Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Šalata 12, 10000, Zagreb, Croatia.
University Psychiatric Hospital Vrapče, Zagreb, Croatia.
Psychopharmacology (Berl). 2021 May;238(5):1303-1314. doi: 10.1007/s00213-019-05303-2. Epub 2019 Sep 4.
Depression, with variable longitudinal patterns, recurs in one third of patients. We lack useful predictors of its course/outcome, and proton magnetic resonance spectroscopy (1H-MRS) of brain metabolites is an underused research modality in finding outcome correlates.
To determine if brain metabolite levels/changes in the amygdala region observed early in the recovery phase indicate depression recurrence risk in patients receiving maintenance therapy.
Forty-eight patients on stable-dose antidepressant (AD) maintenance therapy were analyzed from recovery onset until (i) recurrence of depression or (ii) start of AD discontinuation. Two 1H-MRS scans (6 months apart) were performed with a focus on amygdala at the beginning of recovery. N-acetylaspartate (NAA), choline-containing metabolites (Cho), and Glx (glutamine/glutamate and GABA) were evaluated with regard to time without recurrence, and risks were assessed by Cox proportional hazard modeling.
Twenty patients had depression recurrence, and 23 patients reached AD discontinuation. General linear model repeated measures analysis displayed three-way interaction of measurement time, metabolite level, and recurrence on maintenance therapy, in a multivariate test, Wilks' lambda = 0.857, F(2,40) = 3.348, p = 0.045. Cho levels at the beginning of recovery and subsequent changes convey the highest risk for earlier recurrence. Patients experiencing higher amygdala Cho after recovery are at a significantly lower risk for depression recurrence (hazard ratio = 0.32; 95% confidence interval 0.13-0.77).
Cho levels/changes in the amygdala early in the recovery phase correlate with clinical outcome. In the absence of major NAA fluctuations, changes in Cho and Glx may suggest a shift towards reduction in (previously increased) glutamatergic neurotransmission. Investigation of a larger sample with greater sampling frequency is needed to confirm the possible predictive role of metabolite changes in the amygdala region early in the recovery phase.
抑郁症具有多变的纵向模式，三分之一的患者会复发。我们缺乏对其病程/结局的有用预测指标，而脑代谢物质子磁共振波谱（1H-MRS）是一种在寻找结局相关性方面尚未充分利用的研究方式。
确定在恢复阶段早期观察到的杏仁核区域脑代谢物水平/变化是否表明接受维持治疗的患者的抑郁复发风险。
对 48 名接受稳定剂量抗抑郁药（AD）维持治疗的患者进行分析，从恢复开始到（i）抑郁复发或（ii）开始停用 AD。在恢复开始时进行了两次 1H-MRS 扫描（相隔 6 个月），重点是杏仁核。评估了 N-乙酰天冬氨酸（NAA）、含胆碱代谢物（Cho）和 Glx（谷氨酰胺/谷氨酸和 GABA）与无复发时间的关系，并通过 Cox 比例风险模型评估了风险。
20 名患者出现抑郁复发，23 名患者停止使用 AD。在多变量测试中，重复测量的一般线性模型显示了测量时间、代谢物水平和维持治疗复发之间的三向相互作用，Wilks' lambda=0.857，F(2,40)=3.348，p=0.045。恢复开始时的 Cho 水平及其随后的变化在预测早期复发方面具有最高风险。恢复后杏仁核 Cho 水平较高的患者抑郁复发的风险显著降低（危险比=0.32；95%置信区间 0.13-0.77）。
恢复阶段早期杏仁核的 Cho 水平/变化与临床结局相关。在没有 NAA 大幅波动的情况下，Cho 和 Glx 的变化可能表明（先前增加的）谷氨酸能神经传递减少。需要更大样本量和更高采样频率的研究来证实恢复阶段早期杏仁核区域代谢物变化的可能预测作用。
