Berman R M, Narasimhan M, Miller H L, Anand A, Cappiello A, Oren D A, Heninger G R, Charney D S
Connecticut Mental Health Center, Department of Psychiatry, Yale University School of Medicine, New Haven 06519, USA.
Arch Gen Psychiatry. 1999 May;56(5):395-403. doi: 10.1001/archpsyc.56.5.395.
Although state-related alterations in catecholamine function have been well-described in depressed subjects, enduring abnormalities have been less reliably identified. In our study, medication-free subjects with fully remitted major depression underwent a paradigm of catecholamine depletion, via use of the tyrosine hydroxylase inhibitor alpha-methylparatyrosine.
Subjects underwent 2 sets of testing conditions in a double-blind, random-ordered, crossover design, approximately 1 week apart. They underwent active catecholamine depletion (via oral administration of 5 g alpha-methylparatyrosine) or sedation-controlled, sham catecholamine depletion (via oral administration of 250 mg diphenhydramine hydrochloride), during a 2-day observation. Serial mood ratings and blood samples were obtained.
Fourteen subjects completed the active testing condition; 13 completed sham testing. Subjects experienced marked, transient increases in core depressive and anxiety symptoms, as demonstrated by a mean 21-point increase on Hamilton Depression Rating Scale scores. Furthermore, 10 (71%) of 14 subjects fulfilled relapse criteria during active testing, whereas 1 (8%) of 13 subjects did so during sham testing. The severity of the depressive reaction correlated with baseline plasma cortisol levels (r = 0.59; P =.04).
Euthymic, medication-free subjects with a history of major depression demonstrate significant depressive symptoms when undergoing testing with alpha-methylparatyrosine. This depressive reaction may represent a reliable marker for a history of depression. Further work is needed to clarify the significance of this finding.
尽管在抑郁症患者中，与状态相关的儿茶酚胺功能改变已得到充分描述，但持久的异常现象却较难可靠地识别。在我们的研究中，完全缓解的重度抑郁症无药物治疗受试者接受了通过使用酪氨酸羟化酶抑制剂α-甲基对酪氨酸进行儿茶酚胺耗竭的范式。
受试者在双盲、随机顺序、交叉设计中接受两组测试条件，间隔约1周。在为期2天的观察期间，他们接受了活性儿茶酚胺耗竭（通过口服5克α-甲基对酪氨酸）或镇静对照的假儿茶酚胺耗竭（通过口服250毫克盐酸苯海拉明）。获取了系列情绪评分和血样。
14名受试者完成了活性测试条件；13名完成了假测试。受试者经历了核心抑郁和焦虑症状的显著短暂增加，汉密尔顿抑郁量表评分平均增加21分即证明了这一点。此外，14名受试者中有10名（71%）在活性测试期间符合复发标准，而13名受试者中有1名（8%）在假测试期间符合复发标准。抑郁反应的严重程度与基线血浆皮质醇水平相关（r = 0.59；P =.04）。
有重度抑郁症病史的无症状、无药物治疗受试者在接受α-甲基对酪氨酸测试时表现出显著的抑郁症状。这种抑郁反应可能代表抑郁症病史的一个可靠标志。需要进一步开展工作以阐明这一发现的意义。
