Effectiveness of using the Modified Checklist for Autism in Toddlers in two-stage screening of autism spectrum disorder at the 18-month health check-up in Japan.

To determine whether the Modified Checklist for Autism in Toddlers (M-CHAT) in conjunction with the routine 18-month health check-up identifies Japanese toddlers with autism spectrum disorder (ASD). Two-stage screening using the M-CHAT was conducted with 1,851 children attending the check-up. Final ASD diagnosis was confirmed at age ≥3 years. Screening identified 20/51 children with ASD: 12/20 true positives were developmentally delayed, whereas 16/22 false negatives were high-functioning. Sensitivity was 0.476, specificity 0.986, positive predictive value 0.455, and likelihood ratio 33.4 for children with ASD. With a few modifications, M-CHAT screening successfully detected toddlers with ASD with and without developmental delay and is a promising screening tool to complement existing community surveillance.

A nationwide survey on quality of life and associated factors of adults with high-functioning autism spectrum disorders.

The psychosocial outcomes of individuals with high-functioning autism spectrum disorder (HFASD) appear to be diverse and are often poor relative to their intellectual or language level. To identify predictive variables that are potentially ameliorable by therapeutic intervention, this study investigated self-reported psychosocial quality of life and associated factors for adults with HFASD. All participants (n = 154) had a diagnosis of autism spectrum disorder, were over 18 years of age, lived in the community, and had used one or more support services during the survey period. The results demonstrated that psychosocial quality of life was lower than that of the general Japanese adult population. Environmental factors, such as mother's support and early diagnosis, were associated with better quality of life, and aggressive behaviors were associated with poorer quality of life, while expressive language level at preschool years, a conventional outcome predictor, did not predict quality of life. These results emphasize that quality of life measures should be included as outcome indicators in treating individuals with HFASD.

Reliability and validity of autism diagnostic interview-revised, Japanese version.

To examine the inter-rater reliability of Autism Diagnostic Interview-Revised, Japanese Version (ADI-R-JV), the authors recruited 51 individuals aged 3-19 years, interviewed by two independent raters. Subsequently, to assess the discriminant and diagnostic validity of ADI-R-JV, the authors investigated 317 individuals aged 2-19 years, who were divided into three diagnostic groups as follows: autistic disorder (AD), pervasive developmental disorder not otherwise specified, and other psychiatric diagnosis or no diagnosis, according to the consensus clinical diagnosis. As regards inter-rater reliability, intraclass correlation coefficients of greater than 0.80 were obtained for all three domains of ADI-R-JV. As regards discriminant validity, the mean scores of the three domains was significantly higher in individuals with AD than in those of other diagnostic groups. As regards diagnostic validity, sensitivity and specificity for correctly diagnosing AD were 0.92 and 0.89, respectively, but sensitivity was 0.55 for individuals younger than 5 years. Specificity was consistently high regardless of age and intelligence. ADI-R-JV was shown to be a reliable tool, and has sufficient discriminant validity and satisfactory diagnostic validity for correctly diagnosing AD, although the diagnostic validity appeared to be compromised with respect to the diagnosis of younger individuals.

Longitudinal developmental courses in Japanese children with autism spectrum disorder.

We followed up 67 children with autistic disorder (AD) and 31 children with pervasive developmental disorder not otherwise specified (PDDNOS) for more than 10 years by reviewing medical records at a clinic for children with developmental disabilities. The participants' data were collected between their first visit to the clinic and the visit at which they applied for basic disability benefits. The standardized IQ scores and autistic symptoms were examined as measures of the children's personal functioning. For environmental factors, we examined the participants' educational placements and work and residential status. Using structural equation modeling, we examined the longitudinal developmental courses of AD and PDDNOS. Participants diagnosed with AD consistently showed lower IQ and more severe autistic symptoms than those diagnosed with PDDNOS. Relationships between personal functioning and environmental factors differed between the two groups. AD and PDDNOS are heterogeneous, so they must be treated differently to improve children's prognoses.

Lay diagnoses and views on causes, coping strategies, and treatment for schizophrenia.

