Attentional differences in audiovisual face perception between full- and preterm very low birthweight toddlers.

AIM: To investigate whether rightward attention to the mouth during audiovisual speech perception may be a behavioural marker for early brain development, we studied very preterm and low birthweight (VLBW) and typically developing (TD) toddlers. METHODS: We tested the distribution of gaze points in Japanese-learning TD and VLBW toddlers when exposed to talking, silent and mouth moving faces at 12, 18 and 24 months (corrected age). Each participant was categorised based upon the area they gazed at most (Eye-Right, Eye-Left, Mouth-Right, Mouth-Left) per stimulus per age. A log-linear model was applied to three-dimensional contingency tables (region, side and group). RESULTS: VLBW toddlers showed fewer gaze points than TD toddlers. At 12 months, more VLBW toddlers than TD toddlers showed left attentional bias toward any one face; however, this difference in attention asymmetry receded somewhat by 24 months. In talking condition, TD toddlers showed right attentional bias from 12 to 24 months, whereas VLBW toddlers showed such bias upon reaching 24 months. Additionally, more TD toddlers than VLBW toddlers attended to the mouth. CONCLUSION: Delays in exhibiting the attentional bias for an audiovisual face or general faces displayed by typically developing children might suggest differential developmental timing for hemispheric specialisation or dominance.

Not sleeping soundly in early infancy is not bad.

AIMS: This study sought to determine whether not sleeping soundly in early infancy predicted poor development. This complemented earlier studies of children aged 12 months or older. METHODS: Sleep/wake patterns of 35 Japanese infants (23 males) with a gestational age of 37< weeks were recorded at home using actigraphy. Families were registered with a laboratory-based database for infant research. Follow-up recordings were conducted at 3, 4, 6, 12, and 24 months. Crawling was rated by mothers at 12 months and used to create regular and irregular crawling groups. Temperament was scaled using the Japanese Infant Behaviour Questionnaire-Revised Questionnaire and the Japanese Early Childhood Behaviour Questionnaire. RESULTS: At 4 months, infants with regular crawling style had shorter night-time sleep than infants with irregular crawling style. However, at 12 months, the former had longer motionless sleep at night compared to the latter. Before 6 months, infants with regular crawling style showed lower sleep efficiency, especially during the day, compared to those with irregular crawling style. In addition, the amount of night-time active sleep at 3 and 4 months were positively correlated with day-time activity, but not at 6 months. CONCLUSION: Short fragmental sleep in early infancy did not always predict poor development.

Impact of School Closures due to COVID-19 on Children with Neurodevelopmental Disorders in Japan.

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.

Comprehensive Genetic Analysis of Non-syndromic Autism Spectrum Disorder in Clinical Settings.

Although genetic factors are involved in the etiology of autism spectrum disorder (ASD), the significance of genetic analysis in clinical settings is unclear. Forty-nine subjects diagnosed with non-syndromic ASD were analyzed by microarray comparative genomic hybridization (CGH) analysis, whole-exome sequencing (WES) analysis, and panel sequencing analysis for 52 common causative genes of ASD to detect inherited rare variants. Genetic analysis by microarray CGH and WES analyses showed conclusive results in about 10% of patients, however, many inherited variants detected by panel sequencing analysis were difficult to interpret and apply in clinical practice in the majority of patients. Further improvement of interpretation of many variants detected would be necessary for combined genetic tests to be used in clinical settings.

VLDL-specific increases of fatty acids in autism spectrum disorder correlate with social interaction.

