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Differential diagnosis of young children with suspected autism spectrum disorder (ASD) is challenging, and clinician uncertainty about a child's diagnosis may contribute to misdiagnosis and subsequent delays in access to early treatment. The current study was designed to replicate and expand a recent report in this Journal (McDonnell et al. in J Autism Dev Disord 49:1391-1401, https://doi.org/10.1080/15374416.2020.1823850 , 2019), in which only 60% of diagnoses were made with complete certainty by clinicians evaluating 478 toddlers and preschool children referred for possible ASD to specialized clinics. In this study, secondary analyses were performed on diagnostic, demographic and clinical data for 496 16-30-month-old children who were consecutive referrals to a 6-site clinical trial executed by specialized centers with experienced clinicians following best-practice procedures for the diagnosis of ASD. Overall, 70.2% of diagnoses were made with complete certainty. The most important factor associated with clinician uncertainty was mid-level autism-related symptomatology. Mid-level verbal age equivalents were also associated with clinician uncertainty, but measures of symptomatology were stronger predictors. None of the socio-demographic variables, including sex of the child, was significantly associated with clinician certainty. Close to one third of early diagnoses of ASD are made with a degree of uncertainty. The delineation of specific ranges on the ADOS-2 most likely to result in clinician uncertainty identified in this study may provide an opportunity to reduce random subjectivity in diagnostic decision-making via calibration of young-child diagnostic thresholds based on later-age longitudinal diagnostic outcome data, and via standardization of decision-making in regard to clinical scenarios frequently encountered by clinicians.

Understanding the biological mechanisms underlying human neuropsychiatric disorders, such as autism spectrum disorder (ASD), has been hindered by the lack of a robust, translational animal model. Rhesus monkeys (Macaca mulatta) display many of the same social behaviors that are affected in ASD, making them an excellent animal species in which to model social impairments. However, the social impairments associated with ASD may reflect extreme ends of a continuous distribution of traits. Thus, to validate the rhesus monkey as an animal model for studying social impairments that has strong translational relevance for ASD, researchers need an easily-implemented measurement tool that can quantify variation in social behavior dimensionally. The Social Responsiveness Scale (SRS) is a 65-item survey that identifies both typical and atypical social behaviors in humans that covary with ASD symptom severity. A chimpanzee SRS has already been validated and the current study adapted this tool for use in the rhesus monkey (mSRS). Fifteen raters completed the mSRS for 105 rhesus monkeys living at the Yerkes National Primate Research Center. The mSRS scores showed a unimodal distribution with a positive skew that identified 6 statistical outliers. Inter-rater reliability was very strong, but only 17 of the 36 questions showed positive intra-item reliability. The results of an exploratory factor analysis identified 3 factors that explained over 60% of the variance, with 12 items significantly loading onto the primary factor. These items reflected behaviors associated with social avoidance, social anxiety or inflexibility and social confidence. These initial findings are encouraging and suggest that variability in the social responsiveness of rhesus monkeys can be quantified using the mSRS: a tool that has strong translational relevance for human disorders. With further modification, the mSRS may provide an promising new direction for research on the biological mechanisms underlying social impairments.

As infants develop, caregivers adjust their behaviour to scaffold their infant's emerging skills, such that changes in infants' social abilities are expected to elicit changes in caregiver behaviour. We examined whether changes in the probability of infant-directed caregiving behaviour—specifically, greeting, a ubiquitous signal used by caregivers to initiate reciprocal interactions—differ between infant–caregiver dyads with an infant later diagnosed with autism and dyads with a neurotypically developing infant during infants' first 6 months. Using longitudinal data from 163 dyads, we found that caregivers in autism dyads (n = 40) used greeting less and at later infant ages than caregivers with a neurotypically developing infant (neurotypical dyads, n = 83). Caregivers in dyads with infants at elevated familial genetic likelihood for autism who did not receive an autism diagnosis (EL-non-autism dyads, n = 40) showed no differences in greeting compared with neurotypical dyads. Socioeconomic status partially mediated the difference between autism and neurotypical dyads. These findings show that autism and socioeconomic status were associated with the mutually adapted dynamics of dyadic interaction beginning in the first postnatal weeks. Importantly, differences in caregiver greeting observed in autism dyads are not interpreted as suboptimal behaviour from caregivers but rather indicate how early emerging social differences related to autism, years before overt features are present, may alter social learning opportunities elicited by the infant. [ABSTRACT FROM AUTHOR]

Exposure to stress is a risk factor for perturbed mental health, including impoverished regulation of emotional and physiological responses that accompany anxiety and mood disorders, substance abuse and behavioral disorders. Such disruptions to well‐being could be triggered by discrete environmental events or pervasive early life stress (ELS) resulting for example from adverse caregiving. Recent data mostly collected from rodents exposed to anthropogenic stressors suggest that one way via which the detrimental effects of such stress extend beyond the exposed population to future offspring is via stress‐induced alterations of RNA found in the paternal germline. In contrast, less attention has been paid to how naturally occurring stress in males might influence offspring biology and behavior. In this study, we used a translational nonhuman primate model of ELS caused by naturally occurring adverse caregiving of infant macaques to (1) profile total RNA in the adolescent male germline, and (2) identify how those RNA profiles are affected by exposure to ELS. Our findings that the top 100 transcripts identified correspond to transcripts related to germline biology and reproduction demonstrate the validity and feasibility of profiling RNA in the germline of rhesus macaques. While our small sample sizes precluded definitive assessment of stress‐induced alterations of RNA in the male germline of rhesus macaques that experienced ELS, our study sets the foundation for future investigations of how early adversity might alter the male germline, across species and in experimental protocols that involve anthropogenic vs natural stressors. Research Highlights: The top 100 genes in the male germline for which RNA sequences aligned to the sense strand were relevant to male germline‐related biology and reproduction.Sequences aligned to the antisense strand that may play an important role in regulation of gene expression in the zygote after fertilization were also found. [ABSTRACT FROM AUTHOR]