Antidepressants and Neurogenesis in Humans

How do antidepressants work? Some people will tell you that it’s all about neurogenesis. The theory goes that antidepressants increase the rate at which new neurones are created in a region called the dentate gyrus of the hippocampus, and that, somehow, this boom in the number of new hippocampal cells alleviates depression.

To date, however, all of the research linking antidepressants and neurogenesis has involved animals. It was generally assumed that if drugs altered neurogenesis in mice, the same thing happened in humans – but this was an assumption, and clearly a pretty big one. Now a new report from a New York-based team claims that antidepressants do enhance neurogenesis in people - Antidepressants increase neural progenitor cells in the human hippocampus.

The authors took post-mortem brain samples from three groups of people – those with no history of depression, those with depression who were not on antidepressants when they died, and depressed people who were on antidepressants. They counted the number of neural progenitor cells (NPCs) in the hippocampus using a stain which specifically marks these cells (anti-nestin).

Although like all post-mortem studies the sample size was small (n=19 total), depressed people taking antidepressants when they died had much higher NPC numbers, indicating greater neurogenesis, compared to the other two groups. (Control: 360±246; untreated: 1119±752; treated: 17229±3443).

The picture above illustrates this; the brown cells are NPCs, and there are evidently more of them in the antidepressant-taking person on the right compared to the control on the left. The authors presumably picked these images because they look different, so, pinch of salt. But still, as an antidepressant user myself, it's nice to see what might well be going on inside my skull at this moment.

The dentate gyrus of the hippocampus, the area where neurogenesis happens, was also larger in the antidepressant-treated group.

Is this evidence for the neurogenesis theory? Not exactly. It’s fairly good evidence that some antidepressants do boost hippocampal neurogenesis in humans, in accordance with the animal data. But we really don’t know what that means. It could just be a side effect, and nothing to do with how they work. I’ve previously written about some recent animal experiments finding that antidepressants have effects on behaviour even when neurogenesis is completely blocked. And notably, five of the seven antidepressant-treated patients in this study died from suicide. So, to put it bluntly, the drugs didn’t work very well, despite sending neurogenesis through the roof...

Boldrini, M., Underwood, M., Hen, R., Rosoklija, G., Dwork, A., John Mann, J., & Arango, V. (2009). Antidepressants increase neural progenitor cells in the human hippocampus Neuropsychopharmacology DOI: 10.1038/npp.2009.75