Gastroesophageal reflux disease (GERD) and bipolar disorder impose substantial global burdens on individuals and healthcare systems. Previous studies suggest a bidirectional association between GERD and bipolar disorder. By searching and reviewing the results of existing studies, this systematic review and meta-analysis aims to review the two-way relationship between GERD and bipolar disorder.

This study adhered to PRISMA Guidelines, including a comprehensive search of PubMed and Scopus for observational longitudinal studies. Quality (risk of bias) assessment employed the Newcastle-Ottawa Scale, and RevMan version 5.3 facilitated meta-analysis.

Five longitudinal studies (161888 patients) revealed a significant bidirectional link between GERD and bipolar disorder. Patients with GERD had a 2.29-fold higher risk of bipolar disorder (OR=2.29 [1.64, 3.21]; P<0.001), while individuals with bipolar disorder had a 2.80-fold higher risk of GERD (OR=2.80 [1.36, 5.76]; P=0.005). This study also identified independent risk factors, including sex, age under 60 years, and alcohol consumption disorders, influencing the occurrence of bipolar disorder in patients with GERD, as well as there is an influence of the number of psychoactive drugs in the occurrence of GERD in patients with bipolar disorder.

These findings highlight a bidirectional relationship between GERD and bipolar disorder, emphasizing the necessity for integrated care models and personalized treatment plans. The results underscore the importance of considering both gastrointestinal and mental health aspects in managing these interconnected conditions.

Abnormal psychological profiles are frequently found in patients with functional gastrointestinal disorders (FGIDs). The present study aimed to evaluate the psychological profiles of FGID patients with irritable bowel syndrome (IBS), and IBS phenotypes.

In 608 FGID patients, including 235 with IBS, have filled a Rome III questionnaire and the French version of the Minnesota Multiphasic Personality Inventory 2. Data analysis was performed using univariate analysis and multivariate logistic regression.

This study shows that IBS patients have abnormal psychological profiles with more significant symptom exaggeration and decreased test defensiveness than non-IBS patients. They have a significantly higher score for all clinical scales. Logistic regression analysis showed in IBS patients a decrease of body mass index (P= 0.002), and test defensiveness score K (P= 0.001) and an increase of Hypochondriasis (P< 0.001) and Masculinity-Femininity scale (P= 0.018). By comparison with non-IBS patients, IBS-constipation, IBS-diarrhea, and mixed IBS patients have increased Hypochondriasis value and Depression score, mixed IBS patients have higher Psychasthenia score and higher Hypomania score. No item was significantly different in the IBS-unspecified group.

This study shows that IBS patients have different psychological profiles than other FGID patients and that psychological characteristics are associated with IBS phenotypes except for patients with unsubtyped IBS.

A significant percentage of patients with gastroesophageal reflux disease (GERD) will not respond to proton pump inhibitor (PPI) therapy. The causes of PPI-refractory GERD are numerous and diverse, and include adherence, persistent acid, functional disorders, nonacid reflux, and PPI bioavailability. The evaluation should start with a symptom assessment and may progress to imaging, endoscopy, and monitoring of esophageal pH, impedance, and bilirubin. There are a variety of pharmacologic and procedural interventions that should be selected based on the underlying mechanism of PPI failure. Pharmacologic treatments can include antacids, prokinetics, alginates, bile acid binders, reflux inhibitors, and antidepressants. Procedural options include laparoscopic fundoplication and LINX as well as endoscopic procedures, such as transoral incisionless fundoplication and Stretta. Several alternative and complementary treatments of possible benefit also exist.

Functional gastrointestinal disorders (FGIDs), the most common diagnoses in gastroenterology are recognized by morphological and physiological abnormalities that often occur in combination including motility disturbance, visceral hypersensitivity, altered mucosal and immune function, altered gut microbiota and altered central nervous system processing. Research on these gut-brain interaction disorders is based on using specific diagnostic criteria. The Rome Foundation has played a pivotal role in creating diagnostic criteria thus operationalizing the dissemination of new knowledge in the field of FGIDs. Rome IV is a compendium of the knowledge accumulated since Rome III was published 10 years ago. It improves upon Rome III by: 1) updating the basic and clinical literature, 2) offering new information on gut microenvironment, gut-brain interactions, pharmacogenomics, biopsychosocial, gender and cross cultural understandings of FGIDs, 3) reduces the use of imprecise and occassionally stigmatizing terms when possible, 4) uses updated diagnostic algorithms, 5) incorporates information on the patient illness experience, and physiological subgroups or biomarkers that might lead to more targeted treatment. This introductory article sets the stage for the remaining 17 articles that follow and offers an historical overview of the FGIDs field, differentiates FGIDs from motility and structural disorders, discusses the changes from Rome III, reviews the Rome committee process, provides a biopsychosocial pathophysiological conceptualization of FGIDs, and offers an approach to patient care.

Nutcracker esophagus (NE) is a common esophageal motility disorder chacterized by high amplitude peristaltic contractions in the distal esophagus. While previous studies have examined selected aspects of this condition (e.g. pathogenesis and treatment), there is a paucity of data regarding demographic and clinical features in large cohorts of patients. The aim of this study was to describe demographics, clinical features, comorbidities, time to diagnosis, source of patient referral by specialty, and medication use in a large cohort of patients with NE. We retrospectively analyzed consecutive cases of NE diagnosed from 2008-2010. The electronic medical records of these patients were reviewed, and relevant information was extracted. We identified 115 patients with NE. The median age was 62 years (range 25-87 years), and 63% were female. The median time patients experienced symptoms prior to diagnosis was 24 months (0-480 months). Most patients presented to an internal medicine consultant (42%) or to a gastroenterologist (35%). Presenting symptoms were chest pain (31%) and dysphagia (21%). Gastroesophageal reflux disease (GERD) symptoms were common: heartburn occurred in 51% of patients, 77% had a prior history of GERD, and 78% were receiving acid suppressive medications. GERD was confirmed by testing in at least 35%. Psychiatric comorbidity occurred in 24% with half the patients receiving psychotropic medications. Irritable bowel syndrome (IBS) and fibromyalgia co-existed in 15% and 12% of patients, respectively. Surprisingly, opioids were prescribed to 26% of patients. No statistically significant correlation was found between esophageal motility parameters and symptoms. In this study, NE patients were more commonly middle-aged females experiencing a considerable amount of time between symptom onset and diagnosis. Many were initially evaluated by internists for dysphagia or chest pain and had a history of GERD. Medication prescribed prior to diagnoses frequently involved acid suppression, but narcotic and psychotropic prescriptions were also commonly used. Central sensitization syndromes (fibromyalgia and IBS), psychiatric comorbidity, and reflux commonly coexisted. Our study suggests that future investigations should address the role and interaction of GERD and psychiatric disorders in NE.

