Redux: Do Little Bellyachers Grow up to Become Big Bellyachers?

Abstract

Although stated more than 40 years ago,1Apley J. Hale B. Children with recurrent abdominal pain: how do they grow up?.Br Med J. 1973; 3: 7-9Crossref PubMed Scopus (156) Google Scholar this question is one that scientists are still seeking to answer. Certainly clinicians note that many of their adult patients with functional gastrointestinal disorders (FGIDs) recall gastrointestinal (GI) difficulties in childhood. But to really answer this question we need to look prospectively.In this issue Horst et al2Horst S. Shelby G. Anderson J. et al.Predicting persistence of functional abdominal pain from childhood into young adulthood.Clin Gastroenterol Hepatol. 2014; 12: 2026-2032Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar present data from a cohort of 392 pediatric patients aged 8–16 years who were seen in a subspecialty clinic for recurrent abdominal pain. These patients were followed 5–15 years to determine the presence of Rome III pain-related FGIDs including irritable bowel syndrome (IBS), functional dyspepsia (FD), functional abdominal pain syndrome (FAPS), and abdominal migraine. They found that on average 9 years later, 41% met symptom criteria for FGID (mostly IBS and FD). In addition, when controlling for demographic factors and pain levels, baseline extraintestinal symptoms and depression significantly predicted later having an FGID. Possibly the findings would have been more robust if a variety of psychological domains were assessed, although depression can be seen as a measure in general of psychological distress. Also, less than 1% were eventually diagnosed to have an organic disease (1 was diagnosed with ulcerative colitis, and 2 were diagnosed with multiple sclerosis; the latter seem less likely related to the initial presenting symptoms).This is a sound study because of its prospective design, the retention of a large number of patients during a period of many years, and the use of standard psychometric measures. Although undertaken in a specialty practice, the findings harmonize with and confirm data from population and primary care studies and attest to the important role for psychological factors and somatic reporting tendency in understanding childhood abdominal pain. Furthermore, the study provides some reassurance to clinicians who feel compelled to rigorously evaluate for other disease when children present with functional abdominal pain symptoms. More likely a conservative initial assessment looking for “red flags” and follow-up visits are sufficient, as has been determined in one primary care prospective study in adults3Begtrup L.M. Engsbro A.L. Kjeldsen J. et al.A positive diagnostic strategy is noninferior to a strategy of exclusion for patients with irritable bowel syndrome.Clin Gastroenterol Hepatol. 2013; 11: 956-962Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar and recommended by a consensus group in pediatrics.4Di L.C. Colletti R.B. Lehmann H.P. Chronic abdominal pain In children: a technical report of the American Academy of Pediatrics and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.J Pediatr Gastroenterol Nutr. 2005; 40: 249-261Crossref PubMed Scopus (85) Google ScholarThe authors’ findings of psychological distress and other somatic symptoms raise questions regarding how they lead to pediatric functional GI pain and its persistence; in other words, “How do children become little bellyachers, and why do some also grow up as bellyachers?” This requires an appraisal of the mutually interactive factors relating to biological predisposition, early developmental exposures, parental influences, and psychosocial factors, all of which are subsumed within the biopsychosocial model.5Drossman D.A. Biopsychosocial issues in gastroenterology.in: Feldman M. Friedman L.S. Brandt L.J. Sleisenger and Fordtrans's gastrointestinal and liver disease. 10th ed. Saunders Elsevier, Philadelphia2014Google Scholar, 6Drossman D.A. Presidential address: gastrointestinal illness and biopsychosocial model.Psychosom Med. 1998; 60: 258-267Crossref PubMed Scopus (310) Google ScholarAbdominal pain in childhood first became recognized as an entity from a seminal study by Apley and Naish7Apley J. Naish N. Recurrent abdominal pains: a field survey of 1000 children.Arch Dis Child. 1957; 33: 165-170Crossref Scopus (650) Google Scholar in 1957. The investigators attended 1000 routine student health examinations in the Bristol, England primary and secondary schools to identify the prevalence of recurrent abdominal pain. They found that about 11% of the children met criteria of having at least 3 bouts of usually mid-abdominal pain during a period of 3 months that were severe enough to affect activities, and by using less stringent criteria, one-third of the study group had some abdominal pain. When compared with the group of children who never had pain, the ones with abdominal pain were characterized by 5 important features: (1) abdominal pain onset beginning at around 5 years of age; (2) the prevalence was similar in young boys and girls until early adolescence when it dropped in boys and continued to increase in girls, which is consistent with the higher prevalence of FGIDs seen in girls