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

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.

Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management

“…IBS patients show reduced glutamate and glutamine concentrations, although glutamine was disjointed to psychological or gastrointestinal symptoms [ 96 ]. These results are contradictory regarding pain because glutamate concentrations are elevated in fibromyalgia and chronic pelvic pain [ 97 ].…”

“…GABA levels in the prefrontal cortex appear to be increased in IBS patients with highly severe anxiety symptoms, but not in IBS patients without comorbid anxiety disorders. However, these GABAergic alterations are not related to gastrointestinal symptoms, pain or depression [ 96 ].…”

Functional Neuroimaging in Irritable Bowel Syndrome: A Systematic Review Highlights Common Brain Alterations With Functional Movement Disorders

“…Furthermore, a functional lateralization was observed as glutamate concentrations in the left, but not the right hippocampus of IBS patients negatively correlated with anxiety, pain catastrophizing, and pain duration. Icenhour and colleagues 13 found that IBS patients overall did not differ from HC with respect to mPFC GABA+ or Glx levels; only IBS patients with higher anxiety levels showed increased GABA+ in mPFC, together with lower FC between mPFC and ACC.…”

“…Recent studies implementing quantitative magnetic resonance spectroscopy (qMRS) highlighted an aberrant glutamatergic neurotransmission in limbic structures of IBS patients. [11][12][13] Bednarska et al 11 observed that increased concentration of glutamate was also reported in the posterior insula (pINS) of patients with fibromyalgia. 14 Moreover, according to a recent case-control study from our group, 15 a glutamate increase has been detected in the limbic system of patients suffering from functional movement disorders (FMD, also called conversion disorders) when compared to healthy controls (HC).…”

From gut feelings to memories of visceral pain

“…As a crucial psychological modulator, anxiety likely also plays a pivotal role. Anxiety not only demonstrably affects painrelated memory formation and reinstatement in patients with IBS (Icenhour et al, 2015b) but was also recently linked to aberrant neurotransmitter levels and altered functional connectivity in patients with chronic visceral pain, particularly involving the medial prefrontal cortex as a key hub of the extinction network (Icenhour et al, 2019). Together, a complex interplay between psychological traits, including anxiety, cognitive biases, stress, and stress reactivity, and biological factors such as age, sex, stress hormones, and brain morphology may increase the vulnerability for altered pain-related learning and memory processes, which likely contribute to the transition from acute to chronic pain.…”