Dissertation committee:
Χριστίνα Κανακά-Gantenbein, Καθηγήτρια, Ιατρική, ΕΚΠΑ
Γεώργιος Χρούσος. Καθηγητής, Ιατρική, ΕΚΠΑ
Παναγιώτα Περβανίδου, Επίκουρη Καθηγήτρια, Ιατρική, ΕΚΠΑ
Μαρία Τσολιά, Καθηγήτρια, Ιατρική, ΕΚΠΑ
Δημήτρης Αναγνωστόπουλος, Καθηγητής, Ιατρική, ΕΚΠΑ
Σουλτάνα Σιαχανίδου, Αναπληρώτρια Καθηγήτρια, Ιατρική, ΕΚΠΑ
Γεώργιος Μπάμιας, Αναπληρωτής Καθηγητής, Ιατρική ΕΚΠΑ
Summary:
Introduction: Celiac disease is a disorder characterized by a variety of clinical manifestations, although it may exist in a clinically silent form. It has been linked to many neuropsychiatric disorders and various potential underlying mechanisms have been proposed to explain this comorbidity. The aim of our study was to estimate the prevalence of mental health problems and the stress profile of children and adolescents with celiac disease in Greece and to investigate the potential role of the gut-brain axis in the pathogenesis of the neuropsychiatric complications of celiac disease.
Methods: Our study comprised 50 patients with celiac disease at diagnosis, before initiation of a GFD (group Α, age 8.6±3.7 yrs, 32 female), 39 patients on a GFD for at least 12 months (group Β, age 10.4±3.4 yrs, 28 female) and 77 healthy controls (group C, age 8.25±2.19 yrs, 40 female). For every participant, serum BDNF levels as well as serum and salivary cortisol were measured. Every participant along with his/her parent completed specific questionnaires regarding mental health problems. The SCL-90-R were used to estimate parental psychopathology and the CDI and CBCL to evaluate the depressive symptoms and mental health problems of the children, respectively. In addition, the parents of the patients on GFD answered a specific GFD adherence-related questionnaire. Twenty patients of group A were reevaluated at least 12 months after initiation of a GFD, by collecting serum and saliva and by answering specific questionnaires (group D). From 8 patients of group D, serum was also collected at their reevaluation.
Results: We demonstrated that patients, regardless of being on a GFD or not (28,860 ± 7,992 pg/ml vs 26,110 ± 8,204 respectively), had higher BDNF levels compared to healthy controls (19,630 ± 8,093 pg/ml, p<0.001 for both groups). Moreover, patients on a GFD had even higher BDNF levels than patients at diagnosis (28,860 ± 7,992 pg/ml vs 26,110 ± 8,204 respectively, p<0.001). In addition, patients at diagnosis and on a GFD, had lower levels of salivary cortisol (AUC: 100.89±41.96 μg/dl and 106.413±46.036μg/dl respectively) compared to healthy controls (AUC: 247.10±133.25 μg/dl, p<0.001 for both groups). Patients at diagnosis had comparable serum and salivary cortisol levels compared to those on a GFD. Parental psychopathology was higher for those at diagnosis compared to healthy controls (SCL-90R score: 0.72 ± 0.49 vs 0.54 ± 0.58, p=0.016). Patients at diagnosis and healthy controls had higher CDI scores compared to patients on GFD (8.2 ± 4.7 vs 5.5 ± 4.3, p=0.006 and 9.1 ± 6.1 vs 5.5 ± 4.3, p=0.012 respectively). Patients at diagnosis had higher scores for the internalizing symptoms of the CBCL questionnaire compared to healthy controls (55.7 ± 10.3 vs 47.9 ± 15.4, p=0.007). For the group of patients on a GFD (group B), the presence of positive serology was related with lower CDI scores (positive vs negative serology: β=0.71, 95%ci: -1.37, -0.07, p-value=0.032).
Conclusions: BDNF levels were higher in patients with CD than HC, regardless of adherence to GFD. This finding could suggest a protective role of BDNF against chronic intestinal inflammation or chronic stress from the diet. According to our findings, patients with celiac disease have a deranged stress system response, with a potential blunting of the hypothalamus-pituitary axis, possibly due to the constant triggering by either the stress of the intestinal inflammation or the psychological burden of adhering to a strict GFD and living with a chronic disease.
