EAL

CD: Neurological Outcomes (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To study the prevalence of current and lifetime mental disorders in adolescents with celiac disease.

Inclusion Criteria:

Celiac disease diagnosed by villous atrophy demonstrated in small-bowel biopsy. Aged 12 - 17 years. Comparison patients had serological evidence and clinical symptoms that suggested celiac disease and suspicion had been strong enough to indicate diagnostic biopsy. Most comparison patients with abdominal complaints had experienced recurrent abdominal pain, loose stools or other functional GI symptoms.

Exclusion Criteria:

Patients with inflammatory bowel disease.

Description of Study Protocol:

Recruitment

Celiac disease patients meeting inclusion criteria identified from the Dept of Gastrointestinal Services' records of small-bowel biopsies for children and adolescents conducted during 1982 - 1999.

Design

Case-Control Study.

Blinding used (if applicable)

Neither was blind to the diagnosis of celiac disease.

Intervention (if applicable)

Semistructured psychiatric interviews and symptom measurement scales.

Statistical Analysis

Statistical analyses were performed by using both matched and unmatched group procedures as appropriate (e.g. repeated-measures and one-way ANOVA, dependent and independent group t tests, Wilcoxon signed ranks test, Fisher's exact test, and cross-tabulation with the ordinary chi-square test and McNemar test.) Reflecting the study design, the results reported in the tables are from matched analyses, although statistically significant results were provded mostly by the unmatched analyses. Binary logistic regression and a linear probability model were used to test the effects of celiac disease and of sociodemographic and clinical characteristics (e.g. divorce of parents, family history of psychiatric disorders or celiac disease, and somatic symptoms before the biopsy) on the occurrence of mental disorders. In these analyses, two-tailed p values <0.05 were considered significant.

Data Collection Summary:

Timing of Measurements

Semistructured psychiatric interviews and symptom measurement scales used with adolescents and controls.

Dependent Variables

Present and lifetime psychiatric diagnostic evaluation conducted with the Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime version, a semistructured diagnostic interview. At assessment, first the adolescent and then a parent were interviewed separately
Current psychiatric status and symptoms were assessed by using the Youth Self-Report and the Child Behavior Checklist.
Current depressive symptoms were evaluated using the Beck Depression Inventory and the Hamilton Depression Rating Scale
Anxiety symptoms were assessed using Beck Anxiety Inventory and Hamilton Anxiety Rating Scale

Independent Variables

Data on psychiatric and somatic symptoms and lab test results before the small-bowel biopsy (and for celiac disease patients, before starting gluten-free diet), as well as data on the effects of a gluten-free diet as reported by the patient or by a parent were gathered from pediatric case records and as part of clinical interview.
Questions about family history of mental disorders included in supplementary interview. Interviewer classified parental mental disorders into 4 categories of depressive, anxiety, psychotic, or severe alcohol abuse disorders.

Control Variables

Description of Actual Data Sample:

Initial N: 414 total patients during 1982-1999. 37 met inclusion criteria. 4 excluded - 3 with Down's Syndrome and 1 did not speak Finnish. 4 girls refused to participate.

Attrition (final N): 29 out of 33 (88%) adolescents, 16 girls, 13 boys. 29 matched comparison subjects.

Age: Comparison subjects aged 12 - 18 years.

Ethnicity: All subjects Caucasian and of Finnish nationality.

Other relevant demographics: Not mentioned.

Anthropometrics: Comparison patients matched for gender, age at the time of biopsy (+/- 6 months in patients under 12), and age at time of psychiatric evaluation in adolescence (+/- 1.2 years). All celiac disease patients had 1 - 3 comparison subjects. Celiac disease and comparison patients differed only in poor weight gain, irritability, tiredness and lack of concentration.

Location: Finland

Summary of Results:

Other Findings

Relative to comparison subjects, the celiac disease patients had significantly higher lifetime prevalences of major depressive disorder (31% vs 7%, p < 0.05, Fisher's exact test), double depression (dysthymic disorder superimposed with major depressive disorder episode) (21% vs 0%, p < 0.04) and disruptive behavior disorders (28% vs 3%, p < 0.04).

The risk for any lifetime major depressive disorder was significantly greater in the celiac disease patients than in the comparison patients (odds ratio = 6.06, 95% confidence interval = 1.18 - 31.23, p < 0.04).

The prevalence of any depressive disorder (major depressive disorder, dysthymic disorder, depressive disorder not otherwise specified) before the diagnostic biopsy and its treatment with a gluten-free diet was significantly higher in the celiac disease group (37% vs 0%, p < 0.02).

No significant differences were found in the prevalence of current depressive, anxiety or disruptive behavior disorders between the celiac disease patients and the comparison patients.

Celiac disease and parental history of depressive disorders were the only factors that were significantly associated with the prevalence of prebiopsy or lifetime major depressive disorder. The risk for lifetime major depressive disorder associated with parental depressive disorder (OR = 6.80, 95% CI: 1.45-31.72, p < 0.02) was comparable to the risk for lifetime major depressive disorder associated with celiac disease (OR = 6.06, 95% CI = 1.18 - 31.23, p < 0.04).

Author Conclusion:

We found that celiac disease was associated with higher lifetime prevalences of major depressive disorder and disruptive behavior disorder in adolescents relative to matched comparison subjects without celiac disease. In most cases, depressive disorders and comorbid disruptive behavior disorder manifested before the small-bowel biopsy used to diagnose celiac disease, and significant differences were not found in the prevalence of current mental disorders in adolescents with celiac disease, relative to comparison subjects. It seems possible that at least in some of these patients major depression and disruptive behavior disorder were related to celiac disease and alleviated by treatment of celiac disease with a gluten-free diet.

Funding Source:

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

Current compliance with gluten-free diet not measured. Risk for lifetime major depressive disorder appears to be more strongly correlated with parental depressive disorder rather than celiac disease.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		???
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	Yes
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	Yes
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	???
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		No
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	No
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	No
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	No
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		???
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	Yes
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	No
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	Yes
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes