Fettahoğlu İbrahim, Akşahin İzel Cemre, Yeşiloğlu Buket, Çelik Hidayet Ece Arat, Kaymakçı Esma Çörekli, Kendirlioğlu Burcu Kök, Frye Mark, Özerdem Ayşegül, Ceylan Deniz
Koç University Research Center for Translational Medicine, İstanbul, Türkiye.
Koç University Research Center for Translational Medicine, İstanbul, Türkiye; Department of Neuroscience, Graduate School of Health Sciences, Koç University, İstanbul, Türkiye.
J Affect Disord. 2025 Nov 15;389:119653. doi: 10.1016/j.jad.2025.119653. Epub 2025 Jun 19.
Mitochondrial genome-encoded long non-coding RNAs (mt-LncRNAs) that play roles in regulation of energy metabolism and mitochondrial function, both crucial in mood disorder pathogenesis, yet remain poorly explored despite growing interest. This study examines their expression levels in individuals with major depressive disorder (MDD), bipolar disorder (BD), siblings of individuals with BD (SIB), and healthy controls (HC).
Blood samples from 153 participants (31 MDD, 40 BD, 39 SIB, 43 HC) were analyzed for 10 mt-LncRNAs via RT-qPCR. Samples from a subgroup of 15 remitted MDD (MDD) patients following 8-week treatment were included for exploratory analysis. A composite score for all LncRNAs, global factor, was derived using principal component analysis. All comparisons were adjusted for age, sex, smoking, BMI, and multiple comparisons.
Global scores showed overall downregulation in MDD, BD, and SIB compared to HCs, with BD exhibiting the lowest levels (p < 0.01). All mt-LncRNAs were downregulated in BD and SIB, while 8 (excluding ASncmtRNA-2 and 7S RNA) were downregulated in MDD (p < 0.05). Mt-LncRNA levels were lower in BD than in SIB and MDD (p < 0.05), with 6 also lower in SIB compared to MDD (p < 0.05). Exploratory analysis revealed a significant increase in 8 mt-LncRNAs (excluding LIPCAR and 7S RNA) in MDD compared to baseline MDD (p < 0.05).
Findings show a significant mt-LncRNA downregulation in mood disorders and suggest genetic transmission as well as a capacity to change with treatment. Further research is needed to explore the genetics and modifiability of mt-LncRNAs in mood disorders.
线粒体基因组编码的长链非编码RNA（mt-LncRNAs）在能量代谢和线粒体功能调节中发挥作用，这两者在情绪障碍发病机制中都至关重要，但尽管人们对此兴趣日益浓厚，其仍未得到充分研究。本研究检测了它们在重度抑郁症（MDD）、双相情感障碍（BD）、双相情感障碍患者的兄弟姐妹（SIB）以及健康对照（HC）中的表达水平。
通过逆转录定量聚合酶链反应（RT-qPCR）分析了153名参与者（31名MDD患者、40名BD患者、39名SIB、43名HC）血液样本中的10种mt-LncRNAs。纳入了15名经过8周治疗后缓解的MDD患者亚组的样本进行探索性分析。使用主成分分析得出所有LncRNAs的综合评分，即全局因子。所有比较均针对年龄、性别、吸烟、体重指数和多重比较进行了调整。
与HC相比，MDD、BD和SIB中的全局评分总体下调，BD的水平最低（p < 0.01）。所有mt-LncRNAs在BD和SIB中均下调，而8种（不包括ASncmtRNA-2和7S RNA）在MDD中下调（p < 0.05）。BD中的mt-LncRNA水平低于SIB和MDD（p < 0.05），6种在SIB中也低于MDD（p < 0.05）。探索性分析显示，与基线MDD相比，MDD中有8种mt-LncRNAs（不包括LIPCAR和7S RNA）显著增加（p < 0.05）。
研究结果表明情绪障碍中mt-LncRNAs存在显著下调，并提示了遗传传递以及随治疗改变的能力。需要进一步研究以探索情绪障碍中mt-LncRNAs的遗传学和可修饰性。
