Sex differences in circulating neuregulinl-β1 and β-secretase 1 expression in childhood-onset schizophrenia

Objective: Early-onset schizophrenia is a severe and rare form of schizophrenia that is clinically and neurobiologically continuous with the adult form of schizophrenia. Neuregulin1 (NRG1)-mediated signaling is crucial for early neurodevelopment, which exerts its function by limited beta-secretase 1 (BACE1) proteolysis processing. However, circulating neuregulin1-beta 1 (NRG1-beta 1), an isoform of NRG1, and its cleavage enzyme BACE1 have not been studied in early-onset patients with schizophrenia. Methods: In this study, we collected plasma and clinical information from 71 young patients (7 <= age years <= 20) with schizophrenia and 53 age- and sex-matched healthy controls. Immunoassay was used to test levels of circulating NRG1-beta 1 and BACE1 expression. We further analyzed the relationship of disease-onset age and gender with NRG1-beta 1 and BACE1 levels. Results: We found that circulating plasma levels of NRG1-beta 1 were significantly decreased in young patients with early-onset schizophrenia. In males with childhood onset schizophrenia (COS), NRG1-beta 1 was reduced and was inversely correlated with positive symptom of PANSS; moreover, these male patients with higher plasma BACE1 levels showed more severe general symptoms of PANSS and defective social functioning; whereas, no aforementioned results were found in adolescent-onset schizophrenia (AOS). Notably, young female patients with COS and AOS had no significant change in NRG1-beta 1 and BACE1, which demonstrated a sex-dependent effect in early-onset schizophrenia. Conclusion: Our results suggest that decreased levels of NRG1-beta 1 and its cleavage enzyme BACE1 contribute to increased risk of etiology of schizophrenia. Synthetic biomarkers may have clinical applications for the early diagnosis of male COS. (C) 2020 The Authors. Published by Elsevier Inc.