海马区Cho/Cr比值在青少年抑郁障碍重复经颅磁刺激治疗疗效评价中的预测价值

Predictive value of Cho/Cr in the efficacy evaluation of repetitive transcranial magnetic stimulation treatment for depressive disorders in adolescents

摘要

目的 探讨海马区胆碱(CHo)/肌酸(Cr)比值在青少年抑郁障碍接受重复经颅磁刺激(rTMS)治疗中的预测价值,以提高rTMS治疗的针对性和有效性。方法 招募 2024年 5月—2025 年 3月在乌鲁木齐市友爱医院临床心理科病房住院或门诊治疗的青少年抑郁障碍患者31例作为研究对象。所有入组患者均接受单一舍曲林治疗,以控制药物混杂效应。在 2 周 rTMS 治疗前、后分别采用汉密尔顿抑郁量表-24(HAMD-24)对入组患者的抑郁症状严重程度进行评估,应用氢质子磁共振波谱(¹H-MRS)扫描检测Cho、N-乙酰天门冬氨酸(NAA)、Cr水平。按照HAMD减分率为依据分组,减分率≥50%划为有效组,反之则为无效组。结果 有效组和无效组在HAMD的睡眠障碍因子(t=-2.144,P<0.05)和绝望感因子(t=-2.053,P<0.05)及海马区Cho/Cr比值(t=-2.935,P<0.05)之间差异有统计学意义;在logistic回归分析中,Cho/Cr比值(OR=1.62,95%CI:1.00~2.63)对rTMS抗抑郁疗效的影响具有统计学意义(P<0.05);构建ROC曲线后,Cho/Cr比值的曲线下面积(AUC)为0.735(P<0.05),根据最大Youden指数推算出最佳截断值为1.13,其敏感性为94.7%,特异性为58.3%,这表明在接受rTMS治疗的青少年抑郁障碍患者中,若Cho/Cr比值大于1.13,则可能对rTMS治疗有较好的应答。结论 海马区Cho/Cr比值可能作为青少年抑郁障碍患者接受rTMS治疗疗效的潜在预测指标,为临床提供了个体化治疗的依据。

Abstract

Objective To explore the preliminary value of 1H-MRS in predicting the prognosis of adolescents with depressive disorder before receiving repetitive transcranial magnetic stimulation (rTMS), so as to improve the targeting and effectiveness of rTMS treatment. Methods A total of 31 adolescents with depressive disorder treated at Urumqi Youai Hospital from May 2024 to March 2025 were recruited.All patients received standardized sertraline monotherapy to control for confounding drug effects.Before and after 2 weeks of rTMS treatment, the 24-item Hamilton Depression Scale (HAMD-24) was used to assess symptom severity, and 1H-MRS was applied to detect hippocampal levels of choline (Cho), N-acetylaspartate (NAA), and creatine (Cr).Patients were classified into an effective group (reduction rate ≥50%) or an ineffective group based on HAMD score reduction. Results There were statistically significant differences between the two groups in the sleep disturbance factor (t=-2.144, P<0.05) and hopelessness factor (t=-2.053, P<0.05) of HAMD, as well as the Cho/Cr ratio in the hippocampus (t=-2.935, P<0.05).In the logistic regression analysis, the Cho/Cr ratio (OR=1.62, 95%CI:1.00 - 2.63) had a statistically significant impact on the antidepressant efficacy of rTMS (P<0.05).After constructing the ROC curve, the area under the curve (AUC) of the Cho/Cr ratio was 0.735 (P<0.05).According to the maximum Youden index, the optimal cut-off value was calculated as 1.13, with a sensitivity of 94.7% and a specificity of 58.3%.This indicates that among adolescent patients with depressive disorder receiving rTMS treatment, those with a Cho/Cr ratio greater than 1.13 may have a better response to rTMS treatment. Conclusions The hippocampal Cho/Cr ratio may serve as a potential predictive indicator for rTMS efficacy in adolescents with depressive disorder, providing preliminary evidence for individualized clinical treatment.