We aimed to clarify the relationship between lay diagnoses and perspectives on schizophrenia regarding causes, coping strategies, treatments, prognosis with and without the help of specialists. Our study sample was 500 adults in Japan. Participants read a vignette that depicted moderate to severe schizophrenic symptoms and yielded lay diagnoses. They also expressed their perspectives on the cause of the status in the vignette and coping strategies. We examined the relationship between lay diagnoses and the perspectives. Participants labeled the vignette as 'stress' held low expectations for the effectiveness of mental health professionals and psychiatric treatment. To enhance mental health literacy, it is important to help people distinguish a mental illness from mere stress. Lay diagnoses do not necessary have to be detailed, as long as people recognize a situation as an illness.

Utility of the Japanese version of the Checklist for Autism in Toddlers for predicting pervasive developmental disorders at age 2.

We evaluated the utility of the Japanese version of the Checklist for Autism in Toddlers for predicting pervasive developmental disorders (PDD) among 2-year-old children in clinical settings. Confirmed diagnosis revealed that the pass rate on four items (social interest, proto-imperative pointing, proto-declarative pointing and joint-attention) was significantly lower in 52 PDD children than in 48 non-PDD children, and if abnormal development was reported in two or more items, the sensitivity, specificity, and positive/negative predictive values for PDD diagnosis were 0.85, 0.73, and 0.77/0.81, respectively. This simple screening tool can provide valuable information to clinicians when diagnosing PDD.

Utility of the Kyoto Scale of Psychological Development in cognitive assessment of children with pervasive developmental disorders.

Based on the clinical records of 74 children with pervasive developmental disorders (PDD; mean age, 45.2 months; 62 boys), the utility of the Kyoto Scale of Psychological Development in cognitive assessment of young and/or mentally retarded PDD children was investigated. Because the overall developmental quotient (DQ) had the highest correlation with the IQ (Pearson's r, 0.88) and the Cognitive-Adaptive DQ showed a non-significant difference in mean (65.8) from the IQ (66.4), they both seem useful as an equivalent to an IQ. The test would enable clinicians to carry out continual developmental assessments and to develop appropriate remedial programs for those children from infancy.

Sex differences in WISC-III profiles of children with high-functioning pervasive developmental disorders.

Using the Japanese version of the Wechsler Intelligence Scale for Children-Third Edition (WISC-III), 26 girls with high-functioning (IQ > or = 70) pervasive developmental disorders (HFPDD) (mean age, 8.2 years) were compared with 116 boys with HFPDD (mean age, 9.0 years). Compared with the boys, the girls scored significantly higher on the Processing Speed index, Coding, and Symbol Search, but scored significantly lower on Block Design. Although both groups showed weakness on Comprehension in the verbal domain, the girls' subtest profile in the performance domain was relatively even and significantly different from the boys', which was characterized by a peak on Block Design. Such differences should be replicated, and possible behavioral, neurological, and genetic links to these sex differences should be clarified.

Mental health literacy of autism spectrum disorders in the Japanese general population.

OBJECTIVE: We aimed to clarify the public's mental health literacy of autism spectrum disorders (ASD). METHODS: Using a vignette of a young child, 500 Japanese participants were asked their perspectives, such as causes and appropriate coping strategies. For each response from those respondents who correctly identified the child as having autism, we tested the effects of sex and generation. RESULTS: Two hundred twenty-nine respondents (45.8%) correctly identified the child as having autism. Significantly (P < 0.05) more females planned practical coping strategies such as contacting public agencies, whereas males had relatively more irrelevant perceptions, for example, significantly more males attributed ASD to social environment. Significantly more young respondents expected psychiatric treatments such as antipsychotic administration to be effective, and more seniors estimated low that the prevalence is approximately 0.01% or less. CONCLUSIONS: The mental health literacy of ASD among the Japanese public appears to be acceptable but there is still much room for improvement. Females showed more accurate knowledge, possibly reflecting gender roles. Some young people are not likely to know of the impact of psychiatric treatment, and seniors appear to be unaware of the current broadened recognition of ASD. Continued efforts to disseminate accurate information are required, particularly among males.

Cognitive profile difference between normally intelligent children with Asperger's disorder and those with pervasive developmental disorder not otherwise specified.