in later adolescence and adulthood; (3) those with abdominal pain reported additional symptoms such as headaches and other painful attacks; (4) the afflicted children more likely had family members with complaints of abdominal pain and other somatic symptoms; and (5) the pain was more likely associated with frequent “emotional disturbances” such as undue fears, enuresis, nightmares, and appetite difficulties, and the children were described as high-strung and anxious.Later work built on and refined this information by using more sophisticated evaluation methods. Saps et al8Saps M. Sztainberg M. Di L.C. A prospective community-based study of gastroenterological symptoms in school-age children.J Pediatr Gastroenterol Nutr. 2006; 43: 477-482Crossref PubMed Scopus (55) Google Scholar did weekly assessment of GI and other symptoms, psychological features, and health behaviors in 237 U.S. students in the third through the eighth grades. They found that 38% reported abdominal pain, and the pain was associated with other GI symptoms such as nausea, vomiting, and bowel disturbance, other somatic symptoms such as headache and chest pain, higher anxiety and depression scores, and poorer quality of life with school absences. Furthermore, they found that when adjusting for the abdominal pain, depression, anxiety, and quality of life were no longer associated with school absenteeism, thus indicating the importance of the abdominal pain as a driver of the health behaviors.Recently, by using the same schoolchild cohort, Lavigne et al9Lavigne J.V. Saps M. Bryant F.B. Models of anxiety, depression, somatization, and coping as predictors of abdominal pain in a community sample of school-age children.J Pediatr Psychol. 2014; 39: 9-22Crossref PubMed Scopus (25) Google Scholar explored in more depth the relation of the pain with psychological measures and found that the association of anxiety and depression with abdominal pain may be mediated by the child’s tendency to somatize, ie, to report other symptoms. When put another way, abdominal pain may occur as part of a general tendency to report symptoms, and this seems enabled by psychological factors such as anxiety and depression.Now the study by Horst et al2Horst S. Shelby G. Anderson J. et al.Predicting persistence of functional abdominal pain from childhood into young adulthood.Clin Gastroenterol Hepatol. 2014; 12: 2026-2032Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar adds the prospective component to show that the clinical features of early life abdominal pain associated with emotional distress and somatic symptoms predict the continuation of the abdominal pain many years later as FGIDs. So how do we put these features into a biopsychosocial conceptualization as to why some children get abdominal pain early in life and why some of them grow up to have functional GI diagnoses? We can think of this from the standpoint of predisposing, precipitating, and perpetuating factors.Predisposing factors set the stage for the later development of the FGID given the proper precipitating circumstances. There is a hereditary component to FGIDs,10Levy R.L. Jones K.R. Whitehead W.E. et al.Irritable bowel syndrome in twins: heredity and social learning both contribute to etiology.Gastroenterology. 2001; 121: 799-804Abstract Full Text Full Text PDF PubMed Scopus (340) Google Scholar although genetic investigation is still early in development; only a few gene polymorphisms have been identified that relate to the syndrome per se.11Saito Y.A. Mitra N. Mayer E.A. Genetic approaches to functional gastrointestinal disorders.Gastroenterology. 2010; 138: 1276-1285Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar However, polymorphisms and other genetic changes will not likely typify the disorder; rather they will more likely affect the individual’s susceptibility to acquiring an FGID, its phenotypic expression, or response to treatments. Thus, genetic factors may increase susceptibility to postinfectious IBS by affecting bacterial recognition, inflammatory response, and epithelial integrity.12Craig O.F. Quigley E.M. Bacteria, genetics and irritable bowel syndrome.Expert Rev Gastroenterol Hepatol. 2010; 4: 271-276Crossref PubMed Scopus (10) Google Scholar In addition, the early family environment can influence the child’s experience of illness and subsequent symptom behaviors. In an important study, Levy et al13Levy R.L. Whitehead W.E. Walker L.S. et al.Increased somatic complaints and health-care utilization in children: effects of parent IBS status and parent response to gastrointestinal symptoms.Am J Gastroenterol. 