The Journal of Neuroscience Table of Contents arrived in my inbox last week, and like I do on most such occasions, I browsed it for research in my area and people I know. Very often I see papers that strike my fancy, but for some reason, when I saw this article, I really wanted to...talk about it.  Or blog about it, I suppose. So without further ado, I bring you my very first Research Blogging post.

Dendritic Growth in Medial Prefrontal Cortex and Cognitive Flexibility Are Enhanced during the Postpartum Period J Neurosci. 2010; 30 13499-13503

Benedetta Leuner and Elizabeth Gould

If we were playing a game of word association, and the word I gave you was "postpartum," chances are you'd come up with "depression," am I right? It's totally natural. Postpartum Depression (PPD) is a well-known disorder that affects somewhere around 10% of women who give birth, and whose symptoms are similar to that of Major Depressive Disorder--feelings of sadness, hopelessness, lethargy, and disrupted sleep and appetite, to name but a few.  While these kinds of symptoms are clearly not good for anyone, they're especially bad for new moms, who really need to be on their game in order to adequately take care of a newborn. It's generally thought that PPD results at least in part because of the large fluctuations in hormones that a woman's body undergoes right after she gives birth, but not a lot of work has been done in postpartum animals to really find out what's going on in brain areas commonly associated with depression.

One of the major hormonal changes the postpartum body undergoes is a sustained increase in glucocorticoids. Glucocorticoids are primarily thought of as stress hormones, as they're released during stress and can help bring your body and brain back to normal states after you're done with all that fight-or-flight business. However, too much exposure to glucocorticoids can be a bad thing, and many models of chronic stress involve subjecting animals to repeated glucocorticoids. This has been shown to cause changes in neuronal morphology in two major brain areas associated with depression--the prefrontal cortex (PFC) and the hippocampus. In male rats, prolonged glucocorticoid exposure can lead to reduced spine density in these regions, which theoretically could mean less opportunity for these neurons to connect to other neurons.  Animals exposed to glucocorticoids also are impaired on some cognitive tasks that we know are governed by the PFC and hippocampus, and thus the general dogma is: high glucocorticoids---> fewer spines---> impaired brain. It's much more complicated than that, but this'll do for my purposes here.

So the authors of this paper thought, OK, the postpartum brain is just swimming in glucocorticoids, so maybe the glucocorticoids are causing spine loss and thus the PFC isn't functioning properly, and that's why women get PPD! They tested their hypothesis by comparing postpartum and virgin female rats' performance in a cognitive task known to require an optimally-functioning PFC called attentional set-shifting, and then looked at the rats' spine density in the PFC. They thought that the postpartum animals would be impaired at the task and have fewer spines when compared to the virgins, but in fact, things went in the complete opposite direction! The postpartum dams had greater spine density in the PFC and did better on the attentional set-shifting task then the virgin females. Counter-intuitive, no?

No!! The authors re-evaluated what their results meant in the context of PPD, and I like what they came up with. When you think about it, most women don't develop PPD after giving birth; in fact, most do a pretty good job of taking care of their babies, which it's my understanding is no small feat! It requires being able to nimbly switch your attention between tasks, and make decisions about what's the most important thing at any particular time--activities mediated by the PFC. The authors think their findings may mean that under normal circumstances, the brain responds to giving birth by increasing spines and ramping up PFC function, which could help women better deal with the multi-tasking the postpartum period requires. Perhaps, then, women in whom this response fails to happen are the ones who develop PPD--they're lacking the natural adaptation that the brain needs in order to successfully handle early motherhood.

It's difficult to study psychiatric illnesses in animals, not only because these are very complex--and often very human--disorders, but because they're relatively rare. If only 10% of the population is afflicted with a given affective disorder, what are the chances that your n=12 rats are going to be in any way representative of that 10%?  Pretty slim, I'd say. What I think researchers are now understanding better is that if we want to learn about the pathophysiology of mental illness from animals, the most valuable insights are going to come from looking closely at the extreme ends of the response spectrum, rather than the norms.