Transcriptomic Signatures Associated With Gray Matter Volume Changes in Patients With Functional Constipation.

Wangli Cai,Lidi Wan,Guangyu Tang,Yujing Zhou,Ruiling Zhang,Ting Hua,Bo Yang,Jian Gong

doi:10.3389/fnins.2021.791831

Abstract

Functional constipation, which belongs to the functional gastrointestinal disorder (FGID), is a common disease and significantly impacts daily life. FGID patients have been progressively proven with functional and structural alterations in various brain regions, but whether and how functional constipation affects the brain gray matter volume (GMV) remains unclear; besides, which genes are associated with the GMV changes in functional constipation is largely unknown. On account of the structural MRI image from the 30 functional constipation patients and 30 healthy controls (HCs), GMV analysis showed that functional constipation patients had significantly decreased GMV in the right orbital prefrontal cortex (OFC), left precentral gyrus (PreG), and bilateral thalamus (THA). Correlation analysis showed that the self-rating depressive scale, patient assessment of constipation quality of life (PAC-QOL), and Wexner constipation scores were negatively correlated with GMV of the OFC and negative correlations between PAC-QOL score and GMV of the bilateral THA. Based on the Allen Human Brain Atlas, a cross-sample spatial correlation was conducted and found that 18 genes’ expression values showed robust correlations with GMV changes in functional constipation patients. These outcomes highlight our recognition of the transcriptional features related to GMV changes in functional constipation and could be regarded as candidates to detect biological mechanisms of abnormality in functional constipation patients.

Highlights

Functional constipation, as one type of the functional gastrointestinal disorder (FGID), is portrayed by rare bowel movements, painful defecation, uncomfortable feeling of incomplete evacuation, hard/big stools, and frequently joined with abdominal distension and/or abdominal pain (Alame and Bahna, 2012)
After extracting gene expression data from each sample (820/1,782 samples) and calculating gray matter volume (GMV) changes (t-statistic values) in these samples derived from the two-sample t-test based on the high-resolution structural MRI image of functional constipation patients and healthy controls (HCs), we performed a gene-wise crosssample Spearman correlation analysis to decide the relationships between GMV changes and gene expression values independently (n = 10,185)
After analyzing voxel-wise GMV alterations (P < 0.05, FDR corrected) between the patients with functional constipation and HC, compared to HC groups, we found that functional constipation patients primarily demonstrated decreased GMV in the right orbital prefrontal cortex (OFC, peak MNI coordinates: x = 15, y = 37.5, z = −22.5; cluster size = 230 voxels), left precentral gyrus (PreG, peak MNI coordinates: x = −42, y = 24, z = 52.5; cluster size = 230 voxels), and bilateral thalamus (THA, peak MNI coordinates: x = 4.5, y = −19.5, z = −1.5; cluster size = 338 voxels) (Figure 2)

Summary

INTRODUCTION

Functional constipation, as one type of the functional gastrointestinal disorder (FGID), is portrayed by rare bowel movements, painful defecation, uncomfortable feeling of incomplete evacuation, hard/big stools, and frequently joined with abdominal distension and/or abdominal pain (Alame and Bahna, 2012). Neuroimaging methods have been progressively applied to investigate brain structural and functional anomalies of FGID patients (Blankstein et al, 2010; Zhu et al, 2016; Jin et al, 2019; Hu et al, 2020; Duan et al, 2021; Liu et al, 2021) They found the functional abnormalities in brain regions enrolled in emotion modulating, including the orbitofrontal cortex (OFC), anterior insula, dorsal anterior cingulate cortex, and hippocampus, and motor control, including the precentral gyrus and supplementary motor area.

MATERIALS AND METHODS

RESULTS

DISCUSSION

CONCLUSION

Findings

LIMITATIONS