vital role for physician to prescribe dosage of drugs. The repetitive behavior and more aggressiveness in the autistic child is the symptom for growth of the disease. To control the repetitive behavior, the physician prescribe the dosage level of drug based on Aberrant Behavior Checklist (ABC). The ABC is measured only for few seconds by the physician and such measurement need continuous monitoring for proper prescription of drugs and also to avoid adverse drug effect. The above problem solve through IP Webcam app based ASD recognition for continuous monitoring and replaces the empirical method of ABC measurement. In this paper, the proposed method recognizes behavior and changes in autistic child through activity detection and repetitive behaviour, due to overdosage of drugs. In proposed method, hybrid framework incorporates training of deep CNN model for the monitoring of ASD children in natural environment through Autismdata.Net. Moreover, Transfer learning avoids the over-fitting problem in small size Autismdata.Net dataset through CNN in severity analysis of child. The behavior of ASD children is evaluated through Autismdata.Net dataset and validated through drug thermo regulation of autistic child. Action recognition accuracy of the proposed method is much better than the clinical literate/therapist analysis/observation. The proposed system helps physician for regulation of dosage level to ASD children.

Psychiatric Characteristics Across Individuals With PTEN Mutations.

Germline heterozygous PTEN mutations have been associated with high prevalence of autism spectrum disorder (ASD) and elevated rates and severity of broadly defined behavioral problems. However, limited progress has been made toward understanding whether PTEN mutation is associated with specific psychiatric co-morbidity profiles when compared to idiopathic ASD. The current study aimed to utilize a cross-measure approach to compare concurrent psychiatric characteristics across children and adolescents with PTEN mutation with (PTEN-ASD; n = 38) and without ASD (PTEN-No ASD; n = 23), and ASD with macrocephaly but no PTEN mutation (macro-ASD; n = 25) using the Child Behavior Checklist (CBCL) and the Aberrant Behavior Checklist (ABC). There were significant group effects for the CBCL Internalizing and Externalizing broad symptom score, the majority of specific CBCL syndrome scores, and all ABC subscale scores. Post-hoc comparisons revealed greater behavioral symptoms in the ASD groups (PTEN-ASD and macro-ASD) compared to the PTEN-no ASD group on nearly all subtest scores examined. There were no statistically significant differences between the PTEN-ASD and macro-ASD groups; however, there was a trend for the macro-ASD group showing higher levels of aggressive behaviors. Our findings provide evidence of specific behavior profiles across PTEN-No ASD, PTEN-ASD, and macro-ASD groups and highlight the importance of early identification of behavioral vulnerabilities in individuals with PTEN mutations in order to provide access to appropriate evidence-based interventions.

Comparing visual preferences between autism spectrum disorder (ASD) and normal children to explore the characteristics of visual preference of ASD children by improved visual preference paradigm: a case-control study.

BackgroundOne of features of Visual preference in autism spectrum disorder (ASD) is that they tend to social stimuli to nonsocial stimuli. Though it has been studied widely, until now the results are still not consistent. One of the most important reasons may be that the stimuli of the past visual preference paradigm have different movement patterns. Therefore, the present study aimed to improve the visual preference paradigm to reduce the bias caused by different movement of stimuli and explore the features of visual preference of ASD further.MethodsTwo hundred and seven children who met DSM-5 criteria for ASD and 125 typically developmental (TD) children were enrolled. They were matched in age and gender. Visual preference was measured by eye tracking technology. The subjects presented simultaneously with dynamic object images (DOI) and dynamic social images (DSI) with the same type and same speed of repetitive movement. Social interaction deficits of ASD were assessed by parents with Aberrant Behavior Checklist (ABC).ResultsCompared with TD children, the following findings were noted: (I) children with ASD paid less attention to social stimuli and more attention to nonsocial stimuli (t=6.417, P<0.001). (II) Increased preference to DSI was positively correlated with age (R=0.23, P=0.001). (III) No association was noted between visual preference and IQ in children with ASD (R=0.081, P=0.435). (IV) Reduced preference to DSI was negatively correlated with the severity of social interaction impairment rated by parents with ABC in children with ASD (R=0.237, P=0.010).ConclusionsChildren with ASD exhibited abnormal visual preference for social and nonsocial stimuli.

