Department of Anatomy & Neuroscience, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashiku, Hamamatsu, Shizuoka 431-3192, Japan.
Med Hypotheses. 2013 Jul;81(1):5-9. doi: 10.1016/j.mehy.2013.03.025. Epub 2013 Apr 28.
Depression is one of the most burdensome diseases in the world. Although the exact pathogenesis remains unknown, stress is a well-known risk factor for the development of depression. Recently, stress has been known to induce loss of dendritic spines in neurons. Interestingly, also in human brains, higher levels of anxiety and depression scores are associated with decreased densities of spines in the hippocampus, supporting that the disturbance of spine homeostasis is deeply involved in the pathogenesis of depression. On the other hand, general serotonin vulnerability has been also proposed as a major risk factor in depression, where the paucity of available serotonin is involved in the pathogenesis of depression, indicating that the serotonergic system somehow possesses the ability to regulate spine homeostasis. However, the relationship between spine homeostasis and the serotonergic system is largely unknown. Thus, in this manuscript, I try to find the missing link between spine homeostasis and the serotonergic system. The hypothesis is as follows. First, stress reduces the number of spines. Since spine homeostasis is tightly regulated by the serotonergic system, the spine loss is compensated by activated serotonergic system in normal conditions. However, various factors, such as genetic predispositions and heavy stress, decrease the resilience of spine homeostasis. In such conditions, the serotonergic system cannot compensate spine homeostasis anymore, leading to disrupted spine homeostasis. Finally, disrupted spine homeostasis results in depression. The characteristic point of this hypothesis is that it can monistically explain the pathogenesis of depression, where disturbance of spine homeostasis is the main cause.
抑郁症是世界上最具负担的疾病之一。尽管确切的发病机制尚不清楚，但压力是抑郁症发展的已知危险因素。最近，压力已被证明会导致神经元树突棘的丧失。有趣的是，在人类大脑中，较高的焦虑和抑郁评分与海马体中棘密度的降低有关，这支持了棘状稳态的紊乱深深参与了抑郁症的发病机制。另一方面，一般的血清素易感性也被提出是抑郁症的一个主要危险因素，其中血清素的缺乏涉及抑郁症的发病机制，表明血清素能系统在某种程度上具有调节棘状稳态的能力。然而，棘状稳态和血清素能系统之间的关系在很大程度上是未知的。因此，在本手稿中，我试图在棘状稳态和血清素能系统之间找到缺失的联系。假设如下。首先，压力会减少棘突的数量。由于棘状稳态是由血清素能系统紧密调节的，因此在正常情况下，棘突的减少会被激活的血清素能系统所补偿。然而，各种因素，如遗传倾向和沉重的压力，会降低棘状稳态的弹性。在这种情况下，血清素能系统再也不能补偿棘状稳态，导致棘状稳态失调。最后，失调的棘状稳态导致抑郁症。这个假设的特点是它可以一元论地解释抑郁症的发病机制，其中棘状稳态的紊乱是主要原因。
