Downregulation of NOTCH1 and NOTCH4 signalling influences the modulation of schizophrenia onset

Schizophrenia is a chronic neuropsychiatric disorder characterised by a range of positive and negative symptoms. The genetic aspect of schizophrenia is highly pleiotropic, as the complete set of neurodevelopmental factors contributing to the onset of the disease has yet to be fully identified. The Notch signalling pathway is increasingly recognised as a key player in the neurodevelopmental processes, where disruptions in the signalling may be linked to the development of schizophrenia. This study aims to evaluate the expression pattern of NOTCH1 and NOTCH4 at gene and protein levels among schizophrenia cases while considering lifestyle parameters as potential risk factors.

For this study, data were collected from 75 diagnosed schizophrenia patients and 75 healthy controls through a face-to-face interview. Peripheral whole blood was collected from all the cases and control individuals in the hospital set-up after obtaining proper consent. The gene expression study was conducted using quantitative reverse transcription-PCR, and serum level expression was studied using enzyme linked immunosorbent assay. Finally, statistical analysis was performed using Jamovi software.

In the present study, the mean age of schizophrenia cases was found to be 31.5 (±10.4) years. Among the cases, the majority (45.3%, n  = 34) were aged 20-29 years. Results revealed that NOTCH1 and NOTCH4 expression were significantly reduced in schizophrenia cases compared with healthy controls, both in mRNA and serum protein levels. Further, NOTCH4 expression was significantly reduced in those cases with a chronic mental illness, compared with those without chronic past mental illness.

The findings showed downregulation of NOTCH1 and NOTCH4 in schizophrenia. Moreover, significant reduction of NOTCH4 gene expression in cases with persistent mental illness, highlighting its possible role in the pathophysiology of the disease.