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Background: Since the 1920s, motor development has been a strong research theme, focusing on infants' acquisition of motor skills, such as turning over and crawling. In the 1980s, a dynamic systems approach began emphasizing children's own motivation, which helped explain individual differences in the emergence of motor skills. However, few studies have examined factors contributing to individual differences in early motor development. In response, we investigated directional associations between temperament and motor development in children aged 6 months to 3 years., Method: The Japan Environment and Children's Study (JECS-A) recruited mothers between January 2011 and March 2014. 2,639 mothers were sent a questionnaire at 6 months, and responses were received from 1,657 of them, with full data for children aged 6 months, 2 years, and 3 years, including from three mothers of twins, were analyzed through structural equation modeling. Question items regarding fine and gross motor activities at each age were selected by pediatric neurologists specializing in developmental disorders. The Japanese version of the Little Developmental Coordination Disorder Questionnaire was administered at 42 months. Temperament was assessed through the parent-reported Behavior Questionnaire (short version) for infants, toddlers, and children. In all three measures, Surgency and Negative Affectivity were extracted, and Effortful Control, a major form of self-regulation, was found from toddlerhood onward, as in previous studies., Results: A path diagram reveals that at 6 months, Surgency and Orienting/Regulation interacted positively with the motor function (respectively, r = .57; r = 40, ps < .001). Up to about 3 years, Effortful Control plays a role in facilitating the motor function, resulting in positive effects on Control During Movement (CDM), General Coordination (GC), and Fine Motor Movement (FMM) (β = 14; β = 30; β = 37, ps < .001). Surgency had a positive effect on CDM and GC (β = 18; β = 06, ps < .001), whereas Negative Affect had a negative influence on FMM and GC (β = -.08; β = -.08, ps < .001)., Conclusion: While Surgency may be a key reactive factor in early motor development, Effortful Control and Movement develop in an interactive manner., Trial Registration: UMIN000030786. Scientific Title: The Japan Environment and Children's Study. Date of disclosure of the study: 2018/01/15. Only questionnaires were administered in the study., (© 2024. The Author(s).)

Background and Aims: In the neurobiological theory of attention, the orienting network mainly supports the temperamental regulatory function in infancy, with soothing methods such as visual attention distraction influencing its development. The attention distraction method chosen for soothing is thought to be influenced by maternal sensitivity, which has been found to decrease with poor maternal mental health. We hypothesize that the degree of maternal distress may affect the choice of attention distraction soothing method. Further, individual differences in being soothed by attention distraction will be associated with the temperamental regulation function in infancy/toddlerhood., Method: Structural equation modeling (SEM) was conducted on longitudinal data at 6 and 24 months on a sample ( N  = 1892) drawn from the sub-cohort of the Japan Environment and Children's Study (JECS). Temperament was examined through the short Infant Behavior Questionnaire-Revised (Japanese version) and the Early Childhood Behavior Questionnaire (Japanese version). Distress in caregivers was measured through the Kessler Psychological Distress Scale (Japanese version) at prenatal and 1-year-postnatal stages. Individual differences in using visual distraction soothing methods were also measured using tailor-made items., Results: Postnatal maternal distress at 12 months was negatively related to the tendency to use visual attention distraction as a soothing method (β = -0.06, p  = 0.006) at 24 months. When we applied the subscale of the temperamental regulatory factor in SEM, the more the mothers chose the distraction method for soothing, i.e., the more the toddlers experienced it, the higher their attention shifting scores (β = 0.07, p  = 0.002)., Conclusion: The findings support the view that caregivers' choice of method for distracting offspring's attention from distress may be associated with the development of self-regulation during infancy and toddlerhood., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

