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

• Published in: Scientific reports Vol. 9; no. 1; p. 13590
• Main Authors: Icenhour, Adriane, Tapper, Sofie, Bednarska, Olga, Witt, Suzanne T., Tisell, Anders, Lundberg, Peter, Elsenbruch, Sigrid, Walter, Susanna
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19-09-2019; Nature Publishing Group
• Subjects: 140/131; 59/36; 59/57; 631/477/2811; 692/1807/4024; Adult; Affective Symptoms - diagnostic imaging; Affective Symptoms - etiology; Affective Symptoms - metabolism; Anxiety; Brain mapping; Case-Control Studies; Cortex (cingulate); Female; Functional magnetic resonance imaging; gamma-Aminobutyric Acid - metabolism; Glutamic Acid - metabolism; Glutamine; Glutamine - metabolism; Humanities and Social Sciences; Humans; Intestine; Irritable bowel syndrome; Irritable Bowel Syndrome - diagnostic imaging; Irritable Bowel Syndrome - metabolism; Irritable Bowel Syndrome - psychology; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Mental depression; multidisciplinary; Neural networks; Neuroimaging; Neurotransmission; Prefrontal cortex; Prefrontal Cortex - diagnostic imaging; Prefrontal Cortex - metabolism; Science; Science (multidisciplinary); Young Adult; γ-Aminobutyric acid
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-50024-3

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.