关键词

青少年 / 脑代谢物质 / 重复经颅磁刺激 / 抑郁障碍

Key words

adolescent / cerebral metabolites / repetitive transcranial magnetic stimulation / depressive disorder

[1] Zhou X, Teng T, Zhang Y, et al.Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder:A systematic review and network meta-analysis[J].Lancet Psychiatry, 2020, 7(7):581-601.
[2] 马璐,乔丹,郭倩茹,等.青少年抑郁障碍临床转归及影响因素的研究进展[J].精神医学杂志, 2024,37(1):103-107.
Ma L, Qiao D, Guo QR,et al.Research progress on clinical outcomes and influencing factors of adolescent depressive disorders[J].Journal of Psychiatry, 2024, 37(1):103-107.(in Chinese)
[3] Parhiala P, Marttunen M, Gergov V, et al.Predictors of outcome after a time-limited psychosocial intervention for adolescent depression[J].Front Psychol, 2022,13:955261.
[4] Fitzgerald PB, Hoy KE, Anderson RJ, et al.A study of the pattern of response to rTMS treatment in depression[J].Depress Anxiety, 2016, 33(8):746-753.
[5] George MS.Whither TMS:A one-trick pony or the beginning of a neuroscientific revolution[J].Am J Psychiatry, 2019, 176(11):904-910.
[6] Lisanby SH.Noninvasive brain stimulation for depression-the devil is in the dosing[J].N Engl J Med, 2017, 376(26):2593-2594.
[7] 林红,刘陈,尹娥,等.iTBS模式重复经颅磁刺激联合氟伏沙明治疗首发青少年抑郁症非自杀性自伤行为的临床观察[J].国际精神病学杂志,2023,50(4):716-718.
Lin H, Liu C, Yin E, et al.A clinical observation of iTBS mode rTMS combined with Fluvoxamine on the treatment of first-episode adolescent depression with non-suicidal self-injury behaviors[J].J Int Psychiatry, 2023, 50(4): 716-718.(in Chinese)
[8] Croarkin PE, Macmaster FP.Transcranial magnetic stimulation for adolescent depression[J].Child Adolesc Psychiatr Clin N Am, 2019, 28(1):33-43.
[9] Jupp B, Sawiak SJ, vander Veen B, et al.Diminished myoinositol in ventromedial prefrontal cortex modulates the endophenotype of impulsivity[J].Cereb Cortex, 2020, 30(5):3392-3402.
[10] 汤毓华,张明园.汉密顿抑郁量表(HAMD)[J].上海精神医学,1984,26(2):61-64.
Tang YH, Zhang MY.Hamilton Depression Scale[J].Shanghai Archives of Psychiatry, 1984,26(2): 61-64.(in Chinese)
[11] Argyropoulos GD, Christidi F, Karavvasilis E, et al.A magnetic resonance spectroscopy study on polarity subphenotypes in bipolar disorder[J].Diagnostics, 2024, 14(11):1170.
[12] 王丞基,曲源,张丞,等.伴有焦虑症状青少年双相抑郁患者腹内侧前额叶氢质子磁共振波谱研究[J].中国神经精神疾病杂志,2023,49(10):604-608.
Wang CJ, Qu Y, Zhang C, et al.Proton magnetic resonance spectroscopy in the ventromedial prefrontal lobe of adolescents with bipolar depression with anxiety symptoms[J].Chin J Nerv Ment Dis, 2023, 49(10):604-608.(in Chinese)
[13] Dellósso B, Cremaschi L, Macellaro M, et al.Bipolar disorder staging and the impact it has on its management: An update[J].Expert Rev Neurother, 2024, 24(6):565-574.
[14] Han KM, Kim A, Kang W, et al.Hippocampal subfield volumes in major depressive disorder and bipolar disorder[J].Eur Psychiatry, 2019, 57:70-77.
[15] Roddy DW, Farrell C, Doolin K, et al.The hippocampus in depression: More than the sum of its parts? Advanced hippocampal substructure segmentation in depression[J].Biol Psychiatry, 2019, 85(6): 487-497.
[16] Ping L, Chu Z, Zhou B, et al.Structural alterations after repetitive transcranial magnetic stimulation in depression and the link to neurotransmitter profiles[J].Asian J Psychiatry, 2025, 107:104445.
[17] Zhao TT, Guo HL, Yan JY, et al.Repetitive transcranial magnetic stimulation reversing abnormal brain function in mood disorders with early life stress:From preclinical models to clinical applications[J].Asian J Psychiatry, 2024,97(7):104092.

基金资助

新疆第二医学院科研项目(ZR202419)