What Is Known
- The quality of life of patients with celiac disease is negatively affected by their condition.
- Adherence to a gluten-free diet has positive effects on quality of life and depression.
What Is New
- No differences in quality of life were found between before and after gluten-free diet recommendations in children with celiac disease.
- Patients who strictly adopted a gluten-free diet had significantly decreased depression scores compared with the patients who did not adopt a gluten-free diet.
Celiac disease (CD) is a chronic inflammatory enteropathy that causes malabsorption and damage to the small bowel mucosa. The prevalence of CD has been reported to vary between 0.5% and 1% in the United States, Europe, and Turkey (1,2). Untreated adult celiac patients often have various neurological and psychiatric symptoms. It has been reported that adults and children with untreated CD often have symptoms such as depression, anxiety, apathy, discomfort, and ataxia (3,4). Previous studies have suggested that the prevalence of depression in patients with CD can vary from 6% to 69% (5–7).
Quality of life (QoL) is defined as the perceived quality of an individual's life within his/her cultural and value systems with regard to goals, expectations, standards, and concerns (8). The effects of CD and a gluten-free diet (GFD) on QoL vary. Different studies have shown that QoL has been affected negatively (9,10) or not affected (11), improved at diagnosis, and then decreased (12). Another study has reported decreased QoL after the diagnosis of CD and improvement years later (13). The QoL of children and adolescents with CD has been found to be correlated with age at diagnosis, duration of their GFD, and the initial severity of the disease (14,15). In addition, a GFD leads to significant improvements in the perceived QoL of symptomatic patients with CD; in contrast, a GFD had no effect on the QoL of asymptomatic patients with CD (16).
According to our literature review, a majority of the studies on QoL and depression associated with CD have been performed in adult patients and have reported contradictory results. In addition, only a limited number of studies on the effect of a GFD on QoL and depression in pediatric patients with CD are available. In the present study, we aimed to examine differences between children with CD and a healthy control group in terms of QoL and depression levels. Another purpose of this study was to determine changes in the QoL and depression levels of children with CD before and after receiving recommendations to follow a GFD. Furthermore, we investigated differences in the QoL and levels of depression between patients who strictly adopted versus did not adopt a GFD.
This study was conducted at the Child Psychiatry and Pediatric Gastroenterology Clinics of Dicle University Hospital (Diyarbakır, Turkey) between July 2012 and February 2014. The study included 25 pediatric patients ages 9 to 16 years, who were newly diagnosed as having CD. The age of the participants and the age at diagnosis were the same because participants were enrolled right after the diagnosis. The control group consisted of 25 age- and sex-matched healthy children who presented for routine checkup or minor acute complaints and without chronic physical and psychiatric illnesses. Participants in the control group did not develop gastrointestinal complaints. Considering the possibility of asymptomatic CD, endomysium immunoglobulin (Ig) A antibody levels were analyzed and were found as negative in the control group. The lower age limit was determined to be 9 years so that the participants could properly understand and complete the self-administered surveys. Diagnosis of CD was confirmed by duodenal biopsies compatible with Marsh stage 3 in children who were positive for tissue transglutaminase IgA or endomysium IgA antibodies. Children who tested positive for antibodies but had Marsh stage 0 to 2 biopsies were excluded from the study. The eligible participants completed a form containing information about sociodemographic and clinical characteristics, the Children's Depression Inventory (CDI), and the General-Purpose Health-Related Quality of Life Questionnaire for Children (Kid-KINDL). After giving recommendations to follow a GFD, patients with CD were reevaluated in the child psychiatry polyclinic using the same inventories following a minimum of 6 months. One patient did not attend the second examination, and thus we have no data for that time point. At the repeat evaluation, patients were tested for endomysium IgA or tissue transglutaminase IgA levels to determine their dietary compliance. Participants in the control group were not followed up. Informed consents were obtained from parents and children for all participants. The study was approved by the Dicle University Medical Faculty ethics committee.
Forms and Scales Used
The data form included questions about age, sex, date of examination, educational status, academic success, address, parents’ age, parents’ educational status and profession, number of siblings, and birth order.
Children's Depression Inventory
The Beck Depression Inventory was used as the basis for the CDI, which was developed by Kovacs (17). Specific questions relevant to pediatric depression, however, such as school status and friendship relationships, were added. A 27-item inventory, which was translated into Turkish by Oy (18), was used. Each item was scored as 0, 1, or 2 based on symptom severity; the maximum possible score was 54 points, and the score increased with the level or severity of depression.
