[00:30]
Hello, I’m Dr Stephen Lupe, and welcome to IBDIQ, part of The IBD Project by Takeda, where we’re coming together to help enhance expertise in IBD care—right from the start.
Today, we are going to talk about the bidirectional relationship between inflammatory bowel disease, or IBD, and the mental and behavioral aspects of health. We will present data on the prevalence of anxiety or depression in patients with IBD. We will review the physiological mechanism by which stress affects IBD, and how it is manifested in patients’ symptoms. We will conclude by reviewing some of the tools available for anxiety and depression screening of patients with IBD.
[01:16]
Living with IBD presents ongoing challenges, not just physically but also emotionally and psychologically.
A 2021 meta-analysis of a subset of over 3,000 patients with active and inactive IBD showed that, overall, out of over 2,000 patients with inactive disease, about 38% had anxiety symptoms and about 24% had symptoms of depression.1 The prevalence was highest when patients had active disease, with approximately 58% exhibiting anxiety symptoms and about 39% exhibiting symptoms of depression.
In a prospective, multicenter study, which recruited over 500 patients with IBD from Europe and Israel, almost half experienced symptoms of anxiety and depression, even though they were in clinical remission for the previous 12 months.2
[02:14]
In my clinical experience, symptoms of emotional disorders can be very common in chronic illnesses like IBD. When the life of a patient with IBD gets stressful, it can result in emotional distress that can intensify IBD symptoms.3
Exploring the impact that mental health issues can have on patients with IBD and how they unfold in everyday life requires a comprehensive understanding of the underlying physiological mechanisms.3
Research has begun to define the complicated communication system that connects the brain, gut, and microbiome. The diagram shows how the brain and gastrointestinal - or GI - tract interact with and exacerbate one another, also known as the brain-gut axis.3 When the brain receives stress input, multiple pathways are activated that impact the brain-gut axis, including the hypothalamic-pituitary-adrenal axis, or HPA axis, the autonomic nervous system, or ANS, and enteric nervous system, or ENS.
[03:30]
Stress activates the hypothalamus to release corticotropin-releasing factor, or CRF, which impacts enteric peristalsis and secretion.3 Additionally, CRF can induce mast cell degranulation and increases permeability while also disrupting the mucosal barrier, which plays a key role in the pathophysiology of IBD. In response to stress, effector cells, including mast cells, neutrophils, and lymphocytes, as well as pro-inflammatory cytokines, are placed in a pivotal position to effect changes in the gut.
The ANS is closely connected with the ENS in the gut.3 And these systems work together to regulate secretion, motility, sphincter control, and microcirculation.
The ENS produces large neuropeptides under stress conditions, which influence intestinal immunity and inflammation.3
[04:31]
When stress levels go up the sympathetic ANS is activated, which triggers fight, flight or freeze reactions, and this leads to the eventual increase of central and peripheral inflammatory cytokines.3
When we zoom into the intestine portion of the brain-gut axis, we can see the complex interactions in the microbiota.3 It turns out that the gut microbiome produces neurotransmitters as one of its functions. It may be that patients who have been diagnosed with IBD have a disturbance within the gut microbiome or dysbiosis that is then decreasing neurotransmitter production and potentially affecting mood, memory, and learning.4
[05:21]
Additionally, stress has been shown to promote disturbance in the microbiota by allowing it to cross the gut epithelial barrier, which triggers immune reactions.3
So how does bidirectional stress manifest in patients with IBD?
Unfortunately, or fortunately, we are human, and in my opinion, we are designed with a very specific learning process—a mind that is good at predicting the future. That’s what keeps us alive. We are the grandchildren of the grandchildren of the grandchildren of people who had anxiety, and managed to survive because they thought to cover the cave entrance in case a lion might stride by.
[06:03]
In my opinion, learning how to live with IBD is like avoiding heartburn. Imagine a person eating pasta with tomato sauce. After eating they develop heartburn. Next time they go out to eat, they will avoid foods with tomato sauce.
