Autism Spectrum Disorder Behaviors Research Articles

A Comparison Between Multiple and Single Presentation of Social Stories for Children with Autism Spectrum Disorder

Individuals with Autism Spectrum Disorder (ASD) may exhibit social interaction and communication problems and demonstrate limited and repetitive behaviors. Individuals affected by this complex neurodevelopmental disorder can require different educational arrangements from those of typically developed individuals when developing communication skills, self-care skills, and other daily living skills. Many interventions have been developed for individuals with ASD to acquire social skills and other independent living skills. Social stories represent one of these treatments. The purpose of this research was to determine whether the single and multiple presentations of social story interventions in teaching individuals with ASD behaviors differed in terms of effectiveness and efficiency. The adapted alternating treatments design was used in this research, whose participants were composed of four boys between 9 and 17 years old who had been diagnosed with ASD. The dependent variables of this research were the acquisition level of skills of expressing thanks and participating in the invited activity. The study’s independent variables were the single social story intervention, which involved writing and presenting one story for one target behavior, and the multiple social story intervention, which included writing and presenting more than one story for one target behavior. According to the findings regarding effectiveness, all four participants learned the skills of expressing thanks and participating in the invited activity through single and multiple social story intervention at a level that met the criteria. All participants were observed to demonstrate the skills that were acquired in both interventions and generalized them to the other situations. No difference was determined in terms of follow-up and generalization. When the findings of the two instructional interventions were compared, it was observed that the results didn’t recur consistently for all participants. For two participants, it was determined that the single social story intervention was more efficient, while the multiple social story intervention was more efficient for one participant. For the other participants, two instructional interventions were found to be equally efficient. In this study, data about social validity were gathered from participants, their parents, and their teachers. The findings regarding social validity showed that the participants, their parents, and their teachers expressed positive opinions about the study.

The Role of Gut Microbiota in Gastrointestinal Symptoms of Children with ASD.

Background and objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired communication, social interaction disorder, and repetitive behavior. Dysbiotic gut microbiota (GM) could be a contributing factor to the appearance of ASD, as gastrointestinal (GI) symptoms are comorbidities frequently reported in ASD. As there is a lack of reviews about the role played by GM in the GI symptoms of ASD, this work aimed to carry out a systematic review of current studies comparing the GM of children with ASD and GI symptoms with those of healthy controls in the last six years. Materials and Methods: The systematic review was performed following the PRISMA guidelines. The databases chosen were Web of Science, Scopus, PubMed, and PsycINFO, and the keywords were (gut* OR intestine* OR bowel* OR gastrointestinal*) AND (microbiota* OR microflora* OR bacteria* OR microbiome* OR flora* OR bacterial* OR bacteria* OR microorganism* OR feces* OR stool*) AND (autistic* OR autism* OR ASD*). Results: A total of 16 articles were included. Ten articles performed correlations analysis between GI symptoms and ASD. Among those 10 articles, 7 found differences between the GI symptoms present in children with ASD and healthy controls. The most common GI symptom was constipation. Among the seven articles that found differences, three performed correlations analysis between GI symptoms and gut microbe abundance. Candida, Prevotella, Streptococcus, and Veillonella showed higher and lower abundance, respectively, in children with ASD and GI symptoms in more than one article. Bacteroidetes, Firmicutes, Actinomyces, Dorea, Lactobacillus, Faecalibacterium prausnitzii, and Bacteroidetes/Firmicutes ratios showed abundance discrepancies. Conclusions: It is still too early to draw a conclusion about the gut microbes involved in GI symptoms of ASD. Future research should consider the relationship between ASD behavior, GM, and GI symptoms in a multidisciplinary way and homogenize sample characteristics.

Gaining Insights into Aggressive Behaviour in Autism Spectrum Disorder Using Latent Profile Analysis

Aggressive behaviour is a significant issue for individuals with autism spectrum disorder (ASD), yet our understanding is limited compared to aggression in typically developing populations. This study examined behavioural, adaptive and cognitive data provided by the Simons Simplex Collection (N = 2184) to identify behavioural subgroups in children and adolescents with ASD using latent profile analysis. Results showed five subgroups that differed with regards to behavioural severity, IQ and adaptive behaviour. In two profiles with higher aggression, individuals had greater comorbid anxiety symptoms and attentional deficits and also differed in adaptive behaviour and IQ. These results identify potentially important avenues for research in aggressive behaviour in ASD.

