Impaired adult neurogenesis leads to depression – is it realistic?

depressionAbout a year ago we published a paper linking adult neurogenesis to depression. A causal sort of ‘linking’, right? I mean, we found that, when adult neurogenesis was eliminated, mice had elevated glucocorticoids in response to stress and showed depressive-like behaviours1. So doesn’t this mean that impaired adult neurogenesis could lead to depression in humans, in the real world?

Well, it could…and we did end our paper with the following:

Because the production of new granule neurons is itself strongly regulated by stress and glucocorticoids, this system forms a loop through which stress, by inhibiting adult neurogenesis, could lead to enhanced responsiveness to future stress. This type of programming could be adaptive, predisposing animals to behave in ways best suited to the severity of their particular environments. However, maladaptive progression of such a feed-forward loop could potentially lead to increased stress responsiveness and depressive behaviours that persist even in the absence of stressful events.

We had to end it somehow – I was just happy that after 3 years of work we were DONE2! But our final speculation makes it clear that, while this chapter may be done, the story is not. And this fact was rightly pointed out in a recentĀ commentary by Lucassen et al. in Molecular Psychiatry3, where they continue the discussion and bring up some good points. Here is a loose elaboration on some of the outstanding issues they bring up. Continue reading

Studies of adult hippocampal neurogenesis in humans

As we accumulate more and more data on adult neurogenesis in rodents I keep asking myself what kind of impact these new cells could have. The dearth of literature on primate and human adult neurogenesis seems to make these questions all the more relevant. As a starting point, I created a Pubmed collection of all the studies of adult hippocampal neurogenesis in humans. They’re also listed below in a Google spreadsheet. Note that human studies often do not directly measure neurogenesis but instead measure 1) cell proliferation (which usually correlates with neurogenesis in rodents, but assumes that proliferation results in surviving neurons in humans), 2) stem cell markers (such as nestin, which correlates with neurogenesis only if they indeed divide and produce new neurons), 3) immature neurons (which, technically speaking, is neurogenesis, but whether these neurons mature and become functional remains to be determined), or 4) other factors that correlate with neurogenesis, such as blood flow or stem cell biomarkers. So, while the conclusions of these studies may be exciting (or depressing), they have to be taken with a grain of salt at this point.

Download the list