2004; 99: 2442-2451Crossref PubMed Scopus (161) Google Scholar found that the children whose mothers had IBS, when compared with children whose mothers did not have IBS, reported more frequent stomachaches and non-GI symptoms, and this was associated with more school absences and physician visits for GI and non-GI symptoms. Furthermore, when the mothers with IBS paid more attention to the child’s illness complaints with solicitous behaviors, the children reported even more severe stomachaches and school absences for stomachaches. Subsequently, studies by Walker et al14Walker L.S. Williams S.E. Smith C.A. et al.Parent attention versus distraction: impact on symptom complaints by children with and without chronic functional abdominal pain.Pain. 2006; 122: 43-52Abstract Full Text Full Text PDF PubMed Scopus (225) Google Scholar indicated that these conditioning effects can be unlearned by training parents to modify their responses to the child’s illness reporting. More recently, benefit was seen with a prospective randomized study of 200 children with functional abdominal pain and their parents that involved 3 sessions of social learning and cognitive behavioral therapy. The study showed (1) decreases in GI symptom severity and greater pain coping in children with functional abdominal pain and (2) decreases in solicitous behaviors and reduced maladaptive beliefs regarding their child’s pain in the parents15Levy R.L. Langer S.L. Walker L.S. et al.Twelve-month follow-up of cognitive behavioral therapy for children with functional abdominal pain.JAMA Pediatr. 2013; 167: 178-184Crossref PubMed Scopus (24) Google Scholar; the latter were the factors that mediate the development and perpetuation of the GI symptoms.16Levy R.L. Langer S.L. Romano J.M. et al.Cognitive mediators of treatment outcomes in pediatric functional abdominal pain.Clin J Pain. 2014 Jan 24; (Epub ahead of print)PubMed Google ScholarWith regard to precipitating factors, it is noteworthy that Apley and Naish7Apley J. Naish N. Recurrent abdominal pains: a field survey of 1000 children.Arch Dis Child. 1957; 33: 165-170Crossref Scopus (650) Google Scholar observed the onset of painful symptoms at age 5 when beginning school. For a child of that age, the transition from home to school is probably the greatest stressful life event to occur, which is something that parents often see with their own children. Also children may develop gastroenteritis, and under the proper stressful circumstances as delineated above, they may develop postinfectious IBS.17Collins S.M. Chang C. Mearin F. Postinfectious chronic gut dysfunction: from bench to bedside.Am J Gastroenterol. 2012; 1: 2-8Crossref Google Scholar In one study when exposed to a salmonella gastroenteritis outbreak, children were even more susceptible than adults to develop postinfectious IBS, and having this disorder was independently associated with high levels of anxiety.18Cremon C. Stanghellini V. Pallotti F. et al.Salmonella gastroenteritis during childhood is a risk factor for irritable bowel syndrome in adulthood.Gastroenterology. 2014; 147: 69-77Abstract Full Text Full Text PDF PubMed Scopus (61) Google ScholarPerpetuating factors address why a condition persists when it might not in others. We should again consider early learning factors including the role of family’s influences on the illness as reinforcers. To illustrate, consider this case.5Drossman D.A. Biopsychosocial issues in gastroenterology.in: Feldman M. Friedman L.S. Brandt L.J. Sleisenger and Fordtrans's gastrointestinal and liver disease. 10th ed. Saunders Elsevier, Philadelphia2014Google Scholar A young child wakes up on the day of a school examination with anxiety and “flight-fight” symptoms of tachycardia, diaphoresis, abdominal cramps, and diarrhea. The parent keeps the child home because of a “tummy-ache” and permits staying in bed to watch television and play with toys. Several days later when the child is encouraged to go back to school, the symptoms recur. In this case, the parent focused on the abdominal discomfort as an illness that required absence from school rather than as a physiological response to a distressing situation. Staying home rewarded the child by avoiding the feared situation without addressing the psychological determinants of the fear. Repetition of the feared situation might then lead to a conditionally enhanced psychophysiological symptom response and also may alter the child’s perception of these symptoms to see them as an illness. This can lead to health care–seeking behaviors later in life (illness modeling). If the parent had more specifically addressed the child’s emotional distress, it would have been communicated verbally instead of in a surrogate fashion through physical symptoms. The parent’s acknowledgment of the distress would have been validating and therapeutic. In 2 studies,19Whitehead W.E. Winget C. Fedoravicius A.S. et al.Learned illness behavior in patients with irritable bowel syndrome and peptic ulcer.Dig Dis Sci. 1982; 27: 202-208Crossref PubMed Scopus (240) Google Scholar, 20Lowman B.C. Drossman D.A. Cramer E.M. et al.Recollection of childhood events in adults with irritable bowel syndrome.J Clin Gastroenterol. 1987; 9: 324-330Crossref PubMed Scopus (116) Google Scholar patients with IBS who sought health care recalled more parental attention toward their illnesses than those with IBS who did not seek health care; they stayed home from school and saw physicians more often and received more gifts and privileges. Somatic responses to stressful situations may be reduced when the parent openly solicits and responds to the thoughts and feelings of the child, thus making these thoughts and feelings acceptable.Another perpetuating set of factors seen here relates to the co-occurrence of other psychological and somatic symptoms with the abdominal pain. The frequency of somatic symptoms in adults is strongly related to psychological distress, and their co-occurrence seems to be associated with poorer health outcomes.21Creed F. Levy R. Bradley L. et al.Psychosocial aspects of functional gastrointestinal disorders.in: Drossman D.A. Corazziari E. Delvaux M. Rome III: the functional gastrointestinal disorders. 