Bipolar and major depressive disorders: associations with serum zonulin levels and rs2070937 polymorphism

The underlying pathophysiology of bipolar disorder and major depressive disorder is not fully understood. Inflammation is increasingly recognized as a contributing factor. The gut plays a central role in this process. Increased intestinal permeability, which promotes inflammation, is regulated by tight junctions and influenced by the zonulin protein. This mechanism has been linked to both inflammatory and psychiatric disorders. This study investigates differences in serum zonulin levels and the rs2070937 genetic polymorphism among patients with bipolar disorder, major depressive disorder, and healthy controls. A total of 47 patients with bipolar disorder, 56 patients with major depressive disorder, and 51 healthy controls were enrolled. Manic and depressive symptom severity were assessed with the Young Mania Rating Scale and the Hamilton Depression Rating Scale. Venous blood samples were collected from all participants to evaluate serum zonulin levels and to perform genotyping of the rs2070937 polymorphism. Serum zonulin levels were significantly higher in patients with bipolar disorder compared to healthy controls (padj = 0.012), and in patients with major depressive disorder compared to healthy controls (padj < 0.001). No significant differences were observed between the bipolar disorder and major depressive disorder groups. Analysis of rs2070937 genotypes (AA, AG, GG) revealed no significant differences in serum zonulin levels within genotype groups. Furthermore, the distribution of genotypes did not differ significantly among the bipolar disorder, major depressive disorder, and healthy control groups. Our findings suggest that increased gut permeability may contribute to the pathophysiology of bipolar disorder and major depressive disorder. Recognizing the role of the gut–brain axis in mood disorders could facilitate earlier screening and support the development of personalized treatment approaches.