Children with autism spectrum disorder comorbid with attention-deficit/hyperactivity disorder examined by the Wisconsin card sorting test: Analysis by age-related differences.

The DSM-5 confirmed that autism spectrum disorder (ASD) might be comorbid with attention-deficit/hyperactivity disorder (ADHD). This study investigated the executive function of ASD comorbid with ADHD (ASD + ADHD), ASD, and typically developed (TD) children using the Keio version of the modified Wisconsin card sorting test (KWCST). Children with ASD + ADHD (n = 43), ASD (n = 69), and TD (n = 69) were examined in two age groups: 5-9 years and 10-15 years. Both of the younger clinical groups showed significantly unfavorable scores for many indices in the second step compared to the TD group. As for the older groups, the ASD children showed significantly unfavorable scores in total errors in the second step, while the ASD + ADHD children did not show significant differences in either step. However, some index scores of the two older clinical groups were comparable to the older TD group in the second step. For the cognitive differences between clinical groups, the younger ASD + ADHD showed unfavorable scores in numbers of response cards until the first category achieved in the second step, while the older ASD showed unfavorable scores in categories achieved and perseverative errors of Nelson in the first step. For the degree of improvements in the second step, the older groups did not show significant group differences, while the younger ASD group showed significantly fewer improvements compared to the TD group. Based on these results, it is presumed that younger ASD + ADHD individuals are not sufficiently able to sustain attention and/or memory, and that the older ASD patients have difficulty in terms of flexibility.

Prenatal exposure to outdoor air pollution and child behavioral problems at school age in Japan.

INTRODUCTION: Recent studies suggest positive associations between prenatal exposure to ambient air pollution and neurodevelopment of children, but evidence on the adverse effects of exposure to air pollution on child neurobehavioral development remains limited. We thus examined associations between prenatal exposure to outdoor air pollution and child behavioral problems at school age, using data from a nationwide population-based longitudinal survey in Japan, where participants were recruited in 2001 and are continuously followed. METHODS: Suspended particulate matter (SPM), nitrogen dioxide, and sulfur dioxide concentrations during the 9months before birth were obtained at municipality level and assigned to those participants born in the corresponding municipality. We analyzed data from singleton births with linked pollution data available (e.g., n=33,911 for SPM). We used responses to survey questions about behavioral problems at age 8years. We conducted multilevel logistic regression analysis, adjusting for individual and municipality-level variables. RESULTS: Air pollution exposure during gestation was positively associated with risk for behavioral problems related to attention and delinquent or aggressive behavior. In the fully adjusted models, odds ratios following a one-interquartile-range increase in SPM were 1.06 (95% confidence interval: 1.01, 1.11) for interrupting others, 1.09 (1.03, 1.15) for failure to pay attention when crossing a street, 1.06 (1.01, 1.11) for lying, and 1.07 (1.02, 1.13) for causing public disturbance. CONCLUSIONS: Prenatal exposure to outdoor air pollution was associated with behavioral problems related to attention and delinquent or aggressive behavior at age 8years in a nationally representative sample in Japan.

Children's Media Use and Self-Regulation Behavior: Longitudinal Associations in a Nationwide Japanese Study.

Objective The effect of media use on child behavior has long been a concern. Although studies have shown robust cross-sectional relations between TV viewing and child behavior, longitudinal studies remain scarce. Methods We analyzed the Longitudinal Survey of Babies, conducted by Japan's Ministry of Health, Labour and Welfare since 2001. Among 53,575 families, 47,010 responded to the baseline survey; they were followed up every year for 8 years. Complete data were available for longitudinal analysis among 32,439 participants. Daily media use (TV viewing and video game-playing hours at ages 3, 4, and 5 years) was used as the main exposure. We employed an index of the children's self-regulatory behavior as the outcome variable. Odds ratios and 95 % confidence intervals (CIs) were estimated. Results Among boys, longer TV-viewing times at ages 4 and 5 were related to problematic self-regulatory behavior. Compared with boys who watched just 1-2 h of TV a day, those who watched it 4-5 h had a 1.79-fold greater risk (CI 1.22-2.64) of problematic self-regulatory behavior, according to parental report. Among girls, similar results were evident at ages 4 and 5 (e.g., adjusted odds ratios for 4-5 h daily viewing versus 1-2 h at age 4: 2.59; 95 % CI 1.59-4.22). Video games may have a protective effect on the risk of problematic self-regulatory behavior at ages 3 and 5. Conclusion Longer daily exposure to TV during early childhood (age 4-5) may be associated with subsequent problematic child self-regulatory behavior.

