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Introduction Autism spectrum disorder (ASD) is a complex and prevalent neurodevelopmental disorder characterized by deficits in social communication and social interaction as well as repetitive behaviors. Alterations in function connectivity are widely recognized in recent electroencephalogram (EEG) studies. However, most studies have not reached consistent conclusions, which could be due to the developmental nature and the heterogeneity of ASD. Methods Here, EEG coherence analysis was used in a cohort of children with ASD (n = 13) and matched typically developing controls (TD, n = 15) to examine the functional connectivity characteristics in long‐distance and short‐distance electrode pairs. Subsequently, we explore the association between the connectivity strength of coherence and symptom severity in children with ASD. Results Compared with TD group, individuals with ASD showed increased coherence in short‐distance electrode pairs in the right temporal–parietal region (delta, alpha, beta bands), left temporal–parietal region (all frequency bands), occipital region (theta, alpha, beta bands), right central–parietal region (delta, alpha, beta bands), and the prefrontal region (only beta band). In the long‐distance coherence analysis, the ASD group showed increased coherence in bilateral frontal region, temporal region, parietal region, and frontal–occipital region in alpha and beta bands. The strength of such connections was associated with symptom severity. Discussion Our study indicates that abnormal connectivity patterns in neuroelectrophysiology may be of critical importance to acknowledge the underlying brain mechanism., Alterations in function connectivity are widely recognized in recent electroencephalogram (EEG) studies. Our study indicates that discovery of atypical brain coherence in ASD young children may be of a critical importance to acknowledge the underlying brain mechanism.

Backgroud Autism spectrum disorders (ASD) are a complex group of neurodevelopmental disorders with a genetic basis. The role of long-chain polyunsaturated fatty acids (LC-PUFAs) and the occurrence of autism has been the focus of many recent studies. The present study investigates whether genetic variants of the fatty acid desaturase (FADS) 1/2 and elongation of very long-chain fatty acids protein (ELOVL) 2 genes, which are involved in LC-PUFA metabolism, are associated with ASD risk. Methods A cohort of 243 ASD patients and 243 unrelated healthy controls were enrolled in this case control study. Sixteen tag single nucleotide polymorphisms from the FADS1–2 and ELOVL2 genes were genotyped using the Sequenom Mass Array. Results There were significant differences in allelic distribution of FADS2 rs526126 (OR = 0.55, 95% CI = 0.42–0.72, pFDR

Autism spectrum disorder (ASD) is a neurodevelopment disorder with abnormalities of social interaction, communication and repetitive behaviors. The higher prevalence of ASD in men implies a potential relationship between sex hormones and ASD etiology. The ESR2 gene encodes estrogen receptor beta (ESR2) and plays an important role during brain development. A relationship between ESR2 and ASD has been suggested by studies on single nucleotide polymorphisms and mRNA and protein expression levels in ASD patients. Here, we explored the possible epigenetic regulation of the ESR2 gene in autism. We collected genomic DNA from the peripheral blood of Chinese Han males with autism and age-matched normal males and measured DNA methylation of CpG islands in the ESR2 gene, which consisted of 41 CpG sites among the proximal promoter region and an untranslated exon, by bisulfite sequencing. We also investigated a relationship between DNA methylation and phenotypic features of autism, as assessed by the Children Autism Rating Scale. We found little overall difference in the DNA methylation of the ESR2 5'-flanking region in individuals with autism compared with normal individuals. However, detailed analyses revealed that eight specific CpG sites were hypermethylated in autistic individuals and that four specific CpG sites were positively associated with the severity of autistic symptoms. Our study indicates that the epigenetic dysregulation of ESR2 may govern the development of autism.