Proton (H + ) release is linked to aluminum (Al)-enhanced organic acids (OAs) excretion from the roots under Al rhizotoxicity in plants. It is well-reported that the Al-enhanced organic acid excretion mechanism is regulated by SENSITIVE TO PROTON RHIZOTOXICITY1 (STOP1), a zinc-finger TF that regulates major Al tolerance genes. However, the mechanism of H + release linked to OAs excretion under Al stress has not been fully elucidated. Recent physiological and molecular-genetic studies have implicated the involvement of SMALL AUXIN UP RNAs (SAURs) in the activation of plasma membrane H + -ATPases for stress responses in plants. We hypothesized that STOP1 is involved in the regulation of Al-responsive SAURs , which may contribute to the co-secretion of protons and malate under Al stress conditions. In our transcriptome analysis of the roots of the stop1 (sensitive to proton rhizotoxicity1) mutant, we found that STOP1 regulates the transcription of one of the SAURs , namely SAUR55 . Furthermore, we observed that the expression of SAUR55 was induced by Al and repressed in the STOP1 T-DNA insertion knockout (KO) mutant ( STOP1 -KO). Through in silico analysis, we identified a functional STOP1-binding site in the promoter of SAUR55 . Subsequent in vitro and in vivo studies confirmed that STOP1 directly binds to the promoter of SAUR55 . This suggests that STOP1 directly regulates the expression of SAUR55 under Al stress. We next examined proton release in the rhizosphere and malate excretion in the T-DNA insertion KO mutant of SAUR55 ( saur55 ), in conjunction with STOP1 -KO. Both saur55 and STOP1 -KO suppressed rhizosphere acidification and malate release under Al stress. Additionally, the root growth of saur55 was sensitive to Al-containing media. In contrast, the overexpressed line of SAUR55 enhanced rhizosphere acidification and malate release, leading to increased Al tolerance. These associations with Al tolerance were also observed in natural variations of Arabidopsis. These findings demonstrate that transcriptional regulation of SAUR55 by STOP1 positively regulates H + excretion via PM H + -ATPase 2 which enhances Al tolerance by malate secretion from the roots of Arabidopsis. The activation of PM H + -ATPase 2 by SAUR55 was suggested to be due to PP2C.D2/D5 inhibition by interaction on the plasma membrane with its phosphatase. Furthermore, RNAi-suppression of NtSTOP1 in tobacco shows suppression of rhizosphere acidification under Al stress, which was associated with the suppression of SAUR55 orthologs, which are inducible by Al in tobacco. It suggests that transcriptional regulation of Al-inducible SAUR s by STOP1 plays a critical role in OAs excretion in several plant species as an Al tolerance mechanism., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Authors. Plant Direct published by American Society of Plant Biologists and the Society for Experimental Biology and John Wiley & Sons Ltd.)

Nutritional support is essential for patients with severe motor and intellectual disabilities (SMID) to ensure the smooth provision of medical care. These patients often require long-term tube feeding with enteral formulas, potentially leading to deficiencies in vitamins and trace elements. Additionally, frequent antibiotic use for infections often disrupts gut microbiota, inhibiting vitamin K2 production by intestinal bacteria. We assessed the serum protein induced by vitamin K absence or antagonists-II (PIVKA-II) and undercarboxylated osteocalcin (ucOC) levels to assess the vitamin K status in 20 patients with SMID (median age: 44.1 years, 11 men and 9 women) undergoing long-term tube feeding for durations ranging from 3 to 31 years. Thirteen (65%) and nine (45%) patients had elevated PIVKA-II (<40 mAU/mL) and serum ucOC levels (reference value < 4.50 ng/mL), respectively. Dietary vitamin K1 intake did not differ between patients with and without elevated PIVKA-II levels. Vitamin K2 supplementation for 3 months decreased serum PIVKA-II levels near those within the reference range. Approximately half of the patients with SMID on tube feeding had subclinical vitamin K deficiency. Further studies are needed to ascertain if long-term vitamin K2 supplementation effectively prevents vitamin K deficiency-induced hypercoagulation, osteoporosis, and vascular calcification in patients with SMID.

