Child Developmental MRI (CDM) project: protocol for a multi-centre, cross-sectional study on elucidating the pathophysiology of attention-deficit/hyperactivity disorder and autism spectrum disorder through a multi-dimensional approach.

INTRODUCTION: Neuroimaging studies on attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have demonstrated differences in extensive brain structure, activity and network. However, there remains heterogeneity and inconsistency across these findings, presumably because of the diversity of the disorders themselves, small sample sizes, and site and parameter differences in MRI scanners, and their overall pathogenesis remains unclear. To address these gaps in the literature, we will apply the travelling-subject approach to correct site differences in MRI scanners and clarify brain structure and network characteristics of children with ADHD and ASD using large samples collected in a multi-centre collaboration. In addition, we will investigate the relationship between these characteristics and genetic, epigenetic, biochemical markers, and behavioural and psychological measures. METHODS AND ANALYSIS: We will collect resting-state functional MRI (fMRI) and T1-weighted and diffusion-weighted MRI data from 15 healthy adults as travelling subjects and 300 children (ADHD, n=100; ASD, n=100; and typical development, n=100) with multi-dimensional assessments. We will also apply data from more than 1000 samples acquired in our previous neuroimaging studies on ADHD and ASD. ETHICS AND DISSEMINATION: The study protocol has been approved by the Research Ethics Committee of the University of Fukui Hospital (approval no: 20220601). Our study findings will be submitted to scientific peer-reviewed journals and conferences.

Effectiveness of a Parent Training Programme for Parents of Adolescents with Autism Spectrum Disorders: Aiming to Improve Daily Living Skills.

Parent training (PT) has been well established in younger children with autism spectrum disorder (ASD) but is less well studied in adolescents. This study examined the effects of attempting PT to enhance the daily living skills (DLSs) of adolescents with ASD. Twenty-five parents of adolescents with ASD participated in either the immediate- or delayed-treatment control condition. Children's DLSs were evaluated using the DLS domain of the Vineland Adaptive Behaviour Scales-II, and the achievement of the DLSs practised by the children at home was the subject of the evaluation. The DLS domain score showed no improvement in the treatment group compared to the control group. However, some parents in the treatment group reported that their children acquired the target DLSs and more sophisticated communication behaviours. In addition, one measure suggested that parents increased their praising behaviours. These changes may have been driven by the completion of the parent training. We discuss several aspects of developing parent-mediated interventions based on the current intervention situation and observed changes.

Abnormal cortical responses elicited by audiovisual movies in patients with autism spectrum disorder with atypical sensory behavior: A magnetoencephalographic study.

BACKGROUND: Atypical sensory behavior disrupts behavioral adaptation in children with autism spectrum disorder (ASD); however, neural correlates of sensory dysfunction using magnetoencephalography (MEG) remain unclear. METHOD: We used MEG to measure the cortical activation elicited by visual (uni)/audiovisual (multisensory) movies in 46 children (7-14 years) were included in final analysis: 13 boys with atypical audiovisual behavior in ASD (AAV+), 10 without this condition, and 23 age-matched typically developing boys. RESULTS: The AAV+ group demonstrated an increase in the cortical activation in the bilateral insula in response to unisensory movies and in the left occipital, right superior temporal sulcus (rSTS), and temporal regions to multisensory movies. These increased responses were correlated with severity of the sensory impairment. Increased theta-low gamma oscillations were observed in the rSTS in AAV+. CONCLUSION: The findings suggest that AAV is attributed to atypical neural networks centered on the rSTS.

Examining the Treatment Efficacy of PEERS in Japan: Improving Social Skills Among Adolescents with Autism Spectrum Disorder.

This study examines the efficacy of the Japanese version of the Program for the Education and Enrichment of Relational Skills (PEERS), which focuses on improving social functioning through making friends and maintaining good relationships for adolescents with autism spectrum disorder (ASD) without intellectual disabilities. Originally developed in the United States, PEERS is one of the few evidence-based social skills training programs for youth with ASD. The present study shows that with linguistic and cultural modifications, PEERS is effective in improving social functioning for adolescents with ASD in Japan. Positive results were found specifically in the areas of socialization, communication, knowledge of social skills, autistic mannerisms, and behavioral and emotional problems. In addition, most treatment gains were maintained at a 3-month follow-up assessment. These findings suggest that the Japanese version of PEERS is beneficial across multiple socio-emotional and behavioral domains for adolescents with ASD.

