Childhood functional gastrointestinal disorders (FGIDs) are defined as a variable combination of often age-dependent, chronic, or recurrent gastrointestinal symptoms not explained by structural or biochemical abnormalities (1,2).
An association between having irritable bowel syndrome (IBS) and having a first-degree relative with abdominal pain and bowel problems has been reported in adult populations (3). Whitehead et al (4,5) have proposed that childhood social learning, defined as what an individual learns from those in his or her environment through mechanisms such as modelling and positive reinforcement, contributes to the development of IBS. They hypothesised that when parents provide toys or gifts or special privileges to children who complain of gastrointestinal (GI) symptoms, they are reinforcing somatic complaints, and that when parents avoid unpleasant tasks and expect special consideration when they are ill, they model illness behaviours that their children emulate (4,5).
Levy et al (6) found evidence for both a genetic and a social learning contribution to the intergenerational transmission of IBS symptoms: The concordance for IBS between monozygotic twins was significantly greater than that between dizygotic twins, but the concordance between mothers and their respective children was greater than that between monozygotic twins.
Family members of youths with functional abdominal pain (FAP) report an excess of FAP (7–10), nongastrointestinal somatic symptoms (eg, headache) (11), anxiety symptoms, and/or depressive symptoms (11) compared with families of healthy controls and controls with GI diseases. Unfortunately, studies (12) of the parents of youths with FAP have relied exclusively on self-report questionnaires and have not included standardized interviews capable of generating categorical diagnoses of FGIDs (eg, IBS) or psychiatric disorders (eg, anxiety, depressive, and somatoform disorders).
The aims of this study were to evaluate the prevalence of FGIDs in parents and siblings of children affected by FGIDs, the psychological profile of both children and parents affected by FGIDs, and whether independent factors, such as sex, age, parental occupation, marital status, and level of education, could influence the prevalence of FGIDs in parents of children with and without FGIDs.
SUBJECTS AND METHODS
We prospectively investigated, from May 2 to October 31, 2007, 103 consecutive patients with a diagnosis of FGIDs, based on the Rome III criteria. The subjects had been referred to the outpatient clinic of the Department of Pediatrics, University of Naples “Federico II” Italy. Fifty-one boys and 52 girls (mean age ± standard deviation [SD] 92.5 ± 52.9 months, range 11–215 months) and their first-degree relatives (103 fathers, 103 mothers, 31 brothers, and 26 sisters) were enrolled in the study.
All of the enrolled children and/or their parents underwent validated questionnaires regarding GI symptoms according to Rome III criteria (1,2). The subjects were classified as having an FGID by their responses to the questionnaire. The subjects could meet criteria for multiple disorders. A detailed history was obtained and physical examination including measurements of height and weight was performed to distinguish functional disorders from nonfunctional causes. When necessary, minimal laboratory tests were performed.
The subjects were excluded if they had symptoms or findings suggestive of physical disease (eg, abnormal physical examination or laboratory findings, persistent vomiting, gastrointestinal bleeding, constitutional symptoms such as fever or weight loss), illnesses that may cause GI symptoms, a history of major abdominal surgery, acute or chronic physical disease, or development disability.
All of the children older than 6 years underwent the Children's Depression Inventory (CDI) and the State-Trait Anxiety Inventory for Children (STAIC). CDI is a brief self-reported test that helps to assess cognitive, affective, and behavioural signs of depression in children and adolescents 6 to 17 years old and evaluates the presence and severity of specific depressive symptoms. There are 27 items quantifying symptoms such as depressed mood, hedonic capacity, vegetative functions, self-evaluation, and interpersonal behaviours. For each item, the individual is asked to select the statement that best describes his or her feelings for the past 2 weeks. The assessment is designed for a variety of situations, including schools, child guidance clinics, paediatric practices, and child psychiatric settings (13–15). The STAIC is a trait scale of 20 items rated on a 3-point scale. In the STAIC questionnaire scores, values >35 are considered indicative of anxiety (16).