BACKGROUND: Abnormalities of lipid metabolism contributing to the autism spectrum disorder (ASD) pathogenesis have been suggested, but the mechanisms are not fully understood. We aimed to characterize the lipid metabolism in ASD and to explore a biomarker for clinical evaluation. METHODS: An age-matched case-control study was designed. Lipidomics was conducted using the plasma samples from 30 children with ASD compared to 30 typical developmental control (TD) children. Large-scale lipoprotein analyses were also conducted using the serum samples from 152 children with ASD compared to 122 TD children. Data comparing ASD to TD subjects were evaluated using univariate (Mann-Whitney test) and multivariate analyses (conditional logistic regression analysis) for main analyses using cofounders (diagnosis, sex, age, height, weight, and BMI), Spearman rank correlation coefficient, and discriminant analyses. FINDINGS: Forty-eight significant metabolites involved in lipid biosynthesis and metabolism, oxidative stress, and synaptic function were identified in the plasma of ASD children by lipidomics. Among these, increased fatty acids (FAs), such as omega-3 (n-3) and omega-6 (n-6), showed correlations with clinical social interaction score and ASD diagnosis. Specific reductions of very-low-density lipoprotein (VLDL) and apoprotein B (APOB) in serum of ASD children also were found by large-scale lipoprotein analysis. VLDL-specific reduction in ASD was correlated with APOB, indicating VLDL-specific dyslipidaemia associated with APOB in ASD children. INTERPRETATION: Our results demonstrated that the increases in FAs correlated positively with social interaction are due to VLDL-specific degradation, providing novel insights into the lipid metabolism underlying ASD pathophysiology. FUNDING: This study was supported mainly by MEXT, Japan.

Sexual difference in 2nd-to-4th digit ratio among 1.5-year-old Japanese children: A cross-sectional study of Aichi regional adjunct cohort of the Japan Environment and Children's Study (JECS-A).

BACKGROUND: A sex difference in the second-to-fourth digit ratio (2D:4D, males < females) has been described in Japanese fetuses and children, and its possible links to autism spectrum disorders (ASDs) have been discussed. Accordingly, this sexual difference in representative neonates merits examination. AIMS: This study aimed to examine 2D:4D measurements and sexual differences in Japanese toddlers aged 1.5 years. STUDY DESIGN AND SUBJECTS: The digit lengths used to calculate 2D:4D were measured using an easy-to-use photography method. A total of 1045 JECS-A (the Aichi regional sub-cohort of the Japan Environment and Children's Study) children (males, 523; females, 522) aged 1.5 years were analyzed. RESULTS: The mean ages for the males and females were 575.3 ± 13.1 and 575.9 ± 17.1 days, respectively. Histograms of left and right 2D:4D were normally distributed regardless of sex (left male, 0.909 ± 0.048; left female, 0.913 ± 0.049, d = 0.08; right male, 0.938 ± 0.055; right female, 0.937 ± 0.049, d = 0.02). Because of high dispersion in the data, t-tests did not support a significant sex difference in 2D:4D. Post-hoc statistical power was calculated as 0.124 and the effect size for the sex difference in 2D:4D was 0.036. CONCLUSIONS: This study failed to confirm sexual differences in 2D:4D in 1.5-year-old Japanese children. This may be because digit measurement is difficult in this group, resulting in reduced effect sizes, or because rapid growth attenuates the in utero sexual dimorphism. This evidence is useful for the light it casts on the extreme male brain theory of ASDs.

Cohort profile: Aichi regional sub-cohort of the Japan Environment and Children's Study (JECS-A).

PURPOSE: Effects of fetal, perinatal and childhood environment on the health of children at birth and during later life have become a topic of concern. The Aichi regional sub-cohort of the Japan Environment and Children's Study (JECS-A) is an ongoing birth cohort of pregnant women and their children which has been used to provide unique data, as adjunct studies of JECS, on multifaceted potential factors affecting children's health. PARTICIPANTS: The JECS-A is part of the JECS which follows a total of 100 000 pairs of children and their mothers (fathers' participation is optional) across 15 regions in Japan. In JECS-A, of the 8134 pregnant women living in Ichinomiya City and Nagoya City, Japan, a total of 5721 pregnant women and their 5554 children were included. Sociodemographic and psychological data as well as biological specimens were collected from the pregnant women and their spouses (if available) in the cohort during their pregnancy. Information on children included in the JECS-A was collected from their mothers and includes demographic, behavioural, childcare, psychological and psychiatric data. Urine extracted from disposable diapers and anthropometric data were also obtained from the children. FINDINGS TO DATE: A similar distribution trend for age at delivery was confirmed between the pregnant women enrolled in the JECS-A and the national statistics of the relevant areas. However, differences in education level and household income were observed. A total of 5502 children remained in the cohort at 18 months after delivery. Compared with the national statistics, the basic demographics of the children in the cohort represented the population in the study areas. FUTURE PLANS: The enrolled children in the JECS-A will be followed until the age of 13 years. The studies that come from JECS-A will complement JECS and bring novel results with a high level of generalisability.