In my experience, individuals struggling with IBD symptoms, particularly those with frequent urgency, will react to them even before they happen, much like avoiding tomato sauce to prevent heartburn. Patients often express sentiments such as, ‘I don't go out anymore because I may have to use the bathroom’ and in my experience these patients know the location of bathrooms between them and where they want to go.
[06:51]
Patient experiences with their disease can lead to reports of IBD-related trauma, and this trauma can sometimes correlate to having a negative impact on quality of life.5 So, we need to discuss the psychological factors that might relate to disease activity.
A study with a prospective observational cohort design that included patients with IBD reported that baseline depression was associated with a higher risk of relapse at 22- and 24-months follow-up for Crohn’s disease (or CD) and ulcerative colitis (or UC), respectively.6 A different study that used a longitudinal prospective cohort design and included patients with IBD, showed that baseline depression and anxiety symptoms were associated with a shorter time to relapse for these patients.7
[07:47]
Another systematic review that included 171 studies looked at the prevalence of depression and anxiety in adult patients with IBD, irrespective of treatment.8 This review examined 5 studies assessing depressive disorder using clinical diagnosis and 4 studies assessing generalized anxiety disorder using clinical diagnosis. The prevalence of depression and anxiety was estimated at 15.2% and 20.7% respectively, which, according to their analysis, was considerably higher than what has been estimated in the general population worldwide.
This highlights the incredibly complicated relationship among psychological events, GI functioning, and the nervous system that we are just beginning to understand.4
[08:38]
There have been additional studies that delve deeper into the link between stress in patients with IBD and pain. Let’s look at a systematic review that included 15 studies that reported on pain in adult patients with IBD, and measured at least 1 psychosocial factor.9 They found that emotional factors such as depression, anxiety, and stress were associated with IBD-related pain. Additionally, visceral pain may be attributed to the abnormal interaction in the gut-brain axis that causes visceral hypersensitivity through both peripheral and central systems.3
This highlights the link between IBD-associated stress and the onset and aggravation of pain, which, in turn, can induce stress.3
[09:31]
The bidirectional effect between stress and IBD may lead patients to fall into a vicious cycle, possibly contributing to a poor prognosis.3
Let’s dive deeper and discuss some of the stressors that show up in the lives of people diagnosed with IBD. We will explore 4 areas, including psychological and physical factors, financial and work-related factors, surgery-related anxiety, and overall anxiety about the future.10-16
[10:03]
Let’s start with psychological factors such as depression and anxiety symptoms. These are common comorbidities in patients with IBD, and better understanding the mechanisms that link depression and anxiety with IBD is important.10 The limited research available on this topic suggests that there is a bidirectional relationship between IBD and depression and anxiety, which could indicate that these psychological factors may keep the disease activity in constant flux—although this remains unconfirmed.
[10:40]
When it comes to physical factors affecting patients with IBD, sleep impairment or lack of sleep are other potential stressors.11 On the one hand, IBD symptoms do tend to affect sleep, and on the other, a lack of sleep or poor sleep, then may influence IBD symptoms and disease activity. Overall, sleep is important in the management of IBD, because lack of sleep will have a detrimental effect in the physical and psychological well-being of the patient.12 And for patients with IBD, if they are not sleeping because of symptoms, it may increase the risk of relapse.11
[11:24]
Fatigue, which can be a consequence of sleep impairment, is an IBD symptom that is highly prevalent and one of the most burdensome, especially because it is multifactorial.12 Fatigue can also be caused by malnutrition or lack of iron or vitamin B12.13
Let’s now examine financial stressors affecting patients with IBD. Financial burden and financial distress for patients with IBD can include direct costs such as healthcare spending and insurance costs, and indirect costs such as productivity and wage loss, which can lead to poor health-related quality of life.14 Some of the worries patients may have can manifest in their minds, including: How can I show up for work? How can I afford the medicine and diet I need?
[12:21]
How do I continue going to work if I have to go to the bathroom all the time? And this leads us to work-related stress in patients with IBD. I've heard stories from my patients that they start to get anxious when they have to go to work every day because they worry about their bowel functions. As their anxiety builds, they get to a point where they physically can't work anymore. As they retreat to the safety of their home, anxiety may decrease.
