|Year : 2018 | Volume
| Issue : 2 | Page : 70-81
A review of functional gastrointestinal disorders: A primer for mental health professionals
Suhas Chandran1, SN Prakrithi2, Supriya Mathur3, M Kishor4, T S. Sathyanarayana Rao5
1 Senior Resident, Department of Psychiatry, St. John's Medical College, St. John's National Academy of Health Sciences, Bengaluru, Karnataka, India
2 Intern Resident, Department of Psychiatry, JSS Medical College and Hospital, JSS Academy of Higher Education and Research, Mysore, Karnataka, India
3 Junior Resident, Department of Psychiatry, JSS Medical College and Hospital, JSS Academy of Higher Education and Research, Mysore, Karnataka, India
4 Associate Professor, Department of Psychiatry, JSS Medical College and Hospital, JSS Academy of Higher Education and Research, Mysore, Karnataka, India
5 Professor, Department of Psychiatry, JSS Medical College and Hospital, JSS Academy of Higher Education and Research, Mysore, Karnataka, India
|Date of Web Publication||31-Dec-2018|
Dr. Suhas Chandran
Department of Psychiatry, St. John's Medical College, St. John's National Academy of Health Sciences, Sarjapur Road, Bengaluru - 560 034, Karnataka
Source of Support: None, Conflict of Interest: None
Functional gastrointestinal disorders (FGIDs) are chronic, recurrent, frequently debilitating disorders with no identifiable underlying pathology. They occur due to a complex interplay between biological, psychological, and social factors and are some of the most common conditions encountered in general clinical practice as well as the specialist gastroenterological clinic. The top-down regulation of visceral sensations plays an important role in the pathophysiology of the disease, i.e., the central processing of emotions and stressors altering the sensory and motor components of the gut, which increases hypersensitivity and therefore symptom severity. In addition, the core personality traits of the individual play their part in the way symptoms are perceived, further providing proof for the long-prevailing belief that the gut and emotions are linked, the so-called “gut feeling.” The current diagnostic criteria for FGIDs are entirely based on subjective symptoms, challenging in itself due to the varied presentations, and further complicated by the current unavailability of objective laboratory tests which could confirm its presence in the symptomatic individual. The various treatment modalities include psychotherapies ranging from cognitive behavioral therapy to mindfulness, along with appropriate pharmacotherapy to treat physical and psychiatric comorbidities. Addressing all these underlying causes, in addition to weighing in the genetic makeup of the individual, is necessary for delineating accurate prognosis, reducing attending health-care costs, and improving overall outcome of the individual.
Keywords: Biopsychosocial model, functional gastrointestinal disorders, psychiatric comorbidities, psychological treatments
|How to cite this article:|
Chandran S, Prakrithi S N, Mathur S, Kishor M, Rao T S. A review of functional gastrointestinal disorders: A primer for mental health professionals. Arch Ment Health 2018;19:70-81
|How to cite this URL:|
Chandran S, Prakrithi S N, Mathur S, Kishor M, Rao T S. A review of functional gastrointestinal disorders: A primer for mental health professionals. Arch Ment Health [serial online] 2018 [cited 2019 Sep 18];19:70-81. Available from: http://www.amhonline.org/text.asp?2018/19/2/70/248882
| Introduction|| |
Functional gastrointestinal disorder (FGID) is a term used to describe gastrointestinal (GI) abnormalities and symptoms which are chronic and recurrent and do not have an identifiable underlying pathology. FGIDs are some of the most commonly encountered diagnoses in clinical practice with no biomarkers or gold standard tests available currently for reliable diagnosis. FGIDs do not adhere to an elementary pathophysiological model but instead involve a complex interplay between biological, psychological, and social factors. Biological factors comprise abnormalities in GI motility, mucosal and immune function, gut microbiota, and central nervous system (CNS) processing along with visceral hypersensitivity, which occur in various combinations in different individuals. Psychosocial factors such as anxiety, depression, early life traumatic experiences, and other social learning experiences can either act alone or in synchrony with physiological factors leading to the presentations of FGIDs, influencing the patient's quality of life, physical, and social outcomes.
| Historical Aspects|| |
There have been substantial historical accounts exploring the link between emotional states and changes in GI functions. In 1833, William Beaumont, the father of gastric physiology, stated that “In a healthy state of the stomach, and an equable frame of mind, bile has seldom been found in the stomach. When so found, except under peculiar circumstances of diet, it may generally be regarded as an indication of either mental or corporeal disease, and may be seen as a foreign and offending substance in that organ.” This quote is probably the first reference in the literature toward the idea that a disturbance in gastric function can be the result of central (emotional) mechanisms. Beaumont was one of the earliest investigators to demonstrate a relationship between the psychological factors and the gut functions. He observed a patient called Alexis St. Martin who had developed a traumatic gastric fistula from a gunshot injury and reported that there was a change in the mucosal morphology as well as secretions with change in emotions.
According to the James–Lange theory, response to an external stimulus leads to a physiological response (autonomic arousal) and the interpretation of this response generates emotions. This was the first theoretical account for an influence of bodily, especially visceral, signals on psychological states such as emotions. Cannon and Bard provided an alternative theory that emotions are generated in subcortical brain regions, especially the hypothalamus. Bodily changes invoked by changes in these regions are seen as the by-product rather than constitutive of emotions. This constituted the first attempt to identify the brain mechanisms of psychosomatic interactions. Wolff and Engel also studied gastric fistulas and reported that there was a change in secretion with change in emotional states.,
Drossman noted that the biomedical model, where what could be considered “organic” and conditions for which a pathological etiology could not be found or understood were designated as “functional” problems and that this distinction still existed in current medical practice. The patients with recurrent or chronic GI symptoms for which an underlying pathology cannot be delineated are considered as having functional GI disorders.
Recently, Engel's biopsychosocial model for disease has been used for the description of functional GI disorders, and they are being considered as disorders of gut–brain interaction and are currently not diagnoses of exclusion.
| Classificatory Systems|| |
Although FGIDs have not been designated a separate diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, the individual symptoms such as recurrent abdominal pain, nausea, and others are placed under somatic symptom disorders.
According to the International Classification of Diseases, 10th Revision (ICD-10), FGIDs are placed under F45-somatoform disorder with a code of F45.32-somatoform autonomic dysfunction of the GI system. According to the ICD-10 Clinical Modification, the code K.58.8 is assigned to “other specified functional intestinal disorders,” K.59.9 for “functional intestinal disorder, unspecified,” and K.92.9 for “functional disorder of GI tract.”
The most widely accepted and utilized classification of FGIDs remains the classification from the ROME foundation. It was in the late 1980s that the ROME Foundation came to the forefront, when there was very limited acumen into the pathophysiology of FGIDs, no established classificatory system, and no established management guidelines. Since then, the foundation has played a decisive role in operationalizing the research and streamlining the knowledge encompassing these disorders.
