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Background: Autism spectrum disorder (ASD) and schizotypal disorder (SD) both have a heterogenous presentation, with significant overlaps in symptoms and behaviour. Due to elevated recognition and knowledge of ASD worldwide, there is a growing rate of referrals from primary health professionals to specialised units. At all levels of assessment, the differential diagnostic considerations between ASD and SD exert major challenges for clinicians. Although several validated screening questionnaires exist for ASD and SD, none have differential diagnostic properties. Accordingly, in this study, we aim to develop a new screening questionnaire, the schiZotypy Autism Questionnaire (ZAQ), which provides a combined screening for both conditions, while also indicating the relative likelihood of each. Methods: We aim to test 200 autistic patients and 100 schizotypy patients recruited from specialised psychiatric clinics and 200 controls from the general population (Phase 1). The results from ZAQ will be compared to the clinical diagnoses from interdisciplinary teams at specialised psychiatric clinics. After this initial testing phase, the ZAQ will be validated in an independent sample (Phase 2). Conclusions: The aim of the study is to investigate the discriminative properties (ASD vs. SD), diagnostic accuracy, and validity of the schiZotypy Autism Questionnaire (ZAQ). Funding: Funding was provided by Psychiatric Centre Glostrup, Copenhagen Denmark, Sofiefonden (Grant number: FID4107425), Trygfonden (Grant number:153588), Takeda Pharma. Trial registration: Clinical Trials, NCT05213286, Registered 28 January 2022, clinicaltrials.gov/ct2/show/NCT05213286?cond = RAADS&draw = 2&rank = 1. [ABSTRACT FROM AUTHOR]