Preterm birth and behavioural outcomes at 8†years of age: a nationwide survey in Japan.

OBJECTIVE: To analyse the effect of different preterm birth categories on behavioural outcomes. DESIGN: Prospective cohort design. SETTINGS: The Japanese Longitudinal Survey of Babies in the 21st Century was used for the study. SUBJECTS: Neonates born in 2001 in Japan (n=34,163) and followed up at the age of 8 years. Post-term births were excluded and the sample was divided into four groups according to gestational age: <34 weeks, 34-36 weeks, 37-38 weeks and 39-41 weeks. OUTCOME MEASURES: Seven behavioural outcomes were examined: three attention problems and four delinquent/aggressive behaviours. RESULTS: Logistic regression was used to estimate adjusted ORs and 95% CIs for each outcome. Positive associations were found between preterm birth (<37 weeks) and adverse behavioural outcomes compared with full-term birth (39-41 weeks). For attention problems, the OR for 'inability to wait his/her turn' was increased by 1.72 (95% CI 1.22 to 2.43) for gestational age <34 weeks and by 1.28 (95% CI 1.03 to 1.59) for 34-36 weeks' gestation. For delinquent/aggressive behaviour, the OR for the outcome 'destroying books/toys' was increased by 1.46 (95% CI 1.07 to 1.99) for gestational age <34 weeks, while the outcome 'disturbance in public' was increased by 1.20 (95% CI 1.04 to 1.38) for 34-36 weeks' gestation. CONCLUSIONS: Children who are born <34 weeks, but also between 34 and 36 weeks, are at increased risk of behavioural problems related to attention and delinquent/aggressive behaviour when 8 years old.

Prenatal Exposure to Traffic-related Air Pollution and Child Behavioral Development Milestone Delays in Japan.

BACKGROUND: Recent studies suggest that prenatal exposure to outdoor air pollution is associated with unfavorable neurodevelopment in children. We examined associations between prenatal exposure to traffic-related air pollution and child behavioral development milestone delays, using data from a nationwide population-based longitudinal survey in Japan, where the participants were recruited in 2001 and followed. METHODS: Particulate matter, nitrogen dioxide, and sulfur dioxide concentrations during the 9 months before birth were obtained at the municipality level and assigned to the participants who were born in the corresponding municipality. We analyzed data from singleton births with linked pollution data available (N = 33,911 at the maximum). We used responses to survey questions about age-appropriate behaviors at ages 2.5 and 5.5 years as indicators of behavioral development. We conducted multilevel logistic regression analysis, adjusting for individual and municipality-level variables. RESULTS: Air pollution exposure during gestation was positively associated with the risk of some developmental milestone delays at both ages. Specifically, air pollution was associated with verbal and fine motor development at age 2.5 years, and with behaviors related to inhibition and impulsivity at 5.5 years. In the fully-adjusted models, odds ratios following one-interquartile-range increase in nitrogen dioxide and suspended particulate matter were 1.24 (95% confidence interval: 1.07, 1.43) for inability to compose a two-phrase sentence at ages 2.5 and 1.10 (1.05, 1.16) for inability to express emotions at age 5.5 years, respectively. CONCLUSIONS: Prenatal exposure to traffic-related air pollution was associated with behavioral development milestone delays of children in a nationally representative sample in Japan.

Neurological and neurocognitive functions from intrauterine methylmercury exposure.

In the 1950s, large-scale food poisoning caused by methylmercury was identified in Minamata, Japan. Although severe intrauterine exposure cases (ie, congenital Minamata disease patients) are well known, possible impacts of methylmercury exposure in utero among residents, which is likely at lower levels than in congenital Minamata disease patients, are rarely explored. In 2014, the authors examined neurological and neurocognitive functions among 18 exposed participants in Minamata, focusing on fine motor, visuospatial construction, and executive functions. More than half of the participants had some fine motor and coordination difficulties. In addition, several participants had lower performance for neurocognitive function tests (the Rey-Osterrieth Complex Figure test and Keio version of the Wisconsin card sorting test). These deficits imply diffuse brain damage. This study suggests possible neurological and neurocognitive impacts of prenatal exposure to methylmercury among exposed residents of Minamata.

Intrauterine Exposure to Methylmercury and Neurocognitive Functions: Minamata Disease.

