IBS stress reactivity phenotype is associated with blood transcriptome profiles and microstructural and functional...

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Clinical observations reveal significant individual variability in stress reactivity (SR).
• The underlying biological mechanisms and therapeutic relevance of these SR differences remain largely unexplored.
• Understanding these differences is crucial for conditions like irritable bowel syndrome (IBS).

Purpose of the Study:

• To identify the biological underpinnings of heightened SR.
• To investigate the relationship between a psychometric SR phenotype, blood transcriptomics (sympathetic nervous system (SNS) activation), and brain imaging in IBS patients and healthy controls (HCs).

Main Methods:

• A cross-sectional study involving 291 participants (IBS and HCs).
• Utilized transcriptomics profiling, multimodal brain imaging, and psychosocial assessments.
• Employed unsupervised clustering to define high and low SR subgroups for comparative analyses.

Main Results:

• Higher SR group demonstrated elevated cyclic AMP response element-binding protein (CREB) gene expression, indicating tonic SNS activity and inflammation.
• Brain imaging revealed neuroplastic changes in the high SR group, including upregulated arousal systems and altered functional connectivity within the central autonomic network.
• SR influenced sex-based differences in extraintestinal symptoms.

Conclusions:

• Findings support a model where sustained SNS activity contributes to heightened autonomic reactivity, low-grade immune activation, and potentially IBS.
• These biological insights into SR may pave the way for personalized therapeutic strategies in IBS management.