According to ROME-IV, FGIDs are a class of disorders classified by GI symptoms related to any of the following: motility disturbance, visceral hypersensitivity, altered mucosal and immune function, altered CNS processing, and altered gut microbiota. There are 33 adult and 20 pediatric FGIDs listed under ROME IV [Table 1]. FGIDs have symptom-based criteria for diagnosis with the exception of anorectal disorders which include physiological changes as part of the diagnostic criteria.
|Table 1: ROME-IV classifications of functional gastrointestinal disorders (Drossman, 2016)|
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| Epidemiology|| |
Epidemiological studies reveal that more than one-third of the general population are affected by FGIDs. There is considerable overlap among these disorders, and many patients can suffer from two or more FGIDs at the same time. They can also coexist with other organic disorders. Around 35%–41% of patients presenting to the gastroenterology clinic suffered from FGIDs. Kang et al. noted that 50.4% of patients in an Asian gastroenterological clinic had FGID. Irritable bowel syndrome (IBS) is often the most common FGID reported, followed by functional diarrhea and functional constipation (FC). Functional dyspepsia (FD) and IBS account for nearly 40%–60% of referrals to gastroenterology outpatient clinics. A school-based study conducted in Mediterranean Europe found that FC was the most common FGID in both children and adolescents, followed by IBS in children and abdominal migraine in adolescents.
A literature review of studies examining the prevalence of IBS in individual countries revealed that the prevalence was around 9.6% in Asia, 7.1% in North America/Europe/Australia/New Zealand, and 5.8% in Africa and the Middle East. Most studies show a female predominance. Chang et al. noted that most FGIDs are more prevalent in women than men, especially IBS, constipation, chronic functional abdominal pain (FAP), and pelvic floor dysfunction being significantly higher. Women are two to three times more likely to be diagnosed with IBS and four to five times more likely to seek consultation for it than men, whereas, in India, men more frequently seek consultation for their IBS symptoms. Esophageal disorders, dyspepsia, IBS, functional diarrhea, and chronic FAP decrease with age, whereas dysphagia and fecal incontinence increase with age.
It is important that we keep in mind the extensive cross-cultural variations seen in the reporting of FGIDs when we compare different regions. Diet differences, cultural taboos in discussing topics such as defecation, sexual abuse, and mental illness, language and religious diversities, socioeconomic status, education levels, translation and interpretation of terminologies, and expression of symptoms play an important role in the regional variations noted in the epidemiological studies.
| Pathophysiology|| |
Dr. Tom Almy's experiments set the stage for investigation of the effects of stress on bowel function. In one instance, a medical student undergoing sigmoidoscopy was told that he had cancer, which led to increased contractility of the sigmoid colon. He noted that both healthy individuals and patients with IBS showed motility disturbance with emotional stressors. An increase in tone and wave like contractions of the sigmoid colon were observed with hostility or aggression, and a decrease in tone and contractions were associated with feelings of hopelessness and defeat, underlining the connection between emotion and gut reactivity. Halder et al. conducted a study in the prevalence of FGID over a 12-year period which revealed that point prevalence of FGID was stable over time, but there were transitions between different types of FGIDs in the same individual, which pointed toward a common etiopathogenesis for all FGIDs. A 12-year longitudinal study conducted by Koloski et al. reported that higher levels of anxiety at baseline were an important predictor of developing FGID in the future, whereas FGID at baseline, in turn, was predictive of developing anxiety and depression later in life, thus indicating a bidirectional interaction between the gut and CNS in the pathophysiology of FGID. The symptomatology of FGID is thus a product of aberration in various factors – genetic, social, psychological, physiological, dietary, and environmental, and the disease arises as a result of an interplay among these factors, which can be explained by the biopsychosocial model. The components involved in the biopsychosocial model for FGIDs include the following.
| Biological Factors|| |
Genetic interactions have been postulated to influence visceral hypersensitivity, barrier function (physiological permeability), mast cell function, and colonic transit. TT genotype of GNB3 (G protein subunit polymorphisms), ADBR2 (beta-2 adrenergic receptor) polymorphism, SERT-P (serotonin reuptake transporter gene promoter) deletion in SLC64A gene (solute carrier family 6 member 4, which is involved in serotonin transport) have been found to cause decreased serotonin uptake, which is found to be more common in patients with IBS-diarrhea (IBS-D). Cholecystokinin-A receptor polymorphism, on the other hand, is said to protect against FD.,
Abnormal motility in the GI tract plays an important role in the genesis of symptoms in FGIDs and has been positively correlated with emotional and environmental stressors.
Patients with FGIDs have been found to be more sensitive to otherwise nonnoxious stimuli. Enteral hormones have been found to increase sensitivity in FD. Chronic inflammation sensitizes transient receptor potential cation channel subfamily-V member-1 and increases pain sensitivity due to substance P.
Pain perception in FGID is increased due to the action of sensitizing agents, which decrease the amount of depolarization required to initiate action potential in sensory neurons. These inflammatory mediators include prostaglandin E2, serotonin, bradykinin, epinephrine, adenosine, protease, and nerve growth factor. An increased immunoreactivity of vanilloid receptor-1 in colonic nerve fibers and an increase in acid-sensing ion channel-3 contribute to increased pain transmission.
Central sensitization involves an increase in the excitability of nociceptive neurons in the central pain pathways, triggered by activity, inflammation, and neural injury. Consequently, subthreshold synaptic inputs generate augmented amplified outputs in the central pain pathways. The amygdala, prefrontal cortex (PFC), periaqueductal gray matter, locus ceruleus, rostroventral medulla, and spinoreticular system are involved in the modulation of central pain-processing pathways and are also responsible for the autonomic and endocrine stress responses by modulating activity of the hypothalamic–pituitary–adrenal (HPA) axis.
The gut–brain–microbiome axis
The gut–brain axis (GBA) consists of the brain, enteric nervous system (ENS), vagal branches, and spinal nerves which include the somatic and autonomic connections of the entire gut. The link between the CNS and ENS is formed by the gut microbiota, which brings about neural, immune, humoral, and endocrine changes. The vagus is found to be the major communication link between the brain and the microbiota, as demonstrated by Bravo et al. The GBA can influence the gut microbiota through the autonomic nervous system. The sympathetic and parasympathetic pathways both modulate gut functions, i.e., motility, secretion, and mucosal immune system. Increased motility will decrease GI transit time, thus decreasing the amount of nutrients microbes receive, resulting in decreased microbial growth, and decreased motility will increase the transit time, thereby increasing the bacterial growth. The parasympathetic activity increases the mucosal secretion, which is the most important component of the biofilm, which helps the resident flora survive. Another study showed that stress significantly affected bacterial population in the gut and that microbiota was, in turn, necessary for the stressor-induced increases in the circulating cytokines. In addition, various neurotransmitters are produced by different bacterial species; GABA by Lactobacillus and Bifidobacterium, norepinephrine by Escherichia More Details, Bacillus, and Saccharomyces, serotonin by Streptococcus, Escherichia and Enterococcus, dopamine by Bacillus and Serratia, and acetylcholine by Lactobacillus. These neurotransmitters can potentially cause changes in the motility and visceral sensitivity when the mucosal barrier is breached. In addition to this, neurons also have pattern recognition receptors and can get activated by microbial products, which, in turn, can affect motility and secretion. A study reported that colonic dorsal root ganglia (DRG) neurons contained various Toll-like receptors and other receptors involved in pathogen-associated molecular pattern signaling. These receptors altered the intrinsic excitability of nociceptive DRG neurons, thereby potentially modulating pain signaling and producing hyperalgesia.