We examined and analyzed binocular imbalance in a group of randomly selected normal subjects with corrected visual acuity of 0.8 or more in both eyes without ocular diseases, by using augmented virtual reality system. This study will quantify the correlation between binocular imbalance in these normal subjects and various spatial frequencies and temporal frequencies in the integrated binocular stimulation mode. A retrospective study was carried out and data from 97 patients (51 males and 46 females) who were diagnosed with no eye diseases, and with corrected binocular visual acuity of 0.8 or more, were collected. Their binocular visual function, Hirschberg test refraction status, and binocular imbalance were assessed using the quantified visual perception stimulation mode in an augmented virtual reality platform. When normal subjects (with corrected binocular vision of 0.8 or more without ocular diseases) were assessed using the integrated binocular stimulation mode with different temporal and spatial frequencies, a gradual reduction of binocular imbalance could be observed when spatial frequencies were increased. When contrast balance was adjusted, binocular imbalance was more prevalent in the horizontal state compared with the vertical state. This was seen when patients were stimulated by different temporal frequencies in the virtual reality testing mode. 17.53% and 29.90% of participants reached complete binocular fusion under low temporal frequency stimulation and high temporal frequency stimulation, respectively, while binocular imbalance was found in 65.9% and 62.89% of participants who were stimulated, respectively, by low temporal frequency and high temporal frequency. In addition, 16.5% and 7.21% experienced severe binocular imbalance under low temporal and high temporal frequency stimulation, respectively. The integrated binocular stimulation mode under low temporal frequency was more sensitive in detecting binocular imbalance. The status of binocular balance in normal subjects was not the same when stimulated by the augmented virtual reality platform, as many showed varying degrees of binocular imbalance. The results from our clinical study demonstrate that integrated binocular stimulation with different spatial and temporal frequencies enables a more sensitive detection of binocular imbalance, making it a powerful new tool for the diagnosis and analysis of clinical binocular abnormalities. In addition, since more than half of the normal subjects (without eye diseases who has corrected vision of 0.8 or more) exhibited binocular imbalance in our study, we believe that this brief binocular imbalance is likely a transient physiological phenomenon, which is not pathological to visual acuity and function, and should only be seen as pathological when binocular imbalance is prolonged, causing functional deficits such as reading impairment.

Rationale: This study aimed to investigate the genetic mutation characteristics of congenital idiopathic hypogonadotropic hypogonadism (IHH) through the clinical features and genetic analysis of 2 patients with IHH in 1 pedigree. Patient concerns: A 23-year-old girl presented with primary amenorrhea, sparse pubic hair, lack of breast development, and delayed sexual development. Diagnoses: Combined with the clinical characteristics, auxiliary examinations, and molecular genetic analysis, the patient was diagnosed as IHH. Interventions: Whole exome and Sanger sequencing were performed to validate the mutation in family members. Outcomes: A novel homozygous missense mutation c.521A > G (p.Q174R) in the GNRHR gene was identified in the 2 affected sisters. Familial segregation showed that the homozygous variant was inherited from their parents respectively and the eldest sister was the carrier without correlative symptom. Lessons: We reported a novel GNRHR mutation in a pedigree with congenital idiopathic hypogonadotropic hypogonadism. Glutamine at amino acid position 174 was highly conserved among various species. The molecular structure of GNRHR protein showed that p.Q174R mutation brought in a new stable hydrogen bond between position 174 and 215, may impede conformational mobility of the TMD4 and TMD5. It suggests that the missense mutation c.521A > G related to congenital idiopathic hypogonadotropic hypogonadism was probably a causative factor for both sisters. Through high-throughput sequencing and experimental verification, we had basically determined the patient's pathogenic mutation and inheritance, which could better guide doctors for treatment.

Prenatal exposure to valproic acid (VPA) in rat offspring is capable of inducing experimental autism with neurobehavioral aberrations. This study investigated the effect of docosahexaenoic acid (DHA) on hippocampal cell death, learning and memory alteration in an experimental rat autism model. We found that DHA supplementation (75, 150 or 300 mg/kg/day, 21 days) rescued the VPA (600 mg/kg) induced DHA reduction in plasma and hippocampus in a dose-dependent manner, increased the levels of hippocampal p-CaMKII and p-CREB without affecting total protein level, and altered BDNF-AKT-Bcl-2 signaling pathway, as well as inhibited the activity of caspase-3. DHA also influenced the content of malondialdehyde (MDA) and the activities of antioxidant enzymes in the VPA-treated offspring. Consistent with the previous results, we also observed that 300 mg/kg DHA supplementation markedly increased the cell survival, decreased the cell apoptosis, and increased mature neuronal cell in the hippocampus in VPA-treated offspring. Utilizing the Morris water maze test, we found that DHA prevented cognitive impairment in offspring of VPA-treated rats. The data suggested that DHA may play a neuroprotective role in hippocampal neuronal cell and ameliorates dysfunctions in learning and memory in this rat autism model. Thus, DHA could be used as treatment intervention for mitigating behavioral dysfunctions in autism spectrum disorder (ASD).