General-Purpose Health-Related Quality of Life Questionnaire for Children
The KINDL scale is used to identify aspects of the lives of children with chronic diseases who are most affected by the disease or its treatment. This general-purpose scale measuring QoL consists of 24 items on 6 dimensions (body wellness, emotional wellness, self-respect, family, friends, and school). Items are rated on a Likert-type scale ranging from 1 (never) to 5 (always). The validation and safety of the questionnaire's Turkish version was confirmed by Eser et al (19). General surveys are evaluation tools that cover all fields related to QoL and yield results that provide a comprehensive perspective. The KINDL was chosen to compare children with CD with normal healthy children.
Statistical analyses were performed using SPSS version 15 software (SPSS Inc, Chicago, IL). Data were presented as mean plus-minus standard deviation for normally distributed numerical variables and median (interquartile range) for the not normally distributed variables. Categorical variables were compared using χ2 test. The distribution patterns of numerical data were examined by Kolmogorov-Smirnov and Shapiro-Wilk tests. Student t tests were used to compare independent groups having normally distributed data, and the Mann-Whitney U test was used to compare not normally distributed numerical variables. Comparisons of results of numerical variables before and after recommendations on a GFD were done by Wilcoxon test. P value <0.05 was accepted as statistically significant.
The first clinical evaluation of patients with CD (M/F 7/18), who were not diagnosed/treated previously, were done at a mean age of 11.84 ± 2.1 years. The mean age of the control group (M/F 9/16) was 12.24 ± 2.3 years. In the patient group, the mean number of siblings was 5.8 ± 2.5, the mean education duration of the mothers was 2.3 ± 2.5 years, and the mean education duration of the fathers was 6.2 ± 2.8 years. No significant differences were found between the patient and control groups in terms of the children's mean age and sex distribution, the parents’ age, and the number of siblings (P > 0.05, some data not shown). We did not find significant differences in age, depression scores, QoL (total and subscale) scores, or treatment adherence with respect to sex (P > 0.05, data not shown).
The results of the CDI and Kid-KINDL are presented in Table 1. We found no significant differences between the depression scores of the CD and control groups (P = 0.31) at the baseline evaluation. The QoL total scores and scores on the emotional well-being subscale were significantly lower in the group with CD compared with the control group (P = 0.01 and P = 0.016, respectively) (Table 1). We found no differences between depression and QoL scores with respect to sex (P > 0.05, data not shown).
The second evaluation was performed between 6 and 20 months of the first evaluation, with a mean interval of 9.61 ± 4.35 months. Comparisons of the pre- and postdiet recommendations, questionnaire scores revealed no significant differences in the depression or QoL subscale or total scores. The results with respect to sex were similar. The results obtained before and after the diet recommendation are presented in Table 2.
Dietary compliance at the second evaluation was determined by testing antibody levels. Patients with negative antibody levels at the second evaluation or patients with any reduction in antibody levels compared with those at the start of treatment were considered compliant with the dietary treatment. Accordingly, 7 patients were considered treatment compliant and 17 noncompliant. We did not find significant differences in age, sex, or diet duration between patients who did versus those who did not comply with the diet. Comparisons of the scale scores with respect to treatment compliance revealed that the treatment-compliant patients had lower depression scores than did the noncompliant patients (P = 0.02) (Table 3). The mean depression scores of the treatment-compliant group decreased from 9.17 ± 7 to 4.75 ± 3.3 and those of the noncompliant group increased from 8.8 ± 4.6 to 12.33 ± 5.8 (P = 0.02). Adherence to the diet had no impact on Kid-KINDL scores (Table 3).
In the present study, no significant difference was found in the depression scores between children with CD and the healthy controls. Children with CD, however, had significantly lower emotional well-being subscale and total scores on the QoL questionnaire than those of healthy subjects. Among the patients with CD, no significant differences were found in the QoL subscale or total scores or the depression scores between before to after a GFD diet recommendation. Patients who followed a GFD, however, showed significant reductions in depression scores compared with patients who did not comply.
Similar to the findings of the present study, Esenyel et al (20) did not detect any differences in depression scores between pediatric patients and controls before and after a GFD. Many studies have demonstrated high prevalence of depression, however, in adult patients with CD (7,21,22). One study investigating the relation between GFD and depression reported that the symptoms of depression were completely ameliorated after a GFD (23), and another study reported no change in depression symptoms (24).
