Mental Health Division, Florey Institute of Neuroscience and Mental Health, University of Melbourne , Melbourne, VIC , Australia.
Behavioural Neurosciences Division, Florey Institute of Neuroscience and Mental Health, University of Melbourne , Melbourne, VIC , Australia.
Front Psychiatry. 2015 Mar 9;6:32. doi: 10.3389/fpsyt.2015.00032. eCollection 2015.
There is increasing evidence of prodromal manifestation of neuropsychiatric symptoms in a variety of neurodegenerative diseases such as Parkinson's disease (PD) and Huntington's disease (HD). These affective symptoms may be observed many years before the core diagnostic symptoms of the neurological condition. It is becoming more apparent that depression is a significant modifying factor of the trajectory of disease progression and even treatment outcomes. It is therefore crucial that we understand the potential pathophysiologies related to the primary condition, which could contribute to the development of depression. The hypothalamic-pituitary-adrenal (HPA)-axis is a key neuroendocrine signaling system involved in physiological homeostasis and stress response. Disturbances of this system lead to severe hormonal imbalances, and the majority of such patients also present with behavioral deficits and/or mood disorders. Dysregulation of the HPA-axis is also strongly implicated in the pathology of major depressive disorder. Consistent with this, antidepressant drugs, such as the selective serotonin reuptake inhibitors have been shown to alter HPA-axis activity. In this review, we will summarize the current state of knowledge regarding HPA-axis pathology in Alzheimer's, PD and HD, differentiating between prodromal and later stages of disease progression when evidence is available. Both clinical and preclinical evidence will be examined, but we highlight animal model studies as being particularly useful for uncovering novel mechanisms of pathology related to co-morbid mood disorders. Finally, we purpose utilizing the preclinical evidence to better inform prospective, intervention studies.
越来越多的证据表明，神经精神症状在各种神经退行性疾病中都有前驱表现，如帕金森病（PD）和亨廷顿病（HD）。这些情感症状可能在神经状况的核心诊断症状出现多年前就已经出现。越来越明显的是，抑郁是疾病进展轨迹甚至治疗结果的重要修饰因素。因此，我们必须了解与原发性疾病相关的潜在病理生理学，这可能有助于抑郁的发生。下丘脑-垂体-肾上腺（HPA）轴是一个关键的神经内分泌信号系统，参与生理稳态和应激反应。该系统的紊乱会导致严重的激素失衡，而大多数此类患者还存在行为缺陷和/或情绪障碍。HPA 轴的失调也与重度抑郁症的病理密切相关。与此一致的是，抗抑郁药，如选择性 5-羟色胺再摄取抑制剂，已被证明可以改变 HPA 轴的活性。在这篇综述中，我们将总结目前关于阿尔茨海默病、PD 和 HD 中 HPA 轴病理学的知识状态，区分疾病进展的前驱期和后期阶段，只要有证据可用。我们将检查临床和临床前证据，但我们强调动物模型研究特别有助于揭示与共病情绪障碍相关的病理新机制。最后，我们旨在利用临床前证据为前瞻性干预研究提供更好的信息。