We tested the hypotheses that globus patients demonstrate oesophageal visceral hypersensitivity and aberrant viscerosomatic referral of oesophageal stimuli. Oesophageal visceral perception was assessed by oesophageal balloon distension and electrical stimulation in nine patients with globus and compared with 11 healthy controls. Oesophageal perception and pain thresholds were determined. Subjects recorded the area of thoracic viscerosomatic referral on a body map in response to each stimulus. All the patients reported their first sensation at balloon volumes between 2 and 6 mL whereas controls reported their first sensation at volumes between 3 and 14 mL (P = 0.03). All the patients reported pain at balloon volumes between 5 and 12 mL whereas controls experienced pain at volumes between 8 and 20 mL (P = 0.001). In response to electrical stimulation to the oesophagus patients and controls demonstrated comparable sensory thresholds. In response to oesophageal balloon distension seven of nine patients, but no controls, referred the sensation to the region at or above the suprasternal notch (P = 0.001). Similarly, significant differences in viscerosomatic referral pattern were observed in response to oesophageal electrical stimulation (P = 0.03). Patients with globus demonstrate oesophageal visceral hypersensitivity to mechanical distension. The differential responses to stretch and electrical stimuli may indicate that the hypersensitivity is a peripheral, rather than central, phenomenon. The aberrant referral of oesophageal sensations in response to both mechanical and electrical stimulation supports the hypothesis that referral of symptoms to the neck might be a central phenomenon.

A growing number of studies have shown the impact of psychological comorbidities on gastro-oesophageal reflux disease (GERD) patients' symptom reports and healthcare-seeking behaviour.

To review the reported relationship between GERD and psychological comorbidity.

Review of the literature on GERD and psychological comorbidity.

Psychological comorbidity is common among GERD patients and appears to afflict all GERD phenotypes. Sexual and physical abuse is also common in GERD patients. Stress enhances perception of oesophageal acid exposure. Treatment for GERD, especially in those who are not responsive to antireflux treatment, may require further evaluation for psychological comorbidity.

Psychological comorbidity is very common in GERD patients and is likely to play an important role in response, or failure of response, to proton pump inhibitor treatment.

Heartburn is a typical symptom of GERD. The spectrum of diseases associated with GERD includes reflux esophagitis, Barrett's esophagus and nonerosive reflux disease (NERD). Although acid reflux is the classic cause of heartburn in patients with erosive esophagitis, the relationship between acid and heartburn is far from clear, especially in patients with NERD. Strong evidence exists that weakly acidic reflux and/or non-acid-related events have a significant role in the generation of heartburn. In addition to the role of nonacidic refluxate components, activation of mechanoreceptors and chemoreceptors, and a possible role for central and peripheral sensitization, has been described. Although patients with erosive esophagitis respond well to acid-suppressive therapy, the same does not hold true for those with NERD. NERD represents a major clinical problem, and its management remains a challenge. Discussion of NERD focuses on the mechanisms that cause chest pain in this subgroup of patients. Improved understanding of the pathogenesis underlying heartburn in patients with GERD, in particular those with NERD, will shape our understanding of this condition. Such understanding will serve as a platform for further research and allow additional therapies to be developed for this increasingly encountered clinical condition.

Irritable bowel syndrome (IBS) and chronic pelvic pain (CPP) are both somatoform disorders with a high prevalence within the population in general. The objective was to compare both entities, to find the differences and the similarities related to epidemiology and psychosocial aspects like stressful life events, physical and sexual abuse, illness behaviour and comorbidity. The technical literature was reviewed systematically from 1971 to 2006 and compared. According to literature, IBS and CPP seem to be one rather than two different entities with the same localisation of pain. Both syndromes also are similar concerning prevalence, the coexistence of mental and somatoform disorders, the common history of sexual and physical abuse in the past and their health care utilization. It could be shown that there were many similarities between IBS and CPP. Nevertheless both are traded as different clinical pictures as far. Therefore it seems to be reasonable and necessary to generate a common diagnosis algorithm and to bring gynaecologists and gastroenterologists into dialogue.

Laparoscopic antireflux surgery (LARS) provides effective control of gastroesophageal reflux (GER) in more than 90% of patients. Despite this high success rate, some patients continue to consume acid suppressive medications after surgical intervention. In this study we evaluate the prevalence, clinical indications, and cause of use of acid reducing drugs in patients after LARS. Consecutive patients undergoing LARS for GERD were surveyed 2-3 years after surgery regarding use of acid suppressive medications, surgical outcome, and GERD specific symptoms. During the study period, 119 patients underwent LARS at our center. Ninety-eight (82%) were available for interview. Two patients died of unrelated causes and two declined to be interviewed. The remaining 94 individuals are the subject of this report. Ninety-four percent were satisfied with the outcome of surgery. Despite this high satisfaction rate, 37 of 94 (39%) were on antireflux medication (ARM; 62% proton pump inhibitors, 22% H2-receptor antagonists, and 16% others), with 70% using continuous medication. Of these patients, 54% took ARM after surgery for GERD-related symptoms, 95% of these patients responded to medical therapy, and yet again, 85% remained satisfied with the surgical outcome. Forty-six percent of patients on ARM after surgery had no GERD symptoms and took ARM for nonappropriate indications such as bloating. Only 47% of these responded to ARM; 82% of this group was satisfied with the surgical outcome. In conclusion, the use of ARM after LARS is a common occurrence despite a high satisfaction rate with this operation. Nearly half of patients consuming ARS after LARS are taking these medications for symptoms not necessarily related to GER. These findings underscore the importance of patient education in the use of these agents.

