Fungi: Friend or Foe? A Mycobiome Evaluation in Children With Autism and Gastrointestinal Symptoms.

ABSTRACT: Gastrointestinal (GI) symptoms often affect children with autism spectrum disorders (ASD) and GI symptoms have been associated with an abnormal fecal microbiome. There is limited evidence of Candida species being more prevalent in children with ASD. We enrolled 20 children with ASD and GI symptoms (ASD + GI), 10 children with ASD but no GI symptoms (ASD - GI), and 20 from typically developing (TD) children in this pilot study. Fecal mycobiome taxa were analyzed by Internal Transcribed Spacer sequencing. GI symptoms (GI Severity Index [GSI]), behavioral symptoms (Social Responsiveness Scale -2 [SRS-2]), inflammation and fungal immunity (fecal calprotectin and serum dectin-1 [ELISA]) were evaluated. We observed no changes in the abundance of total fungal species (alpha diversity) between groups. Samples with identifiable Candida spp. were present in 4 of 19 (21%) ASD + GI, in 5 of 9 (56%) ASD - GI, and in 4 of 16 (25%) TD children (overall P = 0.18). The presence of Candida spp. did not correlate with behavioral or GI symptoms (P = 0.38, P = 0.5, respectively). Fecal calprotectin was normal in all but one child. Finally, there was no significance in serum dectin-1 levels, suggesting no increased fungal immunity in children with ASD. Our data suggest that fungi are present at normal levels in the stool of children with ASD and are not associated with gut inflammation.

Are 'leaky gut' and behavior associated with gluten and dairy containing diet in children with autism spectrum disorders?

OBJECTIVES: Studies have suggested a link between diet and behavior in children with autism spectrum disorders (ASDs). Parental reports of behavioral changes upon exposure to gluten and/or casein are common in clinical practice. An association between diet type, intestinal permeability (IP) ('leaky gut'), and behavior has been long proposed but not substantiated. We explored this possible association in this trial. METHODS: This randomized double-blind, placebo-controlled study explored the effects of gluten and milk on IP and behavior in children with ASDs over a period of 4 weeks. IP assessed by lactulose:mannitol (L/M) sugar permeability test and behavior assessed by the Aberrant Behavior Checklist and Conners Parent Rating were measured. Gastrointestinal symptoms in both groups were also monitored. RESULTS: Neither the L/M ratio nor behavioral scores were different between groups exposed to gluten/dairy or placebo. The changes observed were noted to be small and not clinically significant. DISCUSSION: Our study although underpowered to show small differences does not support an association between dietary gluten/milk, IP, and behavioral changes in subjects with ASD.

Executive Function in Autism: Association with ADHD and ASD Symptoms.

There is substantial comorbidity between autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD), and there are well-documented executive functioning (EF) deficits in both populations. An important question concerns whether EF deficits in children with ASD are related to severity of ASD, ADHD, or both. We examined ADHD and ASD symptoms in relation to ratings of EF in the home and classroom. The sample comprised 64 children (55 males) diagnosed with ASD (mean age = 9.26 years; mean FSIQ = 92). Analyses indicated that parent and teacher ratings of EF (except Shift and Emotional Control) were consistently related to ADHD symptom severity, but not to ASD severity. Thus, functioning in the domains of Shift and Emotional control appear relatively spared, whereas performance in all other EF was impaired in relation to ADHD symptoms.

ADHD severity as a predictor of cognitive task performance in children with Autism Spectrum Disorder (ASD).

BACKGROUND: In recent years, a number of studies have begun to explore the nature of Attention-Deficit/Hyperactivity Disorder (ADHD) in children with Autism Spectrum Disorder (ASD). In this study, we examined the relationship between both symptoms of ADHD and symptoms of ASD on cognitive task performance in a sample of higher-functioning children and adolescents with ASD. Participants completed cognitive tasks tapping aspects of attention, impulsivity/inhibition, and immediate memory. AIMS: We hypothesized that children with ASD who had higher levels of ADHD symptom severity would be at higher risk for poorer sustained attention and selective attention, greater impulsivity/disinhibition, and weaker memory. METHODS AND PROCEDURES: The sample included 92 children (73 males) diagnosed with ASD (Mean Age = 9.41 years; Mean Full Scale IQ = 84.2). OUTCOMES AND RESULTS: Using regression analyses, more severe ADHD symptomatology was found to be significantly related to weaker performance on tasks measuring attention, immediate memory, and response inhibition. In contrast, increasing severity of ASD symptomatology was not associated with higher risk of poorer performance on any of the cognitive tasks assessed. CONCLUSIONS AND IMPLICATIONS: These results suggest that children with ASD who have more severe ADHD symptoms are at higher risk for impairments in tasks assessing attention, immediate memory, and response inhibition-similar to ADHD-related impairments seen in the general pediatric population. As such, clinicians should assess various aspects of cognition in pediatric patients with ASD in order to facilitate optimal interventional and educational planning.

Effects of Extended-Release Methylphenidate Treatment on Cognitive Task Performance in Children with Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder.

