Study on exosomes for identifying bipolar disorder in early stage: A cross-sectional and validation study protocol.

Abstract

The difficulty is remained to accurately distinguish bipolar disorder (BD) from major depressive disorder (MDD) in early stage, with a delayed diagnosis for 5-10 years. BD patients are often treated with antidepressants systematically due to being diagnosed with MDD, affecting the disease course and clinical outcomes. The current study aims to explore the role of plasma exosomes as biomarker to distinguish BD from MDD in early stage. Two stages are included. The first stage is a cross-sectional study, comparing the concentrations of plasma exosome microRNA and related proteins among BD group, MDD group, and healthy controls (HC) group (n=40 respectively), to identify target biomarkers preliminarily. The "Latent Class Analysis" and "Receiver Operating Characteristic" analysis will be performed to determine the optimal concentration range for each biomarker. The second stage is to validate target markers in subjects, coming from an ongoing study focusing on patients with a first depressive episode. All target biomarkers will be test in plasma samples reserved at the initial stage to detect whether the diagnosis indicated by biomarker level is consistent with the diagnosis by DSM-5. Furthermore, the correlation between specific biomarkers and the manic episode, suicidal ideation, and adverse reactions will also be observed. Exosome-derived microRNA and related proteins have potential in serving as a good medium for exploring mental disorders because it can pass through the blood-brain barrier bidirectionally and convey a large amount of information stably. Improving the early diagnosis of BD would help implement appropriate intervention strategy as early as possible and significantly reduce the burden of disease.