3rd ed. Degnon Associates, Inc, McLean, VA2006: 295-368Google Scholar, 22Drossman D.A. Li Z. Leserman J. et al.Health status by gastrointestinal diagnosis and abuse history.Gastroenterology. 1996; 110: 999-1007Abstract Full Text Full Text PDF PubMed Scopus (205) Google Scholar The brain’s ability to filter incoming visceral and somatic signals is highly modifiable by environmental and psychological factors, and the greater the anxiety and depression, the more that symptoms are reported.23Bair M.J. Robinson R.L. Katon W. et al.Depression and pain comorbidity: a literature review.Arch Intern Med. 2003; 163: 2433-2445Crossref PubMed Scopus (2335) Google Scholar, 24Zaubler T.S. Katon W. Panic disorder and medical comorbidity: a review of the medical and psychiatric literature.Bulletin of the Menninger Clinic. 1996; 60: A12-A38PubMed Google Scholar This is seen with conditions such as posttraumatic stress from exposure to abuse, war trauma, and other severe life stress associated with multiple symptom reports.25Vaccarino A.L. Sills T.L. Evans K.R. et al.Multiple pain complaints in patients with major depressive disorder.Psychosom Med. 2009; 71: 159-162Crossref PubMed Scopus (57) Google Scholar, 26Mayeux R. Drossman D.A. Basham K.K. et al.The stress response: Gulf war and health—physiologic, psychologic, and psychosocial effects of deployment-related stress.vol 6. the National Academies Press, Washington, DC2008: 49-74Google Scholar, 27Mayeux R. Drossman D.A. Basham K.K. et al.Gulf war and health: physiologic, psychologic, and psychosocial effects of deployment-related stress. the National Academies Press, Washington, DC2008Google Scholar In fact, the recently identified disorder, multisymptom illness, occurs in soldiers returning from deployment after experiencing war trauma.28Rosof B.M. Cardenas D.D. deGruy F.V. et al.Possible factors underlying chronic multisymptom illness: Gulf war and health—treatment for chronic multisymptom illness.1st ed. the National Academies Press–the Institute of Medicine, Washington, DC2013: 203-206Google ScholarThis association of pain and other symptoms with emotional distress relates in part to the effects of stressors on limbic areas of the brain (eg, cingulate cortex) involved with the regulation of pain and symptom experience.28Rosof B.M. Cardenas D.D. deGruy F.V. et al.Possible factors underlying chronic multisymptom illness: Gulf war and health—treatment for chronic multisymptom illness.1st ed. the National Academies Press–the Institute of Medicine, Washington, DC2013: 203-206Google Scholar, 29Ringel Y. Drossman D.A. Leserman J.L. et al.Effect of abuse history on pain reports and brain responses to aversive visceral stimulation: an fMRI study.Gastroenterology. 2008; 134: 396-404Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar This concept is illustrated in Figure 1, which demonstrates that multiple somatic and visceral sensations (for example, muscle pain, fatigue, and abdominal pain) occurring in the body are only experienced as symptoms when the signal amplitude is above the brain’s perception threshold. Thus, peripheral neural signals arising from an injury might be above the perception threshold and be experienced as a symptom, whereas other regulatory signals (for example, increased gut signals after eating) are received in the brain but are not experienced as a symptom unless one overeats or has a GI disorder. In addition, the brain’s ability to down-regulate the incoming signals (that is, raise the threshold level) will depend on regulatory processes and the person’s cognitive and emotional state. In this way, injuring oneself might not be experienced as a symptom when being distracted during a sports event until the game is over. Conversely, anxiety about the injury with hypervigilance to the affected part can lower the brain’s perception threshold and lead to increased pain. From this perspective, centrally targeted treatments such as psychological treatment or psychopharmacologic treatments will likely have therapeutic value by increasing sensation thresholds among children with more severe and persistent symptoms.I believe that the advantage of identifying these psychosocial associations in childhood is that treatments can be implemented early and with lasting benefits. As more stress management, behavioral, and pharmacologic treatment options30Palsson O.S. Whitehead W.E. Psychological treatments in functional gastrointestinal disorders: a primer for the gastroenterologist.Clin Gastroenterol Hepatol. 2013; 11: 208-216Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar emerge in pediatrics, we may in time reduce the incidence of big bellyachers. Although stated more than 40 years ago,1Apley J. Hale B. Children with recurrent abdominal pain: how do they grow up?.Br Med J. 1973; 3: 7-9Crossref PubMed Scopus (156) Google Scholar this question is one that scientists are still seeking to answer. Certainly clinicians note that many of their adult patients with functional gastrointestinal disorders (FGIDs) recall gastrointestinal (GI) difficulties in childhood. But to really answer this question we need to look prospectively. In this issue Horst et al2Horst S. Shelby G. Anderson J. et al.Predicting persistence of functional abdominal pain from childhood into young adulthood.Clin Gastroenterol Hepatol. 