Postinfectious irritable bowel syndrome
Escherichia coli, Salmonella More Details, and Campylobacter are strongly associated with postinfectious IBS. Studies also show that children exposed to Salmonella in childhood had higher prevalence of postinfectious IBS in adulthood. IBS patients have been found to have increased Firmicutes, decreased Bacteroides, and bifidobacteria.
The SERT has been found to have a low expression on epithelial cells of the bowels in IBS-D and IBS-constipation, resulting in consistent decrease in the uptake of intestinal mucosa in both, with more serotonin ending up in the circulation.
Altered mucosal and immune function
There is increased membrane permeability in the gut mucosa in IBS patients and increased innate immune activity in the mucosa along with increased mast cells and monocytes. This can result in more antigens entering the submucosa, further activating the intestinal immune system.
HPA axis disturbances contribute to the pathophysiology of FGIDs. It has been found that CRH induced significantly higher adrenocorticotropic hormone release in IBS patients than normal controls and also caused prolonged motility disturbances and abdominal symptoms in these patients.
The type of food consumed influences and alters the gut microbiota, and the microbes, in turn, act on food molecules to ferment them, the products of which may influence disease process. Diet low in FODMAPs (fermentable oligo-, di-, monosaccharides, and polyols) and gluten have been found to improve symptoms in FGID. FODMAPs constitute food substances that are poorly absorbed, osmotically active, and rapidly fermented by gut bacteria, which result in luminal distension, causing symptoms such as bloating, pain, and nausea. A low FODMAPs diet has been known to improve functional gut symptoms. Another study reported that specific foods such as milk or wheat provoked symptoms in 66% of IBS patients, indicating that diet management can be used as a treatment strategy.
The role of antibiotics
Antibiotics have been known to exacerbate the symptoms of FGID, possibly by altering the normal balance of organisms in the gut microbiome and the attending changes which follow. The evidence, however, still remains inconclusive.
| Psychological and Social Factors|| |
Stress and abuse in early life and psychiatric comorbidities have a significant association with FGID, and in turn, FGID itself has psychosocial consequences as it affects daily life and functioning of the patient. The degree of psychosocial distress depends on coping ability of the patient, which will determine the degree of increased sensitivity to symptoms.
Mayer et al. noted that early life stress and trauma (abuse, neglect, and loss of primary caregiver) and severe life-threatening stress in adulthood (rape, trauma) cause irreversible increase in responsiveness of central stress circuits involved in autonomic, neuroendocrine, and pain modulatory functions. This, in turn, causes alterations in perception of visceral sensations and abnormal GI motility modulation, which predisposes these individuals to develop functional bowel disorders. Transient stressors bring about abnormal responsiveness in central circuits and may lead to symptom exacerbation. This central circuitry is called the emotional motor system, and it integrates visceral sensations and movements with emotions caused by the perception of these stressors through cortical inputs.
Gwee et al. noted that patients who subsequently developed IBS symptoms at the time of their initial illness had higher scores for anxiety, depression, somatization, and neurotic traits than those who returned to normal bowel function. A study investigating the presence of psychiatric disorders in patients with FGIDs reported that 85% of patients were diagnosed with at least one psychiatric disorder, with the most common ones being dysthymia and OCD; it also showed no difference in the prevalence of psychiatric disorders in patients with FGIDs and patients with IBS specifically. IBS was frequently found to be associated with psychiatric illnesses such as anxiety neurosis, depression, and hysteria, and two-third of these patients reported that onset of psychiatric symptoms occurred before symptoms of irritable colon. A study which examined the relationship between posttraumatic stress disorder (PTSD) and IBS reported that a significantly high number of IBS patients had psychiatric diagnoses at some point in their life; 44% of IBS patients had a history of trauma and 36% were diagnosed with PTSD. Decreased activity of perigenual cingulate or medial PFC hippocampal activity has been observed in IBS. Similar changes have been discovered in depression and PTSD., This could possibly explain the frequent co-occurrence of these disorders and the higher incidence of these psychiatric comorbidities in patients of IBS. Somatization and comorbid depression are associated with significantly higher symptom severity and weight loss, due to alteration of GI sensory and motor processes. Anxiety disorders, the most common psychiatric comorbidity found in FGID patients (30%–50%), increase the FGID symptoms due to autonomic arousal, which, in turn, interferes with visceral sensitivity.
Abuse history plays a significant role in FGID symptomatology. The prevalence of history of sexual abuse was more in FGID patients (40%) than in patients with organic disease (10%). Prevalence was also found to be four times more in lower FGID than upper FGID, with the most common complaints being constipation and diarrhea. Patients with FGID had poorer health status and higher frequency of severe abuse than patients with structural GI disease. FGID was associated with significantly greater pain severity, psychological distress, and poorer daily function than structural GID (SGID), independent of abuse history. Irrespective of whether it was FGID or SGID, abuse history significantly contributed to greater pain severity, more psychological distress, and poor daily function. Certain types of abuse such as rape, repeated or multiple abuse, and life-threatening abuse have more symptom severity and adverse health outcomes than other forms of abuse. The study also provided evidence that different types of stressors contributed independently to poor health outcomes. One study found that IBS patients were more anxious and depressed and that these individuals also somatized and dissociated more, when compared to physically diseased patients. Predictably, severe abuse (penetration experiences – attempted or actual intercourse or objects in the vagina) resulted in higher somatization and medical symptoms compared to less severe abuse. It is hypothesized that trauma could downregulate sensation thresholds, thereby increasing visceral sensitivity. Levy et al. stated that concurrent psychiatric disorder, psychological distress, hypervigilance to normal body sensations, catastrophizing, and feeling of helplessness may be responsible for the poorer health outcomes noted in patients with abuse history. The maladaptive coping mechanisms such as catastrophizing could lead to increased illness behaviors and higher psychological distress, thus resulting in increased symptom experiences in patients with FGIDs.
