Morgunova Alice, O'Toole Nicholas, Abboud Fatme, Coury Saché, Chen Gary Gang, Teixeira Maxime, Fitzgerald Eamon, Turecki Gustavo, Gifuni Anthony J, Gotlib Ian H, Nagy Corina, Meaney Michael J, Ho Tiffany C, Flores Cecilia
Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada.
Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
Biol Psychiatry Glob Open Sci. 2025 Apr 14;5(4):100505. doi: 10.1016/j.bpsgos.2025.100505. eCollection 2025 Jul.
Adolescent depression is linked to enduring maladaptive outcomes, chronic severity of symptoms, and poor treatment response. Identifying epigenetic signatures of adolescent depression is urgently needed to improve early prevention and intervention strategies. MicroRNAs (miRNAs) are epigenetic regulators of adolescent neurodevelopmental processes, but their role as markers and mediators of adolescent depression is unknown.
Here, we examined miRNA profiles from dried blood spot samples of male and female adolescents with clinical depression and psychiatrically healthy male and female adolescents ( = 62). We processed and sequenced these samples using a small RNA protocol tailored for miRNA identification.
We identified 9 differentially expressed (DE) miRNAs (adjusted value < .05), all of which were upregulated in adolescents with depression. At future follow-ups post blood collection, expression of miR-3613-5p, mir-30c-2, and miR-942-5p were positively associated with depression severity but not anxiety, suggesting a stronger link to persistent depression symptoms. Expression of miR-32-5p inversely correlated with hippocampal volume, highlighting a potential neurobiological basis. Common predicted gene targets of the DE miRNAs are involved in neurodevelopment, cognitive processing, and depressive disorders.
These findings lay the groundwork for identifying adolescent peripheral miRNA markers that reflect neurodevelopmental pathways that shape lifelong psychopathology risk.
青少年抑郁症与持久的适应不良后果、症状的慢性严重程度以及治疗反应不佳有关。迫切需要确定青少年抑郁症的表观遗传特征，以改进早期预防和干预策略。微小RNA（miRNA）是青少年神经发育过程的表观遗传调节因子，但其作为青少年抑郁症的标志物和介导因子的作用尚不清楚。
在此，我们检测了患有临床抑郁症的青少年以及精神健康的青少年（男女各62例）干血斑样本中的miRNA谱。我们使用专门针对miRNA鉴定的小RNA方案对这些样本进行处理和测序。
我们鉴定出9种差异表达（DE）的miRNA（校正P值<0.05），所有这些miRNA在抑郁症青少年中均上调。在采血后的未来随访中，miR-3613-5p、mir-30c-2和miR-942-5p的表达与抑郁严重程度呈正相关，但与焦虑无关，这表明与持续的抑郁症状有更强的联系。miR-32-5p的表达与海马体积呈负相关，突出了潜在的神经生物学基础。DE miRNA的常见预测基因靶点参与神经发育、认知加工和抑郁症。
这些发现为识别反映影响终身精神病理学风险的神经发育途径的青少年外周miRNA标志物奠定了基础。
