IBS stress reactivity phenotype is associated with blood transcriptome profiles and microstructural and functional
Jennifer S Labus1, Desiree R Delgadillo1, Steve Cole2
1Oppenheimer Center for Neurobiology of Stress and Resilience, Division of Digestive Diseases at UCLA, CHS 42-210 MC737818, 10833 Le Conte Ave, Los Angeles, CA, 90095-7378, USA.
Neurobiology of Stress
|May 11, 2026
Summary
Individuals with high stress reactivity (SR) exhibit increased cyclic AMP response element-binding protein (CREB) gene expression and brain changes linked to sympathetic nervous system (SNS) activity. This suggests a biological basis for heightened stress responses, impacting conditions like irritable bowel syndrome (IBS).
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Interindividual differences in stress reactivity (SR) are significant but poorly understood.
- Mechanisms and therapeutic implications of varying SR require further investigation.
- Irritable bowel syndrome (IBS) and healthy controls (HCs) exhibit diverse SR profiles.
Purpose of the Study:
- Identify the biological basis of increased SR.
- Investigate associations between psychometric SR, blood transcriptomics, and neuroimaging.
- Examine SR in IBS participants and HCs.
Main Methods:
- Cross-sectional study with 291 IBS participants and HCs.
- Transcriptomics profiling, multimodal neuroimaging, and psychosocial assessments.
- Unsupervised clustering to define High and Low SR subgroups.
Main Results:
- High SR group showed greater cyclic AMP response element-binding protein (CREB) gene expression, indicating tonic sympathetic nervous system (SNS) activity and inflammation.
- High SR group exhibited neuroplastic brain changes in arousal, sensory processing, and autonomic networks.
- SR moderated sex differences in extraintestinal symptoms in IBS patients.
Conclusions:
- Tonically increased, unprovoked SNS activity is a risk factor for heightened stress response and immune activation.
- Findings support a biological model for SR differences, particularly relevant in IBS.
- Results suggest potential for personalized treatment interventions based on SR profiles.
Keywords:
CREB transcriptionDiffusion tensor imagingFunctional brain connectivityIrritable bowel syndromeProinflammatory genesStress reactivityMore Related Videos
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