Rigidity coincides with reduced cognitive control to affective cues in children with autism.

The present study tested whether salient affective cues would negatively influence cognitive control in children with and without autism spectrum disorder (ASD). One hundred children aged 6-12 years who were either typically developing or had ASD performed a novel go/no-go task to cues of their interest versus cues of noninterest. Linear mixed-effects (LME) models for hit rate, false alarms, and the sensitivity index d' were used to test for group differences. Caregivers completed the Repetitive Behavior Scale-Revised to test associations between repetitive behaviors and task performance. Children with ASD had reduced cognitive control toward their interests compared with typically developing children. Further, children with ASD showed reduced cognitive control to interests compared with noninterests, a pattern not observed in typically developing children. Decreased cognitive control toward interests was associated with higher insistence on sameness behavior in ASD, but there was no association between sameness behavior and cognitive control for noninterests. Together, children with ASD demonstrated decreased cognitive flexibility in the context of increased affective salience related to interests. These results provide a mechanism for how salient affective cues, such as interests, interfere with daily functioning and social communication in ASD. Further, the findings have broader clinical implications for understanding how affective cues can drive interactions between restricted patterns of behavior and cognitive control. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Clinical phenotype of autism spectrum disorders in children of preschool and school age, burdened epileptic seizures

Background. Clinical polymorphism and polymorphism are inherent in the clinical phenotype of children with autism spectrum disorders (ASD). There is a consensus, relatively high, between 5% and 38% of the prevalence of epilepsy in ASD. There are reasons to believe that ASD with epilepsy and specific epileptic activity on EEG and ASD with hyperkinetic symptoms without signs of epileptic process can be determined by different variants of genetic polymorphism or by different variants of gene expression, determined by different influences.
 Objective – to study the features of the clinical phenotype of ASD in preschool and school-age children with epileptic seizures and specific epileptic activity on EEG.
 Materials and methods. In the Department of Mental Disorders of Children and Adolescents of the Institute of Psychiatry of the Ministry of Health of Ukraine 116 children aged 2-10 years with ASD were examined. The study group was divided into three subgroups: subgroup A – 23 children with a history of epileptic seizures, subgroup B – 35 children with specific forms of epileptic activity on EEG without epileptic seizures, subgroup C – 19 children with ASD having specific epileptic activity for EEG repetitive involuntary movements (motor stereotypes, motor tics) and vocalizations (vocal tics). The control group consisted of 39 children with ASD non a history of seizures and specific epileptic activity on the EEG. The follow-up of children with ASD in the comparison groups was performed for 1-1.5 years. We used such research methods: clinical-psychopathological, psychodiagnostic, psychometric, statistical.
 Results. In children with ASD and comorbid epileptic seizures, disorders of social reciprocity are of crucial diagnostic importance. Communication disorders and recurrent, stereotyped behaviors, movements, and interests in children in this group are significantly less common than in comparison groups. Incidents of repetitive stereotypes in these children are associated with sensory impairments and autostimulations. Children with ASD, complicated by severe and frequent epileptic seizures, are characterized by impaired social reciprocity and communication against the background of regression or stagnation of speech and motor skills development.
 Disorders of communication and repetitive behavior in ASD in children of different ages are represented by different monoqualitative syndrome (phenotypes). Younger children less than 6 years of age are dominant in stereotypical movements, while children aged 6-8 years have repetitive behaviors associated with the overriding interests.
 Two subtypes of clinical phenotypes of ASD were identified: the variant with symptoms, which more closely determined the stereotypical sensor and motor behavior and the variant with symptoms of insistence on equality, with the overriding interests of preservation, identity. Movement stereotypes predominated in children with ASD without epileptic seizures and without epileptic activity on EEG. In children with ASD and epileptic activity on EEG, motor stereotypes and repetitive identity-preserving behavior were equally common.
 Conclusions. Disorders of social reciprocity, communication, repetitive behavior, in particular stereotyped movements are diagnostically significant signs of ASD, in particular ASD complicated by epileptic seizures, ASD with specific epileptic activity on EEG.
 According to the results of a long 1-1.5 years’ prospective study, it was established that the clinical phenotype of ASD with epileptic seizures, ASD without epileptic seizures with specific epileptic activity on EEG and RAS without epileptic seizures and changes in EEG are characterized by differing clinical picture and course.
 Qualitative communication disorders and stereotypical movements in addition to ASD are observed in other psychiatric disorders, including Tourette disorder, obsessive-compulsive disorders, and intellectual disability. Expressed repeated identity-preserving behavior is the basis for dual diagnosis of ASD and obsessive-compulsive disorder. Motor and vocal tics may be the basis for dual diagnosis of ASD and Tourette’s disorder.
 The presence of age-related pathoplasty of clinical manifestations of ASD in the comparison groups was established.