Objective: To examine the effectiveness of four doses of psychostimulant medication, combining extended-release methylphenidate (ER-MPH) in the morning with immediate-release MPH (IR-MPH) in the afternoon, on cognitive task performance. Method: The sample comprised 24 children (19 boys and 5 girls) who met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Text Revision (DSM-IV-TR) criteria for an autism spectrum disorder (ASD) on the Autism Diagnostic Interview-R and the Autism Diagnostic Observation Schedule, and had significant symptoms of attention-deficit/hyperactivity disorder (ADHD). This sample consisted of elementary school-age, community-based children (mean chronological age = 8.8 years, SD = 1.7; mean intelligence quotient = 85; SD = 16.8). Effects of placebo and three dose levels of ER-MPH (containing 0.21, 0.35, and 0.48 mg/kg equivalent of IR-MPH) on cognitive task performance were compared using a within-subject, crossover, placebo-controlled design. Each of the four MPH dosing regimens (placebo, low-dose MPH, medium-dose MPH, and high-dose MPH) was administered for 1 week; the dosing order was counterbalanced across children. Results: MPH treatment was associated with significant performance gains on cognitive tasks tapping sustained attention, selective attention, and impulsivity/inhibition. Dose/response was generally linear in the dose range studied, with no evidence of deterioration in performance at higher MPH doses in the dose range studied. Conclusion: The results of this study suggest that MPH formulations are associated with significant improvements on cognitive task performance in children with ASD and ADHD.

Judgments of auditory-visual affective congruence in adolescents with and without autism: a pilot study of a new task using fMRI.

One of the most widely reported developmental deficits associated with autism is difficulty perceiving and expressing emotion appropriately. Brain activation associated with performance on a new task, the Emotional Congruence Task, requires judging affective congruence of facial expression and voice, compared with their sex congruence. Participants in this pilot study were adolescents with normal IQ (n = 5) and autism or without (n = 4) autism. In the emotional congruence condition, as compared to the sex congruence of voice and face, controls had significantly more activation than the Autism group in the orbitofrontal cortex, the superior temporal, parahippocampal, and posterior cingulate gyri and occipital regions. Unlike controls, the Autism group did not have significantly greater prefrontal activation during the emotional congruence condition, but did during the sex congruence condition. Results indicate the Emotional Congruence Task can be used successfully to assess brain activation and behavior associated with integration of auditory and visual information for emotion. While the numbers in the groups are small, the results suggest that brain activity while performing the Emotional Congruence Task differed between adolescents with and without autism in fronto-limbic areas and in the superior temporal region. These findings must be confirmed using larger samples of participants.

ADHD severity as it relates to comorbid psychiatric symptomatology in children with Autism Spectrum Disorders (ASD).

Comorbid diagnoses identified in pediatric samples have been correlated with a range of outcomes, including greater levels of emotional, behavioral, and educational impairment and the need for more intensive treatment. Given that previous research has documented high levels of comorbid Attention-Deficit/Hyperactivity Disorder (ADHD) in children with Autism Spectrum Disorders (ASD), this study closely examines the relationship between parent-reported ADHD symptoms (i.e., Conners' Parent Rating Scale, Revised [CPRS-R]) and the prevalence of additional comorbid psychiatric diagnoses in a pediatric ASD sample (n=99). Regression analyses revealed that greater severity of ADHD symptomatology was significantly related to a greater number of comorbid psychiatric diagnoses, as identified using the Diagnostic Interview for Children and adolescents, 4th Edition (DICA-IV). Additionally, more severe ADHD symptoms were also associated with higher levels of symptom severity on Child Behavior Checklist (CBCL) syndrome subscales. Interestingly, increasing severity of ASD symptomatology, as measured by the Autism Diagnostic Interview, Revised (ADI-R), was not associated with a higher prevalence of comorbid psychiatric diagnoses or CBCL syndrome severity. Our study concluded that higher levels of ADHD severity-not ASD severity-were associated with a higher prevalence of comorbid psychiatric symptomatology in school-age children with ASD. These findings may encourage clinicians to thoroughly assess ADHD symptomatology in ASD children to better inform treatment planning.

A comparison of behavioral and emotional functioning in children and adolescents with Autistic Disorder and PDD-NOS.

Behavioral symptomatology was compared in 26 children and adolescents with Autistic Disorder ("autism") and 25 children and adolescents with Pervasive Developmental Disorder, Not Otherwise Specified ("PDD-NOS"). Relative to individuals with PDD-NOS, those with autism had more symptoms of depression, social withdrawal, atypical behavior, and immature social skills--and fewer family problems. These differences remained even when group differences in intellectual ability were statistically controlled. No group differences emerged in somatization, anxiety, or hyperactivity. Findings suggest that although both groups demonstrate considerable evidence of behavioral and emotional problems, those with autism are at particularly high risk for comorbid behavioral and emotional disabilities.

Effects of methylphenidate treatment in children with mental retardation and ADHD: individual variation in medication response.

