Elucidating the putative link between prefrontal neurotransmission, functional connectivity, and affective symptoms in irritable bowel syndrome

Altered neural mechanisms are well-acknowledged in irritable bowel syndrome (IBS), a disorder of brain-gut-communication highly comorbid with anxiety and depression. As a key hub in corticolimbic inhibition, medial prefrontal cortex (mPFC) may be involved in disturbed emotion regulation in IBS. However, aberrant mPFC excitatory and inhibitory neurotransmission potentially contributing to psychological symptoms in IBS remains unknown. Using quantitative magnetic resonance spectroscopy (qMRS), we compared mPFC glutamate + glutamine (Glx) and gamma-aminobutyric acid (GABA+) concentrations in 64 women with IBS and 32 age-matched healthy women (HCs) and investigated their association with anxiety and depression in correlational and subgroup analyses. Applying functional magnetic resonance imaging (fMRI), we explored whether altered neurotransmission was paralleled by aberrant mPFC resting-state functional connectivity (FC). IBS patients did not differ from HCs with respect to mPFC GABA+ or Glx levels. Anxiety was positively associated with mPFC GABA+ concentrations in IBS, whereas Glx was unrelated to psychological or gastrointestinal symptoms. Subgroup comparisons of patients with high or low anxiety symptom severity and HCs revealed increased GABA+ in patients with high symptom severity, and lower mPFC FC with adjacent anterior cingulate cortex (ACC), a crucial region of emotion modulation. Our findings provide novel evidence that altered prefrontal inhibitory neurotransmission may be linked to anxiety in IBS. Funding Agencies|Martinos Center for Biomedical Imaging, MGH (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P41-RR14075, R01 RR16594-01A1, R01 NS052585-01]; Child and Adolescent Neuropsychiatric Research Program, Cambridge Health Alliance (NIH) [K08 MH01573, K01 MH01798]; County Council of Ostergotland; AFA research foundation; Bengt-Ihre fund; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)German Research Foundation (DFG) [IC 81/1-1, 316803389 - SFB 1280]; Kurt and Helena Widens Research Fund; Seeing Organ Function project - Knut and Alice Wallenberg Foundation; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P41 015909, R01 016089]