Previously, insomnia and adverse lifestyle were prevalent among truck drivers, but the association between the two remains unknown in this particular occupational cohort. This study aimed to examine the relationship between insomnia and lifestyle-related diseases among truck drivers. We investigated 875 male truck drivers of the Japan Truck Association, Akita branch, as of July 2020. The definition of insomnia was based on the International Classification of Sleep Disorders, Third Edition (ICSD-3). Data from a self-administered questionnaire were merged with health records and health insurance claims data of 2020. In total, 40.1% had either one of the lifestyle-related diseases including hypertension (29.7%), diabetes mellitus (11.7%), and dyslipidemia (24.8%), whereas according to ICSD-3, 13.2% had insomnia. Multivariate logistic regression models demonstrated that individuals with insomnia had approximately 2-fold increased risk of having at least one lifestyle-related disease (p < 0.001), hypertension (p = 0.0027), diabetes mellitus (p = 0.0654) and dyslipidemia (p < 0.001). Occupational characteristics including daily driving hours, driving distance, and travel days were not associated with any lifestyle-related diseases except for an association between short-haul and at least one disease. In conclusion, insomnia is significantly associated with increased risks of lifestyle-related diseases among male truck drivers in Japan.

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., (© 2023 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

This study investigated the intention to get the coronavirus disease of 2019 (COVID-19) vaccine and its associated factors among Japanese university students. A cross-sectional survey was conducted from March to May 2021 via an e-learning platform at Akita University. Participants were 1776 graduate and undergraduate students who answered the survey on vaccine intention, the health belief model (HBM), sociodemographic characteristics, and concerns over COVID-19-related situations. Vaccine intention was stratified into active, slightly less, and no intention, and the associated factors were determined using the multinomial logistic regression model. Results showed that 56.7% of students had active intention, followed by slightly less intention (34.5%) and no intention (8.8%). After adjusting for covariates, healthcare course, perceived severity (life-threatening and serious social consequences), and perceived benefits from HBM were significantly associated with active intention, with adjusted odds ratios of 4.02 (95% confidence interval [CI], 2.11-7.67), 1.40 (95% CI, 1.16-1.69), 1.23 (95% CI, 1.04-1.46), and 2.03 (95% CI, 1.66-2.49), respectively; perceived barriers (side effect, troublesome, and parent disagreement) were adversely associated with active intention. The public health strategy to improve students' vaccine uptake requires providing accurate information on vaccine safety and efficacy while removing any barriers to vaccination.

Objectives: The detrimental impacts of abuse on victims' well-being are well documented globally, including Japan. The ongoing COVID-19 pandemic may increase the incidence of abuse in the community, creating an additional burden amid the crisis. However, the incidence of abuse in Japan during COVID-19 remains to be evaluated. Accordingly, our study aimed to assess the incidence of physical and verbal abuse among the general population in Japan and to identify the associated factors of abuse during COVID-19., Design and Setting: We used the data obtained from a nationwide, cross-sectional internet survey conducted in Japan between August and September 2020. Sampling weights were used to calculate national estimates, and multivariable logistic regression was performed to identify the associated factors for physical and verbal abuse., Results: Out of the total 25 482 participants, 965 (3.8 %) reported experiencing physical abuse and 1941 (7.6%) verbal abuse from April 2020 to September 2020. The incidence of physical and verbal abuse was higher among female participants. Participants who lived in areas where the 'state of emergency' was enforced were more likely to suffer from physical abuse. Similarly, vulnerable participants such as those below age 18, with low income, bad family relationships, and disabled people were more likely to experience both physical and verbal abuse. Participants suffering from COVID-19-related symptoms, who had poor health status and widows/divorcees were more likely to be verbally abused. Furthermore, those who did not follow preventive behaviours such as wearing masks in public places, abusing drugs and drinking alcohol in high amounts were also more likely to experience abuse., Conclusion: The impact of abuse was found disproportionately greater in more vulnerable groups of the population. Pandemic has reinforced the existing social inequalities, which need to be addressed timely to prevent precarious repercussions., Competing Interests: Competing interests: AO received personal fees from MNES, outside the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Dr. Ozaki received personal fees from Medical Network Systems outside the scope of the submitted work; Dr. Tanimoto received personal fees from Medical Network Systems and Bionics Co. Ltd. outside the scope of the submitted work.