Biggs et al. noted that childhood adversity (abuse and lack of social support) was associated directly with poorer outcome in patients with FGIDs. Childhood trauma influences adult levels of somatization significantly. It has been shown that adverse experiences with caregivers in childhood lead to the development of anxious attachment behavior and that these individuals use physical complaints to elicit care, which could explain the increased incidence of FGIDs in these individuals. Abuse history was found to correlate with development of insecure attachment styles in adulthood and also adult depression. Medically unexplained symptoms were found to be considerably associated with insecure (dismissive, preoccupied, and fearful) adult attachment styles. In addition to physical and sexual abuse and trauma, even neglect and emotional abuse were found to correlate with increased somatization in adulthood. Early life noxious stimuli cause neonates to anticipate pain and exhibit intense pain responses during future exposures, due to the high neural plasticity which can alter CNS development. It also leads to visceral hyperalgesia mediated through impaired descending inhibitory control, altered stress response, and neuronal sensitization.
Personality traits such as anger, reactivity, neuroticism, emotional hypersensitivity, aggression, and negativism have been found to be associated with increased number of GI symptoms. In one study, 37% of FGID patients were found to meet the criteria for Type D personality, which is associated with negative affectivity and social inhibition. These patients also reported considerably higher symptom severity, which was related to negative emotions and aberrant social functions.
Spiller et al. reported that women had a three-fold higher risk of developing postinfectious IBS but also suggested that it may be due to female predominance to psychological distress, as another study showed that female sex was not a significant risk factor, whereas hypochondriasis and adverse life events were independent risk factors. Chang and Heitkemper noted that hormonal factors have a significant influence on visceral sensation and GI motility, as estrogen and progesterone affect the peripheral and CNSs, which can, in turn, increase or decrease visceral sensory perception. Taylor et al. hypothesized that higher female preponderance for FGIDs could be explained, in part by the female response to stress – “tend and befriend,” in contrast to the male response of “fight or flight.” The tend-befriend response is associated with downregulation of sympathetic nervous system and also of the HPA axis, which is similar to the physiological changes observed in patients with FGIDs. Gender roles, defined as generalizations about appropriate male and female traits associated with masculinity and femininity, also have a considerable contribution to how symptoms are perceived.
Abnormal cognitive processes such as attention bias, illness anxiety, symptom hypervigilance, and catastrophizing have been found to have a significant association with FGID. Low perceived personal responsibility over illness and pessimistic attitude toward pain were significantly implicated in the level of health-care utilization in patients with functional bowel diseases.
Social factors and social learning
Children learn behaviors from parents with FGID, and this learning has even stronger risk contribution than genetics for developing FGID. Modeling and positive reinforcement are implicated in worsening of symptoms and increased health-care visits in children. It has been found that in these conditions, social support alleviates pain and other symptoms by reducing stress levels in the individuals.
| Clinical Features|| |
The clinical features of FGID occur as a result of the sum total of all the etiopathological entities, i.e., dysmotility, visceral hypersensitivity, altered CNS regulation, mucosal permeability, and immune dysregulation. The symptom cluster varies with each FGID, depending on the structural localization, with possible overlapping of site-specific symptoms of multiple FGIDs which may occur at the same time. The general symptoms include pain abdomen, bloating, nausea, vomiting, diarrhea, and constipation, along with symptoms specifically related to the structures affected. According to ROME-IV, patients may have mild, moderate, or severe symptoms, accounting for approximately 40%, 30–35%, and 20%–25% of the patients, respectively. Patients with minimal pain, no comorbid physical symptoms, usually no dominant psychiatric diagnoses, and a good quality of life are termed as having mild symptoms, Patients with moderate symptoms, on the other hand, have intermittent disruptions in activity, with multiple physical or psychological comorbidities. Patients with severe symptoms have refractory symptoms with psychological comorbidities such as anxiety, depression, somatization, with impaired daily functioning, and catastrophizing behavior and may have a history of major loss or abuse.
Red flag symptoms which can be used to distinguish the organic/structural diseases from FGIDs include: sudden weight loss, history of GI surgery, history of organic GI disease, blood in stool, anemia, pain abdomen during the night which awakens the patient, fever, and arthralgia. In addition, “any inflammatory, anatomic, metabolic, or neoplastic process which explains the patients symptoms” need to be excluded to make a diagnosis of FGID.
FGIDs are the product of interaction between various genetic, psychological, medical, and social components, all of which can affect the disease process. Unless the clinician identifies and addresses all the aspects, the patient will not have a satisfactory recovery and will result in poorer outcomes.
| Treatment|| |
In the last few decades, gastroenterology and psychology have become increasingly juxtaposed, with a considerable arsenal of research to validate the effectiveness of psychological interventions for a range of FGIDs. Psychological management includes the following approaches.
Cognitive behavioral therapy
Cognitive behavioral therapy ( CBT) is based on the principle that maladaptive thoughts are the basis of psychological symptoms, especially anxiety and depression, which can, in turn, exacerbate physical symptoms including GI symptoms. The focal point of the cognitive-behavioral model for treating FGIDs outlines the following components: (1) psychoeducation about the trigger potential of stress responses and its relation to GI symptoms; (2) developing insight into cognitive and behavioral responses to functional symptoms and the associated fear responses; and (3) modulating these responses to reduce the physical reactivity to stress and to decrease their overall levels of distress. To achieve these objectives, therapeutic work is directed at increasing awareness of the interlink between stressors, thoughts, and symptoms; evaluating and correcting irrational beliefs; disputing automatic negative thoughts; observing and problem-solving factors that exacerbate symptoms; and then subsequently identifying and adopting alternative, more efficient coping strategies to meet stressful life situations and deal with GI symptoms. Patients with IBS have been shown to often have distortions about their symptoms; CBT may be especially useful for these patients because it may help patients recognize how distorted beliefs about symptoms may govern pain and pain-related activities. Relaxation techniques are often integrated into CBT modules because of its efficacy in reducing autonomic arousal and anxiety in IBS.
CBT has been studied more extensively than any other mode of psychological intervention for FGIDs. Most of these studies have examined adults with IBS. Studies have compared outcomes for CBT treatment with control groups receiving symptomatic medical care or antispasmodic medication or antidepressants and placebo or active psychological modalities, namely supportive therapy, education, or stress management.,, This substantial body of empirical studies shows that CBT is an effective therapy for improving FGIDs, especially IBS. The GI symptoms were consistently found to be significantly reduced after treatment among the positive trials, sometimes substantially more than in comparison groups.
Improvement has been uniformly maintained at 3-month follow-ups in most studies, and most of them have not included follow-up longer than 3 months posttreatment; there is evidence that therapeutic benefit of CBT for IBS can last for 8 months to 2 years after treatment termination. Along with the improvement in GI symptoms, quality of life and emotional well-being are also often documented to improve significantly from CBT. Drossman et al. found that CBT was significantly more effective than education and desipramine was more effective than placebo for treatment of moderate-to-severe FGIDs. A notable recent development in the field of CBT for FGIDs is testing of self-administered CBT, with nominal involvement of clinicians. The Internet, printed manuals, or personal digital assistants serve as the primary mode of therapy delivery, and this addresses an important limitation of lack of CBT therapists in many geographic locations.