Relations between Temperament, Sensory Processing, and Motor Coordination in 3-Year-Old Children.

Poor motor skills and differences in sensory processing have been noted as behavioral markers of common neurodevelopmental disorders. A total of 171 healthy children (81 girls, 90 boys) were investigated at age 3 to examine relations between temperament, sensory processing, and motor coordination. Using the Japanese versions of the Children's Behavior Questionnaire (CBQ), the Sensory Profile (SP-J), and the Little Developmental Coordination Disorder Questionnaire (LDCDQ), this study examines an expanded model based on Rothbart's three-factor temperamental theory (surgency, negative affect, effortful control) through covariance structure analysis. The results indicate that effortful control affects both sensory processing and motor coordination. The subscale of the LDCDQ, control during movement, is also influenced by surgency, while temperamental negative affect and surgency each have an effect on subscales of the SP-J.

Concordance of DSM-5 and DSM-IV-TR classifications for autism spectrum disorder.

BACKGROUND: The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was published in May 2013. Autism spectrum disorder (ASD) has been structured for the three subtypes of pervasive developmental disorder (PDD), but the number of impairment in social and communication dimension is not stated. METHODS: The subjects were 68 children who visited the Department of Psychology and Development at Nagoya City University Hospital for the first time between the ages of 6 and 15 years old. We retrospectively re-examined the subjects using DSM-IV-TR criteria and DSM-5 criteria with two rules (two of three and one of three on the social and communication dimension) and examined the concordance rate. RESULTS: Forty subjects were diagnosed with PDD, and 28 were not. The mean PDD subject age was 9.4 years, and mean IQ was 84.0 on the Wechsler Intelligence Scale for Children III or 62.7 on the Tanaka-Binet test. Twenty-seven (68%) of the PDD subjects were classified with ASD using DSM-5 criteria when the two of three rule was applied, while 32 (80%) were classified with ASD when the one of three rule was applied. All subjects without PDD were not diagnosed with ASD on DSM-5 criteria. CONCLUSION: DSM-5 criteria may exclude high functioning and older subjects from ASD because they tend to be atypical. The diagnostic procedure for DSM-5 criteria is ambiguous, especially in high functioning subjects and those diagnosed at an older age.

A failure to confirm the effectiveness of a brief group psychoeducational program for mothers of children with high-functioning pervasive developmental disorders: a randomized controlled pilot trial.

OBJECTIVE: The 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. METHODS: Seventy-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. RESULTS: The 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. CONCLUSION: The psychoeducational program did not alleviate maternal distress, aberrant behaviors of the children, or caregiver burden.

Serum levels of soluble platelet endothelial cell adhesion molecule-1 and vascular cell adhesion molecule-1 are decreased in subjects with autism spectrum disorder.

