Autism spectrum disorders (ASDs) are neurodevelopmental disorders with an increasing prevalence but lack reliable biomarkers for early diagnosis. The present study investigated 13 serological metabolites and 2 genetic variants related to folate metabolism in a total of 89 ASD cases and 89 matched controls. Fisher discriminant analysis was used to establish the classification model to recognize ASD cases and controls. Ten metabolites were significantly different between the groups, of which six metabolites were used as predictors to determine the discriminant prediction model: vitamin B12, 5-methylene-tetrahydrofolate, methonine, the ratio of S-adenosylmethionine/S-adenosylhomocysteine, methionine synthase and transcobalamin II. The model had statistical significance (lambda=0.520, χ2=113.103, df=6, P<.001) and correctly identified 84.3% of ASD and normal cohorts. The area under the receiver operating characteristic curve was 0.913, with a sensitivity of 86.5% and a specificity of 85.4%. Overall, the results indicated that folate-related metabolism contributed to predisposition of ASD and the combined detection of folate-related metabolism biomarkers could be effective in distinguishing ASD from healthy controls, and provide new insights for the early diagnosis of ASD in the future.

Growing evidence suggests pivotal roles for epigenetic mechanisms in both animal models of and individuals with autism spectrum disorders (ASD). Neuron-restrictive silencer factor (NRSF) binds to neuron-restrictive silencing elements in neuronal genes and recruits co-repressors, such as mSin3, to epigenetically inhibit neuronal gene expression. Because dysregulation of NRSF is related to ASD, here we examined the effects of mS-11, a chemically optimized mimetic of the mSin3-binding helix in NRSF, on the behavioral and morphological abnormalities found in a mouse model of valproic acid (VPA)-induced ASD. Chronic treatment with mS-11 improved prenatal VPA-induced deficits in social interaction. Additionally, we found that NRSF mRNA expression was greater in the somatosensory cortex of VPA-exposed mice than of controls. Agreeing with these behavioral findings, mice that were prenatally exposed to VPA showed lower dendritic spine density in the somatosensory cortex, which was reversed by chronic treatment with mS-11. These findings suggest that mS-11 has the potential for improving ASD-related symptoms through inhibition of mSin3-NRSF binding.

The Weak Central Coherence account of autism spectrum disorders posits that individuals with ASD utilize a detail-oriented information processing bias. While this local bias is helpful in visual search tasks, ASD individuals falter in social cognition tasks where coherence is advantageous. The present study examined the neural correlates of Weak Central Coherence in ASD during visual and social processing. Fifteen ASD and sixteen typically developing children/adolescents completed a social/visual information processing task in an fMRI scanner. The stimuli consisted of human characters, composed of geometrical shapes, displaying different emotions. In the locally-oriented Shape condition, participants indicated whether a given shape was present in a figure. In the Emotion condition, participants identified the emotion conveyed by the character in the figure at the global-level. Whole-brain within-and-between-group activation and seed-to-voxel functional connectivity analyses were conducted in SPM12 and the CONN toolbox. The ASD group was significantly faster in shape identification, but less accurate in emotion identification. The TD group showed significantly increased areas of activity over the ASD group in the Shape task in regions associated with executive control, such as the medial prefrontal cortex and middle frontal gyrus, suggesting increased interference from the global/social information. During the Emotion condition, the ASD group showed decreased connectivity between frontal and posterior regions and between body perception and motor networks, suggesting a possible difference in mirroring. The findings suggest that social cognitive factors, not visual processing biases, underlie the observed behavioral differences.