Arginine-vasopressin systems in autistic phenotype schizophrenia: effect of a genetic variant of AVPR1a and AVPR1b

Much attention has been devoted to exploring the similarities between schizophrenia and autism spectrum disorder (ASD). Autistic traits in schizophrenia have recently been assessed using the Positive and Negative Syndrome Scale for Schizophrenia Autism Severity Scale (PAUSS). Although studies on arginine-vasopressin (AVP) systems have focused on the etiology of ASD, there are no reports regarding AVP systems and autistic traits in schizophrenia. This study aimed to assess autistic traits in schizophrenia using the PAUSS and examine their associations with the PAUSS and AVP-related biological measures. This is a cross-sectional study. We recruited patients with schizophrenia (n = 80) and healthy controls (HCs; n = 27). Patients with schizophrenia were classified as having either an autistic phenotype schizophrenia (AU) or a non-autistic phenotype (NAU). All patients with schizophrenia underwent clinical assessments focusing on symptom severity, autistic traits, neurocognition, and social cognition. HCs were examined for neurocognition and social cognition. We also evaluated AVP-related biomarkers, including serum AVP levels, single-nucleotide polymorphisms, and promoter-region microsatellites. The AU group showed worse symptom severity and social cognition than the NAU group. The T allele of rs28632197 in the AVP receptor (AVPR)1b was associated with more severe autistic traits in patients with schizophrenia, while the short allele of RS1 in AVPR1a was associated with less severe autistic traits. Our results suggest that autistic traits in schizophrenia are linked to more severe symptoms and poorer social cognition and that AVP system dysfunction may contribute to their etiology. Clinicians should carefully evaluate autistic traits.