Uçak Ekrem Furkan, Altınbaş Kürşat, Koçak Nadir, Güleç Ahmet
Department of Psychiatry, Afyonkarahisar Health Sciences University, Zafer Sağlık Külliyesi Dörtyol Mah, Afyonkarahisar, Turkey.
Department of Psychiatry, Faculty of Medicine, Selcuk University, Konya, Turkey.
Chronobiol Int. 2025 Feb;42(2):225-234. doi: 10.1080/07420528.2025.2455139. Epub 2025 Jan 20.
Lithium has long been used as a cornerstone mood stabilizer in the treatment of bipolar disorder (BD). However, reliable biomarkers that can predict which patients will respond better to lithium are still lacking. This study aims to evaluate the potential of NR1D1 gene SNP; rs2071427 and actigraphic measurements in predicting lithium response. Thirty-one patients diagnosed with BD at Selçuk University Faculty of Medicine and who were euthymic for at least 8 weeks were included in the study. Sleep-wake cycles and circadian rhythms of the participants were monitored by actigraph for approximately 1 week. For genetic analyses, the SNP rs2071427 variant of the NR1D1 gene was evaluated. A significant proportion of patients with homozygous (AA/GG) genotypes responded well to lithium, whereas some patients with heterozygous (AG) genotypes did not respond to lithium. Actigraphic data showed that there were marked variations in the sleep patterns of BD patients. The Morningness-Eveningness Questionnaire scale did not adequately discriminate the morning chronotype. Seasonal Pattern Assessment Questionnaire results showed that most patients had a seasonal pattern, but this was insufficient to predict response to lithium. This study once again demonstrates the need for new biomarkers to predict lithium response. The findings are an important step in the personalization of BD treatment and may improve treatment efficacy and minimize side effects by tailoring the treatment process to the individual characteristics of patients. Future studies should support these findings with larger sample groups and studies on different genetic markers.
长期以来，锂一直被用作治疗双相情感障碍（BD）的基石性心境稳定剂。然而，仍缺乏能够预测哪些患者对锂反应更佳的可靠生物标志物。本研究旨在评估NR1D1基因单核苷酸多态性（SNP）rs2071427以及活动记录仪测量在预测锂反应方面的潜力。研究纳入了塞尔丘克大学医学院诊断为双相情感障碍且至少8周处于心境正常状态的31名患者。通过活动记录仪对参与者的睡眠 - 觉醒周期和昼夜节律进行了约1周的监测。对于基因分析，评估了NR1D1基因的SNP rs2071427变体。相当一部分纯合子（AA/GG）基因型患者对锂反应良好，而一些杂合子（AG）基因型患者对锂无反应。活动记录仪数据显示，双相情感障碍患者的睡眠模式存在显著差异。晨型 - 夜型问卷量表未能充分区分晨型时相。季节性模式评估问卷结果表明，大多数患者有季节性模式，但这不足以预测对锂的反应。本研究再次表明需要新的生物标志物来预测锂反应。这些发现是双相情感障碍治疗个性化的重要一步，通过根据患者个体特征调整治疗过程，可能提高治疗效果并最小化副作用。未来的研究应以更大的样本量和对不同基因标记的研究来支持这些发现。