Purpose: Truck drivers with insomnia are at a high risk of traffic accidents. We aimed to investigate the prevalence of insomnia and identify its associated factors among truck drivers in Japan., Methods: Participants were 2927 male truck drivers younger than 65 years old. Self-administered questionnaires were used to assess insomnia symptoms, State-Trait Anxiety Inventory, drinking, smoking habits, body mass index, caffeine intake, as well as daily driving hours, consecutive days away from home, and driving distance. Insomnia symptoms included difficulty initiating sleep, maintaining sleep and early morning awakening. Insomnia was defined when any of these symptoms were observed with daily tiredness., Results: The prevalence of insomnia among the subjects was 13.3% (n=356), of which 13.5% had difficulty initiating sleep, 78% had difficulty maintaining sleep, and 26.4% had early morning awakening. After adjusting for covariates, drinking habits, daily driving hours, and STAI score were significantly and linearly associated with insomnia; the adjusted odds ratio (OR) of drinking habits for insomnia was 1.74 [95% confidence interval (CI), 1.23-2.47] for heavy drinkers compared to non-drinkers (trend p <0.001); the adjusted OR of daily driving hours was 1.87 (95% CI, 1.00-3.49) for 12 hours or longer in a day compared to <8 hours in a day (trend p <0.001); the adjusted OR of STAI quartiles was 5.30 (95% CI, 3.66-7.67) for the highest quartile compared to the lowest quartile (trend p <0.001)., Conclusion: The present study demonstrated that insomnia is prevalent among truck drivers in Japan, and its risk factors include drinking habits, daily driving hours, and anxiety., Competing Interests: All authors declare no competing interests., (© 2021 Miyachi et al.)

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., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Mathematical modelling studies predicting the spread of the coronavirus disease 2019 (COVID-19) have been used worldwide, but precisions are limited. Thus, continuous evaluation of the modelling studies is crucial. We investigated situations of virus importation in sub-Saharan Africa (SSA) to assess effectiveness of a modelling study by Haider N et al. titled 'Passengers' destinations from China: low risk of novel coronavirus (2019-nCoV) transmission into Africa and South America'. We obtained epidemiological data of 2417 COVID-19 cases reported by 40 countries in SSA within 30 days of the first case confirmed in Nigeria on 27 February. Out of 442 cases which had travel history available, only one (0.2%) had a travel history to China. These findings underline the result of the model. However, the fact that there were numbers of imported cases from other regions shows the limits of the model. The limits could be attributed to the characteristics of the COVID-19 which is infectious even when the patients do not express any symptoms. Therefore, there is a profound need for all modelling researchers to take asymptomatic cases into account when they establish modelling studies.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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.

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.

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., (© 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.)

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.

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.

Although there is accumulating evidence that intelligence quotient (IQ) indexes some aspects of the autistic spectrum disorders (ASDs), the causal relationship between autistic traits and IQ remains controversial. We examined the sources of covariation between autistic traits and IQ. As males have a four times greater risk of ASDs than females, gender-specific effects were also explored. Autistic traits and IQ were assessed in 45 twin male-male, female-female and opposite-sex pairs ascertained by the regional screening system in Nagoya, Japan. Sex-limited Cholesky structural equation models were used to decompose the correlations between autistic traits and IQ into genetic and environmental components, including sex-specific factors. Genetic correlations between autistic traits and IQ were high and not significantly different between boys and girls (-0.94 and -0.95, respectively), but genetic factors underlying the autistic traits were not entirely shared with the IQ. The individual-specific environmental correlation between autistic traits and IQ was estimated at -0.29 for boys and -0.59 for girls. There is a substantial overlap between the genetic factors that influence individual variation in autistic traits and IQ, irrespective of gender. The individual life experiences that increase autistic traits, however, have a moderate overlap with those that contribute to individual IQs.