Re. #1, check out some of the work by Rhodes JS and colleagues. For instance, INTEGR. COMP. BIOL., 45:438–455 (2005). One of the findings they mention in this review is that mice w. high inborn activity levels increase neurogenesis w. voluntary wheel running, but show impaired learning. I also heard this investigator speak a few years ago at the Experimental Biololgy Meeting where her presented data showing lack of increased neurogenesis in mice w. increased voluntary exercise. Though I have not been able to find these data in print. Maybe no one wants to believe these findings, and they keep getting shot down by reviewers (or maybe they are flawed)? In the paper cited above, the authors raise an intriguing possibility that exercise may actually contribute to neuronal death in hippocampus via increased CORT secretion. Increased neurogenesis then may be a compensatory response.

Re. #2, I don’t remember whether the time fram issue was presented. I presume that the subjects were treated w. ADs for a long time. Usually in such studies brains are collected from patients who have had a long history of mental illness and treatment. I’m sure that these investigators are aware of the lag between treatment initiation and clinical response and would have designed their study accordingly. Re. their methodology, it was sound. They didn’t measure BrdU incorporation, but used Ki-67 and doublecortin immunocytochemistry together with neuronal and glial markers.

In any case, I think that neurogenesis is a very interesting phenomenon in it of itself. It’s very exciting in that it shatters the age-old dogma that the adult brain is not capable of generating new neurons. But whether it is responsible for all of the wonderful effects of exercise, environmental enrichment, anti-depressant medications, improved diet, etc. is not clear (at least not to me). What the field clearly needs is a way to cleanly disrupt neurogenesis (and cell death, and differentiation of glial progenitors into neurons, and their insertion into existing circuits, etc.) to see whether such manipulations affect learning, cognition, depressive– and anxiety– like behaviors, etc.

Here are a few of my non-systematic observations. Great communicators can be fit or fat. Also, some very fit people tend to be more comfortable at the gym rather than in a social setting.

1) mice that have inborn predisposition to increased wheel running actually have lower (or no different) levels of neurogenesis than their less active counterparts exposed to running wheels

2) I am aware of only one study that reported differences in neurogenesis in depressed patients. These data were recently presented by the group of Dr. Victoria Arango and Dr. John Mann of Columbia University at the recent Society for Neuroscience meeting. These investigators found lare increases in neurogenesis in depressed individuals treated with antidepressants vs. non-treated depressives and non-depressed controls. Yet, patients in both depressed groups (those on anti-depressants and those not treated) were equivalently depressed.

Clearly these examples indicate that our knowledge about the role of neurogenesis is imperfect. What about alternative mechanisms? Such as changes in serotonergic, noradrenergic, and/or dopaminergic neurotransmission? All of these transmitter systems are impacted by exercise, and all are known to affect mood, affect, and overall brain function.