2014; 12: 2026-2032Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar present data from a cohort of 392 pediatric patients aged 8–16 years who were seen in a subspecialty clinic for recurrent abdominal pain. These patients were followed 5–15 years to determine the presence of Rome III pain-related FGIDs including irritable bowel syndrome (IBS), functional dyspepsia (FD), functional abdominal pain syndrome (FAPS), and abdominal migraine. They found that on average 9 years later, 41% met symptom criteria for FGID (mostly IBS and FD). In addition, when controlling for demographic factors and pain levels, baseline extraintestinal symptoms and depression significantly predicted later having an FGID. Possibly the findings would have been more robust if a variety of psychological domains were assessed, although depression can be seen as a measure in general of psychological distress. Also, less than 1% were eventually diagnosed to have an organic disease (1 was diagnosed with ulcerative colitis, and 2 were diagnosed with multiple sclerosis; the latter seem less likely related to the initial presenting symptoms). This is a sound study because of its prospective design, the retention of a large number of patients during a period of many years, and the use of standard psychometric measures. Although undertaken in a specialty practice, the findings harmonize with and confirm data from population and primary care studies and attest to the important role for psychological factors and somatic reporting tendency in understanding childhood abdominal pain. Furthermore, the study provides some reassurance to clinicians who feel compelled to rigorously evaluate for other disease when children present with functional abdominal pain symptoms. More likely a conservative initial assessment looking for “red flags” and follow-up visits are sufficient, as has been determined in one primary care prospective study in adults3Begtrup L.M. Engsbro A.L. Kjeldsen J. et al.A positive diagnostic strategy is noninferior to a strategy of exclusion for patients with irritable bowel syndrome.Clin Gastroenterol Hepatol. 2013; 11: 956-962Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar and recommended by a consensus group in pediatrics.4Di L.C. Colletti R.B. Lehmann H.P. Chronic abdominal pain In children: a technical report of the American Academy of Pediatrics and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.J Pediatr Gastroenterol Nutr. 2005; 40: 249-261Crossref PubMed Scopus (85) Google Scholar The authors’ findings of psychological distress and other somatic symptoms raise questions regarding how they lead to pediatric functional GI pain and its persistence; in other words, “How do children become little bellyachers, and why do some also grow up as bellyachers?” This requires an appraisal of the mutually interactive factors relating to biological predisposition, early developmental exposures, parental influences, and psychosocial factors, all of which are subsumed within the biopsychosocial model.5Drossman D.A. Biopsychosocial issues in gastroenterology.in: Feldman M. Friedman L.S. Brandt L.J. Sleisenger and Fordtrans's gastrointestinal and liver disease. 10th ed. Saunders Elsevier, Philadelphia2014Google Scholar, 6Drossman D.A. Presidential address: gastrointestinal illness and biopsychosocial model.Psychosom Med. 1998; 60: 258-267Crossref PubMed Scopus (310) Google Scholar Abdominal pain in childhood first became recognized as an entity from a seminal study by Apley and Naish7Apley J. Naish N. Recurrent abdominal pains: a field survey of 1000 children.Arch Dis Child. 1957; 33: 165-170Crossref Scopus (650) Google Scholar in 1957. The investigators attended 1000 routine student health examinations in the Bristol, England primary and secondary schools to identify the prevalence of recurrent abdominal pain. They found that about 11% of the children met criteria of having at least 3 bouts of usually mid-abdominal pain during a period of 3 months that were severe enough to affect activities, and by using less stringent criteria, one-third of the study group had some abdominal pain. When compared with the group of children who never had pain, the ones with abdominal pain were characterized by 5 important features: (1) abdominal pain onset beginning at around 5 years of age; (2) the prevalence was similar in young boys and girls until early adolescence when it dropped in boys and continued to increase in girls, which is consistent with the higher prevalence of FGIDs seen in girls in later adolescence and adulthood; (3) those with abdominal pain reported additional symptoms such as headaches and other painful attacks; (4) the afflicted children more likely had family members with complaints of abdominal pain and other somatic symptoms; and (5) the pain was more likely associated with frequent “emotional disturbances” such