Profiles of Psychosis Symptoms and Neural Predictors of Conversion Among Individuals at Clinical High Risk for Psychosis, with and without Autism Spectrum Disorder

Background: Individuals with autism spectrum disorders (ASD) have symptoms, including social and sensory deficits, and neurobiological alterations that overlap with schizophrenia. Though high rates of psychosis symptoms occur in ASD, little is known about psychosis prodrome or predictors of psychosis conversion in this population.

Objectives: In this study, we leverage data from clinical high risk (CHR) patients from the NAPLS2 consortium to examine: a) baseline differences in psychosis symptoms and social functioning, b) relative risk of conversion, and c) whether electrophysiological markers of attention orienting yield differential predictors of conversion in CHR individuals with and without ASD (CHR/ASD+; CHR/ASD-).

Methods: Clinical, electrophysiological, and 24-month follow-up data were available for 305 individuals (14 CHR/ASD+; 291 CHR/ASD-). We examined baseline differences on the SOPS, GFS, and TASIT, as well as rate of conversion to psychosis, defined as SOPS>6 at 2-year outcome. Using electrophysiological data recorded at baseline, we examined P300 amplitude to infrequent Target(10%) and Novel distractor(10%) stimuli from visual and auditory oddball tasks, and MMN response for duration(5%), frequency(5%), and duration+frequency(5%) deviants.

Results: In line with our expectations, CHR/ASD+ had worse functioning than CHR/ASD- on the GF-Social scale (t=-4.2, p<.01) and TASIT total score (t=-2.9, p=<.01), but groups did not differ in their psychotic symptoms on the SOPS (Positive: p=.72; Negative: p=.13; Disorganization: p=.13; General: p=.86). Groups did not differ in the rate at which they converted to psychosis (CHR/ASD+: 15.4%; CHR/ASD-: 11.1%; p=.50). EEG data revealed dissociable profiles regarding neural response to sensory stimuli in those who did versus did not convert to psychosis, depending on ASD status. P300 amplitude to Novel visual stimuli was smaller in CHR/ASD− converters(n=71) than CHR/ASD− non-converters(n=220), but larger in CHR/ASD+ converters(n=4) than CHR/ASD+ non-converters(n=10) (Modality×ASD×Converter Interaction, F=3.57;p=.06). For auditory and visual Target stimuli, whereas P300 amplitude was similar for CHR/ASD+ non-converters and all CHR/ASD− individuals, CHR/ASD+ converters had larger P300 amplitudes (ASD×Converter interaction, F=12.12;p=.001). For MMN, there were no significant amplitude differences between groups (Conversion,p=0.31; ASD,p=0.57) or deviant type (p=0.56).

Conclusions: Individuals with ASD and CHR have greater social deficits than the general CHR population, but show similar psychotic symptoms and have similar risk for conversion to psychosis. Neural response during orienting of attention to sensory stimuli is important for understanding risk for conversion, and differs among CHR individuals dependent on whether they have ASD. In particular, whereas all CHR individuals who do not convert share a common pattern of attenuated ERP amplitudes reflecting attention allocation to target and novel auditory and visual stimuli, CHR/ASD+ who convert have a unique pattern of heightened P300 responses to infrequent target stimuli. Deviance detection, however, did not differ as a function of ASD status. These findings have two important implications: 1) individuals with ASD do convert to psychosis and have similar CHR symptom and risk profiles clinically; 2) in CHR individuals with ASD in particular, examining neural markers of attention allocation to sensory stimuli may reveal important predictive clues about risk for conversion.