Backgrounds <p>Bipolar disorder (BD) is a highly heterogeneous and multifactorial condition that imposes substantial burdens on both individuals and society. Despite advances in understanding the neurobiology of BD, its precise etiology remains unclear. Long non-coding RNAs (lncRNAs), particularly H19 and ANRIL, have recently emerged as key regulators of inflammatory pathways and may contribute to the dysregulated immune responses observed in BD.</p> Aims <p>This study investigated the expression levels of H19 and ANRIL lncRNAs in individuals with BD and explored their potential role as biomarkers for the disorder.</p> Materials and methods <p>We measured the expression levels of H19 and ANRIL in the peripheral blood of 90 patients with BD and 90 healthy controls using real-time PCR. Furthermore, receiver operating characteristic (ROC) curve analysis and correlation analysis were conducted to evaluate the association between gene expression and specific clinical features of BD. A computational study was conducted to investigate the binding sites of miRNAs on the H19 and ANRIL lncRNAs.</p> Results <p>The expression levels of H19 and ANRIL were significantly higher in patients with BD compared to healthy controls. The area under the curve (AUC) values for H19 and ANRIL were 0.60 and 0.74, respectively. A computational study revealed that miR-339-5p is a common microRNA that may regulate H19 and ANRIL lncRNAs.</p> Conclusions <p>Given the role of miR-339-5p in inhibiting inflammation, the upregulation of H19 and ANRIL may contribute to the pathology of BD through the regulation of miR-339-5p. Moreover, peripheral expression levels of the lncRNA ANRIL may serve as potential biomarkers for BD. Importantly, these findings underscore the therapeutic promise of small RNA–based strategies—such as miRNA mimics or siRNA approaches—to restore immune balance and provide novel treatment options for BD.</p>