as undue fears, enuresis, nightmares, and appetite difficulties, and the children were described as high-strung and anxious. Later work built on and refined this information by using more sophisticated evaluation methods. Saps et al8Saps M. Sztainberg M. Di L.C. A prospective community-based study of gastroenterological symptoms in school-age children.J Pediatr Gastroenterol Nutr. 2006; 43: 477-482Crossref PubMed Scopus (55) Google Scholar did weekly assessment of GI and other symptoms, psychological features, and health behaviors in 237 U.S. students in the third through the eighth grades. They found that 38% reported abdominal pain, and the pain was associated with other GI symptoms such as nausea, vomiting, and bowel disturbance, other somatic symptoms such as headache and chest pain, higher anxiety and depression scores, and poorer quality of life with school absences. Furthermore, they found that when adjusting for the abdominal pain, depression, anxiety, and quality of life were no longer associated with school absenteeism, thus indicating the importance of the abdominal pain as a driver of the health behaviors. Recently, by using the same schoolchild cohort, Lavigne et al9Lavigne J.V. Saps M. Bryant F.B. Models of anxiety, depression, somatization, and coping as predictors of abdominal pain in a community sample of school-age children.J Pediatr Psychol. 2014; 39: 9-22Crossref PubMed Scopus (25) Google Scholar explored in more depth the relation of the pain with psychological measures and found that the association of anxiety and depression with abdominal pain may be mediated by the child’s tendency to somatize, ie, to report other symptoms. When put another way, abdominal pain may occur as part of a general tendency to report symptoms, and this seems enabled by psychological factors such as anxiety and depression. Now the study by Horst et al2Horst S. Shelby G. Anderson J. et al.Predicting persistence of functional abdominal pain from childhood into young adulthood.Clin Gastroenterol Hepatol. 2014; 12: 2026-2032Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar adds the prospective component to show that the clinical features of early life abdominal pain associated with emotional distress and somatic symptoms predict the continuation of the abdominal pain many years later as FGIDs. So how do we put these features into a biopsychosocial conceptualization as to why some children get abdominal pain early in life and why some of them grow up to have functional GI diagnoses? We can think of this from the standpoint of predisposing, precipitating, and perpetuating factors. Predisposing factors set the stage for the later development of the FGID given the proper precipitating circumstances. There is a hereditary component to FGIDs,10Levy R.L. Jones K.R. Whitehead W.E. et al.Irritable bowel syndrome in twins: heredity and social learning both contribute to etiology.Gastroenterology. 2001; 121: 799-804Abstract Full Text Full Text PDF PubMed Scopus (340) Google Scholar although genetic investigation is still early in development; only a few gene polymorphisms have been identified that relate to the syndrome per se.11Saito Y.A. Mitra N. Mayer E.A. Genetic approaches to functional gastrointestinal disorders.Gastroenterology. 2010; 138: 1276-1285Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar However, polymorphisms and other genetic changes will not likely typify the disorder; rather they will more likely affect the individual’s susceptibility to acquiring an FGID, its phenotypic expression, or response to treatments. Thus, genetic factors may increase susceptibility to postinfectious IBS by affecting bacterial recognition, inflammatory response, and epithelial integrity.12Craig O.F. Quigley E.M. Bacteria, genetics and irritable bowel syndrome.Expert Rev Gastroenterol Hepatol. 2010; 4: 271-276Crossref PubMed Scopus (10) Google Scholar In addition, the early family environment can influence the child’s experience of illness and subsequent symptom behaviors. In an important study, Levy et al13Levy R.L. Whitehead W.E. Walker L.S. et al.Increased somatic complaints and health-care utilization in children: effects of parent IBS status and parent response to gastrointestinal symptoms.Am J Gastroenterol. 2004; 99: 2442-2451Crossref PubMed Scopus (161) Google Scholar found that the children whose mothers had IBS, when compared with children whose mothers did not have IBS, reported more frequent stomachaches and non-GI symptoms, and this was associated with more school absences and physician visits for GI and non-GI symptoms. Furthermore, when the mothers with IBS paid more attention to the child’s illness complaints with solicitous behaviors, the children reported even more severe stomachaches and school absences for stomachaches. Subsequently, studies by Walker et al14Walker L.S. Williams S.E. Smith C.A. et al.Parent attention versus distraction: impact on symptom complaints by children with and without chronic functional abdominal pain.Pain. 2006; 122: 43-52Abstract Full Text Full Text PDF PubMed Scopus (225) Google Scholar indicated that these conditioning effects can be unlearned by training parents to modify their responses to the child’s illness reporting. More recently, benefit was seen with a prospective randomized study of 200 children with functional abdominal pain and their parents that involved 3 sessions of social learning and cognitive behavioral therapy. The study showed (1) decreases in GI symptom severity and greater pain coping in children with functional abdominal pain and (2) decreases in solicitous behaviors and reduced maladaptive beliefs regarding their child’s pain in the parents15Levy R.L. Langer S.L. Walker L.S. et al.Twelve-month follow-up of cognitive behavioral therapy for children with functional abdominal pain.JAMA Pediatr. 