OBJECTIVE: Individual variation in cognitive and behavioral response to methylphenidate (MPH) was investigated in children with mental retardation and attention-deficit/hyperactivity disorder. METHOD: Twenty-four children (mean age 10.9 years, SD = 2.4) participated in a placebo-controlled, double-blind, crossover trial with 0.15-, 0.30-, and 0.60-mg/kg b.i.d. doses of MPH. Parent and teacher behavioral ratings, as well as cognitive task performance, were assessed at each dose. RESULTS: Relative to placebo, most children with attention-deficit/hyperactivity disorder and mental retardation showed some degree of behavioral and cognitive improvement with MPH treatment. However, fewer of these children made substantial gains (>30% improvement, relative to placebo) with MPH treatment. At the highest dose, 55% of the children showed substantial behavioral gains and 46% made substantial gains in cognitive task performance. However, there was substantial independence between changes in behavior and changes in cognitive performance. CONCLUSIONS: At the 0.60-mg/kg MPH dose, more children showed substantial cognitive and behavioral gains than those who showed substantial declines in a ratio of more than 5:1. However, it may be prudent to assess cognitive change as well as behavioral effects because improvements in the former do not necessarily forecast improvements in the latter in children with attention-deficit/hyperactivity disorder and mental retardation.

Effects of extended release methylphenidate treatment on ratings of attention-deficit/hyperactivity disorder (ADHD) and associated behavior in children with autism spectrum disorders and ADHD symptoms.

OBJECTIVE: The purpose of this study was to examine the behavioral effects of four doses of psychostimulant medication, combining extended-release methylphenidate (MPH) in the morning with immediate-release MPH in the afternoon. METHOD: The sample comprised 24 children (19 boys; 5 girls) who met American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV-TR) criteria for an autism spectrum disorder (ASD) on the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS), and had significant symptoms of attention-deficit/hyperactivity disorder (ADHD). This sample consisted of elementary school-age, community-based children (mean chronological age=8.8 years, SD=1.7; mean intelligence quotient [IQ]=85; SD=16.8). Effects of four dose levels of MPH on parent and teacher behavioral ratings were investigated using a within-subject, crossover, placebo-controlled design. RESULTS: MPH treatment was associated with significant declines in hyperactive and impulsive behavior at both home and school. Parents noted significant declines in inattentive and oppositional behavior, and improvements in social skills. No exacerbation of stereotypies was noted, and side effects were similar to those seen in typically developing children with ADHD. Dose response was primarily linear in the dose range studied. CONCLUSIONS: The results of this study suggest that MPH formulations are efficacious and well-tolerated for children with ASD and significant ADHD symptoms.

High concordance of parent and teacher attention-deficit/hyperactivity disorder ratings in medicated and unmedicated children with autism spectrum disorders.

OBJECTIVE: Parent and teacher ratings of core attention-deficit/hyperactivity disorder (ADHD) symptoms, as well as behavioral and emotional problems commonly comorbid with ADHD, were compared in children with autism spectrum disorders (ASD). METHOD: Participants were 86 children (66 boys; mean: age=9.3 years, intelligence quotient [IQ]=84) who met American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for an ASD on the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS). Parent and teacher behavioral ratings were compared on the Conners' Parent and Teacher Rating Scales (CPRS-R; CTRS-R). The degree to which age, ASD subtype, severity of autistic symptomatology, and medication status mediated this relationship was also examined. RESULTS: Significant positive correlations between parent and teacher ratings suggest that a child's core ADHD symptoms-as well as closely related externalizing symptoms-are perceived similarly by parents and teachers. With the exception of oppositional behavior, there was no significant effect of age, gender, ASD subtype, or autism severity on the relationship between parent and teacher ratings. In general, parents rated children as having more severe symptomatology than did teachers. Patterns of parent and teacher ratings were highly correlated, both for children who were receiving medication, and for children who were not. CONCLUSIONS: Parents and teachers perceived core symptoms of ADHD and closely-related externalizing problems in a similar manner, but there is less agreement on ratings of internalizing problems (e.g., anxiety). The clinical implication of these findings is that both parents and teachers provide important behavioral information about children with ASD. However, when a clinician is unable to access teacher ratings (e.g., during school vacations), parent ratings can provide a reasonable estimate of the child's functioning in these domains in school. As such, parent ratings can be reliably used to make initial diagnostic and treatment decisions (e.g., medication treatment) regarding ADHD symptoms in children with ASDs.

Detecting social and non-social changes in natural scenes: performance of children with and without autism spectrum disorders and typical adults.

We probed differences in the ability to detect and interpret social cues in adults and in children and young adolescents with and without autism spectrum disorders (ASD) by investigating the effect of various social and non-social contexts on the visual exploration of pictures of natural scenes. Children and adolescents relied more on social referencing cues in the scene as compared to adults, and in the presence of such cues, were less able to use other kinds of cues. Typically developing children and adolescents were no better than those with ASD at detecting changes within the various social contexts. Results suggest children and adolescents with ASD use relevant social cues while searching a scene just as typical children do.