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Altered nonverbal communication patterns especially with regard to gaze interactions are commonly reported for persons with autism spectrum disorder (ASD). In this study we investigate and differentiate for the first time the interplay of attention allocation, the establishment of shared focus (eye contact and joint attention) and the recognition of intentions in gaze interactions in adults with ASD compared to control persons. Participants interacted via gaze with a virtual character (VC), who they believed was controlled by another person. Participants were instructed to ascertain whether their partner was trying to interact with them. In fact, the VC was fully algorithm-controlled and showed either interactive or non-interactive gaze behavior. Participants with ASD were specifically impaired in ascertaining whether their partner was trying to interact with them or not as compared to participants without ASD whereas neither the allocation of attention nor the ability to establish a shared focus were affected. Thus, perception and production of gaze cues seem preserved while the evaluation of gaze cues appeared to be impaired. An additional exploratory analysis suggests that especially the interpretation of contingencies between the interactants' actions are altered in ASD and should be investigated more closely., (© 2024. The Author(s).)

Background: Diagnostic assessment of ASD requires substantial clinical experience and is particularly difficult in the context of other disorders with behavioral symptoms in the domain of social interaction and communication. Observation measures such as the Autism Diagnostic Observation Schedule (ADOS) do not take into account such co-occurring disorders., Method: We used a well-characterized clinical sample of individuals (n = 1,251) that had received detailed outpatient evaluation for the presence of an ASD diagnosis (n = 481) and covered a range of additional overlapping diagnoses, including anxiety-related disorders (ANX, n = 122), ADHD (n = 439), and conduct disorder (CD, n = 194). We focused on ADOS module 3, covering the age range with particular high prevalence of such differential diagnoses. We used machine learning (ML) and trained random forest models on ADOS single item scores to predict a clinical best-estimate diagnosis of ASD in the context of these differential diagnoses (ASD vs. ANX, ASD vs. ADHD, ASD vs. CD), in the context of co-occurring ADHD, and an unspecific model using all available data. We employed nested cross-validation for an unbiased estimate of classification performance and made available a Webapp to showcase the results and feasibility for translation into clinical practice., Results: We obtained very good overall sensitivity (0.89-0.94) and specificity (0.87-0.89). In particular for individuals with less severe symptoms, our models showed increases of up to 35% in sensitivity or specificity. Furthermore, we analyzed item importance profiles of the ANX, ADHD, and CD models in comparison with the unspecific model revealing distinct patterns of importance for specific ADOS items with respect to differential diagnoses., Conclusions: ML-based diagnostic classification may improve clinical decisions by utilizing the full range of information from detailed diagnostic observation instruments such as the ADOS. Importantly, this strategy might be of particular relevance for older children with less severe symptoms for whom the diagnostic decision is often particularly difficult., (© 2022 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Brain-to-brain synchrony has been proposed as an important mechanism underlying social interaction. While first findings indicate that it may be modulated in children with autism spectrum disorder (ASD), no study to date has investigated the influence of different interaction partners and task characteristics. Using functional near-infrared spectroscopy hyperscanning, we assessed brain-to-brain synchrony in 41 male typically developing (TD) children (8-18 years; control sample), as well as 18 children with ASD and age-matched TD children (matched sample), while performing cooperative and competitive tasks with their parents and an adult stranger. Dyads were instructed either to respond jointly in response to a target (cooperation) or to respond faster than the other player (competition). Wavelet coherence was calculated for oxy- and deoxyhemoglobin brain signals. In the control sample, a widespread enhanced coherence was observed for parent-child competition, and a more localized coherence for parent-child cooperation in the frontopolar cortex. While behaviorally, children with ASD showed a lower motor synchrony than children in the TD group, no significant group differences were observed on the neural level. In order to identify biomarkers for typical and atypical social interactions in the long run, more research is needed to investigate the neurobiological underpinnings of reduced synchrony in ASD., (© The Author(s) 2020. Published by Oxford University Press.)

Autism spectrum disorders (ASD) are highly heritable and are characterized by deficits in social communication and restricted and repetitive behaviors. Twin studies on phenotypic subdomains suggest a differing underlying genetic etiology. Studying genetic variation explaining phenotypic variance will help to identify specific underlying pathomechanisms. We investigated the effect of common variation on ASD subdomains in two cohorts including >2500 individuals. Based on the Autism Diagnostic Interview-Revised (ADI-R), we identified and confirmed six subdomains with a SNP-based genetic heritability h 2 SNP  = 0.2-0.4. The subdomains nonverbal communication (NVC), social interaction (SI), and peer interaction (PI) shared genetic risk factors, while the subdomains of repetitive sensory-motor behavior (RB) and restricted interests (RI) were genetically independent of each other. The polygenic risk score (PRS) for ASD as categorical diagnosis explained 2.3-3.3% of the variance of SI, joint attention (JA), and PI, 4.5% for RI, 1.2% of RB, but only 0.7% of NVC. We report eight genome-wide significant hits-partially replicating previous findings-and 292 known and novel candidate genes. The underlying biological mechanisms were related to neuronal transmission and development. At the SNP and gene level, all subdomains showed overlap, with the exception of RB. However, no overlap was observed at the functional level. In summary, the ADI-R algorithm-derived subdomains related to social communication show a shared genetic etiology in contrast to restricted and repetitive behaviors. The ASD-specific PRS overlapped only partially, suggesting an additional role of specific common variation in shaping the phenotypic expression of ASD subdomains.

