Depression and the hippocampus: cause or effect?
Depression and the hippocampus: cause or effect?
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DOI：
10.1016/j.biopsych.2011.06.006
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发表时间：
2011-08-15
影响因子：
10.6
通讯作者：
Sheline, Yvette I.
中科院分区：
文献类型：
--
作者：
Sheline, Yvette I.
关于重性抑郁症（MDD）和海马体积之间关系的研究长期以来一直在争论先有鸡还是先有蛋的问题。从第一份报告发表以来，发现MDD患者的海马体积小于健康对照组（1），文献中已有数百项研究，大多数但并非所有研究都发现MDD患者的海马体积较小（2）。然而，一个潜在的因果箭头的方向仍然没有得到解决。支持MDD发作导致海马体积变小的作用的研究发现，终生抑郁累积持续时间较长、复发发作总数和抑郁发作年龄较早与海马体积损失相关（2，3）。另一方面，证据也支持指向相反方向的因果关系箭头。支持海马结构损伤在抑郁症病因学中的作用的研究发现，较小的海马预示着更差的临床结果，并且在双胞胎研究中已经确定了对大脑结构（包括海马）的遗传影响（4）。MDD和较小海马体积之间关系的一种解释是神经毒性假说（5），这表明，长期暴露于糖皮质激素增加了神经元对损伤的敏感性，从而增加了毒性攻击或普通磨损的损伤率。根据这一假设，海马体积的减少是多年抑郁、创伤后应激障碍或慢性压力的累积过程。除了HPA轴异常外，最近还发现其他生物学异常也会导致海马体积损失：应激诱导的神经营养因子（特别是BDNF）减少，以及应激诱导的神经发生减少。在临床前研究中，几种形式的应激会减少海马中BDNF介导的信号传导，而抗抑郁药的长期治疗会增加BDNF信号传导（6）。类似的变化还有
Research examining the relationship between major depressive disorder (MDD) and hippocampal volume has long wrestled with the chicken and egg question. From the time the first report was published finding smaller hippocampal volumes in patients with MDD compared with healthy controls (1) there have been hundreds of studies in the literature, with the majority but not all finding smaller hippocampal volumes in MDD (2). The direction of a potential causal arrow, however, remains unresolved. Studies supporting a role for episodes of MDD leading to smaller hippocampal volumes have found that longer cumulative duration of lifetime depression, total number of recurrent episodes and earlier age of onset of depression are associated with hippocampal volume loss (2, 3). On the other hand, evidence also supports the causality arrow pointing the opposite direction. Studies supporting the role of hippocampal structural impairment in the etiology of depression have found that a smaller hippocampus predicts worse clinical outcome and genetic influences on brain structures, including the hippocampus, have been identified in twin studies (4).One explanation for the relation between MDD and smaller hippocampal volumes is the neurotoxicity hypothesis (5), which suggests that prolonged exposure to glucocorticoids increases neuronal susceptibility to insults, thereby increasing the rate of damage from toxic challenges or ordinary attrition. According to this hypothesis, the reduction in hippocampal volumes is a cumulative process from many years of depression, PTSD or chronic stress. In addition to abnormalities in the HPA axis, other biological abnormalities have been recently shown to contribute to hippocampal volume loss: stress-induced reduction in neurotrophic factors, in particular BDNF, and stress-induced reduction in neurogenesis. In preclinical studies several forms of stress reduce BDNF-mediated signaling in hippocampus, whereas chronic treatment with antidepressants increase BDNF signaling (6). Similar changes are
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DOI：
10.1126/stke.2252004re5
发表时间：
2004-03-16
期刊：
Science's STKE : signal transduction knowledge environment
影响因子：
--
作者：
Charney, Dennis S;Manji, Husseini K
通讯作者：
Manji, Husseini K
影响因子：
19.7
作者：
McEvoy, Linda K.;Holland, Dominic;Dale, Anders M.
通讯作者：
Dale, Anders M.
影响因子：
11.2
作者：
Morris, John C.;Roe, Catherine M.;Xiong, Chengjie;Fagan, Anne M.;Goate, Alison M.;Holtzman, David M.;Mintun, Mark A.
通讯作者：
Mintun, Mark A.
影响因子：
9.9
作者：
Saczynski, J. S.;Beiser, A.;Au, R.
通讯作者：
Au, R.
DOI：
10.1073/pnas.93.9.3908
发表时间：
1996-04-30
影响因子：
11.1
作者：
Sheline, YI;Wang, PW;Vannier, MW
通讯作者：
Vannier, MW