As you can tell from our discussion thus far, behavioral and psychological factors and IBD symptoms have a bidirectional impact, where they can negatively affect each other.3 This can feed into what is called avoidance.15
[13:08]
Surgery is another source of stress. This can be scary for patients.15 I’m a big fan of bringing the surgeon in early and introducing them to the patient, so they are not as scary and can be seen as just a member of the treatment team should they be needed. It's very helpful. Because for some patients, surgery may become a reality if their disease progresses to that point.16 And being familiar with the team can help them navigate through fearful moments.
Beyond surgery, patients with IBD may also have anxiety about the future and what might come next – including anxiety about when that next flare might come.
Anxiety about the future and/or anxiety rooted in some of the other issues we've discussed today could, for some patients, limit their willingness to go to the hospital.
[14:05]
All these issues must be addressed. So, what can providers do to help patients with IBD who may have psychological issues?
First off, screen for symptoms of anxiety and depression using existing validated tools. I will quickly review some of them next.17
Before we begin, it is important to remember the tools we'll discuss are not meant to be used to formally diagnose depression or anxiety but are rather a starting point to assist in their diagnosis.
[14:40]
Let’s start with Hospital Anxiety and Depression Scale, or HADS-A and HADS-D, a self-reported questionnaire that assesses anxiety and depression levels over the past week.17 It’s often used in patients with IBD in the outpatient setting. However, HADS measures have the lowest sensitivity at detecting anxiety and depression compared with other tools.
Patient-Reported Outcomes Measurement Information System, or PROMIS, which includes PROMIS Anxiety and PROMIS Depression, is an 8-item self-report questionnaire, and can give you an overall picture of how people are doing, mentally and psychologically.17
[15:27]
Hamilton Rating Scale, or HAM-A and HAM-D, are the oldest tools for assessing anxiety and depression; clinicians administer them to evaluate the effectiveness of medication or psychotherapy.17
Generalized Anxiety Disorder, or GAD-7, looks at anxiety symptoms over the last 2 weeks, although this tool may not be able to capture disorders other than generalized anxiety.17
For Depression, the Patient Health Questionnaire, or PHQ-9 may be used, or the shorter PHQ-2 version.17 The shorter version does not include a suicidal ideation item, however. They are self-administered tools to assess for depression.
[16:16]
Finally, we have the World Health Organization Well-Being index, or WBI-5, which is a short questionnaire consisting of five simple questions and has shown to be sufficiently effective at screening depression.17
These screening tools are important, so don’t be scared to ask the patient questions and talk about these mental health conditions; they can affect care and outcome. I understand it’s scary: ‘What's going to happen if I open that can of worms? I’m talking to a patient about their depressive symptoms. Heaven forbid, what do I do if I find there’s suicidal ideation?’18 As a provider, it's important that we ask these questions because in my opinion there is a difference between a patient describing the pain that they are feeling and giving the impression that they might harm themselves.
[17:14]
If your patients do express the intent to harm themselves—or if you or someone else you know is experiencing a mental health crisis—please reach out for help. Call 911, if someone is in immediate danger. Call or text 988 to get connected 24/7 to free and confidential support from the National Suicide Prevention Lifeline.
Let’s recap the topics that were discussed in this chapter. Physiologically, stress results in the activation of multiple pathways, including the HPA axis, the ANS, the ENS, and the microbiome, which may play a role in the pathophysiology of a number of GI disorders, including IBD.3
[18:04]
At the same time, there is a potential bidirectional relationship between stress and psychological factors and IBD symptoms, where they can negatively affect each other.3 Psychological factors such as depression and anxiety symptoms are comorbidities that can be seen in patients with IBD, and having a better understanding of this is important.10
As a provider, you can help patients with IBD by screening for psychological issues.17 And, in my experience as a provider, being engaged with your patients with IBD is another way you can provide support.
[18:49]
Thank you for your interest and for spending some time with IBDIQ today to help adapt to the evolving care needs of all patients with IBD.