The largest randomized controlled trial (RCT) conducted on psychological treatment for FGID is a multicenter National Institute of Health-funded study with estimated enrollment of 480 IBS subjects, which is currently evaluating the potential of self-administered CBT further. Even though such cost-effective therapy is not yet generally available, the consistently positive findings suggest that an affordable and easily accessible form of effective CBT might be on the horizon for IBS and perhaps other FGIDs.
Exposure and response prevention
Exposure treatments aim to reduce excessive avoidance of unpleasant visceral sensations or situations by helping patients confront them in a systematic manner with a reduction of a fear and catastrophic beliefs about these functional symptoms and the resultant hypervigilance. Exposure includes interoceptive cue exposure in which the patient repeatedly provokes unpleasant sensations or in vivo exposure in which feared situations or activities are confronted. The principle behind exposure interventions is that the most potent way to overcome a fear is by facing it directly so that the natural conditioning processes involved in fear reduction such as habituation and extinction can occur. Through exposure treatments, patients learn that the stimuli that are a source of fear and avoidance are not dangerous or intolerable and it is possible for the fear to subside without resorting to avoidance, a behavior that is counterproductive and reinforces hypervigilance in the long run.
Biofeedback is a form of behavioral training that uses continuous visual or auditory feedback from recordings of specific physiological activity to enable patients to learn to voluntarily control those body functions. Biofeedback has been tested in randomized studies almost exclusively as a therapy for FC (16 RCTs) and fecal incontinence (9 RCTs). Comparison conditions have varied, including medical management, sham or nonanorectal biofeedback, balloon defecation training, polyethylene glycol, behavioral modification, diazepam, placebo, Botox, and surgery.
Mindfulness-based therapy (MBT) is a form of psychotherapy that utilizes meditation and relaxation to cultivate awareness and a nonjudgmental acceptance of the present moment. MBT requires individuals to practice being observant to details about their surroundings without passing judgment or reacting to environmental triggers. This practice typically employs formal exercises with the aim of learning to integrate this nonjudgmental and nonreactive mindset into one's day-to-day activities. Although there are many variations of MBTs, most are based on Jon Kabat–Zinn's Mindfulness-Based Stress Reduction module for coping with chronic illness.
Among IBS patients, MBT has been found to decrease hypervigilance to visceral sensations, to decrease catastrophization in the setting of active symptoms, and to lead to an overall improvement in the quality of life. In 2011, a RCT demonstrated a 38.2% reduction in IBS symptom severity, along with improvement in quality of life, after having completed 8 weekly training sessions in mindfulness. In 2013, another study replicated these findings and demonstrated maintenance of improvements in IBS symptom severity and psychological distress up to 6 months posttreatment. However, it should be noted that the participants in these studies were primarily affluent Caucasian women, and these results cannot be generalized to the larger population of IBS sufferers. Without a doubt, the evidence base for MBT is much smaller than for CBT or hypnosis and further research is necessary. In future RCTs, MBT skills may be incorporated into CBT protocols to produce a hybrid treatment (the Mindfulness-Based Cognitive Therapy module); this treatment blend has already been found effective in an exploratory, Internet-based treatment trial.
Gut-directed hypnotherapy is a modification of medical hypnosis that prioritizes posthypnotic suggestions on the health of the GI tract. Therapy usually involves 7–12 weekly sessions in which patients initially learn to achieve and deepen a hypnotic state and are then subsequently guided through a series of scripted, gut-focused imageries with hypnotic suggestions in each session. Patients are encouraged to practice home-based exercises employing audio recordings and are asked to track their progress and symptoms using self-monitoring forms.
Choice of psychological treatment
- If the patient has already been on medical management with inadequate improvement, then CBT offers excellent chances of improvement in IBS symptoms. Relaxation training, especially progressive muscle relaxation, is also a suitable option for IBS treatment in such cases
- Noncardiac chest pain shows a positive response to CBT
- For constipation resulting from pelvic floor dyssynergia, biofeedback is a favorable option. However, slow transit constipation without evidence of dyssynergic defecation is unresponsive to biofeedback therapy
- Single sizable RCTs suggest that biofeedback might be worth considering for levator ani syndrome (especially if patients have puborectalis tenderness on physical examination)
- FAP in children can be treated effectively with family CBT
- There is insufficient empirical evidence to recommend particular therapies for other FGIDs, but CBT and hypnosis show efficacy in FD
- If the primary goal is reduction in comorbid symptoms such as anxiety or depression, CBT is generally the best choice, because there is somewhat better evidence than other forms of psychotherapy that CBT can reliably reduce these affective symptoms in a short course of treatment. Patients with maladaptive coping styles such as a tendency to catastrophize or excessive preoccupation with bowel symptoms which can impair life functioning and quality of life in FGIDs also benefit.
Limitations of psychological management
There are limitations and challenges to the use of psychological treatments in FGIDs, however. Patients with GI symptoms most often visit the general practitioner unless they are of a very severe nature or associated with other psychiatric complaints, which make it especially important for the clinician to identify the disorder and consider prompt referral when required. For good success, referrals for such treatment require good therapeutic alliances between doctor and patient, reassurance, and education. It may be hard to find therapists in certain regions who are skilled in the particular therapy modalities with best effectiveness for a specific FGID. Psychological therapies warrant a certain amount of effort and motivation from patients to make use of, and this can make them unsuitable for certain individuals. Insurance reimbursement for psychological therapies for FGIDs is variable and not available in all insurance packages, so cost may be a barrier for some patients.
Despite these limitations, the current acumen of knowledge clearly indicates that psychological treatment should be considered for FGID patients who do not gain satisfactory symptom relief from standard gastroenterology management and for whom it is likely to significantly improve their clinical outcomes.
Other treatment approaches
Pharmacotherapy with antidepressants such as tricyclic antidepressant and selective serotonin reuptake inhibitor was also found to be useful. Many studies report improved outcomes in patients treated with probiotics. Shen et al. reported that probiotics resulted in additional benefit in inducing and maintaining remission in patients with ulcerative colitis and pouchitis. Probiotics are effective in abdominal pain-related FGID, especially IBS. Lactobacillus has anti-inflammatory action, inducing many immune regulatory pathways. Diet modification can also be tried as different foods impact the gut mucosa and immune system. FODMAPs must be avoided. Vitamin D supplementation has shown improvement in some patients with IBS and merits further research.
| Conclusion|| |
Considerable research has shown the interrelationships among biological, psychological, and social factors and the development and maintenance of the FGIDs. Several promising lines of research have also been investigating possible mechanisms for these relationships. Many treatment strategies have also been shown to be effective, including behavioral/lifestyle recommendations and psychological and psychopharmacologic treatments. Timely liaison between gastroenterologists as well as physicians with psychiatrists and/or psychologists can help improve patient outcomes and their overall quality of life. Further research is essential to expand the existing knowledge base on FGIDs, which will enable the development of novel, more efficacious treatments that are more efficiently delivered as well as tailored to individual patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Beaumont W. Experiments and Observations on the Gastric Juice, and the Physiology of Digestion. Edinburgh: Maclachlan & Stewart, Original from Oxford University; 1838. p. 149.