Reduced social motivation is a hallmark of individuals with autism spectrum disorders (ASDs). Although the exact neural mechanisms are unclear, oxytocin has been shown to enhance motivation and attention to social stimuli, suggesting a potential to augment social reinforcement learning as the central mechanism of behavioral interventions in ASD. We tested how reinforcement learning in social contexts and associated reward prediction error (RPE) signals in the nucleus accumbens (NAcc) were modulated by intranasal oxytocin. Male adults with a childhood diagnosis of ASD (n = 15) and healthy controls (n = 24; aged 18-26 years) performed a probabilistic reinforcement learning task during functional magnetic resonance imaging in a single-center (research center in Germany), randomized double-blind, placebo-controlled cross-over trial. The interventions were intranasal oxytocin (Syntocinon ® , Novartis; 10 puffs = 20 international units (IUs) per treatment) and placebo spray. Using computational modeling of behavioral data, trial-by-trial RPE signals were assessed and related to brain activation in NAcc during reinforcing feedback in social and non-social contexts. The order of oxytocin/placebo was randomized for 60 participants. Twenty-one participants were excluded from analyses, leaving 39 for the final analysis. Behaviorally, individuals with ASD showed enhanced learning under oxytocin when the learning target as well as feedback was social as compared to non-social (social vs. non-social target: 87.09% vs. 71.29%, 95% confidence interval (CI): 7.28-24.33, p = .003; social vs. non-social feedback: 81.00% vs. 71.29%, 95% CI: 2.81-16.61, p = .027). Correspondingly, oxytocin enhanced the correlation of the RPE signal with NAcc activation during social (vs. non-social) feedback in ASD (3.48 vs. -1.12, respectively, 95% CI: 2.98-6.22, p = .000), whereas in controls, this effect was found in the placebo condition (2.90 vs. -1.14, respectively, 95% CI: 1.07-7.01, p = .010). In ASD, a similar pattern emerged when the learning target was social (3.00 vs. -0.64, respectively, 95% CI: -0.13 to 7.41, p = .057), whereas controls showed a reduced correlation for social learning targets under oxytocin (-0.70 vs. 2.72, respectively, 95% CI: -5.86 to 0.98, p = .008). The current data suggest that intranasal oxytocin has the potential to enhance social reinforcement learning in ASD. Future studies are warranted that investigate whether oxytocin can potentiate social learning when combined with behavioral therapies, resulting in greater treatment benefits than traditional behavior-only approaches.

It has been suggested that an early deficit in the human mirror neuron system (MNS) is an important feature of autism. Recent findings related to simple hand and finger movements do not support a general dysfunction of the MNS in autism. Studies investigating facial actions (e.g., emotional expressions) have been more consistent, however, mostly relied on passive observation tasks. We used a new variant of a compatibility task for the assessment of automatic facial mimicry responses that allowed for simultaneous control of attention to facial stimuli. We used facial electromyography in 18 children and adolescents with Autism spectrum disorder (ASD) and 18 typically developing controls (TDCs). We observed a robust compatibility effect in ASD, that is, the execution of a facial expression was facilitated if a congruent facial expression was observed. Time course analysis of RT distributions and comparison to a classic compatibility task (symbolic Simon task) revealed that the facial compatibility effect appeared early and increased with time, suggesting fast and sustained activation of motor codes during observation of facial expressions. We observed a negative correlation of the compatibility effect with age across participants and in ASD, and a positive correlation between self-rated empathy and congruency for smiling faces in TDC but not in ASD. This pattern of results suggests that basic motor mimicry is intact in ASD, but is not associated with complex social cognitive abilities such as emotion understanding and empathy. Autism Res 2017, 10: 298-310. © 2016 International Society for Autism Research, Wiley Periodicals, Inc., (© 2016 International Society for Autism Research, Wiley Periodicals, Inc.)

Background: Group-based psychotherapy in Autism Spectrum Disorder (ASD) has predominantly been studied in the United States by small studies in school-aged children without long-term follow-up. We report results of a large, confirmatory, multicentre randomized-controlled phase-III trial in children and adolescents studying the ASD specific, manualized group-based cognitive behavioural SOSTA-FRA approach., Methods: High-functioning ASD individuals aged 8-19 years old were randomized to 12 sessions SOSTA-FRA or treatment as usual. Primary outcomes were change in total raw score of the parent-rated Social Responsiveness Scale (pSRS) between baseline (T2) and end of intervention (T4), and between T2 and 3 months after end of intervention (T5)., Trial Registration: ISRCTN94863788., Results: Between 20/5/2010 and 14/2/2013, n = 320 ASD patients were screened, n = 228 patients were randomized, and N = 209 analysed. Mean pSRS difference between groups at T4 was -6.5 (95% CI -11.6 to - 1.4; p = .013), and at T5 -6.4 (-11.5 to -1.3, p = .015). Pre-treatment SRS and IQ were positively associated with stronger improvement at T4 and T5., Conclusions: Short-term ASD-specific add-on group-based psychotherapy has shown postintervention efficacy with regard to parent-rated social responsiveness predominantly in male high-functioning children and adolescents with ASD. Future studies should implement blinded standardized observational measures of peer-related social interaction., (© 2015 Association for Child and Adolescent Mental Health.)