Celiac disease poses significant risk in developing depression, anxiety, headache, epilepsy, panic disorder, dysthymia: A meta-analysis

Abstract

Celiac disease (CD) primarily affects the small intestine. Previous studies have identified higher incidences of neuropsychiatric diseases among CD patients compared to non-CD controls. Genome-wide association studies have identified >60 non-human leukocyte antigen (HLA) genes associated with CD, where estimated 15% genes have role in neurological health. We carried out a systematic review and meta-analysis to estimate the potential risk conferred by CD in developing neuropsychiatric diseases. Literature search was performed till June 2019. Incidences of neuropsychiatric diseases were compared among CD and non-CD controls. Funnel plots and Egger's tests were used to evaluate publication bias and estimate study effects. Qualities of the included studies were estimated using Newcastle-Ottawa Scale. Quality of evidence was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Odds of developing neuropsychiatric diseases among CD were evaluated by computing meta-odds ratio (Manten-Haenszel method) and Z test p-value using random and fixed effect models based on the degree of study heterogeneity. Thirteen non-randomized case-control studies were found eligible. Subjects suffering from CD were found to have significantly more risk to develop depression (p<1.00E-05; OR=1.60 [1.37-1.86]), anxiety (p=0.05; OR=1.41 [1.00-1.97]), headache (p<0.1.00E-05; OR=3.27 [2.46-4.34]), epilepsy (p<1.00E-04; OR=11.90 [3.78-37.43]), panic disorder (p<1.00E-04; OR=4.64 [2.22-9.70]), and dysthymia (p=2.00E-03; OR=5.27 [1.83-15.22]). CD is a major predisposing factor in developing array of common neuropsychiatric diseases. Shared biological processes and molecular networks could play a crucial role in disease co-occurrence. Detailed molecular evidences are needed to establish the cause-effect relationship between these diseases.

Keywords: Anxiety; Celiac disease; Co-occurrence; Depression; Dysthymia; Epilepsy; Headache; Meta-analysis; Neuropsychiatric diseases; Panic disorder; Systematic review.