All of the parents underwent the Rome III Psychosocial Alarm Questionnaire (17) and a questionnaire that included demographic data, such as sex, age, marital status (coded as single, married, separated, or divorced), level of education (coded as primary school, secondary school, upper secondary school, university college, or university), occupation (coded as housewife/unemployed, artisan [including carpenters, tailors, farmers, masons, mechanics, and factory workers], employee [including officials, bank employees, municipal employees], and free professional [independent contractor, including lawyers, engineers, architects, doctors]), and standard of living (coded as living in the city, including municipalities with >50,000 residents, or in the country, including towns with <50,000 residents).
The Rome III Psychosocial Alarm Questionnaire was produced by the psychosocial aspects of the Functional GI Disorders Subcommittee for Rome III (17). This questionnaire includes screening questions taken from the Hospital Anxiety And Depression Scale (HADS) (18). For example, every interviewed parent had to respond to the questions “in the last week did you feel tense or wound up?” or “in the last week did you feel downhearted and low?” The answers were “most of the time,” “a lot of the time,” “occasionally,” and “not at all.” The answers “most of the time” and “a lot of the time” identity the majority of depressive or anxiety disorders in the study population. These patients had a mean HADS anxiety score of 13.3 (SD 3.6) compared with 6.0 (SD 2.5) for those who scored “occasionally” or “not at all.” A HADS anxiety score of 10 or more indicates a probable case of anxiety, so this level of anxiety merits referral to behavioural management for these patients.
The control group was composed of 65 children referred to the Primary Care Center of the Department of Paediatrics for routine check-ups (M/F 29/36, mean age ± SD 89.7 ± 51.8 months, range 22–216 months) and their first-degree relatives (65 fathers, 65 mothers, 14 brothers, and 14 sisters).
Informed consent for participation in this study was obtained from parents of all of the patients, and the experimental design was approved by the independent ethics committee of the University of Naples “Federico II.”
All of the data were stored in a common database and statistically analysed using SPSS version 14.0 (SPSS Inc, Chicago, IL). The chi-square analysis was used to compare categorical data (eg, social class, marital status, educational level, presence or absence of FGIDs, psychological symptoms in children and in their parents) to obtain an estimate of the possible association. A P value <0.05 was considered to be statistically significant.
Clinical characteristics of the study population are shown in Table 1. The prevalence of a single FGIDs in children and in their first-degree relatives is reported in Table 2.
The prevalence of FGIDs in the group of parents of children having FGIDs was significantly higher than in the group of parents of children not having FGIDs (66/103, 64.1% vs 20/65, 30.8%; χ2 14.3; P < 0.0001) (Table 2). In contrast, in the group of siblings there was no statistical difference between cases and controls regarding the prevalence of FGIDs (15/57, 26.3% vs 4/28, 14.2%, χ2 1.56; P > 0.05).
In particular, we observed that the prevalence of FGIDs in the group of fathers of children with FGIDs was not statistically higher than in the group of fathers of children without FGIDs (15/103, 14.5%, vs 6/65, 9.2%; χ2 1.20, P > 0.05). On the contrary, the prevalence of FGIDs in the group of mothers of children with FGIDs was statistically higher than in the group of mothers of children with FGIDs (51/103, 49.5% vs 14/65, 21.5%; χ2 28.08, P < 0.00001).
Children affected by GI disorder had mothers who were affected more frequently with similar disorders, although there was no association between patients and their siblings. In particular, 41.0% (16/39) of children with constipation had mothers with constipation, 25% (5/20) of children with dyspepsia had mothers with dyspepsia, and 35.8% (14/39) of children affected by IBS had mothers affected by IBS. In the regression analysis, again, having a mother with FGIDs was a stronger predictor of FGIDs than having a father with FGIDs (χ2 14.9, P < 0.01, odds ratio [OR] 3.5) (Fig. 1).
