Sex differences in circulating neuregulin1-β1 and β-secretase 1 expression in childhood-onset schizophrenia

Abstract

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 β-secretase 1 (BACE1) proteolysis processing. However, circulating neuregulin1-β1 (NRG1-β1), 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-β1 and BACE1 expression. We further analyzed the relationship of disease-onset age and gender with NRG1-β1 and BACE1 levels. Results: We found that circulating plasma levels of NRG1-β1 were significantly decreased in young patients with early-onset schizophrenia. In males with childhood onset schizophrenia (COS), NRG1-β1 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-β1 and BACE1, which demonstrated a sex-dependent effect in early-onset schizophrenia. Conclusion: Our results suggest that decreased levels of NRG1-β1 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.

Keywords

• Early-onset schizophrenia
• Neuregulin1-β1 (NRG1-β1)
• β-Secretase-1 (BACE1)
• Biomarker
• Sex differences