Structural brain abnormalities in children and adolescents with comorbid autism spectrum disorder and attention-deficit/hyperactivity disorder.

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) share high rates of comorbidity, with the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition now acknowledging the comorbid diagnosis of ASD and ADHD. Although structural abnormalities in the prefrontal cortex, cerebellum, and basal ganglia occur in both ASD and ADHD, no structural studies have focused exclusively on patients with comorbid ASD and ADHD. We thus aimed to clarify the structural features and developmental changes in patients with comorbid ASD and ADHD in a relatively large sample from two sites. Ninety-two patients were age-matched to 141 typically developing (TD) controls (age range: 5-16 years) and assessed for volumetric characteristics using structural magnetic resonance imaging (i.e. surface-based morphometry). While there were no significant differences in prefrontal cortex, cerebellum, and basal ganglia volumes, patients with ASD and ADHD exhibited significantly lower left postcentral gyrus volumes than TD controls. We observed significantly lower postcentral gyrus volumes exclusively in children and preadolescents, and not in adolescents. Our findings suggest that abnormal somatosensory, attributed to delayed maturation of the left postcentral gyrus, leads to the core symptoms experienced by patients with comorbid ASD and ADHD.

Lesser suppression of response to bright visual stimuli and visual abnormality in children with autism spectrum disorder: a magnetoencephalographic study.

BACKGROUND: Visual abnormality is a common sensory impairment in autism spectrum disorder (ASD), which may cause behavioral problems. However, only a few studies exist on the neural features corresponding to the visual symptoms in ASD. The purpose of this study was to investigate the relationship between cortical responses to visual stimuli and visual abnormality to examine the neurophysiological mechanisms of the visual abnormality in ASD. METHODS: Twenty-two high-functioning children with ASD (10.95 ± 2.01 years old) and 23 age-matched typically developing (TD) children (10.13 ± 2.80 years old) participated in this study. We measured the cortical responses (i.e., activated intensity and attenuation ratio) elicited by the Original visual image and other two types of bright images (the Dot noise or Blind image, which includes overlapped particles onto the Original image or the enhanced-brightness version of the Original image, respectively) using magnetoencephalography. RESULTS: The severity of visual abnormalities was significantly associated with behavioral problems in children with ASD. In addition, we found the increased cortical activation in response to the Original image in the left supramarginal gyrus (SMG) and middle temporal gyrus in children with ASD. However, there were no inter-group differences in the primary visual and medial orbitofrontal cortices. Furthermore, when we compared cortical responses according to the type of images, children with ASD showed lesser attenuation of the activated intensities than children with TD in response to the bright images compared with the Original image in the right SMG. These attenuation ratios (Dot noise/Original and Blind/Original) were also associated with the severity of visual abnormalities. CONCLUSIONS: Our results show that dysfunction of stimulus-driven neural suppression plays a crucial role in the neural mechanism of visual abnormality in children with ASD. To the best of our knowledge, this is the first magnetoencephalography study to demonstrate the association between the severity of visual abnormality and lower attenuation ratios in children with ASD. Our results contribute to the knowledge of the mechanisms underlying visual abnormality in children with ASD, and may therefore lead to more effective diagnosis and earlier intervention.

Treponema denticola transcriptional profiles in serum-restricted conditions.

Treponema denticola is a major pathogen in periodontal disease and is frequently isolated from the lesions of patients with chronic periodontitis. Treponema denticola utilizes serum components as nutrient sources so as to colonize and proliferate in the gingival crevice. However, the mechanisms of serum utilization remain unclear. Therefore, the aim of the present study was to identify T. denticola serum utilization genes. Precultured T. denticola cells were suspended in a tryptone-yeast extract-gelatin-volatile fatty acids medium containing 0, 1% and 10% serum, respectively, and incubated anaerobically for 17 h. Total RNA was isolated, and T. denticola gene expression was compared by microarray and reverse transcription-polymerase chain reaction. In serum-depleted conditions, the expression levels of a potential hydroxylamine reductase, several ABC transporters, and phosphoenolpyruvate synthase were increased, while those of genes encoding methyl-accepting chemotaxis proteins and a transcriptional regulator were decreased. These results suggest that T. denticola may uptake serum components mainly through the action of ABC transporters. In particular, the decrease in the dmcA expression level with decreasing serum concentration suggests its involvement in chemotaxis toward serum-rich environments.