Differences in the expression of restricted repetitive behaviors in female and male BTBR T + tf/J mice

Autism spectrum disorder (ASD) is characterized by the expression of restricted repetitive behaviors (RRBs) and impairments in social recognition and communication. Epidemiological studies demonstrate males are three times more likely than females to be affected. Although this is the case, more recent studies suggest females may be underrepresented in these numbers due to standard clinical measures of RRBs and social behaviors. In addition, many studies examining mouse models of ASD exclude females due to the sex disparity in diagnoses. The present study examined how female and male BTBR T + Itpr3tf /J (BTBR) compare to control C57BL/6J mice on tests of RRBs (probabilistic reversal learning, repetitive grooming, spontaneous alternation, and marble burying) and social behaviors (three chambered social approach task). Utilizing a spatial reversal learning test with 80/20 probabilistic feedback, in which ASD individuals have exhibited deficits, we find that female BTBR mice do not show the same impairment found in male BTBR mice. Interestingly, control female C57BL/6J mice required more trials to reach criterion. Female BTBR mice expressed comparable rates of repetitive grooming, marble burying and spontaneous alternation compared to female C57BL/6J mice. Male BTBR mice expressed higher rates of grooming behavior and locomotor activity compared to male C57BL/6J mice, as found in previous studies. Similarly, male BTBR mice showed a reduction in both measures of social approach compared to controls. Both male and female BTBR mice showed a reduction in sniff time for the stranger mouse compared to controls. Together these findings demonstrate how female BTBR mice do not display the RRB profile expressed by male BTBR mice. Testing of repetitive behaviors in ASD needs to better reflect the sex differences in how RRBs manifest in females compared to their extensively researched male counterparts.

Do animal models hold value in Autism spectrum disorder (ASD) drug discovery?

ABSTRACTIntroduction: Autism spectrum disorder (ASD) defines impairments in a broad range of behaviors in two domains, social communication and repetitive behaviors and/or restricted interests. Drug discovery is ongoing for ASD, but no drugs have been approved for the core behaviors. Animal models are invaluable for drug discovery, but are limited by the face, construct, and predictive validity for ASD. The genetic construct validity of animal models has provided potential targets including biological events early in development which are indeed challenging to treat pharmacologically.Areas covered: The focus of this review is on the current models for ASD being used to test potential therapeutics. Drugs reviewed include sulforaphane, propranolol, oxytocin, vasopressin antagonists, arbaclofen, and bumetanide, that have been evaluated on behaviors with face validity for both the core behaviors of ASD, social and repetitive behaviors, and the modifying behaviors including learning and memory.Expert opinion: Animal models for the core symptoms of ASD have suffered from the same problems hampering research in humans, including lack of a biomarker, heterogeneity of symptom severity, and appropriate endpoints for evaluation. Despite this, the data from animal models has allowed several drugs to move on to clinical testing.

