Examining the latent structure and correlates of sensory reactivity in autism: a multi-site integrative data analysis by the autism sensory research consortium.

BACKGROUND: Differences in responding to sensory stimuli, including sensory hyperreactivity (HYPER), hyporeactivity (HYPO), and sensory seeking (SEEK) have been observed in autistic individuals across sensory modalities, but few studies have examined the structure of these "supra-modal" traits in the autistic population. METHODS: Leveraging a combined sample of 3868 autistic youth drawn from 12 distinct data sources (ages 3-18 years and representing the full range of cognitive ability), the current study used modern psychometric and meta-analytic techniques to interrogate the latent structure and correlates of caregiver-reported HYPER, HYPO, and SEEK within and across sensory modalities. Bifactor statistical indices were used to both evaluate the strength of a "general response pattern" factor for each supra-modal construct and determine the added value of "modality-specific response pattern" scores (e.g., Visual HYPER). Bayesian random-effects integrative data analysis models were used to examine the clinical and demographic correlates of all interpretable HYPER, HYPO, and SEEK (sub)constructs. RESULTS: All modality-specific HYPER subconstructs could be reliably and validly measured, whereas certain modality-specific HYPO and SEEK subconstructs were psychometrically inadequate when measured using existing items. Bifactor analyses supported the validity of a supra-modal HYPER construct (ωH = .800) but not a supra-modal HYPO construct (ωH = .653), and supra-modal SEEK models suggested a more limited version of the construct that excluded some sensory modalities (ωH = .800; 4/7 modalities). Modality-specific subscales demonstrated significant added value for all response patterns. Meta-analytic correlations varied by construct, although sensory features tended to correlate most with other domains of core autism features and co-occurring psychiatric symptoms (with general HYPER and speech HYPO demonstrating the largest numbers of practically significant correlations). LIMITATIONS: Conclusions may not be generalizable beyond the specific pool of items used in the current study, which was limited to caregiver report of observable behaviors and excluded multisensory items that reflect many "real-world" sensory experiences. CONCLUSION: Of the three sensory response patterns, only HYPER demonstrated sufficient evidence for valid interpretation at the supra-modal level, whereas supra-modal HYPO/SEEK constructs demonstrated substantial psychometric limitations. For clinicians and researchers seeking to characterize sensory reactivity in autism, modality-specific response pattern scores may represent viable alternatives that overcome many of these limitations.

Examining the Latent Structure and Correlates of Sensory Reactivity in Autism: A Multi-site Integrative Data Analysis by the Autism Sensory Research Consortium.

Background Differences in responding to sensory stimuli, including sensory hyperreactivity (HYPER), hyporeactivity (HYPO), and sensory seeking (SEEK) have been observed in autistic individuals across sensory modalities, but few studies have examined the structure of these "supra-modal" traits in the autistic population. Methods Leveraging a combined sample of 3,868 autistic youth drawn from 12 distinct data sources (ages 3-18 years and representing the full range of cognitive ability), the current study used modern psychometric and meta-analytic techniques to interrogate the latent structure and correlates of caregiver-reported HYPER, HYPO, and SEEK within and across sensory modalities. Bifactor statistical indices were used to both evaluate the strength of a "general response pattern" factor for each supra-modal construct and determine the added value of "modality-specific response pattern" scores (e.g., Visual HYPER). Bayesian random-effects integrative data analysis models were used to examine the clinical and demographic correlates of all interpretable HYPER, HYPO and SEEK (sub)constructs. Results All modality-specific HYPER subconstructs could be reliably and validly measured, whereas certain modality-specific HYPO and SEEK subconstructs were psychometrically inadequate when measured using existing items. Bifactor analyses unambiguously supported the validity of a supra-modal HYPER construct (ω H = .800), whereas a coherent supra-modal HYPO construct was not supported (ω H = .611), and supra-modal SEEK models suggested a more limited version of the construct that excluded some sensory modalities (ω H = .799; 4/7 modalities). Within each sensory construct, modality-specific subscales demonstrated substantial added value beyond the supra-modal score. Meta-analytic correlations varied by construct, although sensory features tended to correlate most strongly with other domains of core autism features and co-occurring psychiatric symptoms. Certain subconstructs within the HYPO and SEEK domains were also associated with lower adaptive behavior scores. Limitations: Conclusions may not be generalizable beyond the specific pool of items used in the current study, which was limited to parent-report of observable behaviors and excluded multisensory items that reflect many "real-world" sensory experiences. Conclusion Psychometric issues may limit the degree to which some measures of supra-modal HYPO/SEEK can be interpreted. Depending on the research question at hand, modality-specific response pattern scores may represent a valid alternative method of characterizing sensory reactivity in autism.