Beaumont W. Nutrition classics. Experiments and observations on the gastric juice and the physiology of digestion. By William Beaumont. Plattsburgh. Printed by F. P. Allen 1833. Nutr Rev 1977;35:144-5.
Cannon WB. The James-Lange theory of emotions: A critical examination and an alternative theory. By Walter B. Cannon, 1927. Am J Psychol 1987;100:567-86.
Engel GL, Reichsman F, Segal HL. A Study of an Infant with a Gastric Fistula. In: Psychopathology Source Book. Cambridge: Howard University Press; 1958.
Wolf S. The psyche and the stomach. A historical vignette. Gastroenterology 1981;80:605-14.
Drossman DA. Functional GI disorders: What's in a name? Gastroenterology 2005;128:1771-2.
Engel GL. The need for a new medical model: A challenge for biomedicine. Science 1977;196:129-36.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders DSM-5. Arlington, VA: American Psychiatric Association; 2013.
World Health Organization. Classifications of Mental and Behavioural Disorder: Clinical Descriptions and Disgnostic Guidelines. ICD-10. Geneva: World Health Organization; 2009.
Drossman DA. Functional gastrointestinal disorders: History, pathophysiology, clinical features and Rome IV. Gastroenterology 2016. pii: S0016-5085(16)00223-7.
Corazziari E. Definition and epidemiology of functional gastrointestinal disorders. Best Pract Res Clin Gastroenterol 2004;18:613-31.
Drossman DA, Camilleri M, Mayer EA, Whitehead WE. AGA technical review on irritable bowel syndrome. Gastroenterology 2002;123:2108-31.
Kang JY, Yap I, Gwee KA. The pattern of functional and organic disorders in an Asian gastroenterological clinic. J Gastroenterol Hepatol 1994;9:124-7.
Chang L, Toner BB, Fukudo S, Guthrie E, Locke GR, Norton NJ, et al.
Gender, age, society, culture, and the patient's perspective in the functional gastrointestinal disorders. Gastroenterology 2006;130:1435-46.
Jones J, Boorman J, Cann P, Forbes A, Gomborone J, Heaton K, et al.
British society of gastroenterology guidelines for the management of the irritable bowel syndrome. Gut 2000;47 Suppl 2:ii1-19.
Scarpato E, Kolacek S, Jojkic-Pavkov D, Konjik V, Živković N, Roman E, et al.
Prevalence of functional gastrointestinal disorders in children and adolescents in the Mediterranean region of Europe. Clin Gastroenterol Hepatol 2018;16:870-6.
Sperber AD, Dumitrascu D, Fukudo S, Gerson C, Ghoshal UC, Gwee KA, et al.
The global prevalence of IBS in adults remains elusive due to the heterogeneity of studies: A Rome foundation working team literature review. Gut 2017;66:1075-82.
Drossman DA, Sandler RS, McKee DC, Lovitz AJ. Bowel patterns among subjects not seeking health care. Use of a questionnaire to identify a population with bowel dysfunction. Gastroenterology 1982;83:529-34.
Ghoshal UC, Abraham P, Bhatt C, Choudhuri G, Bhatia SJ, Shenoy KT, et al.
Epidemiological and clinical profile of irritable bowel syndrome in India: Report of the Indian Society of Gastroenterology Task Force. Indian J Gastroenterol 2008;27:22-8.
] [Full text]
Sperber AD, Gwee KA, Hungin AP, Corazziari E, Fukudo S, Gerson C, et al.
Conducting multinational, cross-cultural research in the functional gastrointestinal disorders: Issues and recommendations. A Rome Foundation Working Team Report. Aliment Pharmacol Ther 2014;40:1094-102.
Almy TP. Experimental studies on the irritable colon. Am J Med 1951;10:60-7.
Halder SL, Locke GR 3rd
, Schleck CD, Zinsmeister AR, Melton LJ 3rd
, Talley NJ, et al.
Natural history of functional gastrointestinal disorders: A 12-year longitudinal population-based study. Gastroenterology 2007;133:799-807.
Koloski NA, Jones M, Kalantar J, Weltman M, Zaguirre J, Talley NJ, et al.
The brain – Gut pathway in functional gastrointestinal disorders is bidirectional: A 12-year prospective population-based study. Gut 2012;61:1284-90.
Adam B, Liebregts T, Holtmann G. Mechanisms of disease: Genetics of functional gastrointestinal disorders – Searching the genes that matter. Nat Clin Pract Gastroenterol Hepatol 2007;4:102-10.
Camilleri M, Carlson P, McKinzie S, Zucchelli M, D'Amato M, Busciglio I, et al.
Genetic susceptibility to inflammation and colonic transit in lower functional gastrointestinal disorders: Preliminary analysis. Neurogastroenterol Motil 2011;23:935-e398.
Camilleri M. Peripheral mechanisms in irritable bowel syndrome. N Engl J Med 2012;367:1626-35.
Houghton LA, Lea R, Jackson N, Whorwell PJ. The menstrual cycle affects rectal sensitivity in patients with irritable bowel syndrome but not healthy volunteers. Gut 2002;50:471-4.
Bharucha AE, Camilleri M, Burton DD, Thieke SL, Feuerhak KJ, Basu A, et al.
Increased nutrient sensitivity and plasma concentrations of enteral hormones during duodenal nutrient infusion in functional dyspepsia. Am J Gastroenterol 2014;109:1910-20.
Lapointe TK, Basso L, Iftinca MC, Flynn R, Chapman K, Dietrich G, et al.
TRPV1 sensitization mediates postinflammatory visceral pain following acute colitis. Am J Physiol Gastrointest Liver Physiol 2015;309:G87-99.
Vergnolle N. Modulation of visceral pain and inflammation by protease-activated receptors. Br J Pharmacol 2004;141:1264-74.
Yiangou Y, Facer P, Dyer NH, Chan CL, Knowles C, Williams NS, et al.
Vanilloid receptor 1 immunoreactivity in inflamed human bowel. Lancet 2001;357:1338-9.
Yiangou Y, Facer P, Smith JA, Sangameswaran L, Eglen R, Birch R, et al.
Increased acid-sensing ion channel ASIC-3 in inflamed human intestine. Eur J Gastroenterol Hepatol 2001;13:891-6.
Latremoliere A, Woolf CJ. Central sensitization: A generator of pain hypersensitivity by central neural plasticity. J Pain 2009;10:895-926.
Staud R. Abnormal endogenous pain modulation is a shared characteristic of many chronic pain conditions. Expert Rev Neurother 2012;12:577-85.
Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol 2015;28:203-9.
Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, et al.
Ingestion of lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A 2011;108:16050-5.
Rhee SH, Pothoulakis C, Mayer EA. Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat Rev Gastroenterol Hepatol 2009;6:306-14.
Bailey MT, Dowd SE, Galley JD, Hufnagle AR, Allen RG, Lyte M, et al.