Depression is one of the causes of noncompliance to treatment in chronic diseases (25). Two studies, however, failed to detect any correlation between dietary compliance and depression (3,24). Ludvigsson et al (5) reported that noncompliance with dietary restrictions may affect the risk of depression, although their study provided no information about such compliance. Other studies have shown that depression is strongly associated with noncompliance to a GFD, and patients who did not comply with diet had higher depression scores in CD (12,26,27).
The pathogenesis of depression in patients with CD has not yet been clearly elucidated. Some studies have suggested that deficiencies in folic acid, vitamin B12, vitamin B6, and tryptophan because of dietary noncompliance and malabsorption may play a role in the development of depression in adult patients with CD (28). In contrast, other studies have indicated that a GFD has a therapeutic effect on depression in celiac patients and that the initiation of a GFD can ameliorate depression symptoms (29).
In the present study, the ratio of dietary compliance was well below those previously reported (30). The socioeconomic and educational levels of the parents of children in our sample were quite low, and the mean number of siblings was high. Insufficient psychosocial and financial support may have resulted in the low ratio of dietary compliance. Indeed, growth failure was the most significant complaint for a majority of patients. Patients without active complaints (eg, abdominal pain, diarrhea) may be expected to show lower levels of dietary compliance.
A longitudinal prospective study showed a significant improvement in the first 3 months of initiating a GFD but reported that the rates of change in QoL were reduced during the following years (31). Another study reported that the compliance of patients with CD with a GFD was not adequate at the end of 1 year and that their QoL regressed over the long term (12). A study similar to the present research reported that children with CD did not have any physical health problems but that their QoL was impaired with regard to general and psychosocial health (32). Another similar study, involving 133 children, reported no significant differences in the QoL between children diagnosed as having CD who were undergoing treatment and healthy controls (33). Dietary restrictions render social relationships difficult for children. A child who cannot eat with his/her friends may feel incompetent and different, and his/her QoL is affected by his restricted social life (21). Additionally, children with CD often feel jealousy and anger, and ignore their diets in such social environments (34). Accordingly, dietary compliance has a major effect on the QoL of people with CD (35). Furthermore, dietary noncompliance may also be because of the lack of understanding by the patient and the parents regarding the importance of compliance and the prospective risk factors. Given the limited access to gluten-free products in Turkey and the inadequate dietary compliance, no significant improvements in the QoL of our patients with CD are understandable.
The limitations of the present study were inclusion of patients admitted to a single university clinic, use of self-administered scales, and nonadministration of structured psychiatric interviews. Additionally, the limited sample size did not allow for the investigation of different age groups.
In conclusion, our results suggested that patients with CD had lower QoL compared with the control group, and the low levels of dietary compliance may increase their risk for depression. In terms of preventing depression during the course of CD, clinicians should follow-up these patients more closely with regard to their dietary compliance.
The authors thank Drs Rümeysa Alaca and Hüseyin Aktaş, and our patients and their parents for taking part in this study.
1. National Institutes of Health Consensus Development Conference Statement on Celiac Disease
, June 28–30, 2004. Gastroenterology
2. Dalgic B, Sari S, Basturk B, et al Prevalence of celiac disease
in healthy Turkish school children. Am J Gastroenterol
3. Ciacci C, Iavarone A, Mazzacca G, et al Depressive symptoms in adult coeliac disease. Scand J Gastroenterol
4. Carta MG, Hardoy MC, Boi MF, et al Association between panic disorder, major depressive disorder and celiac disease
: a possible role of thyroid autoimmunity. J Psychosom Res
5. Ludvigsson JF, Reutfors J, Osby U, et al Coeliac disease and risk of mood disorders—a general population-based cohort study. J Affect Disord
6. Pynnönen PA, Isometsä ET, Aronen ET, et al Mental disorders in adolescents with celiac disease