Predictability modulates neural response to eye contact in ASD.

BACKGROUND: Deficits in establishing and maintaining eye-contact are early and persistent vulnerabilities of autism spectrum disorder (ASD), and the neural bases of these deficits remain elusive. A promising hypothesis is that social features of autism may reflect difficulties in making predictions about the social world under conditions of uncertainty. However, no research in ASD has examined how predictability impacts the neural processing of eye-contact in naturalistic interpersonal interactions. METHOD: We used eye tracking to facilitate an interactive social simulation wherein onscreen faces would establish eye-contact when the participant looked at them. In Experiment One, receipt of eye-contact was unpredictable; in Experiment Two, receipt of eye-contact was predictable. Neural response to eye-contact was measured via the N170 and P300 event-related potentials (ERPs). Experiment One included 23 ASD and 46 typically developing (TD) adult participants. Experiment Two included 25 ASD and 43 TD adult participants. RESULTS: When receipt of eye-contact was unpredictable, individuals with ASD showed increased N170 and increased, but non-specific, P300 responses. The magnitude of the N170 responses correlated with measures of sensory and anxiety symptomology, such that increased response to eye-contact was associated with increased symptomology. However, when receipt of eye-contact was predictable, individuals with ASD, relative to controls, exhibited slower N170s and no differences in the amplitude of N170 or P300. LIMITATIONS: Our ASD sample was composed of adults with IQ > 70 and included only four autistic women. Thus, further research is needed to evaluate how these results generalize across the spectrum of age, sex, and cognitive ability. Additionally, as analyses were exploratory, some findings failed to survive false-discovery rate adjustment. CONCLUSIONS: Neural response to eye-contact in ASD ranged from attenuated to hypersensitive depending on the predictability of the social context. These findings suggest that the vulnerabilities in eye-contact during social interactions in ASD may arise from differences in anticipation and expectation of eye-contact in addition to the perception of gaze alone.

Disrupted computations of social control in individuals with obsessive-compulsive and misophonia symptoms.

Misophonia is a disorder in which certain sounds produced by other people lead to intense negative reactions. It remains unknown how misophonia relates to other psychiatric conditions or impairments. To identify latent constructs underlying symptoms, we conducted a factor analysis consisting of items from questionnaires assessing symptoms of misophonia and other psychiatric conditions. One thousand forty-two participants completed the questionnaires and a social exchange task in which they either could ("controllable") or could not ("uncontrollable") influence future monetary offers from other people. Misophonia and obsessive-compulsive (OC) symptoms loaded onto the same factor. Compared with individuals with low Miso-OC factor scores, individuals with high scores reported higher perceived controllability of their social interactions during the uncontrollable condition and stronger aversion to social norm violations in the uncontrollable compared with the controllable condition. Together, these results suggest misophonia, and OC symptoms share a latent psychiatric dimension characterized by aberrant computations of social controllability.

Neural Markers of Auditory Response and Habituation in Phelan-McDermid Syndrome.

Phelan-McDermid Syndrome (PMS) is a rare genetic disorder caused by deletion or sequence variation in the SHANK3 gene at terminal chromosome 22 that confers high likelihood of comorbid autism spectrum disorder (ASD). Whereas individuals with idiopathic ASD (iASD) can demonstrate diverse patterns of sensory differences, PMS is mainly characterized by sensory hyporesponsiveness. This study used electrophysiology and a passive auditory habituation paradigm to test for neural markers of hyporesponsiveness. EEG was recorded from 15 individuals with PMS, 15 with iASD, and 16 with neurotypical development (NT) while a series of four consecutive 1,000 Hz tones was repeatedly presented. We found intact N1, P2, and N2 event-related potentials (ERPs) and habituation to simple auditory stimuli, both in individuals with iASD and in those with PMS. Both iASD and PMS groups showed robust responses to the initial tone and decaying responses to each subsequent tone, at levels comparable to the NT control group. However, in PMS greater initial N1 amplitude and habituation were associated with auditory hypersensitivity, and P2 habituation correlated with ASD symptomatology. Additionally, further classification of the PMS cohort into genetic groupings revealed dissociation of initial P2 amplitude and habituation of N1 based on whether the deletions included additional genes beyond solely SHANK3 and those not thought to contribute to phenotype. These results provide preliminary insight into early auditory processing in PMS and suggest that while neural response and habituation is generally preserved in PMS, genotypic and phenotypic characteristics may drive some variability. These initial findings provide early evidence that the robust pattern of behavioral hyporesponsiveness in PMS may be due, at least in audition, to higher order factors.

