The Scicurious Brain

The Scicurious Brain

The Good, Bad, and Weird in Physiology and Neuroscience

Grab your Coffee, I think this paper may depress you.



A few weeks ago I saw this headline floating around the interwebs. COFFEE: NOW WITH ANTIDEPRESSANT EFFECTS!!! I obviously wanted to look into it. I mean, you’re talking about a girl with caffeine tattooed onto her flesh, here, I have a personal stake in this outcome.

Unfortunately, life and lab (ok, mostly lab) got in the way, and I’m only just now getting to this. But I still have a personal stake! After all, I’m sitting here, writing this to you, and sipping my coffee. It’s 8pm. I don’t have a problem…

So. Coffee. So many of us wanted to think it’s a miracle. And to many of us, it is. It drags us through our first days of parents, through our long work hours, through our longER work hours…For many of us it’s become such a salient drug that it’s only the smell of coffee that hauls our butts out of bed in the morning. It’s the socially acceptable attention and alertness enhancer (nicotine is way out of fashion and prescription drugs still leave people squeamy), and in a society where we value productivity so much, how could we not feel for the great brown bean?

And many of us want to justify ourselves. How else do you rationalize your purchase of beans at $13.99/lb and your own personal grinder? What can you use to justify your cravings for coffee at…8pm? Well, it’d be really nice if coffee was actually GOOD for you. You know, more than just the hallmark of the pale, nervous student pulling an allnighter or the exhausted bedraggled parent. If it was good for you, you would feel all the more justified, right?

That’s really the only reason I can think of as to why so many recent studies have come out on whether caffeine is “good” for you or not. Just keeping you awake and alert apparently isn’t enough of a benefit, now it’s gotta cure your cancer. Or in this case, your depression.

But does it cure your depression? Does it prevent your depression? Well, the authors who wrote up this study seem to think so, but I’m not sure I agree with them. Sci the skeptic strikes again. Depressing? But of course!

Lucas et al. “Coffee, caffeine, and risk of depression among women” Archives of Internal Medicine, 2011.

With all the coffee we drink, you’d think there’d be more studies out there on it. But in fact, there’s only been one other study on coffee and depression, which was done in Finnish men, and found a J shaped relationship between coffee and suicide risk. But no studies have been done in WOMEN. And for depression research in particular, this is…depressing. After all, major depressive disorder afflicts roughly TWICE as many women as men. Up to 20% of women in the US will suffer a depressive episode. That’s a LOT of people. But for all that, relatively few studies on antidepressants are done in women or in female animal models (and I’ll save that for another, longer, more ranty type of post). Anyway, kudos to these researchers for studying women.

So what was the study, and who were the women? In this case, it was a prospective study done on a large group of nurses between 1996 and 2006. It’s a hefty sample, with a lot of nurses and pretty good continuity. This is also a good sample because you can make sure that your participants exhibited NO depression symptoms at baseline, and then look at depression symptoms over time to come up with a measure of “relative risk”.

They asked them for what they typically ate, how much they exercised, marital status, smoking, hormone therapy, heck they even asked if you went to church. And of course, they asked about caffeine consumption, including sodas, coffee, decaf, herbal tea, regular tea, caffeine-free sodas, and chocolate. They estimated each “cup” of coffee the women reported as having an average of 137mg (which I’m a bit leery of, I know my “cups” are about 2x the size of other people’s, and I bet many of these women were the same), and then they tallied the amounts per week. Along with this, they looked at depression scores over the ten years, and looked at the number of depressive episodes. From this, they calculated the relative risk of clinical depression as correlated with coffee consumption.

You can see that there’s a significant trend with decreased risk of depressive episode going with higher consumption of coffee. The authors conclude that coffee may have a protective effect against depression.

I will certainly buy that increased coffee consumption (caffeine in general, but strongest for coffee, probably the cumulative dosing may have something to do with it) correlates with decreased risk for depression. But I was more than a little dismayed to see the headlines trumpeting coffee to prevent or TREAT your depression. Um, correlation with decreased risk? Ok. Preventative? …maaaaaybe. Treatment? I don’t think so.

