Department of Psychiatry, Columbia University, Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York 10032, USA.
Biol Psychiatry. 2012 Oct 1;72(7):562-71. doi: 10.1016/j.biopsych.2012.04.024. Epub 2012 May 30.
Adult neurogenesis is coupled to angiogenesis in neurogenic niches in the dentate gyrus (DG) and increased by antidepressants in rodents. We hypothesized that, in major depressive disorder (MDD), antidepressants increase neural progenitor cells (NPCs) and capillaries in the human DG.
Neural progenitor cells and capillaries, detected on hippocampal sections by immunohistochemistry for neural stem cell protein, were quantified by stereology in matched MDDs (untreated, n = 12), MDD treated with selective serotonin reuptake inhibitors (MDDSSRI, n = 6) or tricyclic antidepressants (MDDTCA, n = 6), and nonpsychiatric control subjects (n = 12), all confirmed by psychological autopsy.
The MDD*SSRI had a larger capillary area and more NPCs versus MDDs (p = .034 and p = .008, respectively) and control subjects (p = .010 and p = .002, respectively) in the whole DG, more NPCs in the anterior (pes, p = .042) and central (midbody, p = .004) DG, and greater capillary area in the pes (p = .002) and midbody (p = .021). The NPC number and capillary area correlated positively in the whole sample (R2 = .454, p < .001) and in treated subjects (R2 = .749, p = .001). We found no NPCs or antidepressant-related angiogenesis in CA1 and parahippocampal gyrus. The DG volume correlated positively with NPC number (p = .004) and capillary area (p < .001) and differed between groups in whole hippocampus (p = .013) and midbody (p = .036). Age negatively correlated with NPC number (p = .042), capillary area (p = .037), and bifurcations (p = .030). No gender effect was detected.
Antidepressants increase human hippocampal NPCs and angiogenesis selectively in the anterior and mid DG. These results raise the possibility of a causal relationship between angiogenesis and neurogenesis, as seen in other proliferating tissues, and support their possible role in the mechanism of action of antidepressants.
成人神经发生与神经发生龛中的血管生成有关，并且在啮齿动物中被抗抑郁药所增强。我们假设，在重度抑郁症（MDD）中，抗抑郁药会增加人类齿状回（DG）中的神经祖细胞（NPC）和毛细血管。
通过免疫组织化学检测神经干细胞蛋白，对海马切片中的神经祖细胞和毛细血管进行立体学定量，在匹配的 MDD 患者（未经治疗，n = 12）、接受选择性 5-羟色胺再摄取抑制剂（MDDSSRIs，n = 6）或三环类抗抑郁药（MDDTCAs，n = 6）治疗的 MDD 患者以及非精神科对照受试者（n = 12）中进行了检测，所有这些均通过心理尸检得到了确认。
与 MDD 患者（p =.034 和 p =.008）和对照受试者（p =.010 和 p =.002）相比，MDD*SSRIs 在前（pes）和中央（midbody）DG 中具有更大的毛细血管面积和更多的 NPC（p =.042 和 p =.004），在整个 DG 中具有更多的 NPC（p =.010 和 p =.002），在 pes（p =.002）和 midbody（p =.021）中具有更大的毛细血管面积。整个样本（R2 =.454，p <.001）和治疗组（R2 =.749，p =.001）中 NPC 数量和毛细血管面积呈正相关。我们在 CA1 和海马旁回中未发现 NPC 或与抗抑郁药相关的血管生成。DG 体积与 NPC 数量（p =.004）和毛细血管面积（p <.001）呈正相关，并且在整个海马体（p =.013）和 midbody（p =.036）之间存在组间差异。年龄与 NPC 数量（p =.042）、毛细血管面积（p =.037）和分叉（p =.030）呈负相关。未检测到性别效应。
抗抑郁药选择性地增加了人类 DG 前部和中部的海马 NPC 和血管生成。这些结果提示了血管生成和神经发生之间存在因果关系的可能性，这与其他增殖组织中所见相似，并支持它们在抗抑郁药作用机制中的可能作用。
