Polygenic effects on brain functional endophenotype for deficit and non-deficit schizophrenia

Area of Science:

• Neuroscience
• Psychiatry
• Genetics

Background:

• Deficit schizophrenia (DS) is a subtype of schizophrenia (SCZ).
• The polygenic effects on neuroimaging alterations in DS remain largely unknown.
• Understanding genetic contributions to brain function in DS is crucial for elucidating its pathogenesis.

Purpose of the Study:

• To calculate polygenic risk scores for schizophrenia (PRS-SCZ) in DS patients.
• To explore associations between PRS-SCZ and functional brain features in DS.
• To investigate differential polygenic effects on neuroimaging in DS versus non-deficit schizophrenia (NDS).

Main Methods:

• Calculated PRS-SCZ using Whole Exome sequencing and GWAS data.
• Acquired resting-state fMRI, biochemical, and neurocognitive data from DS, NDS, and healthy controls (HC).
• Analyzed amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and functional connectivity (FC); performed correlation analyses.

Main Results:

• PRS-SCZ was significantly lower in DS compared to NDS and HC.
• DS exhibited increased ALFF in left inferior temporal and frontal gyri, decreased ALFF in right precuneus, and decreased ReHo in the right middle frontal gyrus compared to NDS.
• Widespread functional connectivity changes were observed in DS, particularly within the default mode network, and correlated with PRS-SCZ.

Conclusions:

• Demonstrated differential polygenic effects on brain functional changes in DS.
• Identified specific neuroimaging-genetic associations relevant to DS.
• Provided a potential neuroimaging-genetic perspective for understanding schizophrenia pathogenesis.