Department of Mental Health, Parc Taulí University Hospital, Sabadell, Barcelona, Spain; Institut d'Investigació i Innovació Parc Taulí (I3PT), Sabadell, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; Department of Psychiatry and Forensic Medicine, Autonomous University of Barcelona (UAB), Cerdanyola del Vallès, Barcelona, Spain; Centre Hospitalier, Pole 8/9, APF2R, Rouffach, France.
Centre Hospitalier, Pole 8/9, APF2R, Rouffach, France.
J Psychiatr Res. 2019 May;112:18-22. doi: 10.1016/j.jpsychires.2019.02.009. Epub 2019 Feb 19.
A large number of studies suggest that dopaminergic function may be impaired in depressed patients, particularly in bipolar patients. The dopamine D2/D1 agonist apomorphine (APO) can be useful in the evaluation of dopaminergic function. However, most studies show conflicting results in APO test responses when evaluating unipolar and bipolar depressed patients. Thus, the objective of this study was to apply the APO test to assess whether hypothalamic-pituitary dopaminergic function is altered in unipolar and bipolar depression.
We evaluated multihormonal responses to APO test (0.75 mg subcutaneous) in 134 drug-free DSM-IV major depressed inpatients (54 with bipolar depression [BD] and 80 with unipolar depression [UD]), compared with 36 healthy controls (HCs). We also examined the cortisol response to the dexamethasone suppression test (DST, 1 mg orally) in all subjects.
No significant differences in prolactin (PRL), cortisol, adrenocorticotropin (ACTH) or growth hormone (GH) baseline values were found across the three groups. ACTH/cortisol and GH responses to APO were also comparable. BD patients showed lower PRL suppression to APO than did UD patients and HCs (both p < 0.00001). Although responses to DST were comparable between UD and BD patients, the former exhibited higher post-DST cortisol levels than did HCs (p < 0.05).
Our results suggest that BD patients, unlike UD patients, have altered post-synaptic D2 receptor sensitivity at the pituitary level. This alteration does not seem secondary to hypercortisolemia. These findings, if confirmed by other studies with larger samples, may support the use of dopamine agents in BD patients treatment.
大量研究表明，多巴胺能功能可能在抑郁患者中受损，尤其是在双相患者中。多巴胺 D2/D1 激动剂阿扑吗啡（APO）可用于评估多巴胺能功能。然而，大多数研究在评估单相和双相抑郁患者的 APO 测试反应时显示出相互矛盾的结果。因此，本研究的目的是应用 APO 测试来评估下丘脑-垂体多巴胺能功能是否在单相和双相抑郁症中发生改变。
我们评估了 134 名未服用药物的 DSM-IV 主要住院抑郁症患者（54 名双相抑郁症[BD]患者和 80 名单相抑郁症[UD]患者）和 36 名健康对照者（HCs）对 APO 测试（皮下 0.75mg）的多激素反应。我们还检查了所有受试者的地塞米松抑制试验（DST，1mg 口服）的皮质醇反应。
三组之间的催乳素（PRL）、皮质醇、促肾上腺皮质激素（ACTH）或生长激素（GH）的基线值无显著差异。APO 对 ACTH/皮质醇和 GH 的反应也相似。BD 患者的 PRL 对 APO 的抑制作用低于 UD 患者和 HCs（均 p<0.00001）。尽管 UD 和 BD 患者对 DST 的反应相似，但前者的 DST 后皮质醇水平高于 HCs（p<0.05）。
我们的结果表明，BD 患者与 UD 患者不同，在下丘脑-垂体水平上存在突触后 D2 受体敏感性改变。这种改变似乎不是皮质醇过多的结果。如果其他研究具有更大的样本量证实了这些发现，它们可能支持在 BD 患者的治疗中使用多巴胺药物。