Extraesophageal manifestations of gastroesophageal reflux disease (GERD) are essentially complications of GERD that primarily involve organs that are in proximity to the esophagus. Non-cardiac chest pain (NCCP) is an atypical manifestation of GERD, because symptoms originate in essence from the esophagus. In both atypical and extraesophageal manifestation of GERD frequent heartburn is uncommon and lack of GERD symptoms is not unusual. Esophageal mucosal injury is rarely present making upper endoscopy a low-yield procedure in both conditions. While association with GERD has been commonly reported, the extent of causality remains unknown. In NCCP, the usefulness of the proton pump inhibitor (PPI) test in diagnosing GERD-related NCCP has been established. Similar value in extraesophageal manifestations of GERD has been proposed, but rarely studied. While treatment of extraesophageal manifestations of GERD remains a challenge, PPIs in at least double the standard dose, should be considered for the initial therapy. Properly designed therapeutic studies are still lacking as well as the exact role of antireflux surgery in this patient population.

Noncardiac chest pain (NCCP) is a common condition with significant morbidity and economic implications. Psychological factors, gastroesophageal reflux disease (GERD), alteration in pain perception, and esophageal dysmotility play an important role in the pathogenesis of the disorder. Proton pump inhibitor (PPI) therapy is the most effective medical intervention for the treatment of GERD-related NCCP, as well as the most cost-effective diagnostic strategy for this condition. Pain modulators such as tricyclic antidepressants, trazodone, and selective serotonin reuptake inhibitors infer a visceral analgesic effect and consequently are the treatment of choice for patients with non-GERD-related NCCP. Furthermore, cognitive behavioral therapy has also been shown to be useful in the management of subset of patients with non-GERD-related NCCP. Newer therapeutic modalities and interventions such as lower esophageal sphincter injection of botulinum toxin in NCCP patients with spastic esophageal motility disorders, theophylline, and 5-HT4 receptor agonists may supplement or replace current treatment for non-GERD-related NCCP. Future compounds may include new visceral analgesics or medications that interfere with the development of peripheral or central sensitization.

Treatment of spastic motility disorders continues to be challenging. Therapeutic options remain limited due in part to our lack of understanding of the pathophysiology and significance of these disorders. Furthermore, most of therapeutic trials to date are hampered by the poorly designed nature of the study, including the small size of the trials and the lack of placebo arm. Most of the available information suggests that there seems to be an important dissociation between symptoms (chest pain/dysphagia) and esophageal dysmotility. Drug treatment aimed at visceral sensitivity seems more effective in relieving symptoms than spasmolytic medications. Recent trials with Botox, nitric oxide derivatives, and SSRIs offer promising results. Rigorous study design that includes large placebo-controlled trials is needed in this area.

NCCP is a common condition in Asia. The diagnostic approach of NCCP in Asians is similar to the Western population. GERD is the most common etiology. PPI therapy is an attractive alternative to other invasive diagnostic tests for NCCP and is equally effective for the Asian population.

Nutcracker esophagus (NE) is defined as the presence of peristaltic contractions in which the average distal esophageal amplitude is greater than 180 mm Hg. The underlying mechanism responsible for these abnormalities is not known. The aim of this study was to test the hypothesis that NE might be caused by a defect in the inhibitory pathway controlling esophageal peristalsis.

Eight patients with NE (seven women, 1 man, mean age 50 yr) and eight age- and sex-matched normal volunteers (seven women, 1 man, mean age 48 yr) underwent a special protocol using three-channel (3, 8, and 16 cm above the lower esophageal sphincter) solid state esophageal manometry to evaluate deglutitive inhibition. Ten pairs of 5 ml of wet swallows were given at each of five different time intervals (30, 20, 15, 10, and 5 s). Pairs of swallows were spaced by 30 s, and different time intervals were spaced by 1 min. Tracings were recorded using a computer program and blindly automatically analyzed for both amplitude and duration of the contraction separately for the first and second swallow of each pair. Presence of deglutitive inhibition or muscle refractoriness was assessed according to interactions between the first and second swallow of the pair. Results were found abnormal when larger than the mean percent variation of the second and first swallow calculated for the 30-s interval, considered as baseline for each participant. Statistics included paired and nonpaired nonparametrical comparisons as appropriate.

The median amplitude for the NE was 202 mm Hg (range 186-376) and for the controls was 118 mm Hg (range 64-167) (p = 0.0002). The median duration in the NE group was 5.1 s (range 4-9.3) versus 4.1 (range 3.3-5.0) for the controls (p = 0.02). The percent variation in duration (p = 0.31), amplitude (p = 0.42), and propagation velocity of the peristaltic waves (p = 0.69) did not differ between the control and NE groups. Peristalsis frequency dropped at the 5-s interval for both studied groups (p = 0.84).

Central and local inhibitory mechanisms induced by closely timed swallows are preserved in the NE and do not explain the mechanism of the high amplitude and long duration contractions.

To test the usefulness of upper gastrointestinal investigations and quality of life assessment in Chinese patients with non-cardiac chest pain.

Seventy-eight consecutive patients with non-cardiac chest pain underwent upper endoscopy. Eight patients had upper gastrointestinal pathology (10%). The remaining 70 patients received acid perfusion test, oesophageal manometry and 24-h ambulatory oesophageal pH (n=65)/manometry (n=61), and the results were compared with those of healthy controls (n=20). Symptoms and quality of life (SF-36) were assessed by standard validated questionnaire.

Significant acid reflux symptoms were present in five (5/70, 7%) patients. Abnormal 24-h oesophageal pH, indicating gastro-oesophageal reflux, was found in 19 (19/65, 29%) patients. The percentage of simultaneous contractions was higher and the percentage peristalsis was lower in patients with non-cardiac chest pain when compared with normal subjects by 24-h ambulatory manometry. Patients with non-cardiac chest pain had a lower SF-36 score when compared to controls.

Typical acid reflux symptoms are uncommon in Chinese patients with non-cardiac chest pain, but abnormal 24-h pH results, indicating gastro-oesophageal reflux, were found in 29% of patients. Ineffective contractions were more frequently found in patients with non-cardiac chest pain by 24-h ambulatory manometry, which may have a bearing on the impaired quality of life in such patients. Upper gastrointestinal investigations are useful for the evaluation of Chinese patients with non-cardiac chest pain.

