Peptic Ulcer Disease And Mental Health

Introduction 

Peptic ulcer disease (PUD) is a condition that involves the formation of acid-induced lesions in the stomach or the proximal duodenum (most commonly), ultimately causing discontinuation of the inner gastrointestinal (GI) tract lining.^1,2 Between 5 and 10% of people worldwide are thought to develop this disease at some point in their lives. Numerous studies suggest that there is a link between mental health issues and PUD. Understanding this correlation is important as it provides essential information to both physicians and patients, potentially helping improve the prevention, treatment and management of PUD.

Understanding peptic ulcer disease (PUD)

Key risk factors and causes

PUD involves an imbalance between the factors that protect versus destroy the gastric mucosa. The two most common risk factors and causes for PUD include Helicobacter pylori (H.pylori) infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, this does not mean that everyone infected with H.pylori or using NSAIDs will develop PUD. An enzyme pepsin, mainly activated by gastric acid, is thought to be involved in the pathogenesis of PUD while H.pylori and NSAIDs are known to influence pepsin and gastric acid release.¹

H.pylorus is a bacillus, found in the gastric epithelial cells, usually acquired during childhood, with some of the risk factors for becoming infected with it include unsanitary conditions and crowding. It has multiple virulence factors, enabling it to adhere and induce gastric mucosal inflammation and ulceration.² Ultimately, H.pylori can induce an inflammatory response in the mucosal layer as well as degeneration and injury of the epithelial cells.¹

Ranking right after H.pylori, NSAIDs are the second most common cause of PUD. These medicines are commonly used for pain relief as well as reducing fever and inflammation. NSAIDs act by inhibiting the COX-1 enzyme and subsequently blocking the synthesis of prostaglandin, the secretion of which is protective of the gastric mucosa. The use of NSAIDs can in turn result in reduced production of gastric mucus and bicarbonate as well as decreased mucosal blood flow, all of which can be associated with PUD.² 

Symptoms and treatment

The main PUD symptoms include upper abdominal pain, burning, early satiety or post-prandial fullness. Individuals with duodenal ulcers commonly exhibit worsening abdominal pain upon an empty stomach as well as report hunger/abdominal pain two to three hours following a meal or at night, whereas, individuals with gastric ulcers often exhibit nausea, weight loss, vomiting and post-meal abdominal pain. It is important to note that elderly patients can often have minimal symptoms while intermittent symptoms can be present in some patients with untreated PUD.¹

H2-receptor blockers and proton pump inhibitors (PPIs) are the main antisecretory drug options with PPIs having largely replaced the H2-receptor antagonists due to their better efficacy and superior healing properties. PPIs work by inhibiting acid production in the stomach, which promotes healing and symptom relief. Calcium supplements can be incorporated into treatment with PPIs, given the possible increased bone fracture risk, associated with long-term PPI use.

Stopping the NSAID use or reducing their dose is a treatment option for NSAID-induced PUDs, with prostaglandin analogues, misoprostol, sometimes being used for prophylactic purposes. If possible, the use of anticoagulants, bisphosphonates and corticosteroids should also be stopped. For H.pylori-induced PUDs, a triple regimen consisting of two antibiotics and a PPI is considered to be the first-line treatment. The drugs act synergistically to eradicate the bacteria. If this regimen fails, quadruple therapy, including bismuth and different antibiotics, is then used.²

Relationship between PUD and mental health

There is evidence to suggest that the relationship between PUDs and mental health could be bidirectional, however, further research is required to explore this, given that the effect of mental health on PUD appears to be more widely studied than the vice-versa. 

Mental health impact on PUD

Over the years, studies have linked various psychological factors to PUDs. For instance, higher rates of anxiety and neurotic personality traits have been reported among adult PUD patients while patients with anxiety/mood disorders have also been found to have higher rates of GI issues compared to the general population.³ Below is a brief overview of some of the key findings: 

• Mental health problems, such as depressed mood, severe stress, suicidal ideation and history of psychological counselling were associated with PUD prevalence, after adjustment for lifestyle as well as medical and environmental factors⁴
• Mood/anxiety disorders were linked to increased PUD rates with the following ranking (strongest association first) – generalised anxiety disorder, panic disorder, dysthymia, and bipolar disorder. Importantly, this relationship was substantially attenuated, following adjustment for nicotine and alcohol dependence, which could be further suggested as a significant factor in explaining this link⁵
  • In contrast, other authors reported that adjustment for alcohol or nicotine use attenuated the association between PUD and mood disorders, but not between PUD and anxiety disorders⁶ 
• The incidence of ulcers was significantly higher among subjects with the highest stress scores compared to the lowest, showing a similar effect on H pylori-associated ulcers and ulcers unrelated to H.pylori or NSAID use⁷
• Following H.pylori eradication, PUD recurrence was higher in depressed versus non-depressed older patients, while this also being influenced by other clinical and behavioural factors⁸

These studies are suggestive of a potential link between mental health and PUD, but what about the vice-versa? 