There was no statistically significant (P > 0.05) difference between the 2 groups of parents regarding marital status, occupation, level of education, and standard of living (Table 1). Anxiety was significantly higher in the group of children with FGIDs compared with the group of children without FGIDs (27.0%, vs 3, 8.3%; χ2 4.94; P = 0.026) (17). However, there was no significant difference in the 2 groups (P > 0.05) for sociability, depression, confidence, irritability, hyperactivity, and disobedience (Table 3). Finally, there was no statistically significant difference between first-degree relatives of children with FGIDs and first-degree relatives of children without FGIDs regarding the presence of anxiety and/or depression (P > 0.05).
In this study, we report that the prevalence of FGIDs in the group of parents of children with FGIDs (64%) was significantly higher than in the group of parents of children without FGIDs (30.7%). An association between the type of GI disorder among children and their parents was found. In particular, 18.4% of children with constipation had parents with constipation, 5.8% of children with dyspepsia had parents with dyspepsia, and 9.7% of children affected by IBS had parents affected by IBS. Having a mother with an FGID was a stronger predictor (OR 3.5) of FGID in a child than having a father with FGID (OR 1.6).
Chan et al (19,20) reported that adults with idiopathic constipation showed a familial aggregation and these patients had more severe or refractory symptoms. In addition, the authors observed that their patients exhibited different clinical characteristics (earlier age of onset, longer duration of symptoms, less precipitating factors, and more complications), and they concluded that genetics may be an important etiological factor in this group of patients. There are also reports (3,21,22) on familial aggregation in adult patients affected by irritable bowel disorders, but no such data are available on functional dyspepsia.
A higher prevalence of FGIDs in parents of children with FGIDs may be caused by both heredity and/or social learning. In our study, we found possible evidence of a genetic link in 33.9% of parents who had the same disorders as their children, but this is not enough to declare that a causal relationship exists. We do not have data on populations of twins or genetic studies of our patients. Heredity has been suggested as an explanation of the finding that IBS tends to run in families (3,6). Levy et al (23,24) found that children of parents with IBS tend to use health care significantly more for GI problems than children of parents who do not have IBS. In a recent study (25) comparing young adults presenting or not presenting with IBS, the presence of 1 sibling with IBS was found to be the most important factor associated with IBS development, confirming that FGIDs tend to run in families.
In adults, it has also been reported that 25 gene probe sets were differentially expressed between patients with IBS and healthy individuals. The majority of the genes identified in the colonic mucosa play a role in the immune response or in the host defence against microbial invasion (26). No data have been reported in children regarding the role of genetic susceptibility.
In our study, no changes were observed for marital status, occupation, level of education, and standard of living between the 2 groups of parents of children with or without FGIDs. This could suggest a greater role for heredity than for environmental factors. Although heredity may contribute to the tendency of IBS to familial aggregation, concordance rates between parents and children, compared with those between identical twins, indicate that the environmental factors, such as learning, are likely to have an equal or greater influence on the development of IBS (6). In particular, even in our study, the transmission of FGIDs from parents to children could be because of social learning. In adults, it has been reported that illness-related social learning may be important in understanding the transmission of vulnerability to functional disorders from 1 generation to the next (24,27,28). Excessive illness behaviour that is observed in some patients with IBS may have its origins in learning experiences during childhood. Although it appears that patterns of illness behaviour may be transferred from parents with IBS to their offspring, the mode of transmission of illness behaviour is not established.
