Abstract Background Bipolar disorder is a chronic and recurrent condition, associated with significantly impaired functioning and reduced quality of life. Given the importance of immune system in the etiology of bipolar disorder, studies on the gut, the largest immune system in the body, represent an important area for research. A change in intestinal permeability may be considered biomarker of local or even distant immune-mediated disorders. Increased gut permeability allows the passage, through the intestinal epithelial layer, of macromolecules, toxins, and bacterial species (both pathogenic and commensal) that may trigger immune-mediated diseases in different systems. Zonulin is regarded as a non-invasive biomarker for intestinal permeability. This study aimed at assessment of the serum zonulin level in patients with bipolar disorder I and its relation with the severity of the symptoms of the disorder, the age of onset of the disorder, the frequency of relapses and response to therapeutic trials. Methods two hundred patients with bipolar I disorder, divided into one hundred patients in acute manic or depressive episode and one hundred patients in full remission were compared to one hundred age and sex matched healthy controls. The patients were administered Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS) to determine the severity of manic and depressive symptoms, respectively. Venous blood samples were collected, and serum zonulin was measured. Results The mean serum zonulin in patients was significantly higher than healthy controls. Serum zonulin levels was significantly higher in patients with acute episodes than patients in remission. Conclusion The current research indicates that zonulin is increased in patients with bipolar disorder and this finding may contribute to the role of intestinal permeability or BBB in the pathogenesis of bipolar disorder.
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