Here are the issues. First, this is a sample composed entirely of nurses. It’s got it’s benefits, and there are many. But it is not exactly unbiased. These are all women in a high stress profession, many are working shift work, active jobs, etc. Things like shift work and high stress jobs are KNOWN to be associated with increased risk of depression. It’s not a problem if you limit your conclusions to nurses, but you can’t extrapolate to all women from this sample.

But the biggest issue is that they found a whole bunch of correlations here. The one they based their CONCLUSIONS on was symptoms of depression. Here are the others.

1) Smoking. The interaction between depression risk, smoking, and coffee consumption was “marginally” significant (p=0.06), but they dismiss it as being due to chance because it was “unexpected”. Um. Wait. Nicotine is a STIMULANT. It is known to have antidepressant like effects in animal models (though the withdrawal is no fun). This is not unexpected.

2) Drinking: heavy coffee drinkers drink more. But note that they don’t say that drinking coffee puts you at risk for drinking alcohol.

3) Obesity: heavy coffee drinkers are, on average, thinner, but not more physically active. They do not conclude that coffee drinking prevents obesity.

4) Church going: heavy coffee drinkers are less likely to go to church. Less likely to go to church, less likely to develop depression…heck, forget depression, maybe coffee prevents religion now! Now THAT would be a heck of a finding.

Here’s the thing. I do believe that high coffee consumption correlates with decreased risk of depression. But a lot of other things do as well. I am not convinced that the high coffee consumption wasn’t part of a lifestyle that correlated with decreased risk of depression, maybe they have stronger support networks or less incidence of depression in the family. It could be many other things. People who consume a lot of coffee may well have something going on neurobiologically which protects against depression (in which case taking up coffee if you don’t like it might not help you). Heck, maybe just staying away from church and having a martini is lifting their spirits! I’m just not convinced that coffee is the real preventative here. And I’m DEFINITELY not convinced that coffee has antidepressant effects.

So, oh most Skeptical Sci, you might say, what WILL prove it to you? Here you go.

1) If you want to prove to me that coffee is having antidepressant effects, I want to see effects in traditional animal models of antidepressant activity. You should be able to do acute and chronic administration either via injection or via the drinking fluid, mice and rats LOVE them some sweetened milk and they’d slurp up milky coffee in a snap. I want to see changes in tail suspension test, forced swim test. I’d like to see chronic effects on neurogenesis if you can get it. I combed through the lit but not a lot has been done on this. And then, I want to see a cohort of depressed people, half given coffee every day, half given decaf, blinded (you can certainly do this, though the IRBs would be awful). I’d want to see depression scores go down. The humans would be the ones I’d really want to see. Considering the common usage of caffeine, you might be able to go straight to humans here.

2) If you want to prove to me that coffee is a PREVENTATIVE, I want to see something similar. This time, I want to see mice/rats given coffee or decaf. I want to see them exposed to stress or other paradigms that create a depression-like model (things like chronic mild stress). I want to see the coffee rats show resistance to the depression-like effects. In humans, I want to see a large study of people over time, controlled for regular coffee vs decaf, and blind to which one they get. I’d like them to be controlled for stressful life events if at all possible (say, a big class of undergrads all taking the same class, though that would have bias of its own). I’d need to see more than nurses. Even then, with the humans, I wouldn’t really be sure.

Yeah, I’m a picky one, aren’t I. But while I’m convinced of the correlation in this study, I’m just not convinced of the causation. The paper didn't really suggest there WAS causation...but the media certainly did, and for those who don't really know what "risk" means in scientific studies (and most people don't), it looks like coffee's going to prevent your depression, and that's not what this study said. That said, they certainly didn’t see any correlations with harm! So in the meantime, I’ll keep on sipping.

Lucas M, Mirzaei F, Pan A, Okereke OI, Willett WC, O'Reilly EJ, Koenen K, & Ascherio A (2011). Coffee, caffeine, and risk of depression among women. Archives of internal medicine, 171 (17), 1571-8 PMID: 21949167

The views expressed are those of the author and are not necessarily those of Scientific American.

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