Expression of miR-140-3p in children with autism spectrum disorders and its correlation with cytokines

Objective To investigate the expression of serum miR-140-3p in children with autism spectrum disorder (ASD) and its correlation with interleukin-4 (IL-4), interleukin-8 (IL-8) and interleukin-17A (IL-17A), and provide evidence for the diagnosis and treatment of ASD. Methods Totally 172 cases of ASD children admitted to Anning Hospital of Hainan Province from January 2015 to June 2018 were selected as case group, 80 cases of healthy subjects as control group.ASD children were divided into mild-moderate group (n=116) and severe group (n=56) by ASD Behavior Rating Scale and Child Autism Rating Scale. Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the changes of serum levels of miR-140-3p, IL-4, IL-8 and IL-17A in each group. ROC curve was used to analyze the diagnostic value of miR-140-3p, IL-4, IL-8 and IL-17A for ASD. Pearson correlation was used to analyze the correlation between serum miR-140-3p and IL-4, IL-8 and IL-17A in children with ASD. Results The serum levels of miR-140-3p(0.86±0.17 vs 0.15±0.03), IL-4(48.65±13.82)pg/ml vs (31.42±7.50)pg/ml), IL-8((7.14±2.05)pg/ml vs (2.30±0.74)pg/ml) and IL-17A((112.35±51.64)pg/ml vs (58.20±26.40)pg/ml) in the case group were significantly higher than those in the control group (P<0.05). Serum levels of miR-140-3p(1.08±0.24 vs 0.71±0.12), IL-4((53.28±16.30)pg/ml vs (43.70±13.52)pg/ml), IL-8((9.42±2.85)pg/ml vs (5.63±1.48)pg/ml) and IL-17A((138.40±65.72)pg/ml vs (96.74±40.83)pg/ml) in severe group were significantly higher than those in mild-moderate group(P<0.05). The AUC (95%CI) of serum miR-140-3p for ASD diagnosis was 0.827 (0.773-0.886), which were significantly higher than that of IL-4 (0.719 (0.651-0.764)pg/ml), IL-8 (0.683 (0.625-0.743)pg/ml) and IL-17A(0.745 (0.683-0.817)pg/ml). The best cut-off value was 0.75, and the sensitivity and specificity were 84.8% and 78.2%, respectively. The best cut-off value of serum miR-140-3p for diagnosing ASD was 0.75, and its sensitivity and specificity were 84.8% and 78.2%, respectively. The correlation analysis showed that serum miR-140-3p was positively correlated with IL-4, IL-8 and IL-17A in children with ASD (r=0.681, r=0.624, r=0.775, all P<0.01). Conclusion Serum levels of miR-140-3p was significantly higher in ASD children, correlated with levels of IL-4, IL-8 and IL-17A, and miR-140-3p was a potential biomarkers for ASD diagnosis. Key words: Autism spectrum disorders; miR-140-3p; Interleukin-4; Interleukin-8; Interleukin-17A

Early-stage paired housing improves social interaction in neuronal Uba6-deficient mice

UBA6 is an alternative enzyme for ubiquitin activation in vertebrates that plays a pivotal role in early mouse development. Previously, we reported that the Uba6 brain-specific knockout (NKO) mouse is a novel autism spectrum disorder (ASD) mouse model that displays decreased social behavior and communication. To determine the therapeutic impact of environmental stimulation in ASDs, we investigated the behavioral and molecular changes of the NKO and control mice after exposure to environmental enrichment and paired housing in different developmental phases. Our results demonstrated that early paired housing could diminish the ASD phenotypes of NKO mice such as impaired nest building and social interaction and anxiety. Additionally, increased histone acetylation in the amygdala was observed in NKO mice after paired housing without a change in Ube3a levels. Our data suggest that paired housing at an early time point can play a crucial role in ameliorating ASD behavior and can be applied in other ASD animal models or clinical settings.

Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice

Autism spectrum disorder (ASD) manifests as alterations in complex human behaviors including social communication and stereotypies. In addition to genetic risks, the gut microbiome differs between typically developing (TD) and ASD individuals, though it remains unclear whether the microbiome contributes to symptoms. We transplanted gut microbiota from human donors with ASD or TD controls into germ-free mice and reveal that colonization with ASD microbiota is sufficient to induce hallmark autistic behaviors. The brains of mice colonized with ASD microbiota display alternative splicing of ASD-relevant genes. Microbiome and metabolome profiles of mice harboring human microbiota predict that specific bacterial taxa and their metabolites modulate ASD behaviors. Indeed, treatment of an ASD mouse model with candidate microbial metabolites improves behavioral abnormalities and modulates neuronal excitability in the brain. We propose that the gut microbiota regulates behaviors in mice via production of neuroactive metabolites, suggesting that gut-brain connections contribute to the pathophysiology of ASD.

