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Review Article

Psychological Comorbidities in Childhood Celiac Disease: A Systematic Review

Coburn, Shayna Skelley∗,†; Puppa, Elaine Leonard; Blanchard, Samra

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Journal of Pediatric Gastroenterology and Nutrition: August 2019 - Volume 69 - Issue 2 - p e25-e33
doi: 10.1097/MPG.0000000000002407
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What Is Known

  • Adults with celiac disease have higher risk for psychological comorbidities than controls.
  • The gluten-free diet has a high treatment burden.
  • Some studies have identified psychological problems in children with celiac disease, but no systematic review has summarized prevalence.

What Is New

  • A systematic review of studies has been completed examining psychological comorbidities in children with celiac disease.
  • Twenty-six studies have studied psychological problems in children with celiac disease.
  • A need has been identified for evidence-based recommendations for psychosocial research and practice in children with celiac disease.

In chronic illnesses, psychological comorbidities are associated with higher medical care utilization and costs (1) as well as poorer adherence and long-term complications (2). Celiac disease (CD) is associated with a high perceived treatment burden (3) and higher rates of psychopathology in adults (4). Preliminary evidence indicates an elevated psychosocial risk in children (5), but summarizing the prevalence of specific psychological symptoms and establishing psychosocial best practices are needed to identify key areas for clinical intervention. This study reviewed existing research on psychological comorbidities in childhood CD to provide recommendations for research and clinical care.

In adults, CD is associated with higher rates of psychopathology (4,6), including major depression and suicide (7), anxiety (6), and eating disorders (ED) (8). Psychological comorbidities may affect dietary adherence and, ultimately, health functioning (6). Two review articles previously examined aspects of psychosocial challenges associated with CD in children (9,10), but none systematically synthesized studies of psychological comorbidity in childhood CD. Although prior reviews identified important psychosocial challenges experienced by children and/or adolescents with CD, none examined the psychological symptoms tied to diagnosable mental disorders.

This systematic review comprehensively examined the literature on psychological comorbidities, quality of life (QOL), and other psychosocial burdens associated with childhood CD. We had 3 primary objectives for the review: synthesize the prevalence of psychological disorders and symptoms in children with CD; summarize the psychosocial experiences and burdens associated with childhood CD; and formulate preliminary psychosocial research and clinical agendas for CD in children.


Data Sources and Search Strategy

This systematic review followed the recommendations outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (11). The PRISMA checklist was used to ensure pertinent elements were included in this systematic review. A literature review was conducted in Scopus using the following initial key words: “celiac” and at least one of the following: “psychopathology,” “psychiatric,” “psychosocial,” or “emotional” indexed through June 30, 2017.

Criteria for inclusion were defined before the initiation of our literature search: youth ages 18 and younger; peer-reviewed using a study sample (case reports were excluded because they do not examine prevalence); published in English; electronically available; quantitative; and examined CD (broader studies were included but studies involving only gluten sensitivity were excluded). In order to synthesize as much available data as possible while ensuring clear and consistent selection procedures, studies examining individuals over age 18 or which included other medical conditions outside of CD were included only if they differentiated findings for children under 18 and those with CD and met all other inclusion criteria. Articles (titles, abstracts, and full-text articles) were screened and reviewed by a behavioral psychologist (S.C.) and/or a nurse (E.P.) with expertise in CD. Additional publications were accessed and reviewed from the initially identified publications. Discrepancies were resolved through discussions with a third reviewer (S.B.), and a consensus was reached through these meetings. Individual study limitations and other commentary on risk for bias within and across studies are provided in the discussion of this review.

Study Selection and Data Extraction

Figure 1 summarizes article retrieval and abstraction using PRISMA guidelines. Studies deemed appropriate for this evaluation were heterogeneous in nature. The studies did not measure the same outcomes and a high proportion were observational studies rather than case-control or clinical trial studies. Therefore, a systematic review, rather than a meta-analysis, was selected as the most appropriate approach for synthesizing the data on psychological comorbidities in CD. Data extraction included prevalence rate(s) of psychological diagnoses and/or psychosocial burden among children with celiac disease (eg, statistical tests indicating significant differences from comparison groups and qualitative themes), whenever available.

PRISMA diagram for article selection process. QOL = quality of life.