A large-scale food poisoning caused by methylmercury was identified in Minamata, Japan, in the 1950s. The severe intrauterine exposure cases are well known, although the possible impact of low-to-moderate methylmercury exposure in utero are rarely investigated. We examined neurocognitive functions among 22 participants in Minamata, mainly using an intelligence quotient test (Wechsler Adults Intelligent Scale III), in 2012/2013. The participants tended to score low on the Index score of processing speed (PS) relative to full-scale IQ, and discrepancies between PS and other scores within each participant were observed. The lower score on PS was due to deficits in digit symbol-coding and symbol search and was associated with methylmercury concentration in umbilical cords. The residents who experienced low-to-moderate methylmercury exposure including prenatal one in Minamata manifested deficits in their cognitive functions, processing speed in particular.

Executive function in children with pervasive developmental disorder and attention-deficit/hyperactivity disorder assessed by the Keio version of the Wisconsin card sorting test.

The Wisconsin card sorting test (WCST) comprehensively examines executive function (EF). The Keio version of the WCST (KWCST) uses fewer cards and presents them in two steps, separated by a short pause during which an instruction is given. Being of short duration, this test is suitable for children with pervasive developmental disorder (PDD) and attention-deficit/hyperactivity disorder (AD/HD), yet few studies have examined the performance of children with such developmental disorders in the second step of a two-step test such as the KWCST. Using the KWCST, this study compares EF in children with PDD (n=52), or AD/HD (n=46) to that in typically developing (TD) children (n=52). Scores for the six indices of this test, including numbers of response cards until the first category achieved (NUCA), total errors (TE), and non-perseverative errors of Nelson (NPEN), were analyzed using ANOVA. Compared to the TD group, scores in the PDD and/or AD/HD groups were significantly lower for all indices except NUCA and NPEN for the first step, and lower for all indices except NUCA for the second step. Moreover, significantly fewer improvements in TE were seen in the PDD group, and significantly fewer improvements in NPEN were seen in the AD/HD group, compared with TD. This study suggests that both PDD and AD/HD make it difficult for children to utilize their experience in the first step and to effectively apply the instruction given before the second step. It also suggests that the two-step nature of the KWCST is clinically important.

[Children with attention deficit/hyperactivity disorder and pervasive developmental disorder:attention and response inhibition in the kiddie continuous performance test].

Continuous Performance Test (CPT) is widely used to assess the attention function and response inhibition in both children and adults. This study attempts to examine the performances of boys with attention deficit/hyperactivity disorder (AD/HD) and pervasive developmental disorder (PDD) with and without comorbid AD/HD using a CPT. Among the various versions of the CPT available, we used the Kiddie CPT (K-CPT) modified for younger children. The K-CPT was administered to children with AD/HD (n=22), those with PDD (n=19), and typically developing children (n=41) from 7 to 12 years of age. All children were drug free at the time of examination. The performances were examined in 6 measures:total number of omission errors (OE), total number of commission errors (CE), mean hit reaction time (HRT), hit reaction time standard error (HRTSE), perceptual sensitivity (d'), and response style (beta). Significantly lower scores in d' and a tendency to more errors in CE were found in the AD/HD group compared with the control group. Significantly lower scores in d' and significantly more errors in CE were also found in the PDD group with AD/HD symptoms compared with the control group. Moreover the AD/HD group showed significantly more errors in OE and higher scores in HRTSE compared with the control group. There were no significant group differences between the PDD group without AD/HD symptoms and the control group on all measures. Less favorable scores in AD/HD suggest inadequate selective attention, sustained attention and/or response inhibition. Results of the PDD group with comorbid AD/HD may reflect a basis of AD/HD impairment. Our findings may provide an understanding of neuropsychological characteristics underlying developmental disorders.

Reading skills of Japanese second-graders.

BACKGROUND: A few studies have explored the prevalence of dyslexia among children who speak Japanese as their native language by evaluating them individually by means of reading-based tasks. The present study was designed to clarify the frequency of suspected dyslexia among second-graders attending ordinary classes. METHODS: The subjects were 40 children (22 males, 18 females; 7 years 4 months-8 years 4 months; mean age, 7 years 11 months) out of 182 second-graders at a public elementary school situated in a local city. Each subject underwent a monomoraic syllable reading task, a word reading task, a non-word reading task, and a short sentence reading task. RESULTS: The scores on the four tests were not normally distributed; rather, they were strongly skewed to shorter reading time or fewer reading errors. In addition, they were significantly extended toward either longer reading time or more reading errors. Except in the non-word reading task, most subjects only made a few reading errors. Seven subjects (17.5%) showed at least one score that was more than 1.5 IQR (interquartile range) higher than the third quartile of that subject's eight scores on the four tasks. Assuming that those seven children are potentially dyslexic, at least 3.8% of second-graders (seven out of 182) are suspected to be suffering from dyslexia. CONCLUSION: It is likely that the prevalence of dyslexia in Japan is comparable to that in Europe and the US. To confirm this, a more comprehensive study on a larger scale should be implemented in the future.

