抑郁症患者接受治疗前后血浆单胺类神经递质代谢产物的差异

,背景抑郁症的单胺假说已得到很多研究证明,但是郁症患者血浆中单胺递质代谢产物与抗抑郁治疗的相关性研究较少报道.目的探讨不同药物治疗抑郁症患者血浆中单胺递质代谢产物的差异,以及抗抑郁治疗与抑郁患者血浆中单胺递质代谢产物水平的相关性.设计病例对照研究.单位南京医科大学脑科研究所和精神科.对象抑郁症组(n=40)为南京脑科医院住院抑郁症患者,汉密顿抑郁量表总分＞17.对照组(n=20)为南京市中心血站健康志愿献血者.干预抑郁症组均用抗抑郁药治疗4周氟西汀20 mg/d,5-羟色胺重摄取抑制剂类];帕罗西汀(20 mg/d,5-羟色胺重摄取抑制剂类);万拉法新20～100 mg/d,5-羟色胺、去甲肾上腺素双重摄取抑制剂类],氟伏沙明(50～100 mg/d,去甲肾上腺素双重摄取抑制剂类).用高效液相色谱法对抑郁症患者治疗前后血浆中单胺递质代谢产物水平进行测定,用汉密顿抑郁量表评定抑郁症患者的临床疗效.主要观察指标抑郁症患者血浆中单胺递质代谢产物5-羟吲哚乙酸、3-甲基-4-羟基苯乙二醇、高香草酸的水平.结果抑郁症患者治疗前血浆中5-羟吲哚乙酸、3-甲基-4-羟基苯乙二醇、高香草酸的水平(20.3±14.6),(124.8±103.6),(54.7±32.1)μg/L]均低于正常对照组(39.5±28.4),(334.5±107.3),(88.5±37.2)μg/L],差异有显著性(P＜0.05).经5-羟色胺重摄取抑制剂治疗的抑郁症患者,5-羟吲哚乙酸含量(37.1±21.9)μg/L]与治疗前比较明显升高,差异有显著性(P＜0.05);3-甲基-4-羟基苯乙二醇和高香草酸与治疗前比较,差异无显著性(P＞0.05);经去甲肾上腺素双重摄取抑制剂治疗后,血浆中5-羟吲哚乙酸,3-甲基-4-羟基苯乙二醇含量(35.4±25.2),(291.2±120.4)μg/L]均比治疗前升高,差异有显著性(P＜0.05);高香草酸水平无明显变化.结论外周的单胺递质代谢产物可反映脑中单胺类神经递质的状态,血浆中单胺类递质的变化可作为抑郁症疗效评定的一个重要参考指标.

Plasma metabolite change of monoamine neurotransmitters in patients with depression after treatment

BACKGROUND: Monoamine hypothesis has been demonstrated by researches. However, the correlation between the metabolite of plasma monoamine neurotransmitter and anti-depression treatment in patients with depression has less been reported.OBJECTIVE: To study the effect of different drugs on metabolite of plaama monoamine neurotransmitter, and the correlation between the metabolite of plasma monoamine neurotransmitter and anti-depression treatment in patients with depression.DESIGN: Case controlled study.SETTING: Neurological Department and Brain Institute of Nanjing Medical University.PARTICIPANTS: Forty patients with depression hospitalized in Nanjing Brain Hospital (depression group) were diagnosed with the second revised edition of China classification of mental diseases(CCMD-2) and the tenth edition of International classification of diseases. And the total score of Hanmilton rating scale for depression(HAMD) was more than 17. Healthy voluntary blood donators in the control group were from Nanjing Municipal Central Blood Station( n = 20).INTERVENTIONS: Antidepressant was used in the depression for 4 weeks: fluoxetine 20 mg per day; 5-serotonin selective reuptake inhibitor (SSRI) paroxetine 20 mg per day; venlafaxime 50- 100 mg per day;5-serotonin and morepinephrine selective reuptake inhibitor(SNRI) fluvoxamine 50-100 mg per day. High performance liquid chromatograpy(HPLC)was used to measure the level of metabolite of plasma monoamine neurotransmitter in patients with depression before and 42 week after treatment, and the HAMD was used to evaluate clinical effect of the patients.MAIN OUTCOME MEASURES: The levels of metabolites of plasma monoamine neurotransmitters in patients with depression: 5-hydroxyindoleace tic acid(5-HIAA), 3-methoxy-4-hydroxyphenylglycol(MHPG) and homovani llic acid(HVA) were measured before and 4th week after treatment.RESULTS: The levels of 5-HIAA, MHPG and HVA of the metabolites of plasma monoamine neurotransmitters in patients with depression before treatment (20.3±14.6), (124.8±103.6), (54.7±32.1) μg/L] were all lower than those in the normal control group (39.5±28.4), (334.5 ±107.3), (88.5±37.2) μg/L], with statistically significant differences (P＜0.05). After SSRI treatment, the 5-HIAA content (37.1±21.9)μg/L]was significantly increased as compared with that before treatment, whose difference indicated significant meaning ( P＜0.05), but the differences in MHPG and HVA had no significant meaning as compared with those before treatment(P＞0.05) . After SNRI treatment, 5-HIAA and MHPG contents (35.4±25.2 ), (291.2±120.4) μg/L] both were significantly increased, which indicated significant difference as compared with those before treatment( P＜0.05); but HVA level had no significant changes.CONCLUSION:'The peripheral neurotransmitter metabolites in plasma can reflect their states in brain. The change of neurotransmitter metabolite in plasma can be regarded as an important reference index for the evaluation of depression.