Japanese Sleep Questionnaire for Elementary Schoolers (JSQ-ES): validation and population-based score distribution.

OBJECTIVE: The Japanese Sleep Questionnaire for Elementary Schoolers (JSQ-ES) was developed to measure the sleep habits and disturbances of Japanese children. The current study aimed to present psychometric properties and describe the score distribution of the JSQ-ES. In addition, it examined correlations between the sleep and daytime behavior of school-aged children. METHOD: Guardians of 4369 elementary school children and 100 children diagnosed with sleep disorders in two clinics completed the JSQ-ES. RESULTS: Exploratory factor analysis and confirmatory factor analysis suggested a nine-factor structure. The JSQ-ES internal consistency was 0.876 and 0.907 for the community and clinical groups, respectively. Score distribution differences were observed between the two groups. A cut-off point of 80 was identified for the total JSQ-ES score. CONCLUSIONS: Exploratory factor analysis and confirmatory factor analysis suggested a nine-factor structure: (1) restless legs syndrome; (2) sleep-disordered breathing; (3) morning symptoms; (4) nighttime awakenings; (5) insomnia; (6) excessive daytime sleepiness; (7) daytime behavior; (8) sleep habits; and (9) irregular/delayed sleep phase. The study verified that the JSQ-ES is a valid and reliable instrument with which to evaluate Japanese sleep habits using a large population-based sample. The JSQ-ES may be useful in both clinical and academic settings.

Investigation of autistic features among individuals with mild to moderate Cornelia de Lange syndrome.

Cornelia de Lange syndrome (CdLS) is a congenital disorder characterized by distinctive facial features, growth retardation, limb abnormalities, intellectual disability, and behavioral problems. Autism has been reported to occur frequently in CdLS, but the frequency of autism in individuals with the milder CdLS phenotype is not well studied. We investigated autistic features by using a screening tool and a diagnostic interview in 49 individuals with the mild to moderate phenotype from a CdLS research database at the Children's Hospital of Philadelphia. The Social Communication Questionnaire (SCQ), a screening instrument for autistic disorder, was completed for all individuals. For individuals who screened positive and a subset of those that screened negative, the Autism Diagnostic Interview-Revised (ADI-R) was administered. Autistic symptom severity was not significantly different by gender, age groups, and genotypes. There was a significant correlation between higher levels of adaptive functioning and lower scores of autistic symptoms. The estimated prevalence of significant autistic features by ADI-R criteria was 43% in our cohort of individuals with the mild to moderate CdLS phenotype, which suggests that prevalence of autistic disorder may be higher than previously described among individuals with mild to moderate phenotype of CdLS. Clinicians who take care of individuals with CdLS should have a high index of suspicion for autistic features, and refer for further evaluation when these features are present in order to expedite appropriate intervention.

Effect of smoking on subgingival microflora of patients with periodontitis in Japan.

BACKGROUND: Smoking is a risk factor for periodontitis. To clarify the contribution of smoking to periodontitis, it is essential to assess the relationship between smoking and the subgingival microflora. The aim of this study was to gain an insight into the influence of smoking on the microflora of Japanese patients with periodontitis. METHODS: Sixty-seven Japanese patients with chronic periodontitis (19 to 83 years old, 23 women and 44 men) were enrolled in the present study. They consisted of 30 smokers and 37 non-smokers. Periodontal parameters including probing pocket depth (PPD) and bleeding on probing (BOP) and oral hygiene status were recorded. Detection of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, Fusobacterium nucleatum/periodonticum, Treponema denticola and Campylobacter rectus in subgingival plaque samples was performed by polymerase chain reaction. Association between the detection of periodontopathic bacteria and smoking status was analyzed by multiple logistic regression analysis and chi-square test. RESULTS: A statistically significant association was found between having a PPD ≥ 4 mm and detection of T. denticola, P. intermedia, T. forsythia, or C. rectus, with odds ratios ranging from 2.17 to 3.54. A significant association was noted between BOP and the detection of C. rectus or P. intermedia, and smoking, with odds ratios ranging from 1.99 to 5.62. Prevalence of C. rectus was higher in smokers than non-smokers, whereas that of A. actinomycetemcomitans was lower in smokers. CONCLUSIONS: Within limits, the analysis of the subgingival microbial flora in smokers and non-smokers with chronic periodontitis suggests a relevant association between smoking and colonization by the specific periodontal pathogens including C. rectus.