# Convergent and divergent genes expression profiles associated with brain-wide functional connectome dysfunction in deficit and non-deficit schizophrenia

## TL;DR

This study explores how brain connectivity and gene expression differ in two schizophrenia subtypes, deficit and non-deficit, revealing shared and unique genetic patterns.

## Contribution

The study identifies convergent and divergent gene expression profiles linked to brain connectivity dysfunction in deficit and non-deficit schizophrenia.

## Key findings

- DS and NDS patients showed distinct brain regions with altered functional connectivity compared to healthy controls.
- 22 overlapping genes were found between DS and NDS, including 12 positive and 10 negative regulation genes.
- Key genes like SCN1B and DPYSL3 showed unique spatio-temporal expression patterns during development.

## Abstract

Deficit schizophrenia (DS) is a subtype of schizophrenia characterized by the primary and persistent negative symptoms. Previous studies have identified differences in brain functions between DS and non-deficit schizophrenia (NDS) patients. However, the genetic regulation features underlying these abnormal changes are still unknown. This study aimed to detect the altered patterns of functional connectivity (FC) in DS and NDS and investigate the gene expression profiles underlying these abnormal FC. The study recruited 82 DS patients, 96 NDS patients, and 124 healthy controls (CN). Voxel-based unbiased brain-wide association study was performed to reveal altered patterns of FC in DS and NDS patients. Machine learning techniques were used to access the utility of altered FC for diseases diagnosis. Weighted gene co-expression network analysis (WGCNA) was employed to explore the associations between altered FC and gene expression of 6 donated brains. Enrichment analysis was conducted to identify the genetic profiles, and the spatio-temporal expression patterns of the key genes were further explored. Comparing to CN, 23 and 20 brain regions with altered FC were identified in DS and NDS patients. The altered FC among these regions showed significant correlations with the SDS scores and exhibited high efficiency in disease classification. WGCNA revealed associations between DS/NDS-related gene expression and altered FC. Additionally, 22 overlapped genes, including 12 positive regulation genes and 10 negative regulation genes, were found between NDS and DS. Enrichment analyses demonstrated relationships between identified genes and significant pathways related to cellular response, neuro regulation, receptor binding, and channel activity. Spatial and temporal gene expression profiles of SCN1B showed the lowest expression at the initiation of embryonic development, while DPYSL3 exhibited rapid increased in the fetal. The present study revealed different altered patterns of FC in DS and NDS patients and highlighted the potential value of FC in disease classification. The associations between gene expression and neuroimaging provided insights into specific and common genetic regulation underlying these brain functional changes in DS and NDS, suggesting a potential genetic-imaging pathogenesis of schizophrenia.