Potential associations between altered brain function, cognitive deficits and gene expressing profiles in bipolar disorder across three clinical stages.

Objective: We aimed to determine the relationship between altered brain imaging characteristics, cognitive function and profiles of gene expression of bipolar disorder (BD).

Methods: Functional magnetic resonance imaging (fMRI) was presented in three groups of BD participants (depressed, manic and euthymic) and healthy controls. Regional Homogeneity (ReHo) and region of interest based functional analysis combining with neuroimaging-transcription association analysis were utilized to investigate abnormalities and their correlation with clinical symptoms.

Results: Our data showed that all three groups of BD patients exhibited significantly altered ReHo values whilst the bilateral precuneus/posterior cingulate cortex (PCC) and lateral occipital cortex exhibited significant increase in BD. Functional connectivity (FC) revealed distinct characteristics of the precuneus/PCC-based default mode network. ReHo values in the Precuneus/middle cingulate cortex displayed significantly negative correlations with cognition and YMRS scores. Gene enrichment analysis also revealed that ReHo values were spatially correlated with pathways including chromatin organization and innate immune response.

Conclusions: Altered ReHo values in specific brain regions may be associated with different clinical stages and increased FC in brain may potentially function as BD imaging biomarkers. The heterogeneity of gene expression was associated with altered brain imaging properties in BD, contributing to distinguishing different stages of BD from healthy individuals.