"The longer I live, the more I am convinced that. . .half the unhappiness in the world proceeds from little stoppages, from a duct choked up, from food pressing in the wrong place, from a vexed duodenum or an agitated pylorus."

(Sydney Smith, 1771–1845)

 

Gut Brain Axis: Depression and Anxiety Driven by the GI tract

A major theme in the field of functional gastrointestinal  disorders like functional dyspepsia (FD) is that psychological/psychiatric problems have a pathogenic role, a fact that is based both on the observation that patients with FD are more anxious and depressed than healthy controls, as well as research linking stress and depression to altered gastrointestinal sensory and motor function. This has led to the widespread belief that the physical symptoms of FD reflect either somatization or stress-induced derangement of upper gastrointestinal physiology. This belief has led to many unintended consequences, including the stigmatization of this syndrome as “all in the head”, dismissal of patients’ suffering, and a lack of organized approach to drug development. More importantly, this has stymied serious attempts to come up with a satisfactory unifying hypothesis that can explain the entire spectrum of symptoms from pain to depression/anxiety.

Our approach is based on an alternative hypothesis, which is that the primary manifestations of functional dyspepsia, including both sensory and psychological disturbances, have their origins in the stomach, driving hyper-responsiveness of both vagal and spinal signaling to the brain, leading to changes in CNS structure and function that result in mood disorders as well as perpetuation of the pain state

We recently showed that rats exposed to a transient gastric irritation in the neonatal period display persistent depression-like and anxiety-like behaviors, increased expression of corticotropin-releasing factor (CRF) in the hypothalamus, and an increased sensitivity of hypothalamic-pituitary-adrenal (HPA) axis to stress as adults. The depression-like behavior is mediated by the CRF1 receptor but not by nociceptive afferents.