BACKGROUND: Adhesion molecules, such as platelet-endothelial adhesion molecule-1 (PECAM-1), platelet selectin (P-selectin), endothelial selectin (E-selectin), intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), are localized on the membranes of activated platelets and leukocytes and on the vascular endothelium. Recently, we measured serum levels of soluble (s) forms of adhesion molecules in adults,18 to 26 years old, with autism spectrum disorder (ASD) and observed low levels of sPECAM-1 and sP-selectin. A subsequent study showed a similar result in children two to four years old with ASD. However, information about school age (five to seventeen years old) ASD subjects is required to determine whether adhesion molecules are also reduced in individuals with ASD in this age range. FINDINGS: Twenty-two subjects with high-functioning ASD and 29 healthy age-matched controls were recruited. ELISA was used for sPECAM-1, and a suspension array system was used for sP-selectin, sE-selectin, sICAM-1 and sVCAM-1 measurements. We found that serum levels of sPECAM-1 (U = 91.0, P<0.0001 by Mann-Whitney U test) and sVCAM-1 (U = 168.0, P = 0.0042) were significantly lower in ASD subjects than in controls. Subsequently, we examined the correlations between serum levels of either sPECAM-1 or sVCAM-1 and clinical variables including Autism Diagnostic Interview - Revised subscores and our previous cytokine profile data from the same ASD subjects. However, we did not find any significant correlations between them. CONCLUSIONS: The present results, taken together with previous results, suggest that sPECAM-1 may play a role in the generation and development of ASD, beginning in childhood and lasting until adulthood.

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.

Downregulation of the expression of mitochondrial electron transport complex genes in autism brains.

Mitochondrial dysfunction (MtD) and abnormal brain bioenergetics have been implicated in autism, suggesting possible candidate genes in the electron transport chain (ETC). We compared the expression of 84 ETC genes in the post-mortem brains of autism patients and controls. Brain tissues from the anterior cingulate gyrus, motor cortex, and thalamus of autism patients (n = 8) and controls (n = 10) were obtained from Autism Tissue Program, USA. Quantitative real-time PCR arrays were used to quantify gene expression. We observed reduced expression of several ETC genes in autism brains compared to controls. Eleven genes of Complex I, five genes each of Complex III and Complex IV, and seven genes of Complex V showed brain region-specific reduced expression in autism. ATP5A1 (Complex V), ATP5G3 (Complex V) and NDUFA5 (Complex I) showed consistently reduced expression in all the brain regions of autism patients. Upon silencing ATP5A1, the expression of mitogen-activated protein kinase 13 (MAPK13), a p38 MAPK responsive to stress stimuli, was upregulated in HEK 293 cells. This could have been induced by oxidative stress due to impaired ATP synthesis. We report new candidate genes involved in abnormal brain bioenergetics in autism, supporting the hypothesis that mitochondria, critical for neurodevelopment, may play a role in autism.

Brain region-specific altered expression and association of mitochondria-related genes in autism.

BACKGROUND: Mitochondrial dysfunction (MtD) has been observed in approximately five percent of children with autism spectrum disorders (ASD). MtD could impair highly energy-dependent processes such as neurodevelopment, thereby contributing to autism. Most of the previous studies of MtD in autism have been restricted to the biomarkers of energy metabolism, while most of the genetic studies have been based on mutations in the mitochondrial DNA (mtDNA). Despite the mtDNA, most of the proteins essential for mitochondrial replication and function are encoded by the genomic DNA; so far, there have been very few studies of those genes. Therefore, we carried out a detailed study involving gene expression and genetic association studies of genes related to diverse mitochondrial functions. METHODS: For gene expression analysis, postmortem brain tissues (anterior cingulate gyrus (ACG), motor cortex (MC) and thalamus (THL)) from autism patients (n=8) and controls (n=10) were obtained from the Autism Tissue Program (Princeton, NJ, USA). Quantitative real-time PCR arrays were used to quantify the expression of 84 genes related to diverse functions of mitochondria, including biogenesis, transport, translocation and apoptosis. We used the delta delta Ct (∆∆Ct) method for quantification of gene expression. DNA samples from 841 Caucasian and 188 Japanese families were used in the association study of genes selected from the gene expression analysis. FBAT was used to examine genetic association with autism. RESULTS: Several genes showed brain region-specific expression alterations in autism patients compared to controls. Metaxin 2 (MTX2), neurofilament, light polypeptide (NEFL) and solute carrier family 25, member 27 (SLC25A27) showed consistently reduced expression in the ACG, MC and THL of autism patients. NEFL (P = 0.038; Z-score 2.066) and SLC25A27 (P = 0.046; Z-score 1.990) showed genetic association with autism in Caucasian and Japanese samples, respectively. The expression of DNAJC19, DNM1L, LRPPRC, SLC25A12, SLC25A14, SLC25A24 and TOMM20 were reduced in at least two of the brain regions of autism patients. CONCLUSIONS: Our study, though preliminary, brings to light some new genes associated with MtD in autism. If MtD is detected in early stages, treatment strategies aimed at reducing its impact may be adopted.

