Wieck A, Davies R A, Hirst A D, Brown N, Papadopoulos A, Marks M N, Checkley S A, Kumar R C, Campbell I C
Institute of Psychiatry, King's College London, De Crespigny Park, London, UK.
J Psychopharmacol. 2003 Jun;17(2):204-9. doi: 10.1177/0269881103017002009.
Neuroendocrine challenge tests of hypothalamic dopamine receptor function in the early postpartum period suggest that the sensitivity of these receptors is increased in women with a history of bipolar disorder after childbirth. We tested the hypothesis that, in women predisposed to bipolar disorder in the puerperium, hypothalamic dopamine receptor function is more sensitive to changes in circulating ovarian hormone concentrations than in women without such histories. Eight fully recovered and drug-free women who had had at least one episode of bipolar illness following childbirth were compared with nine normal controls. Growth hormone (GH) responses to apomorphine (APO 0.005 mg s.c.) were measured in the early follicular phase, when plasma concentrations of ovarian hormones are low, and in the mid-luteal phase, when they are relatively high. The recovered bipolar subjects and the controls did not differ from each other in their follicular and midluteal oestrogen and progesterone concentrations. In the midluteal phase, both groups had increased oestrogen and progesterone levels. The recovered bipolar subjects did not differ from controls in baseline concentrations of GH in either of the menstrual phases. The APO-GH responses of the two groups did not differ in the follicular phase, but in the midluteal phase, when female sex steroids are relatively increased, the recovered group had significantly enhanced APO-GH responses [MANOVA for repeated measures: (i) area under the curve, group by phase effect: p < 0.04; (ii) GH peak rise after APO, group by phase effect: p < 0.056] and the responses were not related to concurrent measures of mood. The results of this small study of women predisposed to bipolar disorder in the puerperium shows an increased dopaminergic receptor sensitivity in the luteal phase of the menstrual cycle. It suggests that their dopaminergic systems have increased sensitivity to changes in circulating female sex steroids. This may be aetiologically relevant to the pathogenesis of puerperal bipolar disorder.
产后早期下丘脑多巴胺受体功能的神经内分泌激发试验表明，有产后双相情感障碍病史的女性中这些受体的敏感性增加。我们检验了这样一个假设：在产褥期易患双相情感障碍的女性中，下丘脑多巴胺受体功能对循环卵巢激素浓度变化的敏感性高于无此类病史的女性。将八名产后至少有一次双相情感障碍发作且已完全康复且未用药的女性与九名正常对照者进行比较。在卵泡早期（此时卵巢激素血浆浓度较低）和黄体中期（此时卵巢激素血浆浓度相对较高）测量生长激素（GH）对阿扑吗啡（皮下注射0.005mg APO）的反应。康复的双相情感障碍受试者和对照组在卵泡期和黄体中期的雌激素和孕酮浓度方面彼此无差异。在黄体中期，两组的雌激素和孕酮水平均升高。康复的双相情感障碍受试者在两个月经周期阶段的GH基线浓度与对照组无差异。两组的APO-GH反应在卵泡期无差异，但在黄体中期，当女性性激素相对增加时，康复组的APO-GH反应显著增强[重复测量的多变量方差分析：（i）曲线下面积，组×阶段效应：p<0.04；（ii）APO后GH峰值上升，组×阶段效应：p<0.056]，且反应与同时测量的情绪无关。这项对产褥期易患双相情感障碍女性的小型研究结果显示，月经周期黄体期多巴胺能受体敏感性增加。这表明她们的多巴胺能系统对循环女性性激素变化的敏感性增加。这可能在病因学上与产褥期双相情感障碍的发病机制相关。
