Reported autism diagnosis strongly predicts psychotic-like experiences in the Adolescent Brain Cognitive Development cohort

Although the schizophrenia rate is increased in autism spectrum disorder (ASD), it is difficult to identify which youth with ASD will go on to develop psychosis. We explored the relationship between ASD and emerging psychotic-like experiences in the Adolescent Brain Cognitive Development (ABCD) cohort of school-aged children. We predicted that ASD would robustly predict psychotic-like experience severity, even relative to other established predictors, and that ASD youth with psychotic-like experiences would have a characteristic neurocognitive profile. In a sample of 9,130 youth aged 9–11, 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) score. We assessed cognitive profiles using analysis of variance on NIH Toolbox measures. ASD increased PQ-BC distress scores by 2.46 points (95% CI 1.32 – 3.60), an effect at least as large as those of family history of psychosis (1.05 points, 95% CI 0.56 – 1.53), Latinx ethnicity (0.99 points, 95% CI 0.52 – 1.45) and black race (0.89 points, 95% CI 0.30 – 1.48). We did not identify a unique cognitive profile for ASD youth with psychotic-like experiences. Our finding that ASD predicts psychotic-like symptoms in youth is consistent with previous literature, and adds new information in suggesting that ASD is a strong predictor of psychotic-like experiences even when compared to other established SCZ risk factors. ### Competing Interest Statement Dr. Veenstra-VanderWeele has consulted or served on an advisory board for Roche Pharmaceuticals, Novartis, and SynapDx; has received research funding from Roche Pharmaceuticals, Novartis, SynapDx, Seaside Therapeutics, and Forest; and has received an editorial stipend from Springer and Wiley. The remaining authors report no biomedical financial interests or potential conflicts of interest. ### Funding Statement This project was financially supported by a Whitaker Scholar in Developmental Neuropsychiatry Award to Dr. Jutla funded by the Marilyn and James Simons Foundation. The ABCD study is supported by the National Institutes of Health and additional federal partners under award numbers U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147. Information about the study’s supporters, participating sites, and study investigators can be found at https://abcdstudy.org. Although ABCD investigators provided data, they did not participate in the analysis or writing of this report. This manuscript therefore reflects the views of the authors and does not necessarily reflect the opinions or views of the NIH or ABCD consortium investigators. ### Author Declarations All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The Adolescent Brain Cognitive Development (ABCD) cohort dataset is available to interested researchers through the NIMH Data Archive. The Adolescent Brain Cognitive Development (ABCD) cohort dataset is available to interested researchers through the NIMH Data Archive.