Fries Gabriel R, Mirza Salahudeen, Wang Jun, Lima Camila N C, Zhang Wei, Tamez Marcela Carbajal, Scaini Giselli, Soares Jair C, Quevedo Joao
Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, 1941 East Rd, Houston, TX, 77054.
Center of Excellence in Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, 1941 East Rd, Houston, TX, 77054.
medRxiv. 2025 Jun 6:2025.06.06.25329080. doi: 10.1101/2025.06.06.25329080.
Bipolar disorder (BD) is a common and yet poorly elucidated psychiatric disorder, with emerging evidence implicating a role for epigenetic mechanisms, including microRNAs (miRNAs), in its pathophysiology. These molecules are secreted from cells in extracellular vesicles (EVs), which can be isolated from bodily fluids and tested as potential biomarkers. In individuals with BD and control participants (CON), we characterized the miRNA expression profiles of peripheral blood EVs selected for L1CAM, a putative neuronal marker, as well as bulk peripheral blood EVs. Peripheral blood EVs were isolated from n=20 BD and 20 CON (L1CAM) and n=21 BD and 20 CON (bulk). Within each study, analyses identified miRNAs that were differentially expressed between BD and CON, followed by functional interrogation and testing for associations with clinical features. Results were then compared to better understand the relative specificity of bulk and L1CAM EV analyses. Thirty-four miRNAs were differentially expressed between groups in L1CAM EVs, whereas 10 differentially expressed miRNAs were identified in bulk EVs. Across both analyses, biological pathways attributed to the differentially expressed miRNAs included insulin receptor pathway and type II diabetes mellitus. Importantly, associations of differentially expressed miRNAs with clinical features were only significant in L1CAM EVs. Our results reiterate a crucial role for miRNAs in the pathophysiology of BD and suggest that miRNA signatures of putative neuronal origin more closely correspond to clinical features.
双相情感障碍（BD）是一种常见但尚未完全阐明的精神疾病，越来越多的证据表明表观遗传机制，包括微小RNA（miRNA），在其病理生理学中发挥作用。这些分子从细胞分泌到细胞外囊泡（EV）中，EV可以从体液中分离出来并作为潜在的生物标志物进行检测。在双相情感障碍患者和对照参与者（CON）中，我们对选择用于神经元标志物L1CAM的外周血EV以及外周血总EV的miRNA表达谱进行了表征。从n = 20例双相情感障碍患者和20例对照（L1CAM）以及n = 21例双相情感障碍患者和20例对照（总样本）中分离出外周血EV。在每项研究中，分析确定了双相情感障碍患者和对照之间差异表达的miRNA，随后进行功能探究并测试其与临床特征的关联。然后比较结果以更好地了解总样本和L1CAM EV分析的相对特异性。在L1CAM EV中，两组之间有34种miRNA差异表达，而在总EV中鉴定出10种差异表达的miRNA。在两项分析中，差异表达的miRNA所涉及的生物学途径包括胰岛素受体途径和II型糖尿病。重要的是，差异表达的miRNA与临床特征的关联仅在L1CAM EV中具有显著性。我们的结果重申了miRNA在双相情感障碍病理生理学中的关键作用，并表明假定神经元来源的miRNA特征与临床特征更密切相关。