To evaluate the frequency of reflux symptoms in patients with a diagnosed psychiatric disorder and to assess potential risk factors for symptom occurrence.

The presence of reflux symptoms was compared between a case population of 94 psychiatric patients and a control population of 198 non-psychiatric patients.

Heartburn, exercise-induced heartburn, cough and dysphagia were all reported significantly more frequently by subjects with psychiatric disorders than by control subjects. The presence of any psychiatric diagnosis exerted an increased risk for both heartburn (odds ratio, 2.71; 95% confidence interval, 1.01-7.30) and exercise-induced heartburn (3.34; 1.12-9.96). The type of psychiatric disorder, the type of psychotropic medication and the lifestyle did not influence the presence of reflux symptoms.

Reflux symptoms occur more frequently in patients with than without a diagnosed psychiatric disorder. The reflux symptoms are not associated with any specific type of medication and may reflect a generally reduced threshold for or distorted perception of symptoms.

Diffuse oesophageal spasm is a functional oesophageal motility disorder of unknown aetiology, which appears to be due to a disturbance of the normal pharmacological timing of propulsive contraction occurring in the oesophageal body after swallowing. The lack of pathophysiological understanding may be due to the fact that there is more than one pathophysiological pathway causing symptoms of diffuse oesophageal spasm. Barium studies, oesophageal scintigraphy and fiberoptic examination can be helpful in finding the correct diagnosis, but manometry is still the gold standard of diagnostic procedures. Similar to other spastic oesophageal motility disorders, pharmacological treatment of diffuse oesophageal spasm includes nitrates, calcium antagonists, anticholinergics and antidepressants with varying beneficial effects. Botulinum toxin, which provides sufficient treatment as measured by symptom score and manometric patterns in patients with achalasia, was recently evaluated for the treatment of diffuse oesophageal spasm in small patient selections with promising results.

The aim of this study was to characterize the psychometric profiles of symptomatic patients with abnormal esophageal motility and symptomatic patients with normal manometric findings compared to asymptomatic controls.

A total of 113 patients with abnormal esophageal motility (7 achalasia, 8 diffuse esophageal spasm, 27 nutcracker esophagus, 37 hypertensive lower esophageal sphincter, 21 hypotensive peristalsis, 13 failed peristalsis), 23 symptomatic controls with similar esophageal symptoms but normal manometry, and 27 asymptomatic controls were enrolled. Validated questionnaires assessing depression (Beck Depression Inventory), anxiety (Spielberger State Anxiety Inventory or Trait Anxiety Inventory), and somatization (Psychosomatic Symptom Checklist) were administered to all subjects.

Patients with both esophageal symptoms and either hypertensive lower esophageal sphincter, nutcracker esophagus, or hypotensive contractions exhibited increased somatization, acute anxiety, or depression compared to asymptomatic controls but not compared to symptomatic controls. On the other hand, the psychometric profiles of patients with achalasia and diffuse esophageal spasm were strikingly normal. Among esophageal symptoms, chest pain was closely correlated with psychometric abnormalities.

The esophageal symptoms of patients with abnormal esophageal motility may relate to the underlying psychological abnormalities, independent of manometric abnormalities.

Nutcracker esophagus is a manometric pattern that is commonly seen in patients with functional (noncardiac) chest pain. However, this pattern is often unassociated with pain. Consequently, the pathophysiology of chest pain in these patients is unclear.

We prospectively examined the sensory perception and biomechanical properties of the esophagus in 10 patients with chest pain and a nutcracker esophagus, along with those properties in 12 healthy controls using impedance planimetry.

Stepwise balloon distentions reproduced typical chest pain in 9/10 (90%) patients. The threshold for chest pain was lower (p < 0.05) in patients than in controls (mean +/- SD 43+/-5 vs 62+/-4 cm H2O) but only 2/12 controls experienced pain. The thresholds for first perception and moderate discomfort were also lower (18+/-8 vs 30+/-11 cm H2O, p < 0.01 and 28+/-9 vs 62+/-5 cm H2O, p < 0.001) in patients than in controls, but only 3/12 controls experienced moderate discomfort. The esophageal reactivity to balloon distention was higher in patients than in controls (p < 0.001). The tension-strain curve shifted to the left in the patient group when compared to that in the controls (p < 0.05).

Patients with a nutcracker esophagus demonstrate a hypersensitive and stiff esophagus. Because balloon distention reproduced their chest pain, visceral hyperalgesia of the esophagus may be relevant to the pathogenesis of their pain. Balloon distention test may be more useful in the evaluation of patients with functional chest pain and a nutcracker esophagus.

Approximately 30% of coronary angiograms performed in this country are negative for significant coronary artery disease. These patients are classified as having noncardiac or unexplained chest pain (UCP). Despite the good overall prognosis, this condition has significant morbidity and costs. The pathophysiology of this condition is likely caused by overlapping cardiac, esophageal, and psychiatric abnormalities with visceral hyperalgesia playing a central role. Gastroenterologists are often consulted in the evaluation of these patients because esophageal disorders are among the most common conditions associated with UCP. However, clinical symptoms are unreliable in differentiating between esophageal and cardiac causes of UCP. Gastroesophageal reflux disease, not esophageal motility disorders, is the most common esophageal disorder present in patients with UCP. The most useful diagnostic test in the evaluation of UCP is 24-h pH monitoring. An initial empiric trial of high-dose acid suppression is the most cost-effective intervention in the management of these patients. A clinical algorithm is suggested for the evaluation and treatment of UCP.

There has been an explosion in understanding of the psychosocial concomitants of functional gastrointestinal disorders. Detecting psychologic disturbance and eliciting a history of physical or sexual abuse are critical in suggesting comprehensive and efficacious treatment strategies for these patients. The challenge is to define further the use of psychopharmacologic agents, including the newer antidepressants, anticonvulsants, and anxiolytic agents, in the treatment of chronic functional gastrointestinal disorders. Further research to evaluate the usefulness of various forms of psychotherapeutic and behavioral interventions needs to be undertaken. Establishing a multicomponent treatment program delivered by a team of caregivers, each bringing their unique skills (internist, psychiatrist, psychologist, and others) to patients, must be based on further research on the efficacy of these modalities as opposed to empiric treatment.

