Heinz A, Weingartner H, George D, Hommer D, Wolkowitz O M, Linnoila M
National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA.
Psychiatry Res. 1999 Dec 20;89(2):97-106. doi: 10.1016/s0165-1781(99)00099-2.
Depressed mood increases the relapse risk of abstinent alcoholics; its neurobiological correlates may include reduced serotonin and norepinephrine turnover rates and increased cortisol concentrations during detoxification stress. Neurosteroids such as dehydroepiandrosterone and its sulfate (DHEA and DHEA-S) may antagonize cortisol action and may have mood-elevating effects on their own. We measured severity of depression with Beck's Depression Inventory (BDI) and Hamilton's Depression Rating Scale (HDRS), plasma concentrations of cortisol, DHEA and DHEA-S, and CSF concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and the dopamine metabolite homovanillic acid (HVA) in 21 abstinent alcoholics after 4 weeks of abstinence and in 11 age-matched healthy control subjects. Only CSF MHPG concentrations were reduced in alcoholics compared to control subjects (41.4 +/- 6.6 vs. 53.3 +/- 8.6 pmol/ml). Self-rated depression was significantly correlated with CSF MHPG (Spearman's R = +0.57, P < 0.01), CSF 5-HIAA (R = +0.51, P < 0.05) and plasma cortisol concentrations (R = +0.50, P < 0.05). Negative correlations were found between DHEA-S concentrations and both self-rated depression (R = -0.45, P < 0.05) and observer-rated depression (R = -0.55, P < 0.05). The ratio of DHEA-S to cortisol serum concentrations was also negatively correlated with depression (BDI: R = -0.55, P < 0.01; HDRS: R = -0.63, P < 0.005). Anxiety (Spielberger's State Anxiety Scale) was only associated with CSF MHPG concentrations (R = +0.58, P < 0.01). Our findings point to the importance of noradrenergic dysfunction in the pathogenesis of depression among abstinent alcoholics and indicate that their mood states may also be modulated by a low DHEA-S to cortisol ratio, hypothetically indicative of low stress protection capacities.
情绪低落会增加戒酒者的复发风险；其神经生物学关联可能包括血清素和去甲肾上腺素周转率降低，以及在脱毒应激期间皮质醇浓度升高。脱氢表雄酮及其硫酸盐（DHEA和DHEA-S）等神经甾体可能拮抗皮质醇的作用，并且自身可能具有提升情绪的作用。我们用贝克抑郁量表（BDI）和汉密尔顿抑郁评定量表（HDRS）测量抑郁严重程度，检测了21名戒酒4周的戒酒者和11名年龄匹配的健康对照者血浆中的皮质醇、DHEA和DHEA-S浓度，以及脑脊液中血清素代谢物5-羟吲哚乙酸（5-HIAA）、去甲肾上腺素代谢物3-甲氧基-4-羟基苯乙二醇（MHPG）和多巴胺代谢物高香草酸（HVA）的浓度。与对照者相比，只有戒酒者脑脊液中的MHPG浓度降低（41.4±6.6对53.3±8.6 pmol/ml）。自我评定的抑郁与脑脊液中的MHPG显著相关（斯皮尔曼相关系数R = +0.57，P < 0.01）、脑脊液中的5-HIAA（R = +0.51，P < 0.05）以及血浆皮质醇浓度（R = +0.50，P < 0.05）。发现DHEA-S浓度与自我评定的抑郁（R = -0.45，P < 0.05）和他人评定的抑郁（R = -0.55，P < 0.05）均呈负相关。DHEA-S与皮质醇血清浓度的比值也与抑郁呈负相关（BDI：R = -0.55，P < 0.01；HDRS：R = -0.63，P < 0.005）。焦虑（斯皮尔伯格状态焦虑量表）仅与脑脊液中的MHPG浓度相关（R = +0.58，P < 0.01）。我们的研究结果表明去甲肾上腺素能功能障碍在戒酒者抑郁发病机制中的重要性，并表明他们的情绪状态也可能受到低DHEA-S与皮质醇比值的调节，推测这表明应激保护能力较低。
