MicroRNA-mediated regulation of BDNF in depressive disorder: a pathway to diagnosis and therapy

Depressive disorder, also known as depression, represents a major global health concern. Effective diagnosis and treatment of depression are critical to moderate its impact. Current diagnostic methods for depression are time-consuming and subjective, which can lead to misdiagnosis and impact treatment effectiveness. Therefore, identifying potential biomarkers for early and accurate diagnosis is critically needed. Although the exact pathophysiology of depression remains unknown, neurotrophic factors, with brain-derived neurotrophic factor (BDNF) being the most important, have been elucidated to play a key role in the pathogenesis of depression. Alterations in functional BDNF may contribute to the pathophysiology of depression by impairing neuroplasticity, a process closely linked to antidepressant action. Meanwhile, advancements in next-generation sequencing (NGS), quantitative polymerase chain reaction (qPCR), and bioinformatics have enabled the identification of various microRNAs (miRNAs) associated with depression. This review aims to assess the role and mechanisms of microRNAs that target BDNF in depression. These microRNAs regulate the pathophysiology of depression, particularly through abnormalities in neuroplasticity and neurogenesis, as well as other mechanisms such as hypothalamic-pituitary-adrenal axis hyperactivity and inflammatory dysregulation. These microRNAs may serve as biomarkers for diagnosis and as targets for novel antidepressants. Our study identifies 16 miRNAs that target BDNF in depression, either directly or indirectly through other molecules. Among these, miR-124, miR-132, and miR-221 are promising candidates for biomarkers of depression. Meanwhile, miR-124 and miR-132 present significant promise for treatment. However, major challenges remain in translating these findings into clinical practice, underscoring the need for further research.