The syndrome of angina-like pain with normal epicardial coronary vessels is a very common and expensive clinical problem. Patients suffering from this condition frequently present a diagnostic challenge. Cardiac and musculoskeletal disorders must be excluded prior to identifying the esophagus as the source of pain. The term "chest pain of undetermined origin" (UCP) has been proposed to refer to this condition. Esophageal dysmotility was previously considered a major source for chest pain; however, recent studies indicate that esophageal reflux is the most common cause of esophageal pain. Two controlled trials of acid suppressive agents in patients with chest pain have shown that omeprazole provides effective pain relief for the majority of these individuals. Visceral hyperalgesia and psychologic disturbances are also commonly noted in patients with UCP. Much remains to be learned about the etiology of visceral hyperalgesia and the precise role of psychologic abnormalities in these patients. Until further information is available, treatment with imipramine or trazodone has been shown to offer effective relief of chest pain for subgroups of patients with UCP. Psychologic intervention is also valuable in the management of some patients. Studies of other therapeutic regimens continue to be conducted.

Swallowing is a complex mechanism based on the coordinated collaboration of tongue, pharynx and esophagus. Disturbances of this interplay or disorders of one or several of these components lead to dysphagia, non-cardiac chest pain or regurgitation. The major primary esophageal motility disorders--achalasia, diffuse esophageal spasm, hypercontractile esophagus ('nutcracker esophagus') and non-specific motility disorder--are of unknown etiology. Other esophageal diseases, such as cervical diverticula or gastroesophageal reflux disease, might also be caused by a primary esophageal motility disorder. Medical treatment of esophageal disorders with esophageal hyper- or dysmotility requires agents that reduce esophageal contractile force (anticholinergic agents, nitrates, calcium antagonists). Despite the beneficial effect of the various drugs on esophageal motility parameters, the clinical benefit of medical treatment of esophageal motility disorders is rather disappointing. Calcium channel antagonist, alone or in combination with anticholinergics or nitrates, can be used as a medical trial, especially in mild achalasia. However, medical therapy is clearly inferior to pneumatic balloon dilation therapy. Recently, botulinum toxin injection was suggested as a therapeutic option in achalasia patients with good results on lower esophageal sphincter pressure (LESP) and symptom scores that were similar to the results achieved by pneumatic balloon dilation. Hypercontractile esophagus shows a good manometric response to calcium channel antagonists, but only little clinical effect in terms of improvement of symptoms. Diffuse esophageal spasm is a relatively rare disease and few clinical studies are available. The use of calcium channel antagonists can be beneficial, at least in some patients with diffuse esophageal spasm. From clinical and epidemiological studies, there is some evidence of a 'psychological' component in the pathogenesis or perception of esophageal symptoms. There is some clinical benefit from centrally acting drugs such as benzodiazepines or antidepressants. With the exception of botulinum toxin for achalasia, medical therapy of primary esophageal motility disorders is rather limited and the clinical results are poor. Further understanding of esophageal pathophysiology as well as development of new receptor-selective drugs might increase our chances of a successful treatment of primary esophageal motility disorders.

The cause of diffuse esophageal spasm (DES) has not been clearly established, and effective treatment is lacking. To determine whether a psychosomatic approach can be effective in treating DES patients, nine patients and 26 healthy volunteers were studied. Esophageal manometry and psychological testing were performed in both groups. The psychological background of the DES patients was investigated. Psychiatric diagnoses were made according to the criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised. The authors started psychosomatic treatment with isosorbide dinitrate for 1 month, then prescribed serotonin reuptake inhibitor antidepressants for an additional month. Anxiety and depression scores were substantially higher for the DES group than for the control group. Five of the nine DES patients (56%) were diagnosed as having major psychiatric disorders. Only one patient showed improvement with isosorbide dinitrate, and eight patients improved with antidepressants. These initial observations suggest that psychosomatic treatment with antidepressants may be effective in the treatment of DES.

Little is known about esophageal nociceptive thresholds in chronic heartburn sufferers with normal clinical findings. The aim of this study was to evaluate and to characterize the pathogenesis of heartburn in subjects who chronically use antacids and had not sought medical attention.

Subjects (N = 152) with chronic heartburn of > or = 3 months duration underwent endoscopic grading of the esophagus, esophageal manometry, Bernstein testing, intraesophageal balloon distention (IEBD), and 24-h esophageal pH monitoring.

Normal acid contact time (ACT < or = 6%) was observed in 43% of these subjects with recurrent heartburn. Of subjects with normal ACT, 64% had normal LES pressure (> or = 10 mm Hg), 79% had normal esophageal endoscopy, 89% developed heartburn during Bernstein acid infusion, and 52% perceived IEBD as painful.

Approximately 30% of individuals chronically using antacids for heartburn had esophageal sensitivity to mechanical or chemical stimuli despite negative endoscopy and pH monitoring. Our findings suggest that a significant subset of typical heartburn sufferers have a lower threshold for esophageal sensation and pain, which may influence options for pharmacological intervention in such subjects.

The purpose of this study was to explore the value of patient self-report assessment in heart transplant candidacy evaluation, utilizing the Millon Behavioral Health Inventory (MBHI). Patient's MBHI measures were related to important pretransplant patient characteristics and posttransplant measures of health behavior, medical morbidity, and mortality.

Ninety heart patients with end-stage cardiac disease completed the MBHI during pretransplant candidacy evaluations, and also were interviewed concerning their coping effectiveness, support resources, and compliance history. Postransplant follow-up of 61 living and 29 deceased patients included measures of survival time, postsurgical medical care, rejection and infection episodes, and nurse ratings of medication compliance and problematic interpersonal health behaviors.

The MBHI coping scales were found to significantly discriminate good and poor pretransplant compliance, and interview judgments of good and poor coping and support resources, with modest accuracy. The MBHI also was superior to these interview judgments in predicting posttransplant survival time and medical care used. Certain scales were also positively associated with physical parameters of pretransplant and posttransplant status.