Investigation of the serum levels of anterior pituitary hormones in male children with autism.

BACKGROUND: The neurobiological basis of autism remains poorly understood. The diagnosis of autism is based solely on behavioural characteristics because there are currently no reliable biological markers. To test whether the anterior pituitary hormones and cortisol could be useful as biological markers for autism, we assessed the basal serum levels of these hormones in subjects with autism and normal controls. FINDINGS: Using a suspension array system, we determined the serum levels of six anterior pituitary hormones, including adrenocorticotropic hormone and growth hormone, in 32 drug-naive subjects (aged 6 to 18 years, all boys) with autism, and 34 healthy controls matched for age and gender. We also determined cortisol levels in these subjects by enzyme-linked immunosorbent assay. Serum levels of adrenocorticotropic hormone, growth hormone and cortisol were significantly higher in subjects with autism than in controls. In addition, there was a significantly positive correlation between cortisol and adrenocorticotropic hormone levels in autism. CONCLUSION: Our results suggest that increased basal serum levels of adrenocorticotropic hormone accompanied by increased cortisol and growth hormone may be useful biological markers for autism.

Evaluation of the Japanese version of the Developmental Coordination Disorder Questionnaire as a screening tool for clumsiness of Japanese children.

Developmental Coordination Disorder (DCD) is characterized by clumsiness and coordination difficulties. DCD interferes with academic performance and participation in physical activities and psychosocial functions, such as self-esteem, cognition, or emotion, from childhood through adolescence to adulthood. DCD is a common pediatric condition and its prevalence is estimated to be 6% worldwide. Although English questionnaires are available, there is no questionnaire to identify DCD in Japan, and therefore, no information on its prevalence is available. Recently, we developed the Japanese version of the Developmental Coordination Disorder Questionnaire (DCDQ-J). The purpose of this study was to describe the applicability of the DCDQ-J for use with a community-based population of children in Japan and to investigate the relationships between coordination and attention-deficit hyperactivity disorder (ADHD) tendencies or intelligence. The DCDQ-J was completed by 6330 parents or guardians of children and adolescents. We employed the ADHD-rating scale and determined the intelligence quotient (IQ) of the children. Two-way analysis of variance showed that the scores linearly increased as the children's grades advanced in 2 subscales, namely, control during movement and fine motor. In contrast, non-linear changes were found in the scores of the general coordination subscale. The total scores of the DCDQ-J and ADHD-RS were significantly correlated, but no relationship between DCDQ-J scores and IQ was found. The DCDQ-J is expected to be a useful screening tool to identify and assess motor coordination difficulties of children in Japan and enable cross-cultural comparisons.

Replication study of Japanese cohorts supports the role of STX1A in autism susceptibility.