Exposure to a social stressor alters the structure of the intestinal microbiota: Implications for stressor-induced immunomodulation. Brain Behav Immun 2011;25:397-407.
Asano Y, Hiramoto T, Nishino R, Aiba Y, Kimura T, Yoshihara K, et al.
Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice. Am J Physiol Gastrointest Liver Physiol 2012;303:G1288-95.
Ochoa-Cortes F, Ramos-Lomas T, Miranda-Morales M, Spreadbury I, Ibeakanma C, Barajas-Lopez C, et al.
Bacterial cell products signal to mouse colonic nociceptive dorsal root ganglia neurons. Am J Physiol Gastrointest Liver Physiol 2010;299:G723-32.
Spiller RC. Postinfectious irritable bowel syndrome. Gastroenterology 2003;124:1662-71.
Cremon C, Stanghellini V, Pallotti F, Fogacci E, Bellacosa L, Morselli-Labate AM, et al.
Salmonella gastroenteritis during childhood is a risk factor for irritable bowel syndrome in adulthood. Gastroenterology 2014;147:69-77.
Distrutti E, Monaldi L, Ricci P, Fiorucci S. Gut microbiota role in irritable bowel syndrome: New therapeutic strategies. World J Gastroenterol 2016;22:2219-41.
Mawe GM, Hoffman JM. Serotonin signalling in the gut – Functions, dysfunctions and therapeutic targets. Nat Rev Gastroenterol Hepatol 2013;10:473-86.
Ohman L, Simrén M. Pathogenesis of IBS: Role of inflammation, immunity and neuroimmune interactions. Nat Rev Gastroenterol Hepatol 2010;7:163-73.
Fukudo S, Nomura T, Hongo M. Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome. Gut 1998;42:845-9.
Gibson PR, Shepherd SJ. Evidence-based dietary management of functional gastrointestinal symptoms: The FODMAP approach. J Gastroenterol Hepatol 2010;25:252-8.
Boettcher E, Crowe SE. Dietary proteins and functional gastrointestinal disorders. Am J Gastroenterol 2013;108:728-36.
Maxwell PR, Rink E, Kumar D, Mendall MA. Antibiotics increase functional abdominal symptoms. Am J Gastroenterol 2002;97:104-8.
Mayer EA, Naliboff BD, Chang L, Coutinho SV. V. Stress and irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 2001;280:G519-24.
Gwee KA, Graham JC, McKendrick MW, Collins SM, Marshall JS, Walters SJ, et al.
Psychometric scores and persistence of irritable bowel after infectious diarrhoea. Lancet 1996;347:150-3.
Fakhraei B, Firouzabadi A, Farjam M, Fattahi MR, Kazemi MH, Naini MA, et al
. Frequency of different psychiatric disorders in patients with functional bowel disorders: A short report. Ann Colorectal Res 2015;3:e27621.
Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: What are the causes and implications? Gastroenterology 2002;122:1140-56.
Irwin C, Falsetti SA, Lydiard RB, Ballenger JC, Brock CD, Brener W, et al.
Comorbidity of posttraumatic stress disorder and irritable bowel syndrome. J Clin Psychiatry 1996;57:576-8.
Naliboff BD, Derbyshire SW, Munakata J, Berman S, Mandelkern MA, Chang L, et al
. Evidence for decreased activation of central fear circuits by expected aversive visceral stimuli in IBS patients. Gastroenterology 2000;118:A137.
Drevets WC, Price JL, Simpson JR Jr., Todd RD, Reich T, Vannier M. Subgenual prefrontal cortex abnormalities in mood disorders. Nature 1997;386:824-7.
Bremner JD, Staib LH, Kaloupek D, Southwick SM, Soufer R, Charney DS. Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: A positron emission tomography study. Biol Psychiatry 1999;45:806-16.
Van Oudenhove L, Vandenberghe J, Geeraerts B, Vos R, Persoons P, Fischler B, et al.
Determinants of symptoms in functional dyspepsia: Gastric sensorimotor function, psychosocial factors or somatisation? Gut 2008;57:1666-73.
Van Oudenhove L, Crowell MD, Drossman DA, Halpert AD, Keefer L, Lackner JM, et al.
Biopsychosocial aspects of functional gastrointestinal disorders. Gastroenterology 2016. pii: S0016-5085(16)00218-3.
Leroi AM, Bernier C, Watier A, Hémond M, Goupil G, Black R, et al.
Prevalence of sexual abuse among patients with functional disorders of the lower gastrointestinal tract. Int J Colorectal Dis 1995;10:200-6.
Drossman DA, Li Z, Leserman J, Toomey TC, Hu YJ. Health status by gastrointestinal diagnosis and abuse history. Gastroenterology 1996;110:999-1007.
Leserman J, Li Z, Hu YJ, Drossman DA. How multiple types of stressors impact on health. Psychosom Med 1998;60:175-81.
Leserman J, Drossman DA, Li Z, Toomey TC, Nachman G, Glogau L. Sexual and physical abuse history in gastroenterology practice: How types of abuse impact health status. Psychosom Med 1996;58:4-15.
Mayer EA, Gebhart GF. Basic and clinical aspects of visceral hyperalgesia. Gastroenterology 1994;107:271-93.
Levy RL, Olden KW, Naliboff BD, Bradley LA, Francisconi C, Drossman DA, et al
. Psychosocial aspects of the functional gastrointestinal disorders. Gastroenterology 2006;130:1447-58.
Biggs AM, Aziz Q, Tomenson B, Creed F. Effect of childhood adversity on health related quality of life in patients with upper abdominal or chest pain. Gut 2004;53:180-6.
Waldinger RJ, Schulz MS, Barsky AJ, Ahern DK. Mapping the road from childhood trauma to adult somatization: The role of attachment. Psychosom Med 2006;68:129-35.
Stuart S, Noyes R Jr. Attachment and interpersonal communication in somatization. Psychosomatics 1999;40:34-43.
Styron T, Janoff-Bulman R. Childhood attachment and abuse: Long-term effects on adult attachment, depression, and conflict resolution. Child Abuse Negl 1997;21:1015-23.
Taylor RE, Mann AH, White NJ, Goldberg DP. Attachment style in patients with unexplained physical complaints. Psychol Med 2000;30:931-41.
Spertus IL, Yehuda R, Wong CM, Halligan S, Seremetis SV. Childhood emotional abuse and neglect as predictors of psychological and physical symptoms in women presenting to a primary care practice. Child Abuse Negl 2003;27:1247-58.
Bonilla S, Saps M. Early life events predispose the onset of childhood functional gastrointestinal disorders. Rev Gastroenterol Mex 2013;78:82-91.
Williams M, Budavari A, Olden KW, Jones MP. Psychosocial assessment of functional gastrointestinal disorders in clinical practice. J Clin Gastroenterol 2005;39:847-57.
