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Biol Psychiatry. 2012 May 30;
Authors: Boldrini M, Hen R, Underwood MD, Rosoklija GB, Dwork AJ, Mann JJ, Arango V
Abstract
BACKGROUND: 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.
METHODS: 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 (MDD*SSRI, n = 6) or tricyclic antidepressants (MDD*TCA, n = 6), and nonpsychiatric control subjects (n = 12), all confirmed by psychological autopsy.
RESULTS: 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 (R(2) = .454, p < .001) and in treated subjects (R(2) = .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.
CONCLUSIONS: 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.
PMID: 22652019
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Given the adverse effects of antidepressants, it would have been nice if the study also looked at subjects without major depressive disorder who were treated with antidepressants. These subjects could have been those with anxiety disorders, irritable bowel syndrome, etc. etc. This would help determine how large the effect on neurogenesis is on subjects without major depressive disorder, and whether antidepressants could potentially be useful in illnesses where improved neurogenesis would be useful – e.g. dementias and other cognitive disorders.