Autism is a pervasive developmental disorder diagnosed in early childhood. Abnormalities of serotonergic neurotransmission have been reported in autism. Serotonin transporter (5-HTT), which modulates serotonin levels, is a major therapeutic target in autism. Therefore, factors that regulate 5-HTT expression might be implicated in autism. One candidate 5-HTT-regulatory protein is the presynaptic protein, syntaxin 1A (STX1A). We examined the association of STX1A with autism in a trio association study using DNA samples from Japanese trios with autistic probands. In TDT analysis, rs69510130 (p=0.027) showed nominal associations with autism; modest haplotype association was also observed. We further compared STX1A mRNA expression between the autistic and control groups in the postmortem brain. In the anterior cingulate gyrus region, STX1A expression in the autism group was found to be significantly lower than that of the control group. Thus, we suggest a possible role of STX1A in the pathogenesis of autism.

Further evidence for the role of MET in autism susceptibility.

MET receptor tyrosine kinase (MET)-mediated signaling has been implicated in multiple aspects of neocortical and cerebellar neuronal growth and maturation. A promoter functional SNP (rs1858830) that disrupts the transcription of MET has been reported to be strongly associated with autism spectrum disorders (ASD) in the Caucasian population. Here, we performed a trio association study of MET with ASD in Japanese subjects (n=126 trios). Based on the HapMap data on the Japanese population, 15 SNPs were chosen for the association study. One SNP located in intron 1, rs38841, showed a nominal association with autism (p=0.044; OR=1.61) when analyzed using the transmission disequilibrium test. To the best of our knowledge, this is the first replication study of the association of MET with autism, in any non-Caucasian population. Association of rs38841 with autism was further confirmed in 252 Caucasian trios from AGRE (p=0.0006). An interesting observation is that all three SNPs of MET (rs1858830, rs38845 and rs38841) shown to be associated with autism in three independent studies including the present one, are located towards the 5'end of the gene at a span of 9.4 kb. Our results provide further evidence for a possible role of MET in the pathogenesis of ASD.

Two genetic variants of CD38 in subjects with autism spectrum disorder and controls.

The neurobiological basis of autism spectrum disorder (ASD) remains poorly understood. Given the role of CD38 in social recognition through oxytocin (OT) release, we hypothesized that CD38 may play a role in the etiology of ASD. Here, we first examined the immunohistochemical expression of CD38 in the hypothalamus of post-mortem brains of non-ASD subjects and found that CD38 was colocalized with OT in secretory neurons. In studies of the association between CD38 and autism, we analyzed 10 single nucleotide polymorphisms (SNPs) and mutations of CD38 by re-sequencing DNAs mainly from a case-control study in Japan, and Caucasian cases mainly recruited to the Autism Genetic Resource Exchange (AGRE). The SNPs of CD38, rs6449197 (p<0.040) and rs3796863 (p<0.005) showed significant associations with a subset of ASD (IQ>70; designated as high-functioning autism (HFA)) in the U.S. 104 AGRE family trios, but not with Japanese 188 HFA subjects. A mutation that caused tryptophan to replace arginine at amino acid residue 140 (R140W; (rs1800561, 4693C>T)) was found in 0.6-4.6% of the Japanese population and was associated with ASD in the smaller case-control study. The SNP was clustered in pedigrees in which the fathers and brothers of T-allele-carrier probands had ASD or ASD traits. In this cohort OT plasma levels were lower in subjects with the T allele than in those without. One proband with the T allele who was taking nasal OT spray showed relief of symptoms. The two variant CD38 poloymorphysms tested may be of interest with regard of the pathophysiology of ASD.

Decreased serum levels of adiponectin in subjects with autism.

The neurobiological basis for autism remains poorly understood. We hypothesized that adipokines, such as adiponectin, may play a role in the pathophysiology of autism. In this study, we examined whether serum levels of adiponectin are altered in subjects with autism. We measured serum levels of adiponectin in male subjects with autism (n=31) and age-matched healthy male subjects (n=31). The serum levels of adiponectin in the subjects with autism were significantly lower than that of normal control subjects. The serum adiponectin levels in the subjects with autism were negatively correlated with their domain A scores in the Autism Diagnostic Interview-Revised, which reflects their impairments in social interaction. This study suggests that decreased levels of serum adiponectin might be implicated in the pathophysiology of autism.