Sun Zuoli, Yang Jian, Zhou Jia, Zhou Jingjing, Feng Lei, Feng Yuan, He Yi, Liu Min, Li Yuhong, Wang Gang, Li Rena
National Clinical Research Center for Mental Disorders and Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.
Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.
Biol Psychiatry Glob Open Sci. 2023 Jan 30;3(4):663-672. doi: 10.1016/j.bpsgos.2023.01.004. eCollection 2023 Oct.
There is growing evidence that disturbances in cholesterol metabolism may be involved in major depressive disorder (MDD). However, it is not known if cholesterol metabolites present in the brain and periphery can be used to diagnose and predict an MDD patient's response to antidepressant treatment.
A total of 176 subjects (85 patients with MDD and 91 healthy control subjects) were included in this study. The expression of peripheral and brain-specific oxysterols and related gene polymorphisms were investigated in all subjects. The severity of depression was measured using the 17-item Hamilton Depression Rating Scale, 16-item Quick Inventory of Depressive Symptoms-Self-Report, and Patient Health Questionnaire-9 for all patients with MDD before and after 12 weeks of antidepressant treatment.
Patients with MDD expressed higher plasma levels of 24(S)-hydroxycholesterol (24OHC) (mainly secreted from the brain) compared with healthy control subjects, and the higher levels of 24OHC were associated with 24OHC synthetase () gene polymorphisms. In patients with MDD, an improved response to the 12-week antidepressant treatment was associated with a reduction of both 24OHC and 27OHC (mainly secreted from the peripheral system) levels relative to baseline levels. Nonresponders exhibited increased levels of oxysterols at the end of treatment compared with baseline. The superior reduction in oxysterol levels correlated with better outcomes from the antidepressant treatment.
These data suggest a potential role for oxysterols as diagnostic and treatment response-related indicators for MDD.
越来越多的证据表明，胆固醇代谢紊乱可能与重度抑郁症（MDD）有关。然而，尚不清楚大脑和外周中存在的胆固醇代谢物是否可用于诊断和预测MDD患者对抗抑郁治疗的反应。
本研究共纳入176名受试者（85例MDD患者和91名健康对照者）。研究了所有受试者外周和脑特异性氧化甾醇的表达及相关基因多态性。使用17项汉密尔顿抑郁量表、16项抑郁症状快速自评量表和患者健康问卷-9对所有MDD患者在抗抑郁治疗12周前后的抑郁严重程度进行了测量。
与健康对照者相比，MDD患者血浆中24(S)-羟基胆固醇（24OHC）（主要由大脑分泌）水平较高，且较高的24OHC水平与24OHC合成酶（）基因多态性有关。在MDD患者中，12周抗抑郁治疗反应改善与24OHC和27OHC（主要由外周系统分泌）水平相对于基线水平降低有关。无反应者在治疗结束时氧化甾醇水平相对于基线升高。氧化甾醇水平的显著降低与抗抑郁治疗的更好结果相关。
这些数据表明氧化甾醇作为MDD的诊断和治疗反应相关指标具有潜在作用。
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