Acute Tryptophan Depletion and Functional Brain Imaging in Irritable Bowel Syndrome (Gut 2011;60:1196-1203)

Abstract

Serotonin (5-hydroxytryptamine; 5-HT) is an important signaling molecule in the brain-gut axis, and abnormalities of 5-HT signaling system in the gastrointestinal (GI) tract have been investigated in irritable bowel syndrome (IBS).1 However, there are few studies on of acute tryptophan depletion (ATD)-induced 5-HT modulation at the brain level in IBS. The current study by Labus et al2 is worth examining because it provides novel information on brain network and the augmented activity that may play an important role in pathophysiology of irritable bowel syndrome. This study was aimed at testing 2 hypotheses. The first was that ATD in healthy women increases the engagement of an emotional arousal circuit during rectal distension. The second was that these changes in the brain are consistent with those changes in female patients with constipation predominant IBS (IBS-C). These 2 hypotheses were tested by ATD and functional magnetic resonance image (fMRI) during visceral stimuli. The subjects were 12 healthy women and 14 female patients with IBS-C. ATD was used as a technique for lowering brain 5-HT. Functional MRI was used as a non-invasive tool to measure brain responses to visceral stimuli. Balloon inflation was used for rectal distension with 2 levels of pressure, including non-painful distension pressure and maximum tolerable pressure. Effective connectivity analysis was used as a mean to test hypotheses regarding neural circuits and network functioning. In healthy women, balloon inflation in the rectum showed changes in brain activity, and ATD enhanced these changes in brain activity. Brain regions activated with ATD and balloon inflation were the homeostatic afferent network and the emotional arousal network. The amygdala, a key brain region in the emotional arousal network, and the thalamus showed a transient high activation during ATD, while other regions showed sustained activity. Effective connectivity analyses revealed that ATD made a stronger engagement of the emotional arousal circuitry compared to placebo in healthy women during balloon inflation. In other words, ATD resulted in reduced feedback inhibition of the amygdala during an aversive visceral stimulus in healthy women. A similar pattern of effective connectivity within the emotional arousal network was observed in IBS-C patients during rectal distension even without ATD.