A case study of suicidality presenting as a restricted interest in autism Spectrum disorder

BackgroundSuicidality has been under-researched in autism spectrum disorders (ASD). Most studies have linked increased suicidality in ASD to psychiatric comorbidities such as depression. Here we investigated, from a neuropsychological and clinical standpoint, the relationship between core ASD symptoms, i.e., restricted behaviors and social and communication impairments, and the suicidal behaviors in an adult male individual with ASD, with no psychiatric comorbidities.Case presentationWe report the case of a 21-year-old male with ASD who attempted suicide twice, in the absence of other psychiatric diagnoses. His behavior and communication skills were rigid. His suicidality was characterized by a rigid, detailed, and pervasive thinking pattern, akin to restricted interests. Consistently, from a neuropsychological standpoint, we found below-average planning and attention skills, and mind-reading skills were rigid and lacked spontaneity.ConclusionsOur case-study suggests that specific clinical and neuropsychological dimensions might be related to suicidal behaviors in ASD. Clinically, the repetitive and rigid suicide-oriented thinking of our patient was not part of a depressive episode. Instead, it followed a purely logical, inflexible, and pervasive reasoning pattern focused on a topic that fascinated him – i.e., suicide --, akin to restricted behaviors. From a neuropsychological standpoint, restrictive suicide-oriented thinking in our patient seems to be related to attention and executive anomalies that have been linked to repetitive and restricted behaviors in ASD. New tools need to be developed to assess persistent suicidal thoughts in this population, as they might be related to intrinsic features of ASD.

Probiotic Therapy for Treating Behavioral and Gastrointestinal Symptoms in Autism Spectrum Disorder: A Systematic Review of Clinical Trials.

The therapeutic potentials of probiotics in autism spectrum disorder (ASD) remains controversial, with the only existing systematic review on this topic published in 2015. Results from new trials have become available in recent years. We therefore conducted an updated systematic review, to assess the efficacy of probiotics in relieving behavioral symptoms of ASD and gastrointestinal comorbidities. Our review includes two randomized controlled trials, which showed improvement of ASD behaviors, and three open trials, all which exhibited a trend of improvement. Four of these trials concluded from subjective measures that gastrointestinal function indices showed a trend of improvement with probiotic therapy. Additional rigorous trials are needed to evaluate the effects of probiotic supplements in ASD.

Saliva MicroRNA Differentiates Children With Autism From Peers With Typical and Atypical Development

Clinical diagnosis of autism spectrum disorder (ASD) relies on time-consuming subjective assessments. The primary purpose of this study was to investigate the utility of salivary microRNAs for differentiating children with ASD from peers with typical development (TD) and non-autism developmental delay (DD). The secondary purpose was to explore microRNA patterns among ASD phenotypes. This multicenter, prospective, case-control study enrolled 443 children (2-6 years old). ASD diagnoses were based on DSM-5 criteria. Children with ASD or DD were assessed with the Autism Diagnostic Observation Schedule II and Vineland Adaptive Behavior Scales II. MicroRNAs were measured with high-throughput sequencing. Differential expression of microRNAs was compared among the ASD (n= 187), TD (n= 125), and DD (n= 69) groups in the training set (n= 381). Multivariate logistic regression defined a panel of microRNAs that differentiated children with ASD and those without ASD. The algorithm was tested in a prospectively collected naïve set of 62 samples (ASD, n= 37; TD, n= 8; DD, n= 17). Relations between microRNA levels and ASD phenotypes were explored. Fourteen microRNAs displayed differential expression (false discovery rate< 0.05) among ASD, TD, and DD groups. A panel of 4 microRNAs (controlling for medical/demographic covariates) best differentiated children with ASD from children without ASD in training (area under the curve= 0.725) and validation (area under the curve= 0.694) sets. Eight microRNAs were associated (R > 0.25, false discovery rate< 0.05) with social affect, and 10 microRNAs were associated with restricted/repetitive behavior. Salivary microRNAs are "altered" in children with ASD and associated with levels of ASD behaviors. Salivary microRNA collection is noninvasive, identifying ASD-status with moderate accuracy. A multi-"omic" approach using additional RNA families could improve accuracy, leading to clinical application. A Salivary miRNA Diagnostic Test for Autism; https://clinicaltrials.gov/; NCT02832557.

BOLD signal variability and complexity in children and adolescents with and without autism spectrum disorder

Variability of neural signaling is an important index of healthy brain functioning, as is signal complexity, which relates to information processing capacity. Alterations in variability and complexity may underlie certain brain dysfunctions. Here, resting-state fMRI was used to examine variability and complexity in children and adolescents with and without autism spectrum disorder (ASD). Variability was measured using the mean square successive difference (MSSD) of the time series, and complexity was assessed using sample entropy. A categorical approach was implemented to determine if the brain measures differed between diagnostic groups (ASD and controls). A dimensional approach was used to examine the continuum of relationships between each brain measure and behavioral severity, age, IQ, and the global efficiency (GE) of each participant’s structural connectome, which reflects the structural capacity for information processing. Using the categorical approach, no significant group differences were found for neither MSSD nor entropy. The dimensional approach revealed significant positive correlations between each brain measure, GE, and age. Negative correlations were observed between each brain measure and the severity of ASD behaviors across all participants. These results reveal the nature of variability and complexity of BOLD signals in children and adolescents with and without ASD.

Beneficial Effects of GLP-1 Agonist in a Male With Compulsive Food-Related Behavior Associated With Autism

Individuals with autism spectrum disorder (ASD) frequently display intensely repetitive, restricted thoughts, and behaviors. These behaviors have similarities to compulsions and/or obsessions in obsessive compulsive disorder (OCD) and are primarily treated with behaviourally-based interventions and serotonin uptake inhibitors (SSRIs). Due to the lack of treatment responses in many cases, however, new treatments are being sought. Here we report beneficial effects of treatment with liraglutide, a glucagon-like peptide-1 (GLP-1) analog, on severe obsessive food craving, binge eating, weight gain, and behavioral problems in an adolescent male with infantile autism and moderate intellectual impairment. Liraglutide treatment reduced weight and unwanted behavior seemingly by preventing food-related repetitive thoughts and compulsions. Our report provides clinical evidence that GLP-1 signaling pathway may represent a novel target for treating food-related behavioral problems and aggressive behavior in ASD.

A Randomised Placebo-Controlled Trial to Determine If Fluoxetine Is Effective for Improving Autistic Behaviours

Background: Selective Serotonin Receptor Inhibitors (SSRIs) are often used to reduce the severity of core behaviours of Autism Spectrum Disorders (ASD) but their efficacy remains uncertain. This study was a multi-centre randomized, placebo-controlled trial examining the efficacy and tolerability of fluoxetine, a commonly prescribed SSRI, for reducing the frequency and severity of restricted, repetitive and stereotypic behaviours in ASD. Methods: Participants were aged 7·5-18 years with ASD, who were randomised to receive fluoxetine or placebo. Study medication was commenced at 4 or 8mg/day for the first week (4mg if <40Kg; 8mg if ≥40Kg), then titrated up to a maximum dose of 20mg/day for participants <40kg and 30mg/day for participants ≥40kg, over 4 weeks. Participants remained on the medication for a total of 16 weeks. The primary outcome was the total score on the Children's Yale-Brown Obsessive Compulsion Scale - Modified for Pervasive Developmental Disorders at 16 weeks. A range of secondary outcomes were also examined, measuring anxiety, repetitive and challenging behaviours at 16 weeks. Findings: 146 participants (124 male, 85%) were enrolled in the trial (75 fluoxetine, 71 placebo). The mean age of study participants was 11·2 (standard deviation 2·9) years, and 30% (n = 44) had an intellectual disability. There was little evidence that fluoxetine reduced obsessivecompulsive behaviours at 16 weeks compared with placebo (mean difference -1·62 (CI -3·57; 0·33), p = 0·10), with little evidence of group differences in any of the secondary outcomes (all p>0.07). Adverse events were similar in the two groups. Interpretation: This randomised placebo-controlled trial did not demonstrate that fluoxetine reduced the restricted and repetitive behaviours associated with ASD compared with placebo. Fluoxetine is therefore not recommended in the routine treatment of ASD symptoms. Trail Registration Number: Australian and New Zealand Clinical Trials Registry (ACTRN12608000173392). Funding Statement: The study was funded by the National Health and Medical Research Council of Australia (NHMRC project grant number 607332) and the Royal Children’s Hospital Foundation, Melbourne, Australia. Infrastructure support was provided by the Victorian Government’s Operational Infrastructure Support Program. Declaration of Interests: Dinah Reddihough, Catherine Marraffa, Anissa Mouti, Molly O’Sullivan, Katherine Lee, Francesca Orsini, Joanna Granich, Andrew Whitehouse, John Wray, David Dossetor, Natalie Silove and Michael Kohn all have no conflicts of interest to declare. Philip Hazell’s employer has received payment from Shire for speaker fees. Paramala Santosh’s employer has received payment from Medice for speaker fees and from Newron Pharma for conducting clinical trials. Ethics Approval Statement: The study was approved by Human Research Ethics Committees (HRECs) at each site: The Royal Children’s Hospital Human Research Ethics Committee (EC00238) for the site in Victoria, the Sydney West Area Health Service Human Research Ethics Committee, Westmead Campus (EC00152) for the site in New South Wales and the Princess Margaret Hospital for Children Ethics Committee (EC00268) for the site in Western Australia.