Cognitive assessment using the Rapid Assessment for Developmental Disabilities, Second Edition (RADD‐2)

Individuals with developmental disabilities (DD) often have severe impairments and maladaptive behaviours that make it difficult to reliably assess their cognitive abilities. Given these challenges, the Rapid Assessment of Developmental Disabilities, Second Edition (RADD-2), was designed to measure general cognitive ability in this population. The purpose of this study is to demonstrate the battery's psychometric properties when used with individuals with DD who have challenging behavioural and psychiatric conditions and for those who have limited verbal skills. The cognitive and adaptive behaviour skills of 193 children and adults with DD and considerable medical, behavioural and/or psychiatric problems were evaluated using the first and second editions of the RADD, Kaufmann Brief Intelligence Test - 2nd Edition, and Scales of Independent Behaviour - Revised Edition. Medication side effects and challenging behaviours were assessed using the Aberrant Behaviour Checklist. There were no floor or ceiling effects on the RADD-2. Both the nonverbal index and total scores had strong concurrent validity with other abbreviated tests of intellectual ability and good discriminant validity from measures of adaptive behaviour and medication side effects. RADD-2 scores also had strong criterion validity as they successfully differentiated between all levels of intellectual functioning. Age and sex did not differentially affect RADD-2 performance, and the co-occurrence of psychiatric conditions did not negatively affect performance. The only medical condition associated with lower RADD-2 performance was epilepsy. The RADD-2 can quantify the differential cognitive abilities of individuals with DD, even for those with minimal communication skills, challenging behaviours or severe medication side effects that can typically complicate assessment. This brief cognitive battery can be used to measure changes due to interventions, on the one hand, and progression of neurological disease, on the other.

Gastrointestinal symptoms and sensory abnormalities associated with behavioral problems in children with neurodevelopmental disorders.

Behavioral problems directly affect the quality of life of caregivers and children with autism spectrum disorder (ASD) and/or attention-deficit/hyperactivity disorder (ADHD), and is known to be associated with clinical factors such as gastrointestinal (GI) symptoms, sensory abnormalities, intellectual abilities, and use of medication. However, previous studies have not considered these relationships comprehensively. We conducted a cross-sectional study of 6-12-year-old children with diagnoses of ASD and/or ADHD at two hospitals in Japan. Scores for the aberrant behavior checklist (ABC), autism-spectrum quotient (AQ), and Conners 3, as well as information on daily sleep and exercise, GI symptoms, and Short Sensory Profile, were collected. Each factor was subjected to a correlation analysis to investigate its effect on ABC scores. A stepwise multiple linear regression analysis for the factors with p < 0.05 was performed. Data were obtained from 60 patients with a mean age of 8.3 years; 21 had ASD alone, 18 had ADHD alone, and 21 had ASD + ADHD. The correlation analyses identified six factors associated with ABC severity: (a) methylphenidate use, (b) Conners hyperactivity score, (c) Conners inattention score, (d) AQ score, (e) SSP score, and (f) GI symptom score. The multiple regression showed that "GI symptoms" and "sensory abnormalities" were independently associated with ABC severity. Although further studies are needed to show a causal relationship, appropriate assessment of GI symptoms and sensory abnormalities may help alleviate some problematic behaviors and improve the quality of life of children with neurodevelopmental disorders and their families. LAY SUMMARY: Behavioral problems in children with neurodevelopmental disorders are known to be associated with many factors. This study aimed to comprehensively investigate the known factors. We have discovered that "gastrointestinal symptoms" and "sensory abnormalities" were independently associated with Behavioral problems. Our results suggest that it is important for clinicians and caregivers to pay more attention to children's GI symptoms and sensory abnormalities that may not present as obvious symptoms or complaints.

A Systematic Review and Meta-Analysis of Immunoglobulin G Abnormalities and the Therapeutic Use of Intravenous Immunoglobulins (IVIG) in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting approximately 2% of children in the United States. Growing evidence suggests that immune dysregulation is associated with ASD. One immunomodulatory treatment that has been studied in ASD is intravenous immunoglobulins (IVIG). This systematic review and meta-analysis examined the studies which assessed immunoglobulin G (IgG) concentrations and the therapeutic use of IVIG for individuals with ASD. Twelve studies that examined IgG levels suggested abnormalities in total IgG and IgG 4 subclass concentrations, with concentrations in these IgGs related to aberrant behavior and social impairments, respectively. Meta-analysis supported possible subsets of children with ASD with low total IgG and elevated IgG 4 subclass but also found significant variability among studies. A total of 27 publications reported treating individuals with ASD using IVIG, including four prospective, controlled studies (one was a double-blind, placebo-controlled study); six prospective, uncontrolled studies; 2 retrospective, controlled studies; and 15 retrospective, uncontrolled studies. In some studies, clinical improvements were observed in communication, irritability, hyperactivity, cognition, attention, social interaction, eye contact, echolalia, speech, response to commands, drowsiness, decreased activity and in some cases, the complete resolution of ASD symptoms. Several studies reported some loss of these improvements when IVIG was stopped. Meta-analysis combining the aberrant behavior checklist outcome from two studies demonstrated that IVIG treatment was significantly associated with improvements in total aberrant behavior and irritability (with large effect sizes), and hyperactivity and social withdrawal (with medium effect sizes). Several studies reported improvements in pro-inflammatory cytokines (including TNF-alpha). Six studies reported improvements in seizures with IVIG (including patients with refractory seizures), with one study reporting a worsening of seizures when IVIG was stopped. Other studies demonstrated improvements in recurrent infections, appetite, weight gain, neuropathy, dysautonomia, and gastrointestinal symptoms. Adverse events were generally limited but included headaches, vomiting, worsening behaviors, anxiety, fever, nausea, fatigue, and rash. Many studies were limited by the lack of standardized objective outcome measures. IVIG is a promising and potentially effective treatment for symptoms in individuals with ASD; further research is needed to provide solid evidence of efficacy and determine the subset of children with ASD who may best respond to this treatment as well as to investigate biomarkers which might help identify responsive candidates.

Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder

BackgroundSulforaphane (SF), an isothiocyanate in broccoli, has potential benefits relevant to autism spectrum disorder (ASD) through its effects on several metabolic and immunologic pathways. Previous clinical trials of oral SF demonstrated positive clinical effects on behavior in young men and changes in urinary metabolomics in children with ASD.MethodsWe conducted a 15-week randomized parallel double-blind placebo-controlled clinical trial with 15-week open-label treatment and 6-week no-treatment extensions in 57 children, ages 3–12 years, with ASD over 36 weeks. Twenty-eight were assigned SF and 29 received placebo (PL). Clinical effects, safety and tolerability of SF were measured as were biomarkers to elucidate mechanisms of action of SF in ASD.ResultsData from 22 children taking SF and 23 on PL were analyzed. Treatment effects on the primary outcome measure, the Ohio Autism Clinical Impressions Scale (OACIS), in the general level of autism were not significant between SF and PL groups at 7 and 15 weeks. The effect sizes on the OACIS were non-statistically significant but positive, suggesting a possible trend toward greater improvement in those on treatment with SF (Cohen’s d 0.21; 95% CI − 0.46, 0.88 and 0.10; 95% CI − 0.52, 0.72, respectively). Both groups improved in all subscales when on SF during the open-label phase. Caregiver ratings on secondary outcome measures improved significantly on the Aberrant Behavior Checklist (ABC) at 15 weeks (Cohen’s d − 0.96; 95% CI − 1.73, − 0.15), but not on the Social Responsiveness Scale-2 (SRS-2). Ratings on the ABC and SRS-2 improved with a non-randomized analysis of the length of exposure to SF, compared to the pre-treatment baseline (p < 0.001). There were significant changes with SF compared to PL in biomarkers of glutathione redox status, mitochondrial respiration, inflammatory markers and heat shock proteins. Clinical laboratory studies confirmed product safety. SF was very well tolerated and side effects of treatment, none serious, included rare insomnia, irritability and intolerance of the taste and smell.LimitationsThe sample size was limited to 45 children with ASD and we did not impute missing data. We were unable to document significant changes in clinical assessments during clinical visits in those taking SF compared to PL. The clinical results were confounded by placebo effects during the open-label phase.ConclusionsSF led to small yet non-statistically significant changes in the total and all subscale scores of the primary outcome measure, while for secondary outcome measures, caregivers’ assessments of children taking SF showed statistically significant improvements compared to those taking PL on the ABC but not the SRS-2. Clinical effects of SF were less notable in children compared to our previous trial of a SF-rich preparation in young men with ASD. Several of the effects of SF on biomarkers correlated to clinical improvements. SF was very well tolerated and safe and effective based on our secondary clinical measures.Trial registration: This study was prospectively registered at clinicaltrials.gov (NCT02561481) on September 28, 2015. Funding was provided by the U.S. Department of Defense.

Probiotic and Oxytocin Combination Therapy in Patients with Autism Spectrum Disorder: A Randomized, Double-Blinded, Placebo-Controlled Pilot Trial.

Autism spectrum disorder (ASD) is a rapidly growing neurodevelopmental disorder. Both probiotics and oxytocin were reported to have therapeutic potential; however, the combination therapy has not yet been studied. We conducted a randomized, double-blinded, placebo-controlled, 2-stage pilot trial in 35 individuals with ASD aged 3–20 years (median = 10.30 years). Subjects were randomly assigned to receive daily Lactobacillus plantarum PS128 probiotic (6 × 1010 CFUs) or a placebo for 28 weeks; starting on week 16, both groups received oxytocin. The primary outcomes measure socio-behavioral severity using the Social Responsiveness Scale (SRS) and Aberrant Behavior Checklist (ABC). The secondary outcomes include measures of the Clinical Global Impression (CGI) scale, fecal microbiome, blood serum inflammatory markers, and oxytocin. All outcomes were compared between the two groups at baseline, 16 weeks, and 28 weeks into treatment. We observed improvements in ABC and SRS scores and significant improvements in CGI-improvement between those receiving probiotics and oxytocin combination therapy compared to those receiving placebo (p < 0.05). A significant number of favorable gut microbiome network hubs were also identified after combination therapy (p < 0.05). The favorable social cognition response of the combination regimen is highly correlated with the abundance of the Eubacterium hallii group. Our findings suggest synergic effects between probiotics PS128 and oxytocin in ASD patients, although further investigation is warranted.