2013; 167: 178-184Crossref PubMed Scopus (24) Google Scholar; the latter were the factors that mediate the development and perpetuation of the GI symptoms.16Levy R.L. Langer S.L. Romano J.M. et al.Cognitive mediators of treatment outcomes in pediatric functional abdominal pain.Clin J Pain. 2014 Jan 24; (Epub ahead of print)PubMed Google Scholar With regard to precipitating factors, it is noteworthy that Apley and Naish7Apley J. Naish N. Recurrent abdominal pains: a field survey of 1000 children.Arch Dis Child. 1957; 33: 165-170Crossref Scopus (650) Google Scholar observed the onset of painful symptoms at age 5 when beginning school. For a child of that age, the transition from home to school is probably the greatest stressful life event to occur, which is something that parents often see with their own children. Also children may develop gastroenteritis, and under the proper stressful circumstances as delineated above, they may develop postinfectious IBS.17Collins S.M. Chang C. Mearin F. Postinfectious chronic gut dysfunction: from bench to bedside.Am J Gastroenterol. 2012; 1: 2-8Crossref Google Scholar In one study when exposed to a salmonella gastroenteritis outbreak, children were even more susceptible than adults to develop postinfectious IBS, and having this disorder was independently associated with high levels of anxiety.18Cremon C. Stanghellini V. Pallotti F. et al.Salmonella gastroenteritis during childhood is a risk factor for irritable bowel syndrome in adulthood.Gastroenterology. 2014; 147: 69-77Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar Perpetuating factors address why a condition persists when it might not in others. We should again consider early learning factors including the role of family’s influences on the illness as reinforcers. To illustrate, consider this case.5Drossman D.A. Biopsychosocial issues in gastroenterology.in: Feldman M. Friedman L.S. Brandt L.J. Sleisenger and Fordtrans's gastrointestinal and liver disease. 10th ed. Saunders Elsevier, Philadelphia2014Google Scholar A young child wakes up on the day of a school examination with anxiety and “flight-fight” symptoms of tachycardia, diaphoresis, abdominal cramps, and diarrhea. The parent keeps the child home because of a “tummy-ache” and permits staying in bed to watch television and play with toys. Several days later when the child is encouraged to go back to school, the symptoms recur. In this case, the parent focused on the abdominal discomfort as an illness that required absence from school rather than as a physiological response to a distressing situation. Staying home rewarded the child by avoiding the feared situation without addressing the psychological determinants of the fear. Repetition of the feared situation might then lead to a conditionally enhanced psychophysiological symptom response and also may alter the child’s perception of these symptoms to see them as an illness. This can lead to health care–seeking behaviors later in life (illness modeling). If the parent had more specifically addressed the child’s emotional distress, it would have been communicated verbally instead of in a surrogate fashion through physical symptoms. The parent’s acknowledgment of the distress would have been validating and therapeutic. In 2 studies,19Whitehead W.E. Winget C. Fedoravicius A.S. et al.Learned illness behavior in patients with irritable bowel syndrome and peptic ulcer.Dig Dis Sci. 1982; 27: 202-208Crossref PubMed Scopus (240) Google Scholar, 20Lowman B.C. Drossman D.A. Cramer E.M. et al.Recollection of childhood events in adults with irritable bowel syndrome.J Clin Gastroenterol. 1987; 9: 324-330Crossref PubMed Scopus (116) Google Scholar patients with IBS who sought health care recalled more parental attention toward their illnesses than those with IBS who did not seek health care; they stayed home from school and saw physicians more often and received more gifts and privileges. Somatic responses to stressful situations may be reduced when the parent openly solicits and responds to the thoughts and feelings of the child, thus making these thoughts and feelings acceptable. Another perpetuating set of factors seen here relates to the co-occurrence of other psychological and somatic symptoms with the abdominal pain. The frequency of somatic symptoms in adults is strongly related to psychological distress, and their co-occurrence seems to be associated with poorer health outcomes.21Creed F. Levy R. Bradley L. et al.Psychosocial aspects of functional gastrointestinal disorders.in: Drossman D.A. Corazziari E. Delvaux M. Rome III: the functional gastrointestinal disorders. 