School-age social behavior and pragmatic language ability in children with prenatal serotonin reuptake inhibitor exposure.

Studies examining associations between fetal serotonin reuptake inhibitor (SRI) exposure and child autism spectrum disorder (ASD) diagnoses or delayed language remain mixed and rarely prospectively follow children or employ gold-standard assessments. We prospectively followed a cohort of mother-child dyads from pregnancy through early elementary school (N = 178), and obtained maternal and alternate-caregiver ratings of behaviors related to ASD (N = 137), as well as direct, gold-standard assessments of child ASD symptoms and pragmatic language among dyads who experienced prenatal depression and either took SRIs or were medication free during pregnancy (N = 44). Prenatal SRI exposure was related to maternal ratings of ASD-related behaviors (β = 0.24 95% confidence interval; CI [0.07, 0.48]), and, among boys, alternative caregiver ratings (males-only β = 0.28 95% CI [0.02, 0.55], females-only β = -0.21 95% CI [-0.63, 0.08]). However, results of our direct assessments suggest an association between SRI exposure and reduced pragmatic language scores (β = -0.27, 95% CI [-0.53, -0.01], but not ASD (Autism Diagnostic Observation Schedule β = 0.14 95% CI [-0.15, 0.41]; Social Responsiveness Scale β = 0.08 95% CI [-0.25, 0.40]). These discrepancies point to issues regarding how ASD is assessed, and the possibility that SRIs may be more strongly associated with language or other broader behaviors that coincide with ASD. Larger prospective studies that incorporate thorough, gold-standard assessments of ASD, language, and other ASD-related behaviors are needed.

Reduced Amygdala–Prefrontal Functional Connectivity in Children With Autism Spectrum Disorder and Co-occurring Disruptive Behavior

BackgroundDisruptive behaviors are prevalent in children with autism spectrum disorder (ASD) and often cause substantial impairments. However, the underlying neural mechanisms of disruptive behaviors remain poorly understood in ASD. In children without ASD, disruptive behavior is associated with amygdala hyperactivity and reduced connectivity with the ventrolateral prefrontal cortex (vlPFC). This study examined amygdala reactivity and connectivity in children with ASD with and without co-occurring disruptive behavior disorders. We also investigated differential contributions of externalizing behaviors and callous-unemotional traits to variance in amygdala connectivity and reactivity. MethodsThis cross-sectional study involved behavioral assessments and neuroimaging in three groups of children 8 to 16 years of age: 18 children had ASD and disruptive behavior, 20 children had ASD without disruptive behavior, and 19 children were typically developing control participants matched for age, gender, and IQ. During functional magnetic resonance imaging, participants completed an emotion perception task of fearful versus calm faces. Task-specific changes in amygdala reactivity and connectivity were examined using whole-brain, psychophysiological interaction, and multiple regression analyses. ResultsChildren with ASD and disruptive behavior showed reduced amygdala–vlPFC connectivity compared with children with ASD without disruptive behavior. Externalizing behaviors and callous-unemotional traits were associated with amygdala reactivity to fearful faces in children with ASD after controlling for suppressor effects. ConclusionsReduced amygdala–vlPFC connectivity during fear processing may differentiate children with ASD and disruptive behavior from children with ASD without disruptive behavior. The presence of callous-unemotional traits may have implications for identifying differential patterns of amygdala activity associated with increased risk of aggression in ASD. These findings suggest a neural mechanism of emotion dysregulation associated with disruptive behavior in children with ASD.