Reported autism diagnosis is associated with psychotic-like symptoms in the Adolescent Brain Cognitive Development cohort.

Although the schizophrenia (SCZ) rate is increased in autism spectrum disorder (ASD), it is difficult to identify which ASD youth will develop psychosis. We explored the relationship between ASD and emerging psychotic-like experiences (PLS) in a sample of 9127 youth aged 9-11 from the Adolescent Brain Cognitive Development (ABCD) cohort. We predicted that parent-reported ASD would be associated with PLS severity, and that ASD youth with PLS (ASD+/PLS+) would differ from ASD youth without PLS (ASD+/PLS-) and youth with PLS but not ASD (ASD-/PLS+) in cognitive function. We fit regression models that included parent-reported ASD, family history of psychosis, lifetime trauma, executive function, processing speed, working memory, age, sex, race, ethnicity, and income-to-needs ratio as predictors of Prodromal Questionnaire-Brief Child (PQ-BC) distress score, a continuous index of PLS severity. We assessed cognitive differences using regression models with ASD/PLS status and relevant covariates as predictors of NIH Toolbox measures. ASD increased raw PQ-BC distress scores by 2.47 points (95% CI 1.33-3.61), an effect at least as large as Black race (1.27 points, 95% CI 0.75-1.78), family history of psychosis (1.05 points, 95% CI 0.56-1.54), and Latinx ethnicity (0.99 points, 95% CI 0.53-1.45. We did not identify differences in cognition for ASD+/PLS+ youth relative to other groups. Our finding of association between ASD and PLS in youth is consistent with previous literature and adds new information in suggesting that ASD may be a strong risk factor for PLS even compared to established SCZ risk factors.

Strong evidence for genotype-phenotype correlations in Phelan-McDermid syndrome: results from the developmental synaptopathies consortium.

Individuals with Phelan-McDermid syndrome (PMS) present with a wide range of developmental, medical, cognitive and behavioral abnormalities. Previous literature has begun to elucidate genotype-phenotype associations that may contribute to the wide spectrum of features. Here, we report results of genotype-phenotype associations in a cohort of 170 individuals with PMS. Genotypes were defined as Class I deletions (including SHANK3 only or SHANK3 with ARSA and/or ACR and RABL2B), Class II deletions (all other deletions) or sequence variants. Phenotype data were derived prospectively from direct evaluation, caregiver interview and questionnaires, and medical history. Analyses revealed individuals with Class I deletions or sequence variants had fewer delayed developmental milestones and higher cognitive ability compared to those with Class II deletions but had more skill regressions. Individuals with Class II deletions were more likely to have a variety of medical features, including renal abnormalities, spine abnormalities, and ataxic gait. Those with Class I deletions or sequence variants were more likely to have psychiatric diagnoses including bipolar disorder, depression, and schizophrenia. Autism spectrum disorder diagnoses did not differ between groups. This study represents the largest and most rigorous genotype-phenotype analysis in PMS to date and provides important information for considering clinical functioning, trajectories and comorbidities as a function of specific genetic alteration.

Investigating Motor Preparation in Autism Spectrum Disorder With and Without Attention Deficit/Hyperactivity Disorder.

This study investigated motor preparation and action-consequence prediction using the lateralized readiness potential (LRP). Motor impairments are common in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which commonly co-occur. Alterations in predictive processes may impact motor planning. Whether motor planning deficits are characteristic of ASD broadly or magnified in the context of co-morbid ADHD is unclear. ASD children with (ASD + ADHD; n = 12) and without (ASD - ADHD; n = 9) comorbid ADHD and typical controls (n = 29) performed voluntary motor actions that either did or did not result in auditory consequences. ASD - ADHD children demonstrated LRP enhancement when their action produced an effect while ASD + ADHD children had attenuated responses regardless of action-effect pairings. Findings suggest influence of ADHD comorbidity on motor preparation and prediction in ASD.

