Sex, Stress, and Neurogenesis

There’s an article in the latest issue of Wired by Jonah Lehrer explaining just how dangerous stress can be to our health.  It’s a fascinating read -- and instead of relying on my poor attempt to paraphrase -- I suggest checking out the article in its entirety.

The part of the story that struck a particular chord with me was Lehrer’s explanation of the experiments done by Elizabeth Gould, who studies how stress hormones affect the growth of new brain cells in adult brain, a process called neurogenesis.  Gould’s previous work, as noted by Lehrer, showed that when animals get stressed out, levels of glucocorticoids -- one type of stress hormone -- skyrocket in their brains.  With brain cells wading in a constant bath of these stress hormones, neurogenesis comes to a screeching halt.

The take-home message from Lehrer’s article: glucocorticoids are bad.  And indeed, they do make bad things happen in the brain.  Aside from the fact that stressed-out animals have less neurogenesis, if you take an animal and inject glucocorticoids directly, new brain cells also stop forming.  Lehrer’s suggests that if we find ways to prevent or otherwise interfere with stress hormones (through a vaccine or otherwise), we could mitigate the effect stress has on our emotional well-being and, ultimately, its complex interaction with disease.

I’ve been putting off (for several weeks now) writing a post on the most recent experiment to come out of Gould’s lab, published in mid-July in PLoS One.  Lehrer’s story finally lit the fire under me.

The term “stress” has a very deliberate negative connotation.  We need this term to bucket somewhat-hard-to-explain feelings, like experiencing “pressure” at work.  But the term is far more encompassing than that.  Stress, by definition, is a measure of how the body responds to a challenge.  Sometimes the challenge can be a threat -- a deadline at work or a difficult family situation -- and triggers the all-too-familiar anxiety we’ve come to expect.  This is the bad type of stress Lehrer discussed.  But the challenge can also be a something, well, good, that temporarily takes our body out of balance.  Consider what happens when you exercise.  Going out for a run will create a physiological burden as the heart beats faster and faster, trying to match blood flow to the demands of the muscles and lungs.  This physical exertion is also a type of stress, a good kind of stress, if you will.

The effects of the two types of stress on the brain are completely different: While the bad stress decreases neurogenesis, the good type of stress, on the other hand,  actively stimulates extra brain cell growth.  Although the brain responds in different ways, both good and bad stress increase the levels of glucocorticoids in the body.  Knowing glucocorticoids are dangerous to the brain, researchers still scratch their heads over how exercise could battle these stress hormones, and win.

But Elizabeth Gould has a new theory.

Exercise makes us feel good about ourselves.  We like the sense of accomplishment.  We celebrate the weight we’ve lost and our increased fitness.  Gould believes that this hedonistic value of exercise could somehow trump the nasty effects seen when glucocorticoid levels rise.  But exercise is such a complex action.  Sure, there’s a hedonistic component, but there’s also a hefty physiologic one.

To give her theory some teeth, Gould would have to prove that another stressor with hedonistic value also boosts neurogenesis.  So this time around, instead of exercise, Gould’s lab used a simpler, less physically-demanding, but equally powerful positive stressor: sex.

While not typically considered a stress by popular definition, sex fits the bill, as it’s been shown to increase glucocorticoid levels in the brain.

Gould’s results show that a single sexual encounter is enough to raise glucocorticoids and increase neurogenesis in the hippocampus of male mice.  After repeated sexual experiences, the glucocorticoid levels stabilize, but the brain continues to grow new neurons and the number of synapses increases.

While this study doesn’t answer all of the questions surrounding glucocorticoids, stress, and the brain, it shows the story is far more complicated than initially thought.  Chronic good stress continually increases neurogenesis, but it also seems to level off the stress hormones themselves.  Gould’s results support the notion that the hedonistic aspect of good stress may in fact be the active ingredient that keeps the dangerous effects of glucocorticoids at bay.

Leuner, B., Glasper, E., & Gould, E. (2010). Sexual Experience Promotes Adult Neurogenesis in the Hippocampus Despite an Initial Elevation in Stress Hormones PLoS ONE, 5 (7) DOI: 10.1371/journal.pone.0011597

Exercise and Anger

CrossFit Trainer Certification (via Wikimedia)

Exercising people are happy people.

Nonsense. Ever see someone’s face at mile 20 of a marathon? Do they look happy to you?

OK, maybe people aren’t happy while exercising, but evidence shows they’re better off, in general, after the fact. Physical activity has a positive effect on mood, and is considered a valid treatment strategy to battle anxiety disorders and even depression. Although most explanations are somewhat wishy-washy, researchers believe that hedonistic value of exercise is important in mental health. Exercise simply makes us feel good about ourselves. And this is not only true in humans, but in animals, as well. Rats and mice that are given free access to a running wheel will use it, and lab rodents typically won’t do anything that doesn’t provide them some sort of pleasure.