PUD influence on mental health

A 2020 study was the first one to demonstrate the reciprocal association between peptic ulcers and depression. The authors found depression to be associated with increased PUD risk and for PUD to be related to increased depression risk. The interplay between the brain and the gut in the hormonal and immune systems could help explain these results (sections below explore these mechanisms in more detail). The elevated depression risk could also be attributed to the PUD disease burden and the chronic pain associated with it.⁹

Mechanisms underlying this connection 

The brain and the GI system are closely connected via the brain-gut axis. Stressful or depressed conditions might result in neurologic function disturbance and subsequent elevation in pepsin and gastric acid secretion, inducing mucosal injury.⁴

Psychological issues can affect cortisol secretion by influencing the hypothalamic-pituitary-adrenal (HPA) axis. Stress generally increases cortisol levels, which may result in increased gastric acid secretion. The elevated cortisol and gastric acid levels can further hinder the normal inflammatory response, occurring in the GI tract.⁴

As a less direct link, alcohol and/or tobacco use tends to be more common in individuals with mental health issues. With regards to PUD, smoking can lead to a disturbance of the mucosal blood flow while alcohol can promote the release of inflammatory and vasoactive molecules, which further disturb the mucosal barrier.⁴

Alongside the HPA axis, various stressors can also activate the sympathetic-adrenal-medullary axis. The activation of either can lead to significant effects in the GI tract, for instance, influencing acid production, gastric motility and emptying rate, mucosal circulation, immunity and integrity. Acid is the primary aggressive agent, involved in stomach ulcer development, and it has been shown that emotional state modulates its production in the stomach. Studies have also shown that psychological stress can enhance H.pylori infection and colonisation of the stomach.¹⁰

Regarding the PUD link to depression, consistent HPA axis activation in depressed individuals could influence PUD via immune system disturbance. Additionally, the corticotropin-releasing hormone, seen to be elevated in patients with depression, can increase GI permeability. Depression and stress can also lead to the release of substance P, oxytocin, prolactin and opioids, which can further result in gastric hypomotility and gastric mucosal hypoperfusion. At the same time, PUD is also linked to increased expression of substance P and its receptors, this way potentially increasing depression risk, further suggestive of a bidirectional relationship between PUD and depression.^9,11

Finally, dietary habits are key to maintaining a healthy GI system and can be strongly affected by mental health issues. For instance, having an abnormally high-fat diet is linked to oesophageal acid exposure as well as gastro-oesophageal reflux, which can further increase PUD risk. This risk can also be elevated by an unbalanced diet, often associated with depression, as this may influence the gut microbiota.^9,10

Summary

Based on the scientific evidence, the relationship between mental health and PUD is clear, with a variety of underlying mechanisms linking the brain and the gut. Numerous psychological factors appear to play significant predisposing, modulatory and sustaining roles in PUD. However, it is important to continuously distinguish causation versus correlation, and direct versus indirect effects, and keep in mind the variety of factors interplaying in every individual case.

Having said that, the competition between psychology and physiology is not the way forward while cooperation between the professionals in both fields could be incredibly useful in achieving holistic and effective treatment options. 

PUD appears to be an integrated organism response, an interdependent play of behaviour, anticipations, emotions as well as physiological processes, occurring in the brain and gut. Against this background, patients likely require an assessment of a variety of factors, such as: 

• H.pylori infection
• NSAID use
• Social-environmental factors
• Smoking/drinking behaviours
• Experiences of current stress and the ability to cope with it

Therefore, it appears that a biopsychosocial model of treatments would be incredibly useful for PUD patients, given that numerous relevant co-factors need a psychological assessment and behavioural management while other factors, such as the need for H.pylori elimination and management of acid production, call for medical interventions.