Social visual attentional engagement and memory in Phelan-McDermid syndrome and autism spectrum disorder: a pilot eye tracking study.

BACKGROUND: The current study used eye tracking to investigate attention and recognition memory in Phelan-McDermid syndrome (PMS), a rare genetic disorder characterized by intellectual disability, motor delays, and a high likelihood of comorbid autism spectrum disorder (ASD). Social deficits represent a core feature of ASD, including decreased propensity to orient to or show preference for social stimuli. METHODS: We used a visual paired-comparison task with both social and non-social images, assessing looking behavior to a novel image versus a previously viewed familiar image to characterize social attention and recognition memory in PMS (n = 22), idiopathic ASD (iASD, n = 38), and typically developing (TD) controls (n = 26). The idiopathic ASD cohort was divided into subgroups with intellectual disabilities (ID; developmental quotient < 70) and without (developmental quotient > 70) and the PMS group into those with and without a co-morbid ASD diagnosis. RESULTS: On measures of attention, the PMS group with a comorbid ASD diagnosis spent less time viewing the social images compared to non-social images; the rate of looking back and forth between images was lowest in the iASD with ID group. Furthermore, while all groups demonstrated intact recognition memory when novel non-social stimuli were initially presented (pre-switch), participants with PMS showed no preference during the post-switch memory presentation. In iASD, the group without ID, but not the group with ID, showed a novelty preference for social stimuli. Across indices, individuals with PMS and ASD performed more similarly to PMS without ASD and less similarly to the iASD group. CONCLUSION: These findings demonstrate further evidence of differences in attention and memory for social stimuli in ASD and provide contrasts between iASD and PMS.

Hippocampal contributions to social and cognitive deficits in autism spectrum disorder.

Autism spectrum disorder (ASD) is characterized by hallmark impairments in social functioning. Nevertheless, nonsocial cognition, including hippocampus-dependent spatial reasoning and episodic memory, is also commonly impaired in ASD. ASD symptoms typically emerge between 12 and 24 months of age, a time window associated with critical developmental events in the hippocampus. Despite this temporal overlap and evidence of hippocampal structural abnormalities in ASD individuals, relatively few human studies have focused on hippocampal function in ASD. Herein, we review the existing evidence for the involvement of the hippocampus in ASD and highlight the hippocampus as a promising area of interest for future research in ASD.

Oculomotor corollary discharge signaling is related to repetitive behavior in children with autism spectrum disorder.

Corollary discharge (CD) signals are "copies" of motor signals sent to sensory regions that allow animals to adjust sensory consequences of self-generated actions. Autism spectrum disorder (ASD) is characterized by sensory and motor deficits, which may be underpinned by altered CD signaling. We evaluated oculomotor CD using the blanking task, which measures the influence of saccades on visual perception, in 30 children with ASD and 35 typically developing (TD) children. Participants were instructed to make a saccade to a visual target. Upon saccade initiation, the presaccadic target disappeared and reappeared to the left or right of the original position. Participants indicated the direction of the jump. With intact CD, participants can make accurate perceptual judgements. Otherwise, participants may use saccade landing site as a proxy of the presaccadic target and use it to inform perception. We used multilevel modeling to examine the influence of saccade landing site on trans-saccadic perceptual judgements. We found that, compared with TD participants, children with ASD were more sensitive to target displacement and less reliant on saccade landing site when spatial uncertainty of the post-saccadic target was high. This pattern was driven by ASD participants with less severe restricted and repetitive behaviors. These results suggest a relationship between altered CD signaling and core ASD symptoms.

Face perception predicts affective theory of mind in autism spectrum disorder but not schizophrenia or typical development.

Autism spectrum disorder (ASD) and schizophrenia spectrum disorder (SCZ) have overlapping symptomatology related to difficulties with social cognition. Yet, few studies have directly compared social cognition in ASD, SCZ, and typical development (TD). The current study examined individual differences in face recognition and its relation to affective theory of mind (ToM) in each diagnostic group. Adults with ASD (n = 31), SCZ (n = 43), and TD (n = 47) between the ages of 18 and 48 years-old with full scale IQ above 80 participated in this study. The Reading the Mind in the Eyes Test (RMET) measured affective ToM, and the Benton Facial Recognition Test (BFRT) measured face perception. Adults with ASD and SCZ did not differ in their affective ToM abilities, and both groups showed affective ToM difficulties compared with TD. However, better face recognition ability uniquely predicted better affective ToM ability in ASD. Results suggest that affective ToM difficulties may relate to face processing in ASD but not SCZ. By clarifying the complex nature of individual differences in affective ToM and face recognition difficulties in these disorders, the present study suggests there may be divergent mechanisms underlying pathways to social dysfunction in ASD compared with SCZ. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Reduced engagement of visual attention in children with autism spectrum disorder.

