Páez X, Hernández L, Baptista T
Facultad de Medicina, Universidad de los Andes, Mérida, Venezuela.
Rev Neurol. 2003;37(5):459-70.
The objective of this study is to survey present and future antidepressant drug therapy based on the progress made in the field of biotechnology.
The simplistic and mistaken view that one single system of neurotransmission is altered in depression and that there is, therefore, just one single treatment has changed. Molecular biology and Genetics have enabled us to determine other possible chemical alterations in the brain, beyond the sole participation of the monoaminergic modulation systems, which is the classical hypothesis. In this paper we describe the evidence for the relations between depression and the therapeutic effect the classical antidepressants have on: 1. The peptidergic system of the corticotropin-releasing hormone, cortisol and the functional state of its receptors; 2. Intracellular signalling systems such as cAMP on transcription factors like CREB and neurotrophins; 3. The immune system and cytosines; 4. Glutamate transmission; and 5. The neuropeptidergic system of substance P, neuroactive steroids and the neuroglia. This has allowed other biochemical hypotheses about depression and the possibility of new treatments to be put forward.
We are still not certain about the exact cause or the processes that determine mental illnesses such as depression or how improvements are achieved with the antidepressants we currently have available. Nevertheless, biotechnology is expected to be a great help in advancing towards a better understanding of the interrelations between the nervous, immune and endocrine systems, with their intracellular cascades and final outcomes in genetic expression and protein function, in depression. This will enable more efficient, more selective and faster-acting drugs to be developed and, in the future and with the help of psychogenomics, even make it possible to produce tailor-made medication for each patient.
本研究的目的是基于生物技术领域取得的进展，调查当前及未来的抗抑郁药物治疗情况。
那种认为抑郁症中只有单一神经传递系统发生改变，因此只有单一治疗方法的简单且错误的观点已经改变。分子生物学和遗传学使我们能够确定大脑中除了经典假设的单胺能调节系统单独参与之外的其他可能的化学变化。在本文中，我们描述了抑郁症与经典抗抑郁药对以下方面的治疗效果之间关系的证据：1. 促肾上腺皮质激素释放激素、皮质醇的肽能系统及其受体的功能状态；2. 细胞内信号系统，如环磷酸腺苷（cAMP）对转录因子如环磷腺苷效应元件结合蛋白（CREB）和神经营养因子的作用；3. 免疫系统和胞嘧啶；4. 谷氨酸传递；5. P物质、神经活性类固醇和神经胶质细胞的神经肽能系统。这使得关于抑郁症的其他生化假设以及新治疗方法的可能性得以提出。
我们仍然不确定诸如抑郁症等精神疾病的确切病因或决定因素，也不确定我们现有的抗抑郁药是如何实现病情改善的。然而，生物技术有望极大地帮助我们更好地理解抑郁症中神经、免疫和内分泌系统之间的相互关系，以及它们在细胞内的级联反应及其在基因表达和蛋白质功能方面的最终结果。这将使开发出更高效、更具选择性且起效更快的药物成为可能，并且在未来借助精神基因组学，甚至有可能为每位患者生产量身定制的药物。