AIM: Asperger's disorder (Asperger syndrome, AS) and pervasive developmental disorder not otherwise specified (PDD-NOS) are different subtypes of mild pervasive developmental disorders (PDD). METHODS: Using the Japanese version of the Wechsler Intelligence Scale for Children-Third Edition (WISC-III), 28 AS children (mean age, 9.3 years, 24 male) were compared with 78 PDD-NOS children (mean age, 7.6 years, 64 male) with normal intelligence (IQ > or = 85), using analysis of covariance (ancova) with the chronological age of a child as a covariate. RESULTS: Verbal IQ tended to be higher in the AS children than in the PDD-NOS children (mean raw scores, AS vs PDD-NOS: 103.9 vs 99.6; P < 0.10), although full-scale and performance IQ did not differ significantly. Compared with the PDD-NOS children, the AS children scored significantly higher on Freedom from Distractibility index (110.1 vs 104.5; P < 0.05) consisting of Arithmetic (11.0 vs 9.9, P = 0.04) and Digit Span (12.4 vs 11.6, P = 0.051), but tended to score lower on Coding (8.5 vs 9.8, P = 0.08). CONCLUSION: The typical cognitive profile of PDD (i.e. low score on Comprehension and high score on Block Design) was shared by both groups, which may support the validity of the current diagnostic classification of PDD. Relatively better verbal ability in AS children seems to reflect their normal language acquisition in infancy, and strong numeric interest may produce the AS children's mathematical excellence over PDD-NOS children. A low score on Coding in AS children might reflect their extreme slowness, circumstantiality and/or drive for perfection.

Predicting children with pervasive developmental disorders using the Wechsler Intelligence Scale for Children-Third Edition.

An original combination score (i.e. the sum of Vocabulary and Comprehension subtracted from the sum of Block Design and Digit Span) was created from the four Wechsler Intelligence Scale for Children-Third Edition (WISC-III) subtests identified by discriminant analysis on WISC-III data from 139/129 children with/without pervasive developmental disorders (PDD; mean, 8.3/8.1 years) and its utility examined for predicting PDD. Its best cut-off was 2/3, with sensitivity, specificity, positive and negative predictive values of 0.68, 0.61, 0.65 and 0.64, respectively. The score seems useful, so long as clinicians are aware of its limitations and use it only as a supplemental measure in PDD diagnosis.

Reliability and validity of the Pervasive Developmental Disorders Assessment System.

AIM: To test the reliability and validity of the Pervasive Developmental Disorders Assessment System (PDDAS), a Japanese semistructured interview system. METHODS: The PDDAS, consisting of 91 items including 12 major items corresponding to 12 items in criterion A of DSM-IV autistic disorder criteria, 36 items on autistic symptoms and three Asperger's disorder (AS) screening items for diagnosing pervasive developmental disorders (PDD) and their subtypes and 40 items for other information including early development and past/family histories, was administered to mothers of 77 PDD children and 64 non-PDD children. RESULTS: The PDDAS had satisfactory interrater reliability (ranges of kappa, r and raw agreement rate were 0.69-1.00 in 76 items, 1.00 in 11 items and 0.91-1.00 in four kappa un-calculable items, respectively). Thirty-three of the 36 items and all of the 12 major items scored significantly higher in the PDD than non-PDD groups to show satisfactory discriminant validity. PDDAS and consensus DSM-IV diagnoses agreed in the 77 children in PDD diagnosis and disagreed in only two children in subtype diagnoses of autistic disorder and PDD not otherwise specified. CONCLUSIONS: The PDDAS, which takes 1.5 h to administer, seems to have clinical and research utility, although further investigation is necessary.

The photoreaction of the photoactive yellow protein domain in the light sensor histidine kinase Ppr is influenced by the C-terminal domains.

To study the role of the C-terminal domains in the photocycle of a light sensor histidine kinase (Ppr) having a photoactive yellow protein (PYP) domain as the photosensor domain, we analyzed the photocycles of the PYP domain of Ppr (Ppr-PYP) and full-length Ppr. The gene fragment for Ppr-PYP was expressed in Escherichia coli, and it was chemically reconstituted with p-coumaric acid; the full-length gene of Ppr was coexpressed with tyrosine ammonia-lyase and p-coumaric acid ligase for biosynthesis in cells. The light/dark difference spectra of Ppr-PYP were pH sensitive. They were represented as a linear combination of two independent difference spectra analogous to the PYP(L)/dark and PYP(M)/dark difference spectra of PYP from Halorhodospira halophila, suggesting that the pH dependence of the difference spectra is explained by the equilibrium shift between the PYP(L)- and PYP(M)-like intermediates. The light/dark difference spectrum of Ppr showed the equilibrium shift toward PYP(L) compared with that of Ppr-PYP. Kinetic measurements of the photocycles of Ppr and Ppr-PYP revealed that the C-terminal domains accelerate the recovery of the dark state. These observations suggest an interaction between the C-terminal domains and the PYP domain during the photocycle, by which light signals captured by the PYP domain are transferred to the C-terminal domains.

Comparison of developmental/intellectual changes between autistic disorder and pervasive developmental disorder not otherwise specified in preschool years.

This study is the first to compare the change in developmental quotient (DQ) or IQ between autistic disorder (AD) and pervasive developmental disorder not otherwise specified (PDDNOS) in preschool years. Forty-nine AD children and 77 PDDNOS children were evaluated at age 2 and at age > or =5. The AD children were significantly lower in DQ/IQ at initial evaluation and outcome evaluation (also with initial DQ being controlled for) than the PDDNOS children.

Parental ages at birth of children with pervasive developmental disorders are higher than those of children in the general population.

To examine whether parental ages at birth of children with pervasive developmental disorders (PDD) are elevated, maternal/paternal ages at birth of 309 PDD children born in 1993-2003 (mean age, 8.4 years) were compared with those of children in the Japanese national statistics (general population). The mean maternal/paternal ages (years) at birth of PDD children of 31.7/34.6 were significantly higher even than the highest mean maternal/paternal ages at birth of children of 31.2/33.6 in the national statistics in 2003. This first Japanese study to report elevated parental ages at birth of PDD children underscores the need of further extensive studies.

Cognitive and symptom profiles in Asperger's syndrome and high-functioning autism.

Asperger syndrome (AS) and autistic disorder are two subtypes of pervasive developmental disorders (PDD), but there has been considerable debate over whether AS and autistic disorder without mental retardation (IQ > or = 70), called high-functioning autism (HFA), are distinct conditions or not. The aim of the present paper was to clarify this issue through a comparison of cognitive function and autistic symptom profiles. Based on the DSM-IV and ICD-10 definitions of language acquisition, 36 age- and IQ-balanced subjects with AS (mean age, 12.8 years; mean full-scale IQ, 98.3) were compared with 37 subjects with HFA (mean age, 12.6 years; mean full-scale IQ, 94.6) on the Japanese version of the Wechsler Intelligence Scales and the Childhood Autism Rating Scale-Tokyo Version (CARS-TV). Compared with the HFA subjects, the AS subjects scored significantly higher on Verbal IQ, Vocabulary, and Comprehension, but scored significantly lower on Coding. Although the total CARS-TV score did not differ significantly between the two groups, AS subjects scored significantly lower (i.e. less abnormal) on Verbal communication and Non-verbal communication than did the HFA subjects. A history of normal language acquisition in early childhood could predict his/her better verbal ability in mid-childhood or later. Autistic cognitive characteristics shared by both AS and HFA subjects appear to support the validity of the current diagnostic classification of PDD.

Autism-spectrum quotient Japanese version measures mental health problems other than autistic traits.

The purpose of the present paper was to examine the extent to which the Autism Spectrum Quotient Japanese version (AQ-J) measures mental health problems other than autistic traits, with the 12-item General Health Questionnaire Japanese version (GHQ-12) as a criterion. A questionnaire involving AQ-J and GHQ-12 was sent to 2000 adults aged 20-39 randomly selected from the general population, and intact data were obtained from 215 (mean age, 30.4 years; 86 male). The AQ-J score was significantly associated with the GHQ-12 score (r=0.518) and was significantly higher in 111 scoring >or=4 on the GHQ-12 (mean=24.8+/-6.5) than in 104 scoring <4 (mean=19.4+/-5.5). At a cut-off 22, the AQ-J had modest sensitivity (0.64) and specificity (0.66) for predicting mental health problems. The 21-item mental health AQ-J (AQJ-21MH; range, 0-21; cut-off, 9; sensitivity, 0.69; specificity, 0.76), items of which had a significant odds ratio (OR) for GHQ-12>or=4, and the AQ-J-4MH (range, 0-4; cut-off, 2; sensitivity, 0.68; specificity, 0.74) consisting of four items with a significant OR adjusted for collinearity selected from the 21 items by multiple logistic regression, were more efficient than the AQ-J. Because the AQ-J and its short forms measure mental health problems other than autistic traits, it is important to consider such problems in interpreting AQ-J scores to identify persons who may need professional help when screening normally intelligent adolescents and adults with pervasive developmental disorders.

