An investigation of genetic structures underlying autistic traits was performed with samples from twins for which at least one proband had been ascertained as having autism spectrum disorders (ASDs) in our catchment area. In order to adjust for recent concepts of autism, we employed criteria for the broad spectrum of disease and the childhood autism rating scale (CARS) for quantitative assessment. The CARS test was performed on 45 twin pairs (19 monozygotic, 26 dizygotic) detected with a regional routine screening system. The obtained CARS scores were subjected to structural equation modeling (SEM), incorporating sex differences for each causal influence ascertainment correction, using the Mx software. A best fitting model of causal influences on autistic traits measured continuously, incorporating additive genetic (A) and non-shared environmental influences (E), was generated. With this AE model, the estimated heritability was 0.73 for males and 0.87 for females, based on the continuous CARS scores. There was no evidence for the existence of sex-specific genetic influences. Autistic traits were highly heritable in twins with even broad spectrum of autism, corresponding to the results of early studies based on classical autism. Additive genetic factors were more influential in females than males.

Dihydropyrimidinase (DHP) deficiency (MIM 222748) is characterized by dihydropyrimidinuria and is associated with a variable clinical phenotype. This disease might be associated with a risk of 5-fluorouracil toxicity, although no cases have been reported. We present here both the molecular characterization of the human DHP gene and, for the first time, the mutations causing DHP deficiency. The human DHP gene spans >80 kb and consists of 10 exons. It has been assigned to 8q22, by FISH. We performed mutation analysis of genomic DNA in one symptomatic and five asymptomatic individuals presenting with dihydropyrimidinuria. We identified one frameshift mutation and five missense mutations. Two related Japanese adult subjects were homozygous for the Q334R substitution, whereas two other, unrelated Japanese infant subjects were heterozygous for the same mutation, but this mutation is not common in the Japanese population. A Caucasian pediatric patient exhibiting epileptic attacks, dysmorphic features, and severe developmental delay was homozygous for W360R. Using a eukaryotic expression system, we showed that all mutations reduced enzyme activity significantly, indicating that these are crucial DHP deficiency-causing mutations. There was no significant difference, in residual activity, between mutations observed in the symptomatic and those observed in the asymptomatic individuals.

To evaluate the prevalence of dihydropyrimidinuria (DHPuria), we analyzed urine samples from 21,200 healthy Japanese infants, and found two cases of DHPuria without clinical symptoms. Based on this result, we estimated the prevalence to be approximately 1/10,000 births in Japan. In addition, we analyzed pyrimidine catabolism on a previously reported family with an adult DHPuria case. We newly identified the sister of the propositus as the second case of DHPuria in this family, because she excreted large amounts of dihydrouracil and dihydrothymine. The parents and the child of the propositus showed slight increases of dihydrouracil and dihydrothymine. This is the first family with 2 cases of DHPuria, indicating that DHPuria is an inherited condition. To determine the inheritance of DHPuria in this family and to examine the risk of 5-fluorouracil (5-FU) toxicity, a uracil loading test was performed on the parents. Urinary dihydrouracil concentrations in the parents after the loading were several times higher than those in normal control persons, the finding being consistent with DHPuria heterozygotes. This, along with data on the propositus, his sister, and his child, indicates that DHPuria is an autosomal recessive condition. In addition, DHPuria homozygotes may have a high risk of 5-FU toxicity, while the risk is relatively low in heterozygotes.

ObjectiveThe purpose of this study was to examine the effectiveness of group psychoeducation to relieve the psychological distress of mothers of children with high-functioning pervasive developmental disorders (HFPDD) and to improve the behaviors of the children.MethodsSeventy-two mothers of preschool outpatients with HFPDD were randomly assigned to a four-session brief group psychoeducational program (GP). The sessions were held every second week in addition to the usual treatment (GP + treatment as usual [TAU] group), or to a TAU-alone group. The primary outcome was self-reported symptoms of maternal mental health as assessed using the 28-item General Health Questionnaire (GHQ-28) at 21 weeks post-randomization (week 21). The GHQ-28 at the end of the intervention (week 7), Aberrant Behavior Checklist (ABC) for the behavior of the children, the Zarit Burden Interview (ZBI), and the Medical Outcomes Study 36-item Short Form Health Survey (SF-36) were carried out at weeks 7 and 21. We tested the group effects with the interaction between the intervention and the evaluation points.ResultsThe GHQ-28 score at week 21 was significantly higher in the GP + TAU group as compared to that in the TAU-alone group, indicating a greater improvement in the TAU-alone group. There was no evidence that GP + TAU led to a greater improvement of maternal mental health than TAU-alone at week 7. Similarly, no evidence was obtained to indicate that GP + TAU led to a reduction in the ABC or ZBI scores by week 7 or 21. The adjusted scores for the RF (role emotional) and MH (mental health) subscales of the SF-36 at week 21 were also significantly lower in the GP + TAU group, indicating a similar tendency to that of the change of the GHQ-28 score at week 21.ConclusionThe psychoeducational program did not alleviate maternal distress, aberrant behaviors of the children, or caregiver burden.

In March 2020, many schools were closed to prevent the spread of COVID-19 in Japan, and it is predicted that many children, especially those with neurodevelopmental disorders (NDDs), will be affected emotionally and behaviorally. Here, we examined the impact of school closures due to COVID-19 on school-aged children with NDDs using the Child Behavior Checklist. Totally, data on 121 children diagnosed with autism spectrum disorder, attention-deficit hyperactivity disorder, and/or intellectual disorder were analyzed and it was found that externalizing and aggressive behavior increased in all NDDs, regardless of the type of diagnosis. A clear prospect is important for children with NDDs children to lead a stable life, and more generous supports for children with NDDs and their families are needed. Supplementary Information The online version contains supplementary material available at 10.1007/s10803-021-05119-0.