Trinity Centre for Health Sciences, AMNCH (Tallaght) Hospital, Tallaght, Dublin 24, Ireland.
Psychoneuroendocrinology. 2012 Oct;37(10):1589-99. doi: 10.1016/j.psyneuen.2012.03.009. Epub 2012 Apr 10.
Depression is a clinically heterogenous condition defined by sub-types that can have diametrically opposed features, such as sleep and appetite. Within the same individual these features may change over time, and different symptom clusters may respond selectively to different treatments. It has been hypothesized that different pathophysiological processes may be operating in the different sub-types of depression and specifically that Melancholic depression may be associated with relative overactivity, and Atypical depression with relative hypoactivity, of the hypothalamic drive of the HPA axis. A consistent finding that emerges from the literature is that the experience of depression alters over the course of the illness with the features of Atypical depression dominating a more chronic clinical picture. This suggests that different stress states characterize the different profiles of depression as the illness becomes more chronic. There is evidence that the corticotropin-releasing hormone (CRH) control of HPA axis output is reduced in Atypical, compared to Melancholic, sub-types, but there is no convincing evidence that overall HPA activity, i.e., cortisol output, reduces. We suggest that there is a "switch" in the regulation of the HPA system from CRH to arginine vasopressin (AVP) control as stress becomes more sustained or repeated; resulting in an altered homeostasis within the HPA system. Cortisol, and the neuropeptides CRH and AVP, have different neurobiological, behavioural and experiental effects. The "switch" process should result in different neuropeptide/cortisol combinations and ratios and may explain the changing profile of depression over time. The heuristic merit in making a distinction between the different clinical states of depression will be discussed.
抑郁症是一种临床上表现多样的疾病，其亚型之间可能存在截然相反的特征，例如睡眠和食欲。在同一个体中，这些特征可能随时间而变化，不同的症状群可能对不同的治疗方法有选择性反应。有人假设，不同的病理生理过程可能在抑郁症的不同亚型中起作用，特别是忧郁型抑郁症可能与下丘脑-垂体-肾上腺轴（HPA 轴）驱动的相对过度活跃有关，而非典型型抑郁症可能与相对的低活跃性有关。文献中一致发现，随着疾病的发展，抑郁症的体验会发生变化，非典型型抑郁症的特征会主导更慢性的临床图景。这表明，随着疾病变得更加慢性，不同的应激状态会使抑郁症的不同特征更加明显。有证据表明，与忧郁型亚型相比，非典型型抑郁症中促肾上腺皮质激素释放激素（CRH）对 HPA 轴输出的控制降低，但没有令人信服的证据表明整体 HPA 活性，即皮质醇输出降低。我们认为，随着应激的持续或反复，HPA 系统的调节从 CRH 向精氨酸加压素（AVP）控制发生“转换”；导致 HPA 系统内的内稳态发生改变。皮质醇、CRH 和 AVP 等神经肽具有不同的神经生物学、行为学和体验效应。“转换”过程应导致不同的神经肽/皮质醇组合和比值，并可能解释抑郁症随时间变化的特征。我们将讨论在区分抑郁症的不同临床状态方面的启发价值。