Hansel SL, Umar SB, Lunsford TN, Harris LA, Dibaise JK, Crowell MD. Personality traits and impaired health-related quality of life in patients with functional gastrointestinal disorders. Clin Gastroenterol Hepatol 2010;8:220-2.
Spiller RC. Postinfectious irritable bowel syndrome1. Gastroenterology. 2003;124:1662-71.
Chang L, Heitkemper MM. Gender differences in irritable bowel syndrome. Gastroenterology 2002;123:1686-701.
Taylor SE, Klein LC, Lewis BP, Gruenewald TL, Gurung RA, Updegraff JA. Biobehavioral responses to stress in females: Tend-and-befriend, not fight-or-flight. Psychol Rev 2000;107:411-29.
Toner BB, Akman D. Gender role and irritable bowel syndrome: Literature review and hypothesis. Am J Gastroenterol 2000;95:11-6.
Drossman DA, Hu Y, Jia H, Toner BB, Whitehead WE, Diamant NE, et al
. The influence of psychosocial factors on health care utilization in patients with functional bowel disorders (FBD). Gastroenterology 2000;118:A842.
Levy RL, Jones KR, Whitehead WE, Feld SI, Talley NJ, Corey LA, et al.
Irritable bowel syndrome in twins: Heredity and social learning both contribute to etiology. Gastroenterology 2001;121:799-804.
Whitehead WE, Crowell MD, Heller BR, Robinson JC, Schuster MM, Horn S. Modeling and reinforcement of the sick role during childhood predicts adult illness behavior. Psychosom Med 1994;56:541-50.
Lackner JM, Brasel AM, Quigley BM, Keefer L, Krasner SS, Powell C, et al.
The ties that bind: Perceived social support, stress, and IBS in severely affected patients. Neurogastroenterol Motil 2010;22:893-900.
Drossman DA. Rome III: The new criteria. Chin J Dig Dis 2006;7:181-5.
Hauser G, Pletikosic S, Tkalcic M. Cognitive behavioral approach to understanding irritable bowel syndrome. World J Gastroenterol 2014;20:6744-58.
Guthrie E, Creed F, Dawson D, Tomenson B, Perry SW. A randomised controlled trial of psychotherapy in patients with refractory irritable bowel syndrome. Year Book Psychiatry Appl Ment Health1995;1995:116.
Palsson OS, Whitehead WE. Psychological treatments in functional gastrointestinal disorders: A primer for the gastroenterologist. Clin Gastroenterol Hepatol 2013;11:208-16.
Ballou S, Keefer L. Psychological interventions for irritable bowel syndrome and inflammatory bowel diseases. Clin Transl Gastroenterol 2017;8:e214.
Payne A, Blanchard EB. A controlled comparison of cognitive therapy and self-help support groups in the treatment of irritable bowel syndrome. J Consult Clin Psychol 1995;63:779-86.
Moss-Morris R, McAlpine L, Didsbury LP, Spence MJ. A randomized controlled trial of a cognitive behavioural therapy-based self-management intervention for irritable bowel syndrome in primary care. Psychol Med 2010;40:85-94.
Craske MG, Wolitzky-Taylor KB, Labus J, Wu S, Frese M, Mayer EA, et al.
Acognitive-behavioral treatment for irritable bowel syndrome using interoceptive exposure to visceral sensations. Behav Res Ther 2011;49:413-21.
Drossman DA, Toner BB, Whitehead WE, Diamant NE, Dalton CB, Duncan S, et al.
Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders. Gastroenterology 2003;125:19-31.
Rao SS. Biofeedback therapy for constipation in adults. Best Pract Res Clin Gastroenterol 2011;25:159-66.
Kabat-Zinn J, Hanh TN. Full Catastrophe Living: Using the Wisdom of Your Body and Mind to Face Stress, Pain, and Illness. New York: Delta; 2009.
Gaylord SA, Palsson OS, Garland EL, Faurot KR, Coble RS, Mann JD, et al.
Mindfulness training reduces the severity of irritable bowel syndrome in women: Results of a randomized controlled trial. Am J Gastroenterol 2011;106:1678-88.
Zernicke KA, Campbell TS, Blustein PK, Fung TS, Johnson JA, Bacon SL, et al.
Mindfulness-based stress reduction for the treatment of irritable bowel syndrome symptoms: A randomized wait-list controlled trial. Int J Behav Med 2013;20:385-96.
Ljótsson B, Falk L, Vesterlund AW, Hedman E, Lindfors P, Rück C, et al.
Internet-delivered exposure and mindfulness based therapy for irritable bowel syndrome – A randomized controlled trial. Behav Res Ther 2010;48:531-9.
Whorwell PJ. Review article: The history of hypnotherapy and its role in the irritable bowel syndrome. Aliment Pharmacol Ther 2005;22:1061-7.
Schey R, Villarreal A, Fass R. Noncardiac chest pain: Current treatment. Gastroenterol Hepatol (N Y) 2007;3:255-62.
Chiarioni G, Nardo A, Vantini I, Romito A, Whitehead WE. Biofeedback is superior to electrogalvanic stimulation and massage for treatment of levatorani syndrome. Gastroenterology 2010;138:1321-9.
Levy RL, Langer SL, Walker LS, Romano JM, Christie DL, Youssef N, et al.
Cognitive-behavioral therapy for children with functional abdominal pain and their parents decreases pain and other symptoms. Am J Gastroenterol 2010;105:946-56.
Calvert EL, Houghton LA, Cooper P, Morris J, Whorwell PJ. Long-term improvement in functional dyspepsia using hypnotherapy. Gastroenterology 2002;123:1778-85.
Nieuwsma JA, Trivedi RB, McDuffie J, Kronish I, Benjamin D, Williams JW, et al.
Brief psychotherapy for depression: A systematic review and meta-analysis. Int J Psychiatry Med 2012;43:129-51.
Hofmann SG, Smits JA. Cognitive-behavioral therapy for adult anxiety disorders: A meta-analysis of randomized placebo-controlled trials. J Clin Psychiatry 2008;69:621-32.
Drossman DA, Creed FH, Olden KW, Svedlund J, Toner BB, Whitehead WE. Psychosocial aspects of the functional gastrointestinal disorders. Gut 1999;45 Suppl 2:II25-30.
Shen J, Zuo ZX, Mao AP. Effect of probiotics on inducing remission and maintaining therapy in ulcerative colitis, crohn's disease, and pouchitis: Meta-analysis of randomized controlled trials. Inflamm Bowel Dis 2014;20:21-35.
Korterink JJ, Ockeloen L, Benninga MA, Tabbers MM, Hilbink M, Deckers-Kocken JM, et al.
Probiotics for childhood functional gastrointestinal disorders: A systematic review and meta-analysis. Acta Paediatr 2014;103:365-72.
Williams CE, Williams EA, Corfe BM. Vitamin D status in irritable bowel syndrome and the impact of supplementation on symptoms: What do we know and what do we need to know? Eur J Clin Nutr 2018;1: doi: 10.1038/s41430-017-0064-z.