Twenty-six publications met inclusion criteria for the literature review on psychological comorbidities in childhood CD including 9 observational studies, 16 case-control studies, and 1 clinical trial (Table 1  ). Publications were heterogeneous in symptoms examined, methodology, and population characteristics. Screening studies testing for comorbidity in children with either CD or a psychological diagnosis (and met inclusion criteria) were deemed appropriate for this review because either approach would be aligned with the primary objective to comprehensively synthesize the extant research on the comorbidity of CD and psychiatric diagnoses. Compared with the general population or other matched controls, most publications detected elevated psychological disorders or symptoms.

Summary of studies observing celiac disease and psychological comorbidities in children
TABLE 1 (Continued):
Summary of studies observing celiac disease and psychological comorbidities in children
TABLE 1 (Continued):
Summary of studies observing celiac disease and psychological comorbidities in children

Overall Risk

Four observational studies examined children with established psychiatric conditions and screened for CD, 5 observational studies screened for psychological symptoms among children with CD, and 1 validated a measure on childhood QOL specific to CD. Most case-control studies investigated specific psychiatric conditions in children diagnosed with CD. Typically, studies compared a healthy group with CD, but some studies compared other GI conditions. Summaries below include studies investigating the incidence rates of CD and psychological symptoms, grouped by category of symptom. Studies that examined more than 1 set of symptomatology are summarized when first introduced; specific findings are noted within the appropriate category.

Specific Psychological Symptoms

Anxiety, Depression, and Mood Disorders

Anxiety and depression were the most commonly examined psychological studies of CD (12–14). Butwicka et al (5) found higher risk for developing anxiety disorders in children with CD than healthy children. Similarly, Mazzone et al (13) and Jafari et al (15) found more symptoms of anxiety and depression in children with CD. Mazzone et al (13) also noted that girls had more internalizing symptoms, such as depression, than boys. Esenyel et al (12), Fidan et al (16), and Simsek et al (14), found no differences in prevalence of depressive symptoms between youth with CD and without CD; Esenyel et al (12) and Fidan et al (16) investigated anxiety and found no difference compared with controls (2,16).

Symptoms may improve after initiation of the gluten-free diet (GFD). Simsek et al (14) found a reduction in depressive symptoms among children with CD who adhered to the GFD. Pynnönen et al (17) found no significant differences in current mental disorders among adolescents with CD compared with controls, but did observe increased lifetime incidence of major depressive disorder in adolescents with CD before the initiation of the GFD. A small follow-up observational study from the same authors (18) found incidence of anxiety disorders was no different than adolescents with CD compared with matched controls, but psychiatric symptoms decreased after 3 months on the GFD.

The only study to examine pediatric comorbid mood disorders and CD found more mood disorders in children with CD (5). In addition, among all children with mood disorders, a slightly greater risk existed for later developing CD.

Behavior Problems and Attention-deficit/Hyperactivity Disorder

Studies found comorbidity between behavior problems and CD, with mixed findings regarding comorbidity between attention-deficit/hyperactivity disorder (ADHD) and CD. Smith et al (19) found more mother-reported aggressive behavior in children with positive CD serology screening compared with controls. Although Mazzone et al (13) found no differences in behavior or attention problems among children with celiac disease and healthy children, they noted that boys had higher externalizing, social, thought, and attention problems than girls. Butwicka et al (5) found that children with CD had a higher risk for behavioral disorders and ADHD, and children with a history of behavior problems were at increased risk for developing CD. Pynnönen et al (17) found more disruptive behavior disorders in children with CD compared with matched controls, but no increased incidence of ADHD. Among children diagnosed with ADHD, Güngör et al (20) reported no increased incidence of CD.

Eating Disorders

Butwicka et al (5) found that children with CD have increased risk of developing ED, and children with a history of ED have increased risk for developing CD. Data regarding comorbidity of ED and CD have been mixed. Wagner et al (21) reported that 15.5% of adolescents with CD had a comorbid ED but did not compare these rates to the general population. In addition, they found that adolescents with both CD and ED had more depressive symptoms, were older, had higher BMI, and lower QOL compared with those with 1 or no diagnosis. However, Basso et al (22) observed no increased prevalence of CD among children with diagnosed ED over the general population. No studies investigated the relatively new ED introduced by the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V)(23), avoidant-restrictive food intake disorder (ARFID). ARFID is a condition in which a child severely limits their diet in some manner.