Relationship of the Acoustic Startle Response and Its Modulation to Adaptive and Maladaptive Behaviors in Typically Developing Children and Those With Autism Spectrum Disorders: A Pilot Study.

Background: Autism spectrum disorder (ASD) is associated with persistent impairments in adaptive functioning across multiple domains of daily life. Thus, investigation of the biological background of both adaptive and maladaptive behaviors may shed light on developing effective interventions for improving social adaptation in ASD. In this study, we examined the relationship between adaptive/maladaptive behaviors and the acoustic startle response (ASR) and its modulation, which are promising neurophysiological markers for ASD translational research.Method: We investigated the ASR and its modulation in 11 children with ASD and 18 with typical development (TD), analyzing the relationship between startle measures and adaptive/maladaptive behaviors assessed with the Vineland Adaptive Behavior Scales (VABS) Second Edition.Results: Peak-ASR latency was negatively correlated with the VABS total score and socialization domain score of adaptive behaviors, while the ASR magnitude for relatively weak stimuli of 75–85 dB was positively correlated with VABS maladaptive behavior scores. Prepulse inhibition (PPI) at the prepulse intensity of 70–75 dB was also correlated with VABS maladaptive behavior. However, these relationships did not remain significant after adjustment for multiple comparisons.Conclusions: Our results indicate that the prolonged peak-ASR latency of ASD children might be associated with impairment in the developmental level of adaptive behavior, and that the greater ASR magnitude to relatively weak acoustic stimuli and smaller PPI of ASD children might increase the risk of maladaptive behavior. Future studies that have larger sample sizes will be important for further elucidating the neurophysiological factors that underpin adaptive as well as maladaptive behaviors in ASD.

Predicting Child Behavior: A Comparative Analysis between Autism Spectrum Disorder and Attention Deficit/Hyperactivity Disorder

Understanding factors that impact child adjustment is imperative. Parental adjustment, parenting behaviors, and environmental factors (e.g., child routines) have been linked to child behavior. In clinical child populations, these factors are particularly important given the increased demands the child’s disorder often places on caregivers. Furthermore, children in clinical populations often engage in increased levels of internalizing and externalizing behaviors both related to and in addition to the core symptoms of their disorder. Two such clinical child populations are Attention Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). The first goal of the present study was to elucidate parental and environmental factors that predicted child behavior in ADHD and ASD. Based on Sameroff’s Transactional Model of Development (2009), it was hypothesized that parental adjustment, parenting behaviors and child routines would collectively predict child behavior. A second goal was to examine differences in patterns of association between ADHD and ASD groups. Due to differences in the core symptoms of each disorder, it was hypothesized that the strength of associations would vary between groups. Researchers examined the impact of parental adjustment, parenting behaviors, and child routines on internalizing and externalizing child behavior using parent-report measures (CBCL, CRQ, HSCL-25, APQ) of children ages 6 to 12. Results indicated that for both groups, poor parental adjustment directly predicted externalizing child behavior and indirectly through harsh/disengaged parenting behavior. Fewer warm/supportive parenting behaviors predicted internalizing behavior, and more harsh/disengaged parenting predicted externalizing behavior. Higher levels of child routines predicted internalizing behavior for both groups but had a significantly stronger effect for children with ASD than ADHD. Findings have important implications for interventions on several levels (e.g., parental adjustment, parenting behaviors, and environmental supports) in both the ADHD and ASD populations.