3rd ed. Degnon Associates, Inc, McLean, VA2006: 295-368Google Scholar, 22Drossman D.A. Li Z. Leserman J. et al.Health status by gastrointestinal diagnosis and abuse history.Gastroenterology. 1996; 110: 999-1007Abstract Full Text Full Text PDF PubMed Scopus (205) Google Scholar The brain’s ability to filter incoming visceral and somatic signals is highly modifiable by environmental and psychological factors, and the greater the anxiety and depression, the more that symptoms are reported.23Bair M.J. Robinson R.L. Katon W. et al.Depression and pain comorbidity: a literature review.Arch Intern Med. 2003; 163: 2433-2445Crossref PubMed Scopus (2335) Google Scholar, 24Zaubler T.S. Katon W. Panic disorder and medical comorbidity: a review of the medical and psychiatric literature.Bulletin of the Menninger Clinic. 1996; 60: A12-A38PubMed Google Scholar This is seen with conditions such as posttraumatic stress from exposure to abuse, war trauma, and other severe life stress associated with multiple symptom reports.25Vaccarino A.L. Sills T.L. Evans K.R. et al.Multiple pain complaints in patients with major depressive disorder.Psychosom Med. 2009; 71: 159-162Crossref PubMed Scopus (57) Google Scholar, 26Mayeux R. Drossman D.A. Basham K.K. et al.The stress response: Gulf war and health—physiologic, psychologic, and psychosocial effects of deployment-related stress.vol 6. the National Academies Press, Washington, DC2008: 49-74Google Scholar, 27Mayeux R. Drossman D.A. Basham K.K. et al.Gulf war and health: physiologic, psychologic, and psychosocial effects of deployment-related stress. the National Academies Press, Washington, DC2008Google Scholar In fact, the recently identified disorder, multisymptom illness, occurs in soldiers returning from deployment after experiencing war trauma.28Rosof B.M. Cardenas D.D. deGruy F.V. et al.Possible factors underlying chronic multisymptom illness: Gulf war and health—treatment for chronic multisymptom illness.1st ed. the National Academies Press–the Institute of Medicine, Washington, DC2013: 203-206Google Scholar This association of pain and other symptoms with emotional distress relates in part to the effects of stressors on limbic areas of the brain (eg, cingulate cortex) involved with the regulation of pain and symptom experience.28Rosof B.M. Cardenas D.D. deGruy F.V. et al.Possible factors underlying chronic multisymptom illness: Gulf war and health—treatment for chronic multisymptom illness.1st ed. the National Academies Press–the Institute of Medicine, Washington, DC2013: 203-206Google Scholar, 29Ringel Y. Drossman D.A. Leserman J.L. et al.Effect of abuse history on pain reports and brain responses to aversive visceral stimulation: an fMRI study.Gastroenterology. 2008; 134: 396-404Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar This concept is illustrated in Figure 1, which demonstrates that multiple somatic and visceral sensations (for example, muscle pain, fatigue, and abdominal pain) occurring in the body are only experienced as symptoms when the signal amplitude is above the brain’s perception threshold. Thus, peripheral neural signals arising from an injury might be above the perception threshold and be experienced as a symptom, whereas other regulatory signals (for example, increased gut signals after eating) are received in the brain but are not experienced as a symptom unless one overeats or has a GI disorder. In addition, the brain’s ability to down-regulate the incoming signals (that is, raise the threshold level) will depend on regulatory processes and the person’s cognitive and emotional state. In this way, injuring oneself might not be experienced as a symptom when being distracted during a sports event until the game is over. Conversely, anxiety about the injury with hypervigilance to the affected part can lower the brain’s perception threshold and lead to increased pain. From this perspective, centrally targeted treatments such as psychological treatment or psychopharmacologic treatments will likely have therapeutic value by increasing sensation thresholds among children with more severe and persistent symptoms. I believe that the advantage of identifying these psychosocial associations in childhood is that treatments can be implemented early and with lasting benefits. As more stress management, behavioral, and pharmacologic treatment options30Palsson O.S. Whitehead W.E. Psychological treatments in functional gastrointestinal disorders: a primer for the gastroenterologist.Clin Gastroenterol Hepatol. 2013; 11: 208-216Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar emerge in pediatrics, we may in time reduce the incidence of big bellyachers. Predicting Persistence of Functional Abdominal Pain From Childhood Into Young AdulthoodClinical Gastroenterology and HepatologyVol. 12Issue 12PreviewPediatric functional abdominal pain has been linked to functional gastrointestinal disorders (FGIDs) in adulthood, but little is known about patient characteristics in childhood that increase the risk for FGID in young adulthood. We investigated the contribution of gastrointestinal symptoms, extraintestinal somatic symptoms, and depressive symptoms in pediatric patients with functional abdominal pain and whether these predicted FGIDs later in life. Full-Text PDF