This week, an article appeared in the L.A. Times online, and was recycled in the Chicago Tribune and a number of other media sources. It focused on a study that was just published in the Journal of Neuroscience. In the study, Iniguez et al. gave fluoxetine (aka Prozac) to male adolescent mice for 15 days. Three weeks after ending the fluoxetine treatment, the researchers tested the mice on two measures that are purported to assess depression in rodents and one that is a suggested measure of anxiety. They found that the mice previously treated with fluoxetine displayed less “depression-like” behavior, but more “anxiety-like” behavior.
The article in the L.A. Times was titled Prozac during adolescence protects against despair in adulthood. This title is problematic to me for a couple of reasons. First, because another species isn’t mentioned in the title, it is likely on first glance that most readers will assume that the finding occurred in, or was directly relatable to, humans. The author (Melissa Healy) mentions in the second paragraph that the study was done in mice, but continues to draw direct parallels to humans throughout the article. For example, Healy asks, “So how does a medication that treats depression in children and teens -- and that continues to protect them from depression as adults -- also heighten their sensitivity to stress?” when referring to the contradictory findings of increased anxiety and decreased depression-like behavior. The use of this vernacular (e.g. children and teens) makes it sound as if the observance made in the study means the same phenomenon would occur in humans who take Prozac. However, anyone who is familiar with rodent behavior knows that, for every behavior for which we can draw direct parallels to human behavior, there are many others for which the link is much more ambiguous.
Also, it is a bit of stretch to say that we can measure “despair” in mice. The researchers in this study used two tests to measure depression-like behavior: the response to social defeat stress and the forced-swim test. In the social defeat test, a mouse is forced to interact with another very aggressive mouse every day for 10 consecutive days. The aggressive mouse will typically force the experimental mouse into a subordinate position. After repeated exposure to this aggression, the subordinated mice become more submissive, antisocial, and withdrawn - symptoms which are thought to resemble human depression. These depression-like symptoms can be reversed with chronic antidepressant treatment. In the forced-swim test, mice are dropped into a beaker of water from which they cannot escape. Eventually, mice will stop trying to escape and move just enough to keep their head above water; this is interpreted as a form of helplessness, analogous to depression. Numerous experiments have shown, however, that acute treatment with antidepressants causes mice to continue attempting to escape for a longer period of time, which is taken as a sign of decreased depressive-like symptoms.
Do these tests measure depression in a way that is relevant to humans? Maybe, maybe not. There are those who would argue that we should be very cautious making such interpretations. Interestingly, one of the coauthors of the Iniguez et al. study, Eric J. Nestler (a prominent name in psychopharmacology research), wrote a paper in 2010 with Steven E. Hyman that focused on using animal models to understand human psychiatric disorders. The paper emphasized that many animal models are inadequate for making assumptions about human psychiatric conditions. Nestler and Hyman specifically mentioned the forced-swim test as one of two that “...are not models of depression at all. Instead, they are rapid, black-box tests developed decades ago to screen compounds for antidepressant activity.” They go on to say that the assumption that the increased activity in a forced swim test is related to alleviating depressive symptoms is an “...enormous anthropomorphic leap…” and that the test “...has not been convincingly related to pathophysiology.”
So, at least one coauthor in the Iniguez et al. study doesn’t seem to be completely confident that these types of findings are directly relatable to humans. Unfortunately, these doubts aren’t expressed within the Inguinez et al. paper. Instead, the authors use terms like “behavioral despair” when describing rodent behavior and fail to discuss limitations in attempting to relate their findings to a human population.
So, perhaps the author of the L.A. Times article isn’t completely to blame. I could argue that Iniguez et al. also could have been more specific about the implications of their study. However, I focused on the L.A. Times article because I feel like this sort of misinterpretation is rampant in popular science writing. Indeed, I have been guilty of it on this blog. It can often be well-intentioned. At least in my mind, the justification is that increasing interest in the article by the lay public increases interest in science in general, which is the goal of science writing - isn’t it?
Perhaps. It could be considered one goal of popular science writing, although one could argue that discussing science without taking a critical perspective is at odds with the historical tradition of science. Regardless, when speaking about a psychiatric disorder as common as depression, it may be a disservice to spread information that further supports the use of antidepressants. 11% of the American population already take antidepressants, and some studies have suggested that, except in the most severe cases, the difference between taking an antidepressant or placebo is small or negligible. For the superficial reader, the message of this L.A. Times article will clearly be that there are benefits to Prozac that go beyond simply treating depression at the point in time someone takes the drug. The message should, however, be that this study (if replicated) may tell us something about how rodents respond to antidepressants. What that means for humans, until a similar hypothesis is tested in humans, is completely unclear.
Iñiguez SD, Alcantara LF, Warren BL, Riggs LM, Parise EM, Vialou V, Wright KN, Dayrit G, Nieto SJ, Wilkinson MB, Lobo MK, Neve RL, Nestler EJ, Bolaños-Guzmán CA. (2014). Fluoxetine Exposure during Adolescence Alters Responses to Aversive Stimuli in Adulthood Journal of Neuroscience DOI: 10.1523/JNEUROSCI.5725-12.2014