7. Ciacci C, Iovino P, Amoruso D, et al Grown-up coeliac children: the effects of only a few years on a gluten-free diet
in childhood. Aliment Pharmacol Ther
8. WHOQOL Group. Study protocol for the World Health Organization project to develop a Quality of Life
assessment instrument (WHOQOL). Qual Life Res
9. Norström F, Lindholm L, Sandström O, et al Delay to celiac disease
diagnosis and its implications for health-related quality of life
. BMC Gastroenterol
10. De Lorenzo CM, Xikota JC, Wayhs MC, et al Evaluation of the quality of life
of children with celiac disease
and their parents: a case-control study. Qual Life Res
11. Nordyke K, Norström F, Lindholm L, et al Health-related quality of life
in adolescents with screening-detected celiac disease
, before and one year after diagnosis and initiation of gluten-free diet
, a prospective nested case-referent study. BMC Public Health
12. Nachman F, Del Campo MP, González A, et al Long-term deterioration of quality of life
in adult patients with celiac disease
is associated with treatment noncompliance. Dig Liver Dis
13. Van Koppen EJ, Schweizer JJ, Csizmadia CG, et al Long-term health and quality-of-life consequences of mass screening for childhood celiac disease
: a 10-year follow-up study. Pediatrics
14. Byström I-M, Hollén E, Fälth-Magnusson K, et al Health-related quality of life
in children and adolescents with celiac disease
: from the perspectives of children and parents. Gastroenterol Res Pract
15. Wagner G, Berger G, Sinnreich U, et al Quality of life
in adolescents with treated coeliac disease: influence of compliance and age at diagnosis. J Pediatr Gastroenterol Nutr
16. Ukkola A, Mäki M, Kurppa K, et al Diet
improves perception of health and well-being in symptomatic, but not asymptomatic, patients with celiac disease
. Clin Gastroenterol Hepatol
17. Kovacs M. The Children's Depression
Inventory (CDI). Psychopharmocol Bull
18. Oy B. The Children's Depression
Inventory: validity and reliability study. Turk J Psychiatry
19. Eser E, Yuksel H, Baydur H, et al The psychometric properties of the new Turkish generic health-related quality of life
questionnaire for children (Kid-KINDL). Turk J Psychiatry
20. Esenyel S, Unal F, Vural P. Depression
and anxiety in child and adolescents with follow-up celiac disease
and in their families. Turk J Gastroenterol
21. Addolorato G, Capristo E, Ghittoni G, et al Anxiety but not depression
decreases in coeliac patients after one-year gluten-free diet
: a longitudinal study. Scand J Gastroenterol
22. Carta MG, Hardoy MC, Usai P, et al Recurrent brief depression
in celiac disease
. J Psychosom Res
23. Pynnönen PA, Isometsä ET, Verkasalo MA, et al Gluten-free diet
may alleviate depressive and behavioral symptoms in adolescents with coeliac disease: a prospective follow-up case-series study. BMC Psychiatry
24. Fera T, Cascio B, Angelini G, et al Affective disorders and quality of life
in adult coeliac disease patients on a gluten-free diet
. Eur J Gastroenterol Hepatol
25. DiMatteo MR, Lepper HS, Croghan TW. Depression
is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression
on patient adherence. Arch Intern Med
26. Addolorato G, De Lorenzi G, Abenavoli L, et al Psychological support counselling improves gluten-free diet
compliance in coeliac patients with affective disorders. Aliment Pharmacol Ther
27. Pietzak MM. Follow-up of patients with celiac disease
: achieving compliance with treatment. Gastroenterology
2005; 128 (4 suppl 1):135–141.
28. Hallert C, Svensson M, Tholstrup J, et al Clinical trial: B vitamins improve health in patients with coeliac disease living on a gluten-free diet
. Aliment Pharmacol Ther
29. Pynnönen PA, Isometsä ET, Verkasalo MA, et al Untreated celiac disease
and development of mental disorders in children and adolescents. Psychosomatics
30. Greco L, Mayer M, Ciccarelli G, et al Compliance to a gluten-free diet
in adolescents, or “what do 300 coeliac adolescents eat every day?”. Ital J Gastroenterol Hepatol
31. Nachman F, Mauriño E, Vázquez H, et al Quality of life
in celiac disease
patients: prospective analysis on the importance of clinical severity at diagnosis and the impact of treatment. Dig Liver Dis
32. Fidan T, Ertekin V, Karabag K. Depression
-anxiety levels and the quality of life
among children and adolescents with coeliac disease. Düşünen Adam J Psychiatry Neurol Sci
33. Kokkonen J, Viitanen A, Similä S. Coping with a coeliac diet
after adolescence. Helv Paediatr Acta
34. Lohiniemi S, Mustalahti K, Collin P, et al Measuring quality of life
in coeliac disease patients. Chang Featur Coeliac Dis Tamp Finl Finn Coeliac Soc
35. Ciacci C, D’Agate C, De Rosa A, et al Self-rated quality of life
in celiac disease
. Dig Dis Sci