Reduced brain norepinephrine and dopamine release in treatment-refractory depressive illness -: Evidence in support of the catecholamine hypothesis of mood disorders
Reduced brain norepinephrine and dopamine release in treatment-refractory depressive illness -: Evidence in support of the catecholamine hypothesis of mood disorders
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DOI：
10.1001/archpsyc.57.8.787
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发表时间：
2000-08-01
影响因子：
--
通讯作者：
Friberg, P
中科院分区：
文献类型：
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作者：
Lambert, G;Johansson, M;Friberg, P
背景资料：抑郁症的病因已与脑单胺能神经元功能障碍，但内源性depression.Methods的敏感标志物的发展已被证明是困难的：使用导管放置在颈内静脉，我们估计释放脑单胺神经递质在19名健康志愿者和9例非双相抑郁症难治性药物在休息和静脉注射盐酸地昔帕明。使用静脉动脉血浆浓度梯度来量化源自大脑的神经递质的量。通过区域间接量热法同时测量氧气和二氧化碳气体交换来评估脑氧化代谢。这些患者的大脑表现出静脉动脉去甲肾上腺素减少（4.0 +/- 2.7 nmol/L vs 0.7 +/- 1.3 nmol/L）和高香草酸浓度梯度（8.3+/-7.8 nmol/L vs 3.1+/-1.9 nmol/L），并使用葡萄糖以外的能量源。抑郁症患者颈内静脉5-羟基吲哚乙酸浓度梯度没有降低。去甲肾上腺素周转率的降低和脑代谢的缺陷在去甲肾上腺素转运蛋白用地昔帕明的药理学阻断后均正常化，但矛盾的是，脑多巴胺周转率与患者的临床状态显著相关（r（s）=0.79，P = 0.02）。这种关系的积极性质仍然难以调和。结论：按照单胺假说，大脑中的去甲肾上腺素和多巴胺的赤字存在于抑郁症患者。此外，这些患者的大脑使用葡萄糖以外的能量来源，这种情况在用三环类抗抑郁药地昔帕明急性药理学阻断去甲肾上腺素转运蛋白后正常化。
Background: The etiology of depressive illness has been linked with brain monoaminergic neuronal dysfunction, yet the development of sensitive markers of endogenous depression has proven difficult.Methods: Using catheters placed in an internal jugular vein, we estimated the release of brain monoamine neurotransmitters in 19 healthy volunteers and in 9 patients with nonbipolar depressive illness refractory to medication at rest and following intravenous desipramine hydrochloride. Venoarterial plasma concentration gradients were used to quantify the amount of neurotransmitters stemming from the brain. Cerebral oxidative metabolism was assessed concurrently from measurements of oxygen and carbon dioxide gas exchange via the process of regional indirect calorimetry.Results: The brains of these patients exhibited reduced venoarterial norepinephrine (4.0 +/- 2.7 nmol/L vs 0.7 +/- 1.3 nmol/L) and homovanillic acid concentration gradients (8.3+/-7.8 nmol/L vs 3.1+/-1.9 nmol/L), and used an energy source other than glucose. Internal jugular 5-hydroxyindoleacetic acid concentration gradients were not reduced in the patients with depressive illness. While both the reduction in norepinephrine turnover and the defect in cerebral metabolism were normalized following pharmacological blockade of the norepinephrine transporter with desipramine, paradoxically it was the brain's turnover of dopamine that bore a significant relation to the patients' clinical status (r(s) =0.79, P = .02). The positive nature of this relationship remains difficult to reconcile.Conclusions: In accordance with the monoamine hypothesis, a deficit in brain norepinephrine and dopamine exists in patients with depressive illness. Moreover, the brains of these patients use an energy source other than glucose, a situation that is normalized following the acute pharmacological blockade of the norepinephrine transporter with the tricyclic antidepressant, desipramine.