[Clinical application of the modified Stroop test to children with attention deficit/hyperactivity disorder].

The Stroop test has been already applied to many children with attention deficit/hyperactivity disorder (AD/HD). There are, however, differences in the measurement of the Stroop test, and also in the background conditions of the patients, such as the status of comorbidity with learning disorder (LD), medication and the level of Intelligence Quotient (IQ), and presumably as a result, the outcome of the Stroop test shows a diversity. This study was undertaken to compare the performances of children with AD/HD to normal controls using the modified Stroop test according to the subtypes of AD/HD. Subjects in this study were 23 unmedicated children with AD/HD, ranging from 6 to 14 years of age, and 69 normal controls who were matched on sex and age. Children with AD/HD whose verbal IQ and performance IQ were above 80 showed significant differences in such indices as Incongruent Color Naming time (ICN) and the resulting index of subtracting Color Naming time (CN) from ICN (ICN-CN). As to the analysis according to the subtypes excluding 8 cases with comorbid LD, both the predominantly inattentive type and the group putting together the predominantly hyperactive-impulsive type and the combined type showed significant differences in ICN--CN compared with the normal controls. These results suggest that the inattentiveness relevant factor affects the performance of the interference task in children with AD/HD.

[Developmental changes in the kiddie continuous performance test and its appropriate age for application].

The Kiddie Continuous Performance Test (K-CPT) was produced by Conners for children in age from 4 to 5 years. This study attempted to examine the developmental changes and gender differences of this test in children from preschool to adolescence, to verify its appropriate age range for application, and also to obtain a norm for clinical applications. K-CPT was administered to 327 healthy participants from 4 to 18 years of age. Participants were divided into 7 age groups. The performances were examined in 6 measures: the total number of omission errors (OE), the total number of commission errors (CE), the mean hit reaction time (HRT), the hit reaction time standard error (HRTSE), perceptual sensitivity (d') and response style (beta). All measures showed significant developmental changes. OE and beta showed floor effects around 10 years. Such measures as CE, HRT, HRTSE and d' showed significant developmental changes until adolescence. The effect of gender was found in performances in OE, CE, d' and beta. Male participants made more errors and showed less favorable perceptual sensitivity than did female participants. Results suggested that K-CPT would be appropriate for use with preschoolers and school-aged children. Findings also suggested that it is a potential diagnostic tool in children with developmental disorders.

[Standard value and developmental changes in the indices of interference effect in the modified Stroop test].

The Stroop test was originally invented by Stroop to measure selective attention and cognitive flexibility and various versions of this test have been developed by many other researchers. Since the Stroop test requires the examinee's sustained efforts, it is not readily applicable to children with developmental disorders. In order to overcome this weakness, a modified Stroop test by reducing the total number of stimulations from 300 to 72 was proposed for clinical use. This study was performed to obtain the standard value of the modified Stroop test, and also to clarify the developmental changes in indices of interference effect. Two hundred eighty one normal children and adults, ranging from 6 to 20 years of age were examined. A simple regression analysis was performed to examine the relation between age and the score of indices such as Incongruent Color Naming (ICN), ICN--Color Naming (CN), ICN/CN. The results from this analysis showed significant age-related changes. Subjects between sixteen and seventeen showed the best score in each index. These findings suggest that a brain region and/or functional system of late maturation might participate in the execution of the interference task.

Predicting executive function task scores with the Rey-Osterrieth Complex Figure.

The Boston Qualitative Scoring System (BQSS) is one of the scoring methods of the Rey-Osterrieth Complex Figure Test (ROCF). With BQSS, 17 qualitative ratings are generated, and subsequently 6 summary scores are calculated by combining several qualitative scores. Previously we showed that 5 of 6 BQSS summary scores were correlated with the scores of the several executive function tests in children. The objective of this study was to develop a new summary score which correlates with the executive function test scores more strongly than the existing summary scores. For this purpose, we conducted multiple regression analysis to predict PEN, CA, DSM of the Wisconsin Card Sorting Test Keio Version, and the Mazes scores from WISC-III, by the BQSS qualitative scores derived from ROCF drawings in copy condition. The subjects were 78 children with various neuropsychological disorders (5 years 5 months-14 years 11 months; mean: 9 years 2 months; F 22, M 56). Significant predictive models were generated for PEN, CA, and Mazes scores. Among them the models for the Mazes scores were the most accurate. The second model for the Mazes scores was most suitable for a new summary score. Its degree-of-freedom-adjusted coefficient of multiple determination and multiple correlation coefficient reached 0.467 and 0.695, respectively. A new summary score should be applied in future studies to evaluate its clinical usefulness.

