Autism spectrum traits are postulated to lie on a continuum that extends between individuals with autism and individuals with typical development (TD). Social cognition properties that are deeply associated with autism spectrum traits have been linked to functional connectivity between regions within the brain’s default mode network (DMN). Previous studies have shown that the resting-state functional connectivities (rs-FCs) of DMN are low and show negative correlation with the level of autism spectrum traits in individuals with autism spectrum disorder (ASD). However, it is unclear whether individual differences of autism spectrum traits are associated with the strength of rs-FCs of DMN in participants including the general population. Using the seed-based approach, we investigated the rs-FCs of DMN, particularly including the following two core regions of DMN: the anterior medial prefrontal cortex (aMPFC) and posterior cingulate cortex (PCC) in 19 young male adults with high-functioning ASD (mean age = 25.3 ± 6.9 years; autism-spectrum quotient (AQ) = 33.4 ± 4.2; full scale IQ (F-IQ) = 109.7 ± 12.4) compared with 21 age- and IQ-matched young male adults from the TD group (mean age = 24.8 ± 4.3 years; AQ = 18.6 ± 5.7; F-IQ = 109.5 ± 8.7). We also analyzed the correlation between the strength of rs-FCs and autism spectrum traits measured using AQ score. The strengths of rs-FCs from core regions of DMN were significantly lower in ASD participants than TD participants. Under multiple regression analysis, the strengths of rs-FCs in brain areas from aMPFC seed showed negative correlation with AQ scores in ASD participants and TD participants. Our findings suggest that the strength of rs-FCs in DMN is associated with autism spectrum traits in the TD population as well as patients with ASD, supporting the continuum view. The rs-FCs of DMN may be useful biomarkers for the objective identification of autism spectrum traits, regardless of ASD diagnosis.

Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD.

Gaze abnormality is a diagnostic criterion for autism spectrum disorder (ASD). However, few easy-to-use clinical tools exist to evaluate the unique eye-gaze patterns of ASD. Recently, we developed Gazefinder, an all-in-one eye-tracking system for early detection of ASD in toddlers. Because abnormal gaze patterns have been documented in various ASD age groups, we predicted that Gazefinder might also detect gaze abnormality in adolescents and adults. In this study, we tested whether Gazefinder could identify unique gaze patterns in adolescents and adults with ASD. We measured the percentage of eye fixation time allocated to particular objects depicted in movies (i.e., eyes and mouth in human face movies, upright and inverted biological motion in movies that presented these stimuli simultaneously, and people and geometry in movies that presented these stimuli simultaneously) by male adolescents and adults with ASD (N = 26) and age-matched males with typical development (TD; N = 35). We compared these percentages between the two groups (ASD and TD) and with scores on the social responsiveness scale (SRS). Further, we conducted discriminant analyses to determine if fixation times allocated to particular objects could be used to discriminate between individuals with and without ASD. Compared with the TD group, the ASD group showed significantly less fixation time at locations of salient social information (i.e., eyes in the movie of human faces without lip movement and people in the movie of people and geometry), while there were no significant groupwise differences in the responses to movies of human faces with lip movement or biological motion. In a within-group correlation analysis, a few of the fixation-time items correlated with SRS, although most of them did not. No items significantly correlated with SRS in both ASD and TD groups. The percentage fixation times to eyes and people, which exhibited large effect sizes for the group difference, could differentiate ASD and TD with a sensitivity of 81.0 % and a specificity of 80.0 %. These findings suggest that Gazefinder is potentially a valuable and easy-to-use tool for objectively measuring unique gaze patterns and discriminating between ASD and TD in male adolescents and adults.

Patients with autism spectrum disorders (ASDs) exhibit core autistic symptoms including social impairments from early childhood and mostly show secondary disabilities such as irritability and aggressive behavior based on core symptoms. However, there are still no radical treatments of social impairments in these patients. Oxytocin has been reported to play important roles in multiple social behaviors dependent on social recognition, and has been expected as one of the effective treatments of social impairments of patients with ASDs. We present a case of a 16-year-old girl with autistic disorder who treated by long-term administration of oxytocin nasal spray. Her autistic symptoms were successfully treated by two month administration; the girl’s social interactions and social communication began to improve without adverse effects. Her irritability and aggressive behavior also improved dramatically with marked decreases in aberrant behavior checklist scores from 69 to 7. This case is the first to illustrate long-term administration of oxytocin nasal spray in the targeted treatment of social impairments in a female with autistic disorder. This case suggests that long-term nasal oxytocin spray is promising and well-tolerated for treatment of social impairments of patients with ASDs.

Autism spectrum traits exist on a continuum and are more common in males than in females, but the basis for this sex difference is unclear. To this end, the present study draws on the extreme male brain theory, investigating the relationship between sex difference and the default mode network (DMN), both known to be associated with autism spectrum traits. Resting-state functional magnetic resonance imaging (MRI) was carried out in 42 females (mean age ± standard deviation, 22.4 ± 4.2 years) and 43 males (mean age ± standard deviation, 23.8 ± 3.9 years) with typical development. Using a combination of different analyses (viz., independent component analysis (ICA), fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and seed-based analyses), we examined sex differences in the DMN and the relationship to autism spectrum traits as measured by autism-spectrum quotient (AQ) scores. We found significant differences between female and male subjects in DMN brain regions, with seed-based analysis revealing a significant negative correlation between default-mode resting state functional connectivity of the anterior medial prefrontal cortex seed (aMPFC) and AQ scores in males. However, there were no relationships between DMN sex differences and autism spectrum traits in females. Our findings may provide important insight into the skewed balance of functional connectivity in males compared to females that could serve as a potential biomarker of the degree of autism spectrum traits in line with the extreme male brain theory.