Patient self-report with the MBHI can contribute to identification of patients at risk for a problematic outcome with transplant, by providing information pertinent to clinical decision making and outcome management analysis with this special population of cardiac patients.

Clinical and experimental observations indicate that the motility of the oesophagus may be affected by emotional stimuli. The aim of this study was to evaluate the incidence of oesophageal contractility impairment in patients suffering from a psychiatric disorder. Fifty-one patients admitted to the psychiatric department were submitted to an oesophageal transit study by means of krypton-81m. All patients with an abnormal oesophageal transit underwent manometry and endoscopy. The level of depression and anxiety was evaluated by the treating psychiatrist, using the Hamilton Depression and Anxiety Rating Scales. The oesophageal transit was abnormal in 13 patients. Two of these 13 patients refused manometric investigation. In ten of the 11 remaining patients, the manometry revealed functional motor abnormalities. Endoscopy, performed in all these ten patients, was normal. In conclusion, a high percentage of oesophageal contractility disturbances was found in psychiatric patients complaining of anxiety and/or depression. These abnormalities were detected by scintigraphy as well as by manometry. Owing to the normal endoscopic findings, these contraction abnormalities are likely to reflect a functional motor impairment.

Prokinetic therapy has been shown to improve patients' symptoms associated with gastrointestinal motility disorders and quality of life. This study investigated the correlation between clinical improvement and quality of life after 12 months of treatment with cisapride or domperidone in patients with severe dyspepsia. Psychological and quality-of-life measures were assessed at baseline and after 12 months of therapy using three patient-administered, standardized questionnaires: the Minnesota Multiphasic Personality Inventory, the Millon Behavioral Health Inventory, and the Sickness Impact Profile. Changes in clinical symptoms were correlated with changes in these measures. Twenty-seven patients with symptoms of severe dyspepsia were treated with cisapride or domperidone (60-80 mg/day) for 12 months. Symptoms and quality-of-life measures were improved at the end of therapy. There were significant correlations between improvement in clinical symptoms and improvement in quality of life parameters. Patients with more marked symptom improvement had more significant improvements in quality of life measures. We conclude that prokinetic therapy improved symptoms and quality of life. Standardized questionnaires can be used to quantify response to prokinetic therapy and to individualize treatment regimens for patients with dyspepsia who have specific psychologic or behavioral characteristics.

Increased numbers of psychiatric diagnoses and increased levels of psychological distress are seen in the majority of medical clinic patients with gastrointestinal motility disorders. In IBS, psychological symptoms are believed to be comorbid conditions, which do not cause the motility disorder but which do influence the patient's decision to consult a physician. In functional dyspepsia, psychological symptoms are present in many patients, but their role is not known; the available data suggest that psychological symptoms do not predict which patients will consult a physician. Among constipated patients, anxiety is believed to contribute to the development and course of pelvic floor dyssynergia by increasing pelvic floor muscle tension. Constipated patients without physiologic abnormalities to explain their constipation appear to have more psychological symptoms than those with delayed colonic transit, but there is significant psychological distress even in patients with slow transit constipation. Psychological symptoms do not seem to predict which constipated patients will consult a physician. There is an increased incidence of psychiatric diagnoses in patients with esophageal motility disorders as well, but the role that these psychological symptoms play in the course of the disorder is not known. Patients with the most common gastrointestinal motility disorders, IBS and dyspepsia, report experiencing more stressful life events, and IBS patients appear to show a greater increase in gastrointestinal symptoms when exposed to stressors. Laboratory studies document that acute psychological stressors do alter gastric, small bowel, and colonic motility, and patients with IBS appear to show a greater change in colonic and ileal motility with stress than healthy controls. Greater reactivity has not been demonstrated for the esophagus or stomach, however, and it has not been demonstrated for other gastrointestinal motility disorders. A characteristic of many patients who consult gastroenterologists for IBS and other motility disorders is a tendency to report multiple somatic complaints (including many nongastrointestinal complaints) and to overuse medical resources. This pattern of behavior is referred to as somatization or abnormal illness behavior. One source of abnormal illness behavior is childhood social learning, which occurs (1) when parents provide gifts or special privileges to a child who reports somatic symptoms or (2) when parents model abnormal illness behaviors themselves.

We hypothesized that patients who complain of dysphagia without demonstrable organic abnormality may have an underlying psychological dysfunction. We thus conducted a comprehensive assessment in three groups of patients with dysphagia. Dysphagia was classified as obstructive (Obst) when an obstructive lesion was present on esophagoscopy or barium swallow, motility-related (Mot) when abnormal motility was shown on esophageal manometry in the presence of normal esophagoscopy or barium swallow, or nonobstructive, nonmotility-related (NONM) when manometry and esophagoscopy or barium swallow were both normal. We prospectively evaluated 71 patients with Obst-dysphagia, 15 patients with Mot-dysphagia and 10 patients with NONM-dysphagia with a battery of standardized psychological tests including the Minnesota Multiphasic Personality Inventory (MMPI), the Symptom Checklist-90-Revised (SCL-90-R), and the Millon Behavioral Health Inventory (MBHI). The results indicate that patients with NONM-dysphagia have psychological attributes similar to those found in patients with Obst-dysphagia or Mot-dysphagia. Combination of scores for parameters such as somatization, depression, and anxiety could not distinguish among the three groups of dysphagia patients. We thus conclude that patients with NONM-dysphagia, as a group, have similar psychological profiles compared to patients with dysphagia due to organic causes.