Autism Spectrum Disorder and Intellectual Disabilities

The only study in this review, which examined intellectual disabilities (ID) in CD (5) found an increased risk for ID and autism spectrum disorder (ASD). Calderoni et al (24) found CD prevalence was significantly higher in preschool children with ASD than in the general Italian population. They noted that half of children diagnosed with ASD had no symptoms or risk factors for CD at the time of screening. Proposed explanations for this link include nutritional deficiency (25) and increased intestinal permeability in some children with ASD (26). Children with ASD tend to have higher levels of IgG antibodies to gliadin without histological evidence of CD (27), and mothers with a history of CD or other autoimmune conditions are more likely to have children with ASD (28).

Other Disorders

Butwicka et al (5) found no differences in psychotic disorders and substance misuse between children with CD and healthy controls.

Psychosocial Burden

QOL tends to be poorer in youth with CD and their parents compared with the general population. Several case-control studies examined QOL in addition to specific psychiatric conditions noted in prior sections. Compared with healthy children, children with CD have lower QOL related to emotions (14), psychosocial health (29), leisure (30), and overall QOL (14,16). Finally, Sevinc et al (31) found all QOL subscales of the PEDS-QL (Pediatric Quality of Life Scale) were significantly lower than healthy controls. Despite identifying specific areas of poorer QOL compared with controls, Jafari et al (15) and Biagetti et al (32) reported no differences in overall QOL.

Studies of QOL in CD noted variability in attachment style (33), psychosocial morbidities (34), and general psychosocial experiences (35) based on participant characteristics. Barrio et al (36) found that children who were diagnosed with CD at younger ages and longer ago reported higher QOL. Related, Wagner et al (37) found lower QOL and higher CD-associated burden when diagnosed later, and lower QOL and more subjective burden in nonadherent patients. Biagetti et al (32) found that factors, such as diet difficulties and comorbidity affected QOL in CD. Jordan et al (38) developed a screening tool and measured general QOL in children with CD. The only clinical trial identified in this review was a small study examining children's QOL before and after attending a summer camp for children with CD in the United States (39). Children reported improved QOL after attending the camp.


Studies tend to indicate elevated rates of psychological comorbidities and symptoms in children with CD ranging from 1.2 to 1.8 times higher than children without CD. One study reported an odds ratio as high as 10.67 in the case of disruptive behavior disorders (17). Elevated risk for mental disorders and/or overall psychological symptoms were found both preceding diagnosis of CD and following diagnosis (5). Prevalence rates of psychological comorbidities and childhood CD require further study using larger samples across various countries. Increased rates of psychological symptoms would warrant inclusion of psychological screening as an integrated aspect of treatment.

Compared with controls, most evidence supports increased prevalence of depressive symptoms in youth with CD (17), similar to findings in children with inflammatory bowel disease (40). Depressive symptoms may improve after diagnosis and with adherence to the GFD (14,17). The prevalence of anxiety disorders is also supported in research. Environmental factors, stressors related to the GFD, and the country of residence likely affect the prevalence rates of anxiety and depression in CD following diagnosis. Future research could elucidate the relationships between these stressors and the prevalence of anxiety and depression.

Disruptive behavior disorders and aggression may be more severe or more common in youth with CD. Prevalence data on ADHD in this population have been inconsistent thus far. Multiple studies have drawn an association between CD and ADHD-like symptoms (5,41,42), whereas other studies found no differences (17,20).

Undiagnosed CD might be over-represented in children with ED including ARFID, or in contrast, perhaps children with CD are at risk for developing ARFID-like symptoms because of their already restricted diet. However, the potential for severe restriction of gluten intake inherent in ED makes CD screening unreliable (22). Research of adults with CD suggests individuals with higher BMI may attribute weight gain to their GFD, triggering maladaptive beliefs about CD, poor GFD management, and restricted or binge type ED (43). The consequences for individuals who further limit their diet beyond the GFD prescribed for CD could potentially result in further health and psychological complications.

Children with ASD or ID could be over-represented in CD and/or family history of CD. Some hypothesize that behavioral symptoms of ASD stem from gastrointestinal distress caused by CD, suggesting ASD may be improved on the GFD (24). Future research should not only further investigate whether there are clear associations between CD and ASD or ID, but also what shared mechanisms, if any, that may underly both conditions.