LAY ABSTRACT: Limited eye contact and difficulty tracking where others are looking are common in people with autism spectrum disorder. It is unclear, however, whether these are specifically social differences; it is possible that they are a result of broader alterations in engaging and disengaging visual attention. We used eye-tracking technology with children with autism spectrum disorder (n = 35) and typical development (n = 32), showing them both social and nonsocial imaging to test their visual attention. Children with autism spectrum disorder had a significant difference in how long it took them to look from an image in the middle to one on the side, depending on whether the middle image stayed on the screen or flashed off before the one on the side appeared. This difference was present for both social and nonsocial images, and was related to cognitive ability for only the children with autism spectrum disorder. Our findings suggest that children with autism spectrum disorder have differences in general processes of engaging visual attention that are not specifically social in nature, and that these processes may relate to cognitive ability in autism spectrum disorder. Affected processes of visual engagement in autism spectrum disorder may contribute to symptoms like reduced eye contact, but social-specific symptoms of autism spectrum disorder likely do not stem from reduced visual engagement alone.

Prospective and detailed behavioral phenotyping in DDX3X syndrome.

BACKGROUND: DDX3X syndrome is a recently identified genetic disorder that accounts for 1-3% of cases of unexplained developmental delay and/or intellectual disability (ID) in females, and is associated with motor and language delays, and autism spectrum disorder (ASD). To date, the published phenotypic characterization of this syndrome has primarily relied on medical record review; in addition, the behavioral dimensions of the syndrome have not been fully explored. METHODS: We carried out multi-day, prospective, detailed phenotyping of DDX3X syndrome in 14 females and 1 male, focusing on behavioral, psychological, and neurological measures. Three participants in this cohort were previously reported with limited phenotype information and were re-evaluated for this study. We compared results against population norms and contrasted phenotypes between individuals harboring either (1) protein-truncating variants or (2) missense variants or in-frame deletions. RESULTS: Eighty percent (80%) of individuals met criteria for ID, 60% for ASD and 53% for attention-deficit/hyperactivity disorder (ADHD). Motor and language delays were common as were sensory processing abnormalities. The cohort included 5 missense, 3 intronic/splice-site, 2 nonsense, 2 frameshift, 2 in-frame deletions, and one initiation codon variant. Genotype-phenotype correlations indicated that, on average, missense variants/in-frame deletions were associated with more severe language, motor, and adaptive deficits in comparison to protein-truncating variants. LIMITATIONS: Sample size is modest, however, DDX3X syndrome is a rare and underdiagnosed disorder. CONCLUSION: This study, representing a first, prospective, detailed characterization of DDX3X syndrome, extends our understanding of the neurobehavioral phenotype. Gold-standard diagnostic approaches demonstrated high rates of ID, ASD, and ADHD. In addition, sensory deficits were observed to be a key part of the syndrome. Even with a modest sample, we observe evidence for genotype-phenotype correlations with missense variants/in-frame deletions generally associated with more severe phenotypes.

Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome.

BACKGROUND: Phelan-McDermid Syndrome (PMS) is a rare condition caused by deletion or mutation of the SHANK3 gene. Individuals with PMS frequently present with intellectual disability, autism spectrum disorder, and other neurodevelopmental challenges. Electroencephalography (EEG) can provide a window into network-level function in PMS. METHODS: Here, we analyze EEG data collected across multiple sites in individuals with PMS (n = 26) and typically developing individuals (n = 15). We quantify oscillatory power, alpha-gamma phase-amplitude coupling strength, and phase bias, a measure of the phase of cross frequency coupling thought to reflect the balance of feedforward (bottom-up) and feedback (top-down) activity. RESULTS: We find individuals with PMS display increased alpha-gamma phase bias (U = 3.841, p < 0.0005), predominantly over posterior electrodes. Most individuals with PMS demonstrate positive overall phase bias while most typically developing individuals demonstrate negative overall phase bias. Among individuals with PMS, strength of alpha-gamma phase-amplitude coupling was associated with Sameness, Ritualistic, and Compulsive behaviors as measured by the Repetitive Behavior Scales-Revised (Beta = 0.545, p = 0.011). CONCLUSIONS: Increased phase bias suggests potential circuit-level mechanisms underlying phenotype in PMS, offering opportunities for back-translation of findings into animal models and targeting in clinical trials.