Coeliac sprue is a relatively frequent disease with protean clinical manifestations. Recent studies suggest that gastrointestinal motor abnormalities may explain some symptoms complained of by such patients. We investigated whether coeliac patients have oesophageal motor abnormalities from both a clinical and a physiological point of view. Thirty-six consecutive adult sprue subjects (14 during the florid phase and 22 on gluten-free diet) were studied. A clinical questionnaire on gastrointestinal symptoms (with emphasis on those of oesophageal origin) was administered. Moreover, 18 patients (13 on free and five on gluten-free diet) gave their consent for oesophageal manometry and eight subjects for pH-metry also. Oesophageal clinical symptoms were compared with those of 144 age- and sex-matched controls from a general population sample, and manometry with that of 34 healthy volunteers. Of coeliac patients 50% complained of dysphagia (P < 0.001 vs. controls) and 14% noncardiac chest pain (P = NS vs. controls). Manometric examination showed motor abnormalities in 67% of the subjects examined, consisting of nutcracker oesophagus, hypotonic lower oesophageal sphincter associated with simultaneous contractions, and frequent repetitive (> 3 peaks) contractions. These abnormalities were equally distributed among free and gluten-free diet patients. pH-metry showed only one pathological reflux out of eight subjects studied. We conclude that patients with coeliac sprue may display abnormal oesophageal motility. This confirms previous studies suggesting that gastrointestinal motor abnormalities should probably be added to the clinical spectrum of the disease.

In 40% of patients presenting to medical clinics with heartburn, no objective evidence of gastro-oesophageal reflux disease can be demonstrated. Little research has been performed regarding the psychological characteristics of these patients. The aim of this study was to assess the psycho-social profiles of patients presenting with heartburn in an attempt to discriminate between those with pathological reflux and those with functional disease.

One hundred and thirty-eight patients presenting with heartburn underwent endoscopy and oesophageal pH monitoring. They were divided into those with oesophagitis or abnormal degrees of acid reflux into the oesophagus and those with normal endoscopy and normal pH profile. The psychological questionnaires used were the Hassles Scale, the State-Trait Anxiety Index, the Crown-Crisp Experiential Index and the Interview Schedule for Social Interaction.

Patients with functional heartburn did not report any increase in daily hassles nor did they have higher levels of anxiety, depression or other psychological characteristics than those with objective reflux disease. In terms of their available social support, the two groups were similar.

Differences in psychological characteristics and social support structures do not offer an explanation for the heartburn experienced by patients in the absence of objective evidence of reflux disease. Other explanations, including visceral hypersensitivity, should be sought in these patients.

Irritable bowel syndrome may be influenced by the autonomic nervous system. Abnormalities in autonomic function, colon transit time, and psychological profiles in 21 patients were assessed.

Using modified Manning criteria for irritable bowel syndrome, patients were classified as constipation-predominant or diarrhea-predominant. Autonomic function was determined by one vagal cholinergic and two sympathetic adrenergic measures. Colon transit was assessed by radiopaque markers, and psychological profiles were determined by three inventories.

Autonomic function tests showed that diarrhea-predominant subgroup values for one sympathetic adrenergic measure (postural adjustment ratio) were significantly different from controls (P < 0.01). Constipation-predominant subgroup values were significantly lower for the vagal cholinergic measure R-R interval (P < 0.05). Colon transit measures differed by subgroup in left, right, rectosigmoid, and total colon transit times. Both subgroups differed significantly from controls on psychological measures; the constipation subgroup showed more psychological distress.

Irritable bowel syndrome specific-symptom subgroups had different patterns of autonomic functioning, colonic transit, and psychological measures. The constipation subgroup is associated with a cholinergic abnormality and the diarrhea-predominant subgroup with an adrenergic abnormality. These findings suggest specific associations between the autonomic nervous system, predominant physical symptoms, colon transit time, and psychological factors in patients with irritable bowel syndrome.

Angina pectoris is a pain syndrome caused by coronary arteriosclerosis but also by a number of other disorders, including microvascular angina, gastroesophageal reflux (GER), and esophageal dysmotility. The relationship between abnormal physiology and pain in these conditions is complex. Simultaneous ambulatory monitoring of esophageal pH and motility has demonstrated that patients may have identical episodes of chest pain with acid reflux, dysmotility, both types of events, or neither. Patients may have anginal chest pain with inflation of an esophageal balloon, and patients with microvascular angina may have pain with catheter manipulation in the right atrium. Recent evidence suggests that disorders of visceral pain perception may play a role in both chest pain of esophageal origin and microvascular angina. The physiology of visceral pain is reviewed, including concepts of convergence of somatic and visceral afferent input, descending modulation of pain perception, and sensitization of visceral pain afferents. An approach to evaluation and treatment of chest pain in patients with angiographically normal coronary arteries is outlined.

This article presents the normal physiology of esophageal peristalsis. It discusses current approaches to the diagnosis and treatment of primary disorders of the esophagus, including achalasia, nutcracker esophagus, diffuse esophageal spasm, as well as the secondary disorder, scleroderma.

Swallowing is a complex mechanism that is based on the coordinated interplay of tongue, pharynx, and esophagus. Disturbances of this interplay or disorders of one or several of these components lead to dysphagia, non-cardiac chest pain, or regurgitation. The major esophageal motility disorders include achalasia, diffuse esophageal spasm, hypercontractile esophagus ("nutcracker esophagus"), and hypocontractile esophagus ("scleroderma esophagus"). Other esophageal diseases such as hypopharyngeal (Zenker's) diverticula or gastroesophageal reflux disease also may be sequelae of primary esophageal motility disorder. Finally, a substantial group of patients referred for evaluation of possible esophageal motor disorders have milder degrees of dysmotility--referred to as nonspecific esophageal motor disorder--that are of unclear clinical significance. Medical treatment of esophageal motility disorders involves the uses of agents that either reduce (anti-cholinergic agents, nitrates, calcium antagonists) or enhance (prokinetic agents) esophageal contractility. Despite the beneficial effect of the various drugs on esophageal motility parameters, the clinical benefit of medical treatment is often disappointing. From clinical and epidemiological studies there is some evidence for a "psychological" component in the pathogenesis or perception of esophageal symptoms. Further understanding of esophageal pathophysiology, as well as development of new receptor selective drugs, might increase our chances of successful treatment of esophageal motility disorders.