In addition, it has been reported (29) that increased numbers of psychiatric diagnoses and increased levels of psychological distress are seen in the majority of adult patients with GI motility disorders. Hodges et al (30), using the CDI and a psychiatric structured interview, the Child Assessment Schedule, in 25 children with recurrent abdominal pain (RAP) as well as in 67 behaviourally disordered and 42 healthy children, reported that the mothers of both the RAP group and the behaviourally disordered group had significantly higher depression scores than the mothers of healthy children. There were no group differences for fathers and it was suggested that although depression is not prevalent in children with RAP, depressive characteristics in the family may play a role in the origin of their abdominal pain. In contrast, in our study there was no statistically significant difference between parents of children with FGIDs and parents of children without FGIDs in the presence of anxiety and/or depression. In our paediatric population, no statistically significant difference was found for the incidence of sociability, depression, confidence, irritability, and disobedience between the 2 groups, whereas only anxiety in the group of children with FGIDs seemed to be significantly higher than in the group of children without FGIDs. It has been reported that psychological factors have a major and unique negative impact on health-related quality of life. Walker et al (31) reported that children with RAP also have higher levels of anxiety and depression than healthy children, and levels of anxiety and depression are often related to the duration of symptoms in these children (32).
To our knowledge, our study is the first to demonstrate that a large number of parents of children with FGIDs experience the same FGIDs as their children. Although the role of heredity or social learning in the prevalence of FGIDs is still unclear, we suggest that when a functional disorder is suspected, having a mother affected by the same disorder could support a diagnosis of FGID. We reaffirm the hypothesis that FGIDs are genetically based and influenced by environmental factors. A mother with an FGID could predispose her already genetically predisposed child to FGIDs. It is possible that on top of the genetic predisposition, a mother with FGIDs could place her siblings at higher risk for FGIDs.
A potential limitation of our study is that, because the sample did not include either twins reared apart or the parents of twins, we were unable to resolve shared environmental effects as distinct from nonadditive genetic effects. Further research needs to be done to examine this role.
1. What is current knowledge: A higher prevalence of FGIDs in parents of children with FGIDs may be caused by heredity and/or social learning.
2. What is new here: Our study demonstrates that a large number of parents of children with FGIDs have the same FGIDs as their children.
1. Hyman PE, Milla PJ, Benninga MA, et al
. Childhood functional gastrointestinal disorders: neonate/toddler. Gastroenterology 2006; 130:1519–1526.
2. Rasquin-Weber A, Di Lorenzo C, Forbes D, et al
. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology 2006; 130:1527–1537.
3. Locke GR III, Zinsmeister AR, Talley NJ, et al
. Familial association in adults with functional gastrointestinal disorders. Mayo Clin Proc 2000; 75:907–912.
4. Whitehead WE, Winget C, Fedoravicius AS, et al
. Learned illness behavior in patients with irritable bowel syndrome and peptic ulcer. Dig Dis Sci 1982; 27:202–208.
5. Levy RL, Whitehead WE, Walker LS, et al
. Increased somatic complaints and health-care utilization in children: effects of parents IBS status and parent response to gastrointestinal symptoms. Am J Gastroenterol 2004; 99:2442–2451.
6. Levy RL, Jones KR, Whitehead WE, et al
. Irritable bowel syndrome in twins: hereditary and social learning both contribute to etiology. Gastroenterology 2001; 121:799–804.
7. Kovacs M. The children's depression inventory. Psychopharm Bull 1985; 21:995–998.
8. Bode G, Brenner H, Adler G, et al
. Recurrent abdominal pain in children: evidence from a population-based study that social and familial factors play a major role but not Helicobacter pylori
infection. J Psychosom Res 2003; 54:417–421.
9. Oster J. Recurrent abdominal pain, headache and limb pains in children and adolescents. Pediatrics 1972; 50:429–443.
10. Walker LS, Greene JW. Children with recurrent abdominal pain and their parents: more somatic complaints, anxiety, and depression than other patient families? J Pediatr Psychol 1989; 14:231–243.
11. Mortimer MJ, Kay J, Jaron A, et al
. Does a history of material migraine or depression predispose children to headache or stomach-ache? Headache 1992; 32:353–355.
12. Campo JV, Bridge J, Lucas A, et al
. Physical and emotional health of mothers of youth with functional abdominal pain. Arch Pediatr Adolesc Med 2007; 161:131–137.
13. Walker LS, Garber J, Greene JW. Somatization symptoms in pediatric abdominal pain patients: relation to chronicity of abdominal pain and parent somatization. J Abnorm Child Psychol 1991; 19:379–394.