Objective: A study in a Caucasian population has identified two single-nucleotide polymorphisms (SNPs) in ZNF533, one in DOCK4, and two in IMMP2L, which were all significantly associated with autism. They are located in AUTS1 and AUTS5, which have been identified as autism susceptibility loci in several genome-wide screens. The present study aimed to investigate whether ZNF533, DOCK4, and IMMP2L genes are also associated with autism in a northeastern Chinese Han population. Methods: We performed a similar association study using families with three individuals (one autistic child and two unaffected parents). A family-based transmission disequilibrium test (TDT) was used to analyze the results. Results: There were significant associations between autism and the two SNPs of ZNF533 gene (rs11885327: χ 2=4.5200, P=0.0335; rs1964081: χ 2=4.2610, P=0.0390) and the SNP of DOCK4 gene (rs2217262: χ 2=5.3430, P=0.0208). Conclusions: Our data suggest that ZNF533 and DOCK4 genes are linked to a predisposition to autism in the northeastern Chinese Han population.

Aims To investigate the effect of FTY720 on the valproic acid (VPA) rat model of autism. Main methods As an animal model of autism, we used intraperitoneal injection of VPA on embryonic day 12.5 in Wistar rats. The pups were given FTY720 orally at doses of 0.25, 0.5 and 1 mg/kg daily from postnatal day 15 to 35. Social behavior, spatial learning and memory were assessed at the end of FTY720 treatment. The histological change, oxidative stress, neuroinflammatory responses, and apoptosis-related proteins in the hippocampus were evaluated. Key findings FTY720 (1 mg/kg) administration to VPA-exposed rats (1) improved social behavior, spatial learning and memory impairment; (2) resulted in a reduction in neuronal loss and apoptosis of pyramidal cells in hippocampal CA1 regions; (3) inhibited activation of microglial cells, in turn lowering the level of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-6 in the hippocampus; (4) changed Malondialdehyde (MDA) levels, Glutathione (GSH) levels, superoxide dismutase (SOD) activity and Glutathione Peroxidase (GSH-Px) activity in the hippocampus; (6) inhibited the elevated Bax and caspase-3 protein levels and enhanced the relative expression level of Bcl-2 in the hippocampus; and (7) increased phospho-Ca2 +/calmodulin-dependent protein kinase II (p-CaMKII), phospho-cAMP-response element binding protein (p-CREB) and Brain Derived Neurotrophic Factor (BDNF) protein expression in the hippocampus. Significance FTY720 rescues social deficit, spatial learning and memory impairment in VPA-exposed rats. FTY720 exerts both a direct protection for neurons and an indirect modulation of inflammation-mediated neuron loss as a possible mechanism of neuroprotection.

To investigate whether the decreased level of serum polyunsaturated fatty acids (PUFAs) in patients with autism is associated with the expression of related liver metabolic enzymes, we selected rats that were exposed to valproic acid (VPA) on embryonic day 12.5 (E12.5) as a model of autism. We observed the serum levels of PUFAs and the expression of related liver metabolic enzymes, including Δ5-desaturase, Δ6-desaturase and elongase (Elovl2), in VPA-exposed and control rats on postnatal day 35 (PND35) and conducted sex dimorphic analysis. We found that the levels of serum PUFAs and related liver metabolic enzymes in the VPA rats were significantly reduced, in association with autism-like behavioral changes, the abnormal expression of apoptosis-related proteins and hippocampal neuronal injury, compared to the control rats and showed sex difference in VPA group. This finding indicated that rats exposed to VPA at the embryonic stage may exhibit reduced synthesis of serum PUFAs due to the down-regulation of liver metabolic enzymes, thereby inducing nervous system injury and behavioral changes, which is affected by sex in the meantime.

Background Autism is a common, severe and highly heritable neurodevelopmental disorder in children, affecting up to 100 children per 10,000. The MET gene has been regarded as a promising candidate gene for this disorder because it is located within a replicated linkage interval, is involved in pathways affecting the development of the cerebral cortex and cerebellum in ways relevant to autism patients, and has shown significant association signals in previous studies. Principal Findings Here, we present new ASD patient and control samples from Heilongjiang, China and use them in a case-control and family-based replication study of two MET variants. One SNP, rs38845, was successfully replicated in a case-control association study, but failed to replicate in a family-based study, possibly due to small sample size. The other SNP, rs1858830, failed to replicate in both case-control and family-based studies. Conclusions This is the first attempt to replicate associations in Chinese autism samples, and our result provides evidence that MET variants may be relevant to autism susceptibility in the Chinese Han population.