Quality of life measures have received little attention in evaluation of therapy for dyspepsia. To examine the effect of cisapride on gastrointestinal symptoms and quality of life measures, we studied eight patients with chronic, severe dyspepsia, before and after therapy with cisapride (20 mg three times daily) for 12 months. Gastrointestinal (GI) Total Symptom Score (TSS), Overall Patient Assessment (OPA), and quality of life by both trait (Minnesota Multiphasic Personality Inventory (MMPI)) and physical function (Sickness Impact Profile (SIP)) were measured at base line and at month 12 of cisapride therapy. Results showed significant improvement in TSS, OPA, and the MMPI Depression and Anxiety scales (all, p < 0.05). Improvement in the SIP physical dimension score approached significance (p = 0.065). We conclude that, in this group of patients with severe dyspepsia, both GI symptoms and quality of life measures improved with 12 months of cisapride therapy. These quality of life measures may prove useful in evaluating the efficacy of drug treatment for dyspepsia.

The authors reviewed the literature to assess the relationship between psychological factors and gastrointestinal conditions. The conditions that were found to be more relevant and worthy of future investigation were nonulcerative dyspepsia, inflammatory bowel disease (regional enteritis), and irritable bowel syndrome. The pertinent findings suggest that an important link exists between psychological factors and gastroenterological disorders, which supports the need for modification of the DSM-III-R's diagnostic category, "Psychological Factors Affecting Physical Condition." In concert with a subcommittee addressing other organ systems and psychological factors, the authors conclude that a diagnostic approach with greater utility would be useful for both researchers and clinicians. A conceptual framework as proposed in DSM-IV could also advance knowledge of psychological factors and their contribution or role in the etiology, perpetuation, and exacerbation of certain gastrointestinal conditions.

Identifying the cause of recurrent chest pain may be difficult. Significant coronary artery disease must be excluded before patients can be assured that their symptoms are truly "noncardiac." A normal coronary angiogram is the most definitive test but this may not preclude the presence of a new "fly in the ointment," i.e., microvascular angina. Musculoskeletal pain syndromes, psychological problems, and esophageal disorders, including both esophageal motility disorders and gastroesophageal reflux disease, are the most common causes of noncardiac chest pain. Nearly 30% of these patients will have an esophageal motility disorder, although its clinical relevance in the asymptomatic patient is controversial. Simple, inexpensive, provocation tests (most commonly edrophonium, bethanechol, and/or balloon distention) have been developed to recreate motility-related chest pain in the laboratory. These tests can identify the esophagus as the source of pain, but in most cases they do not direct therapy. Other disadvantages of provocation tests include the lack of a gold standard reference point, side effects, and the need for placebo because of a subjective end point. Recently, ambulatory esophageal pH and pressure monitoring have been used to define precisely the cause of esophageal chest pain. These systems can record multiple episodes of pain for up to 24 hours in an outpatient setting and have shown that gastroesophageal reflux (rather than motility disorders) is the most common esophageal cause of pain. However, these studies also suggest that many episodes of chest pain do not have an identifiable esophageal cause. Furthermore, this equipment is expensive, uncomfortable, may alter normal activity, and is not useful in patients having infrequent pain episodes. Psychological disturbances should be carefully sought in any patient with noncardiac chest pain: Many patients have anxiety, depression, or panic attacks that may complicate or contribute to their reported symptoms. It is questionable if these patients need additional testing. Rather, the challenge of the future is to prove that the multitude of tests aid in the overall treatment and outcome of patients with noncardiac chest pain.

It is imperative to assess the psychosocial factors that may influence the subjective experiences and pain behavior of persons with chronic unexplained chest pain. Both psychologists and physicians tend to rely on self-report measures of psychological distress, which provide little unique information about patients with chronic chest pain to differentiate them from patients with other painful disorders such as irritable bowel syndrome, gastroesophageal reflux disease, or coronary artery disease. However, assessment of pain-coping strategies, spouse responses to the patient's pain behaviors, and pain thresholds for esophageal balloon distention do differentiate patients with chronic chest pain from healthy controls and patients with various other chronic pain disorders. Specifically, chronic chest pain patients tend to use relatively passive pain-coping strategies such as praying and hoping, and to report relatively high levels of spouse reinforcement of pain behaviors. Finally, in response to esophageal balloon distention, chronic chest pain patients display low pain thresholds that do not generalize to stimulation by mechanical finger pressure. Preliminary evidence suggests these low thresholds are due primarily to a tendency to set low standards for making pain judgments regarding esophageal stimuli of moderate-to-high intensity levels.

Psychoactive medications have been used to manage chest pain of presumed esophageal origin, especially in syndromes associated with esophageal motor dysfunction. The rationale for their use is based on (a) the high prevalence of psychiatric disorders reported in patient groups with esophageal symptoms and minor motor dysfunction, (b) recognized psychophysiologic effects on esophageal motor activity, (c) the potential benefits that nerve-modulating drugs may have on the pathogenesis of the syndromes (independent of psychiatric factors), and (d) observations from treatment trials for chronic pain--including irritable bowel syndrome, a disorder that shares some clinical features with functional esophageal chest pain. Although psychiatric factors may have interactive effects on the presentation and course of reflux disease, the use of psychoactive drugs in reflux disease has not been tested. The effects of psychoactive drugs have been systematically explored and documented in only one study. At present, the mechanisms of esophageal symptom reduction resulting from psychopharmacologic treatments are not clear, but reduced sensitivity to visceral stimuli remains one possibility.

The ability to reproduce chest pain and to identify the esophagus as the source of this pain are the major reasons why provocation testing has become standard in the evaluation of patients with noncardiac chest pain. Recent studies that challenge the validity of performing provocation tests have polarized experts into two camps: those who would abandon such testing because of its low sensitivity and low specificity, and those who would use testing judiciously because of moderate increases in diagnostic yield. Use of 24-hour pH and pressure testing has shown a high number of chest pain events associated with acid reflux in patients with positive cholinergic stimulation tests and esophageal dysmotility, as well as pain with esophageal dysmotility in patients with positive acid infusion tests. Mechanisms of esophageal chest pain are not known. All provocation agents can decrease coronary flow reserve (i.e., induce microvascular angina), thus raising the question of a cardiac source of pain even in patients with positive presumed esophageal provocation. Acid infusion, cholinergic stimulation, and balloon distention are discussed in light of 24-hour pH and pressure monitoring. Esophageal distention and the role of acid in inducing chest pain are emphasized. The role of stress, the use of defined stressors to induce chest pain, and altered pain perception as a final common pathway for chest pain are examined.