Abstract
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 γ-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.
Highlights
The relevance of bidirectional communication pathways between the brain and the gastrointestinal system, the brain-gut-axis, is increasingly acknowledged in health and in the pathophysiology of various somatic and neuropsychiatric disturbances[1]
Patients presented with moderate to severe irritable bowel syndrome (IBS) and were characterized by greater symptom-specific anxiety, higher pain intensity, and more interference compared to healthy controls (HCs)
Based on correlational findings suggesting distinct associations between medial prefrontal cortex (mPFC) GABA+ concentrations and anxiety in patients, GABA+ was solely considered for further analyses and we focused on anxiety symptoms in subsequent subgroup analyses with patient subgroups based on Hospital Anxiety and Depression Scale (HADS) anxiety scores, as described below
Summary
The relevance of bidirectional communication pathways between the brain and the gastrointestinal system, the brain-gut-axis, is increasingly acknowledged in health and in the pathophysiology of various somatic and neuropsychiatric disturbances[1]. Cardinal symptoms of the heterogeneous disease are gastrointestinal in nature, yet psychiatric comorbidities with anxiety and depression affect a large proportion of IBS patients[2,3], with profound clinical implications[4,5,6] While this key role of psychological symptoms in altered brain-gut communication is increasingly appreciated, distinct neural correlates of anxiety and depression symptoms in IBS are only beginning to be elucidated. A dysregulation of prefrontal inhibitory control, possibly due to an abundance of GABA inhibiting regulatory circuits, may be involved in aberrant emotion regulation and increased psychological complaints[25], which remains to be elucidated in patients with IBS In this combined qMRS and resting-state fMRI study, we aimed to investigate mPFC Glx and GABA+ concentrations and their relation to psychological as well as gastrointestinal symptoms in female patients with IBS and age-matched healthy women. We hypothesized disrupted connectivity within these circuits in patients with a high severity of anxiety/depression
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