The Rey-Osterrieth Complex Figure as a measure of executive function in childhood.

In adults, the Rey-Osterrieth Complex Figure (ROCF) can be used for the assessment of not only visuoconstructional ability and visual memory, but also executive function in adults. We studied whether ROCF scores also correlated with executive function in childhood. The subjects consisted of 56 patients with various neurological diseases (5 years 7 months-14 years 11 months; mean: 8 years 8 months; M 42, F 14) whose full-scale IQs were 70 or higher (mean: 93.3). All subjects underwent the Wechsler Intelligence Scale for children third edition (WISC-III) and various psychological tests focusing on executive function. We evaluated the ROCF with the Boston Qualitative Scoring System (BQSS). We calculated the partial correlation coefficients between the BQSS Summary Scores and representative scores of other executive function tests, using age as the control variable. Among the scores of the various examinations, the Perseverative Errors of Nelson of the Wisconsin Card Sorting Test, the raw scores of the Mazes (WISC-III), the Digit Span (WISC-III), and the Block Design (WISC-III) were correlated significantly with two to four BQSS Summary Scores (P<0.05 or P<0.01). In contrast, the scores of the Trail Making Test, the Stroop Test, and the Commission Error of Continuous Performance Test-II did not show a significant correlation with any of the BQSS Summary Scores. The ROCF evaluated with the BQSS reflects not only visuoperceptual ability and visuoconstructional ability, but also executive function, especially planning and organization. However, a new BQSS Summary Score should be devised since no existing BQSS index specifically reflects executive functions with an outstandingly strong correlation.

[Clinical application of the modified wisconsin card sorting test to children with attention deficit/hyperactivity disorder].

The cases with attention deficit/hyperactivity disorder (AD/HD) are known to have difficulties in performing various neuropsychological tests related to the executive function. Among them, the Wisconsin Card Sorting Test (WCST) is already applied to many children with AD/HD. There are, however, differences in the measurement of WCST, and also in the background conditions of the patients, such as the status of medication and the level of Intelligence Quotient (IQ), and presumably as a result, the outcome of WCST shows a diversity. The Keio version WCST (KWCST) is a modified WCST by reducing the number of cards and presenting subjects in two steps separated by a short pause, during which a brief instruction is given. This study was undertaken to compare the performances of children with AD/HD to normal controls using KWCST according to full-scale IQ (FIQ) and also the subtypes of AD/HD. Subjects in this study were 21 unmedicated children with AD/HD, ranging from 5 to 15 years of age, and 21 normal controls who were matched on sex and age. Children with AD/HD whose FIQ was above 80 showed significant low scores in such indices as categories achieved (CA), total errors (TE) , and nonperseverative errors of Nelson (NPEN) in the second step. As to the analysis according to the subtypes, the predominantly inattentive type showed significant low scores in CA, TE and NPEN of the second step, while the combined and predominantly hyperactive-impulsive types showed no significant differences compared with the normal controls. These results suggest that patients with AD/HD have difficulties in effectively utilizing their experiences in the first step as well as instructions which are given before the second step, and also indicate the importance of the second step from a view of the clinical applications.

[Effect of development and aging on the modified Wisconsin Card Sorting Test in normal subjects].

The Wisconsin card sorting test (WCST) is applied to various types of neurological disorders. Since WCST requires the examinee's sustained efforts, it is not readily applicable to children with developmental disorders. In order to overcome this weakness, Keio version WCST (KWCST) was developed by reducing the number of cards from 128 to 48 and presenting them in two steps separated by a short pause. During which a brief instruction was given. This study was performed to clarify the changes with age in indices of KWCST and to obtain the normative value. Three hundred thirty five normal subjects, ranging from 5 to 82 years of age were examined. A simple regression analysis showed a significant age-related changes. Subjects between the middle thirties and the middle forties showed the best score in such indices as the categories achieved, perseverative errors of Nelson, difficulties of maintaining set, numbers of response cards until the first category achieved, and total errors. Most of the scores were improved in the second step across the all age groups, which might have resulted from learning during the first step and the instruction provided before the second step. KWCST can be performed briefly, and is suitable for cases with attention deficit/hyperactivity disorder and pervasive developmental disorder.