Psychotic disorders and substance misuse were rarely examined in children with CD. One challenge in establishing prevalence rates in children with CD is the low rate of psychosis in general during childhood. The mechanisms of a possible link between sensitivity to gluten and psychosis are currently under investigation (44). Substance abuse and misuse is prominent in adolescents (45), and warrants investigation to determine whether any vulnerabilities are associated with CD.

Consistently, the largest psychosocial burden in children was overall decreased QOL, although findings have varied greatly from study to study (14,36,46). Poorer QOL has been observed in many studies when no psychological disorder was identified. Thus, in the absence of psychopathology, children and their families still experience poorer QOL compared with healthy children. QOL varies by timing of diagnosis, suggesting adaptation occurs over time (36). Studies explicitly examining timing of diagnosis and GFD adherence are needed to establish temporal precedence and understand mechanisms associated with psychosocial improvement.

Only 1 clinical trial attempted to establish efficacy of an intervention (a summer camp for children with CD) (39). However, limitations, such as a lack of control/comparison group, no randomization, and no follow-up evaluation preclude determination of efficacy and generalization of findings. Clinical trials are needed to investigate programs designed to improve the lives of children with CD and their families. Educational workshops, coping skills groups, and cooking classes present opportunities for investigation of benefits to psychological and psychosocial health.

The geographical location and the population from which studies are drawn are crucial to understanding the likelihood for psychological comorbidity. The country of residence may have a large impact on QOL and psychological health in CD because of differences in food availability, labeling, and preparation laws. Socioeconomic factors influencing the ability to follow the GFD could magnify this effect (15,36). In some countries, gluten-free food is available at the pharmacy and subsidized; others have no such supports (eg, United States). Studies that found no elevation in psychological symptoms tended to come from countries with better aforementioned GFD supports. The prevalence of psychological comorbidities is not well studied in North America, where federal food labeling and protections laws for individuals with CD are not well established (47). Children's psychological health in the United States merits examination because of potential adverse effects from a less protective environment for CD self-management.

Summary and Clinical Implications

This review emphasizes a need for psychosocial screening and support in children with CD and their families. Children with comorbid chronic illness and psychological disorders are at increased risk for poorer health outcomes, including increased rates of hospitalizations and morbidities (1). Children with both psychological disorders and CD may have more difficulty adhering to the gluten-free diet and coping with the emotional burden associated with its management. However, no psychosocial guidelines have been included within best practice models for CD (29); an important priority should be developing psychosocial best practice guidelines in CD care. Preliminary clinical and research priorities are suggested in Table 2. More research is needed to inform guidelines with a firm evidence base. Identification and treatment of youth with symptoms of mental illness and/or poor QOL should be an important component of future clinical and research priorities.

Proposed clinical and research agendas

Limitations to Existing Studies

Although several large database studies have been completed, many other studies were limited by small sample sizes, inconsistent or nonvalidated approaches to measuring psychological symptoms, and lack of a formal diagnosis by a mental health professional. Most studies measured mental health in individuals at varying points in their treatment; few studies accounted for the duration or age of diagnosis. Studies combining participants prediagnosis and postdiagnosis obscure the identification of risk at a specific time point in diagnosis and treatment of CD. Finally, a large number of studies reported diminished QOL without identifying any specific psychological comorbidities underlying these problems.


The majority of existing studies support an increased prevalence of comorbid CD and psychological symptoms or diagnoses. This indicates a potential psychological vulnerability in children with CD, which may complicate or interfere with CD management and treatment, although these associations are yet to be tested in children with CD. Psychological comorbidities are associated with poorer adherence in other illnesses [eg, inflammatory bowel disease (48) and diabetes (49)] and higher frequency and cost of medical care (1,18). Findings highlight the need to screen for psychosocial burdens in CD.

It is still uncertain as to whether CD is over-represented in psychiatric populations and this may vary depending on the psychological condition. Still, children whose psychological symptoms are not well controlled may benefit from CD screening, as approximately 1 in 3 people with CD are still undiagnosed (50) and psychological symptoms could be a sign of “masked” or nonclassical CD (51). Although some hypotheses have been proposed, mechanisms of risk are not yet fully established (5). Possible mechanisms include hormonal, immunological, intestinal, and nutritive factors as well as adverse psychosocial effects of physical symptoms themselves and social limitations of the diet. With the increasing incidence of CD diagnosis, it should be a priority to assess for a broad range of psychological comorbidities among children with CD.


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celiac; gluten-free diet; mental health; psychopathology

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