Sensory Reactivity Symptoms Are a Core Feature of ADNP Syndrome Irrespective of Autism Diagnosis.

Background: Activity dependent neuroprotective protein (ADNP) syndrome is one of the most common single-gene causes of autism spectrum disorder (ASD) and intellectual disability, however, the phenotypes remain poorly described. Here we examine the sensory reactivity phenotype in children and adolescents with ADNP syndrome. Methods: Twenty-two individuals with ADNP syndrome received comprehensive clinical evaluations including standardized observations, caregiver interviews, and questionnaires to assess sensory reactivity symptoms. Relationships between sensory symptoms and age, sex, ASD, IQ, and adaptive behavior were examined. Genotype-phenotype correlations with the recurrent p.Tyr719* variant were also explored. Results: Sensory reactivity symptoms were observed and reported in all participants. A syndrome-specific phenotype was identified, characterized by high levels of sensory seeking across tactile, auditory, and visual domains. Tactile hyporeactivity, characterized by pain insensitivity, was reported in the majority of participants. Sensory symptoms were identified across individuals regardless of age, sex, IQ, adaptive ability, genetic variant, and most importantly, ASD status. No significant differences were identified between participants with and without the recurrent p.Tyr719* variant on any sensory measure. Conclusions: Sensory reactivity symptoms are a common clinical feature of ADNP syndrome. Quantifying sensory reactivity using existing standardized measures will enhance understanding of sensory reactivity in individuals with ADNP syndrome and will aid in clinical care. The sensory domain may also represent a promising target for treatment in clinical trials.

Abnormally Large Baseline P300 Amplitude Is Associated With Conversion to Psychosis in Clinical High Risk Individuals With a History of Autism: A Pilot Study.

Psychosis rates in autism spectrum disorder (ASD) are 5-35% higher than in the general population. The overlap in sensory and attentional processing abnormalities highlights the possibility of related neurobiological substrates. Previous research has shown that several electroencephalography (EEG)-derived event-related potential (ERP) components that are abnormal in schizophrenia, including P300, are also abnormal in individuals at Clinical High Risk (CHR) for psychosis and predict conversion to psychosis. Yet, it is unclear whether P300 is similarly sensitive to psychosis risk in help-seeking CHR individuals with ASD history. In this exploratory study, we leveraged data from the North American Prodrome Longitudinal Study (NAPLS2) to probe for the first time EEG markers of longitudinal psychosis profiles in ASD. Specifically, we investigated the P300 ERP component and its sensitivity to psychosis conversion across CHR groups with (ASD+) and without (ASD-) comorbid ASD. Baseline EEG data were analyzed from 304 CHR patients (14 ASD+; 290 ASD-) from the NAPLS2 cohort who were followed longitudinally over two years. We examined P300 amplitude to infrequent Target (10%; P3b) and Novel distractor (10%; P3a) stimuli from visual and auditory oddball tasks. Whereas P300 amplitude attenuation is typically characteristic of CHR and predictive of conversion to psychosis in non-ASD sample, in our sample, history of ASD moderated this relationship such that, in CHR/ASD+ individuals, enhanced - rather than attenuated - visual P300 (regardless of stimulus type) was associated with psychosis conversion. This pattern was also seen for auditory P3b amplitude to Target stimuli. Though drawn from a small sample of CHR individuals with ASD, these preliminary results point to a paradoxical effect, wherein those with both CHR and ASD history who go on to develop psychosis have a unique pattern of enhanced neural response during attention orienting to both visual and target stimuli. Such a pattern stands out from the usual finding of P300 amplitude reductions predicting psychosis in non-ASD CHR populations and warrants follow up in larger scale, targeted, longitudinal studies of those with ASD at clinical high risk for psychosis.

Visual-Tactile Spatial Multisensory Interaction in Adults With Autism and Schizophrenia.

