Brewerton T D, Mueller E A, Lesem M D, Brandt H A, Quearry B, George D T, Murphy D L, Jimerson D C
Section on Biomedical Psychiatry, National Institute of Mental Health, Bethesda, Md.
Arch Gen Psychiatry. 1992 Nov;49(11):852-61. doi: 10.1001/archpsyc.1992.01820110016002.
Preclinical and clinical evidence supports a theory of serotonin (5-hydroxytryptamine [5-HT]) dysregulation in bulimia. We therefore studied the prolactin (PRL) and cortisol responses following challenges with the postsynaptic 5-HT receptor agonist m-chlorophenylpiperazine (m-CPP), 0.5 mg/kg orally, the 5-HT precursor L-tryptophan, 100 mg/kg intravenously, and placebo in a group of 28 normal weight bulimic patients and 16 healthy controls. Patients with bulimia, regardless of the presence of major depression, had significantly blunted PRL responses following m-CPP administration compared with those in controls. In contrast, only bulimic patients with concurrent major depression had significantly blunted PRL responses following L-tryptophan administration compared with those in nondepressed bulimic patients and controls. Cortisol responses following m-CPP were not significantly different for bulimic patients vs controls, although there was a trend toward blunted cortisol responses following L-tryptophan administration in the depressed bulimic patients. These differences in neuroendocrine responses were not related to differences in age, percent of average body weight, medications, time of day, peak plasma drug levels, or baseline estradiol levels. Seasonal variations in PRL responses to both agents were identified, although covariation for season did not alter the group differences. The PRL responses following m-CPP administration were inversely correlated to baseline cortisol levels in the bulimic patients, but not in the controls, suggesting a dampening effect by hypothalamic-pituitary-adrenal axis dysfunction on postsynaptic 5-HT receptor sensitivity. The reasons for the differing hormonal responses to these two serotonergic agents may relate to differential involvement of presynaptic and postsynaptic mechanisms, 5-HT receptor subtypes, and anatomical loci of action. The blunted PRL responses to m-CPP administration suggest that postsynaptic 5-HT receptor sensitivity is altered in bulimia nervosa, and that similar alterations in 5-HT receptors at or above the level of the hypothalamus may contribute to binge eating and other behavioral symptoms.
临床前和临床证据支持贪食症中血清素（5-羟色胺[5-HT]）调节异常的理论。因此，我们研究了28名体重正常的贪食症患者和16名健康对照者在口服突触后5-HT受体激动剂间氯苯哌嗪（m-CPP，0.5mg/kg）、静脉注射5-HT前体L-色氨酸（100mg/kg）以及安慰剂激发后的催乳素（PRL）和皮质醇反应。无论是否伴有重度抑郁，贪食症患者在服用m-CPP后PRL反应与对照组相比均显著减弱。相比之下，只有同时患有重度抑郁的贪食症患者在服用L-色氨酸后PRL反应与未患抑郁症的贪食症患者及对照组相比显著减弱。贪食症患者与对照组在服用m-CPP后的皮质醇反应无显著差异，不过抑郁的贪食症患者在服用L-色氨酸后有皮质醇反应减弱的趋势。这些神经内分泌反应的差异与年龄、平均体重百分比、药物、一天中的时间、血浆药物峰值水平或基线雌二醇水平的差异无关。尽管季节协变量并未改变组间差异，但已确定对这两种药物的PRL反应存在季节性变化。贪食症患者服用m-CPP后的PRL反应与基线皮质醇水平呈负相关，而对照组则不然，这表明下丘脑-垂体-肾上腺轴功能障碍对突触后5-HT受体敏感性有抑制作用。对这两种5-羟色胺能药物产生不同激素反应的原因可能与突触前和突触后机制、5-HT受体亚型以及作用的解剖位点的不同参与有关。服用m-CPP后PRL反应减弱表明神经性贪食症中突触后(5-HT)受体敏感性发生改变，并且下丘脑及以上水平的(5-HT)受体类似改变可能导致暴饮暴食和其他行为症状。