14. Kovacs M. A Self-Rated Depression Scale for School-Aged Youngsters
. Thesis. Pittsburgh, PA: University of Pittsburgh School of Medicine; 1983.
15. Cho SC, Lee YS. Development of the Korean form of the Kovacs' children's depression inventory. J Korean Neuropsychiatr Assoc 1990; 29:943–956.
16. Di Lorenzo C, Youssef N, Sigurdsson L, et al
. Visceral hyperalgesia in children with functional abdominal pain. J Pediatr 2001; 139:838–843.
17. Creed F, et al. Psychosocial aspects of functional GI disorders subcommittee for Rome III. In: Drossman DA, et al, eds. Rome III. The Functional Disorders
, 3rd ed. McLean, VA: Rome Foundation; 2006.
18. Bjelland I, Dahl AA, Haug TT, et al
. The validity of the Hospital Anxiety and Depression Scale. An update literature review. J Psychosom Res 2002; 52:69–77.
19. Chan AOO, Lam KF, Hui WM, et al
. Influence of positive family history on clinical characteristics of functional constipation. Clin Gastroenterol Hepatol 2007; 5:197–200.
20. Chan AOO, Lam KF, Hui WM, et al
. Familial aggregation in constipated subjects in a tertiary referral center. Am J Gastroenterol 2007; 102:149–152.
21. Morris-Yates A, Talley NJ, Boyce PM, et al
. Evidence of a genetic contribution to functional bowel disorder. Am J Gastroenterol 1998; 93:1311–1317.
22. Kalantar JS, Locke GR, Zinsmeister AR, et al
. Familial aggregation of irritable bowel syndrome: a prospective study. Gut 2003; 52:1703–1707.
23. Levy RL, Whitehead WM, Von Korff MR, et al
. Intergenerational transmission of gastrointestinal illness behaviour. Am J Gastroenterol 2000; 95:451–456.
24. Levy RL, et al
. Children of women with irritable bowel syndrome: evidence for more GI illness behaviour. Gastroenterology 1998; 114:T1668.
25. Pace F, Zuin G, Di Giacomo S, et al
. Family history of irritable bowel syndrome is the major determinant of persistent abdominal complaints in young adults with a history of paediatric recurrent abdominal pain. World J Gastroenterol 2006; 12:3874–3877.
26. Aerssens J, Camilleri M, Talloen W, et al
. Alterations in mucosal immunity identified in the colon of patients with irritable bowel syndrome. Clin Gastroenterol Hepatol 2008; 6:194–205.
27. Crane C, Martin M. Adult illness behaviour: the impact of childhood experience. Pers Individ Dif 2002; 32:785–798.
28. Crane C, Martin M, et al
. Illness-related parenting in mothers with functional gastrointestinal symptoms. Am J Gastroenterol 2004; 99:694–702.
29. Whitehead WE. Psychosocial aspects of functional gastrointestinal disorders. Gastroenterol Clin North Am 1996; 25:21–34.
30. Hodges K, Kline JJ, Barbero G, et al
. Depressive symptom in children with recurrent abdominal pain and in their families. J Pediatr 1985; 107:622–626.
31. Walker LS, Garber J, Greene JW. Psychosocial correlates of recurrent childhood pain: a comparison of pediatric patients with recurrent abdominal pain, organic illness, and psychiatric disorders. J Abnorm Psychol 1993; 102:248–258.
32. Walker LS, Heflinger CA. Quality of life predictors in paediatric abdominal pain patients: findings at initial assessment and five year follow up. In: Drotar DD, editor. Measuring Health-Related Quality of Life in Children and Adolescents: Implications for Research and Practice. Mahwah, NJ: Lawrence Erlbaum; 1998. pp. 237–252.
Keywords:© 2010 Lippincott Williams & Wilkins, Inc.
familial aggregation; functional constipation; functional gastrointestinal disorders; irritable bowel syndrome; psychiatric disorders