Background: Individuals with autism spectrum disorder (ASD) and schizophrenia (SZ) exhibit multisensory processing difficulties and social impairments, with growing evidence that the former contributes to the latter. However, this work has largely reported on separate cohorts, introducing method variance as a barrier to drawing broad conclusions across studies. Further, very few studies have addressed touch, resulting in sparse knowledge about how these two clinical groups may integrate somatic information with other senses. Methods: In this study, we compared adults with ASD (n = 29), SZ (n = 24), and typical developmental histories (TD, n = 37) on two tasks requiring visual-tactile spatial multisensory processing. In the first task (crossmodal congruency), participants judged the location of a tactile stimulus in the presence or absence of simultaneous visual input that was either spatially congruent or incongruent, with poorer performance for incongruence an index of spatial multisensory interaction. In the second task, participants reacted to touch in the presence or absence of dynamic visual stimuli that appeared to approach or recede from the body. Within a certain radius around the body, defined as peripersonal space (PPS), an approaching visual or auditory stimulus reliably speeds reaction times (RT) to touch; outside of this radius, in extrapersonal space (EPS), there is no multisensory effect. PPS can be defined both by its size (radius) and slope (sharpness of the PPS-EPS boundary). Clinical measures were administered to explore relations with visual-tactile processing. Results: Neither clinical group differed from controls on the crossmodal congruency task. The ASD group had significantly smaller and more sharply-defined PPSs compared to the other two groups. Small PPS size was related to social symptom severity across groups, but was largely driven by the TD group, without significant effects in either clinical group. Conclusions: These results suggest that: (1) spatially static visual-tactile facilitation is intact in adults with ASD and SZ, (2) spatially dynamic visual-tactile facilitation impacting perception of the body boundary is affected in ASD but not SZ, and (3) body boundary perception is related to social-emotional function, but not in a way that maps on to clinical status.

Autism Spectrum Disorder and Schizophrenia Are Better Differentiated by Positive Symptoms Than Negative Symptoms.

Autism spectrum disorder (ASD) and schizophrenia (SZ) are heterogenous neurodevelopmental disorders that overlap in symptom presentation. The purpose of this study was to specify overlapping symptom domains and to identify symptoms that can reliably differentiate adults with ASD (n = 53), SZ (n = 39), and typical development (TD; n = 40). All participants regardless of diagnosis were administered gold-standard diagnostic assessments of ASD and SZ characteristics including the Autism Diagnostic Observation Schedule (ADOS-2) and the Positive and Negative Syndrome Scale (PANSS). Sensitivity and specificity of the ADOS were assessed using diagnostic cut-off scores. The degree of symptom overlap on these measures between participant groups was analyzed using Analyses of Variance (ANOVAs), Receiver Operating Characteristic (ROC) Curves, and Analyses of Covariance (ANCOVAs) to control for group differences in IQ and sex distributions. The ADOS reliably discriminated ASD and TD adults, but there was a high rate of "false positives" in SZ patients who did not meet the DSM-5 criteria for ASD. To identify the reasons for low specificity in the SZ sample, we categorized ASD and SZ symptoms into 'positive' (presence of atypical behaviors) and 'negative' (absence of typical behaviors) symptoms. ASD and SZ groups overlapped on negative symptoms largely related to the absence of typical social and communicative behaviors, whereas disorder-specific positive symptoms differentiated ASD and SZ. For example, those with ASD scored higher on restricted and repetitive behaviors and stereotyped language, whereas those with SZ scored higher on psychotic symptoms such as delusions and hallucinations. These results suggest that, when making a differential diagnosis between ASD and SZ, clinicians may benefit from focusing on the presence or absence of positive ASD and SZ symptoms. Standardized measures to classify ASD symptoms into positive and negative symptoms have not yet been developed but represent a potentially viable clinical tool.

Brief Report: A Job-Based Social Skills Program (JOBSS) for Adults with Autism Spectrum Disorder: A Pilot Randomized Controlled Trial.

Adults with autism spectrum disorder (ASD) have low employment rates; even those who are employed have low wages and limited hours. This study evaluated the effectiveness of the Job-Based Social Skills (JOBSS) curriculum, a manualized, 15-week, group-delivered intervention for adults with ASD. The intervention aimed to increase social-pragmatic skills necessary to obtain and maintain employment. Twenty-two adults were randomly assigned to either JOBSS intervention or wait-list control groups. Results showed significant improvement in social cognition, as reported by caregivers, among JOBSS group participants compared to wait-list control participants. Forty-five percent of intervention participants gained employment in the six months following participation. This curriculum has potential to improve social skills of adults with ASD, thereby increasing successful employment.