Cognitive and symptom profiles in high-functioning pervasive developmental disorder not otherwise specified and attention-deficit/hyperactivity disorder.

Age- and IQ-balanced 27 children with high-functioning (IQ>or=70) pervasive developmental disorder not otherwise specified (HPDDNOS) and 27 children with attention-deficit/hyperactivity disorder (ADHD) were compared on the Japanese version of Wechsler Intelligence Scale for Children Third Edition (WISC-III) and the Childhood Autism Rating Scale-Tokyo Version (CARS-TV). Compared with the ADHD children, the HPDDNOS children scored significantly lower on verbal comprehension, vocabulary, and comprehension, but significantly higher on block design. After controlling for the total CARS-TV score, the HPDDNOS children were significantly more abnormal on "relationships with people," "nonverbal communication," and "general impressions," but less abnormal on "near receptor responsiveness" and "activity level." These differences in cognitive and autistic symptom profiles may help professionals to distinguish clinically between both conditions.

Autism-Spectrum Quotient-Japanese version and its short forms for screening normally intelligent persons with pervasive developmental disorders.

A Japanese version of the Autism Spectrum Quotient (AQ), AQ-J was administered to 25 normally intelligent high-functioning pervasive developmental disorder (HPDD) patients (mean age, 24.2 years; 24 male, one female) and 215 controls (mean age, 30.4 years; 86 male, 129 female) randomly selected from the general population. The AQ-J had satisfactory internal consistency reliability (Cronbach's alpha > 0.70 in the two groups), test-retest reliability, and discriminant validity [i.e. the AQ-J score was significantly higher in the HPDD (mean, 29.6) than controls (mean, 22.2)]. At a cut-off of 26, the AQ-J had satisfactory sensitivity, specificity, and negative predictive value, but it had low positive predictive value (0.24) possibly due to the facts that the 25 mild HPDD patients scored lower and the controls scored higher on the AQ-J than British counterparts on the AQ. The AQ-J-21 (consisting of 21 items significantly associated with HPDD diagnosis) and the AQ-J-10 (consisting of 10 of the 21 items with an effect size > 0.17) had higher, although not satisfactory, positive predictive values of 0.35 and 0.46 at cut-offs of 12 and 7, respectively, than the AQ-J. The AQ-J and two short forms are useful not to predict but to rule out mild HPDD, the most difficult part of HPDD to be distinguished from non-PDD conditions, in persons scoring under the cut-offs and to consider professionals' examination of HPDD in persons scoring over them, because their negative predictive values were satisfactory.

Comparison of childhood disintegrative disorder and disintegrative psychosis not diagnosed as childhood disintegrative disorder.

To clarify the difference of Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV) childhood disintegrative disorder (CDD) from International Classification of Diseases (9th revision; ICD-9) disintegrative psychosis (DP), 10 CDD children (mean age, 7.7 years) and 18 DP children (mean, 6.5 years) not diagnosed as CDD divided into DSM-IV autistic disorder (DP-AD; n = 11) and pervasive developmental disorders not otherwise specified (DP-PDDNOS; n = 7) were compared on 31 variables not directly related to the normalcy before regression. The CDD, DP-AD, and DP-PDDNOS groups did not differ significantly in 28 variables. The DP-PDDNOS group met significantly a smaller number of items in criterion A of DSM-IV autistic disorder criteria than the CDD and DP-AD groups, both of which did not differ significantly in this respect. The CDD group tended to be more abnormal in auditory responsiveness and verbal communication than the DP-PDDNOS group. While CDD is distinct from DP-PDDNOS, its validity apart from AD with regression remains to be studied.