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

Thomas H Mcglashan ,Peter Bachman,Ming T Tsuang ,Tyrone D Cannon,Carrie E Bearden,Scott W Woods ,Barbara A Cornblatt ,Margaret A Niznikiewicz ,Jason Johannesen,Sylvia Guillory ,Elaine F Walker,Ricardo Carrión ,Jennifer H Foss‐Feig ,Daniel H Mathalon,Larry J Seidman,Kristin S Cadenhead,Diana O Perkins ,William S Stone,Brian Roach ,Erica Duncan,Eva Velthorst,Holly Hamilton,Gregory A Light,Jean Addington ,Ayşenil Belger

doi:10.3389/fpsyt.2021.591127

Abstract

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.

Highlights

While autism spectrum disorder (ASD) and the schizophrenia spectrum disorders (SCZ) are considered diagnostically distinct, they share phenotypic features, genetic overlap, and a common historical background [1, 2] that highlight the possibility of related neurobiological substrates
We present exploratory analyses of the utility of EEG markers for predicting conversion to psychosis in a unique, albeit small, sample of individuals with ASD at clinical high risk for psychosis, followed longitudinally for two years
We find that P300 amplitude profiles to visual target and novel and auditory target stimuli in CHR patients differentially predict conversion to psychosis as a function of ASD status

Summary

Introduction

While autism spectrum disorder (ASD) and the schizophrenia spectrum disorders (SCZ) are considered diagnostically distinct, they share phenotypic features, genetic overlap, and a common historical background [1, 2] that highlight the possibility of related neurobiological substrates. ASD diagnosis –characterized by impaired social interaction and communication, alongside repetitive and restricted behaviors and interests [3] occurs in early childhood. SCZ is characterized by impairments in social interactions, but hallmark symptoms of delusions, hallucinations, disorganized thought and behavior, and a constellation of negative symptoms, typically emerge in late adolescence and early adulthood [4]. Prodromal symptoms of SCZ that precede full-blown illness include social deficits [9] that share some overlap with core features of ASD. Cognitive deficits are pervasive in both ASD and SCZ, as well as in prodromal SCZ. Tasks that probe attention, memory, and executive functioning find differences in processing speed, accuracy, and perceptual discrimination/detection thresholds compared to typically developing (TD) control cohorts across disorders [10,11,12]

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