But what about anger -- can exercise prevent us from getting angry in the first place?

Gretchen Reynolds’ new post on the ‘NYT Well’ column discuss new evidence that shows exercise -- even a single, isolated session -- can alter how we respond to challenges that angered us in the past.

In one particular study, researchers showed a group of undergraduate students a series of images while recording EEG signals from their brains. Some of the images were pleasant, while others were meant to make the participants angry. After the students watched the videos, they rated their current anger on a scale from 0 to 9. At baseline, the electrical activity in the brains of students showed they were disturbed by the nastier images, and they all rated their anger on the high-side of the 0-9 scale.

The students were then divided into two groups. And on the days between the experiment, one group did some light/moderate exercise (like 30 minutes on a stationary bike), while the other group did not exercise at all. When re-tested, the electrical activity of the brains of all the students, regardless if they exercised or not, showed that they became angry while watching the videos. But the students that had exercised the day before were able to shake-off their anger, and at the end of the session, they just weren’t as upset as those in the physically-inactive group.

The results suggest that exercise may in fact be a preventive measure against the buildup of anger.

The rest of Reynolds’ post talks about the mechanism of how exercise could make us less like to boil over in anger. She provides some hand-waiving explanations, saying changes in serotonin levels in chronic exercisers make them less angry. While this may be true, exercise is a complex activity that changes so much in the body -- neurotransmitter levels, blood flow, hormone levels, just to name a few -- so I’d caution readers that it’s hard to pinpoint which physiological catalyst could be real the anger-fighting superhero. Or maybe it’s not one particular molecule, but the sum total that makes exercise so powerful.

Curiosity as Vice and Virtue

Copernicus and Galileo had it easy. Those two lived during the middle of the European Renaissance, a time when creativity and curiosity were norms in society.  Sure, the church came down hard on their views on where the earth stood in relation to the rest of the universe.  But, basically, the church simply disagreed with the details of their argument.  (Well, I guess calling someone a heretic is slightly more than disagreeing with someone, but you know what I mean...)

The scientific minds who really had rough run-ins with the church lived during the fourth century, under the moral guidance of Augustine, the Catholic archbishop of Hippo.  At that time, science was a sin, as Augustine likened inquisitiveness to a form of lust.  Not a "lust of the flesh", but more of a "lust to find out and know".  According to author, William Eamon, Augustine saw no difference between people-watching at the circus or the piazzas and enduring the rigors of scientific study.  Check out the rest of Eamon's fascinating analysis here.

Should We Fear Genetic Testing?

Though the prospect of learning about our DNA might seem wrapped in mystery and intrigue, genetic information is not so different from any other metrics we know about ourselves: Our age, our weight, our blood pressure. With a little scrutiny, any of these numbers can tell us something about our health and ourselves. It’s the same with a genetic scan – it gives us some perspective on our health, though far from the complete picture. It is, in other words, a place to start thinking about how we’re living our lives. It’s important to remember, though, that genetics is a very new science, and that getting a scan today is the equivalent of buying the first generation iPod – it’s a work in progress, and will get much better as time goes on. There’s a lot that science doesn’t know yet about the exact influence of DNA on our health, and the journey is part of the ride. But it’s a rare opportunity, unprecedented, perhaps, in history, that the general public might be granted unfettered access to experience science as it happens. It’s not something that everyone will be comfortable with, but we shouldn’t underestimate how profound this opportunity is.

So when it comes to choosing a service, beware the hype – and use the same sort of common sense that we use as consumers apply when we choose a bank, a cell-phone provider, or a grocery store. Those companies that promise to give definitive insight into the future, the “if your kids have this gene they’ll be Olympic athletes” sort of promises, are overpromising and exaggerating what science actually knows. They may act as if our DNA was a crystal ball, but the fact is, it’s not: while our DNA has a large influence in our health, it is largely just that – an influence, along with all sorts of other factors like our diet, our environment, and other behavioral factors. Our health, in other words, is an equation where our DNA is just one factor, one input. The legitimate services understand this, and make this clear. Indeed, it’s a selling point for them: the fact that we can respond to our DNA, that we can actually use it to inform the way we live our lives, is part of the rare opportunity we’re being granted. Rather than fear this opportunity, we should consider it as straightforward as any risk we’re alerted to in life.

The fact that DNA is not destiny is, to me, a reason to consider getting a scan: understanding that we can act in response to our DNA, that we can change our lives to minimize the predispositions that our genes may create, should be a source of empowerment and reassurance. Our DNA is just the blueprint for our lives and our health. How much we choose to follow the plans or tweak along the way is up to us.

To me, the role of DNA in our health is no different for most people than any other blood test result or risk factor – it’s a best guess, a probability that we can choose to heed, or can choose to ignore. Medicine is always a numbers game – it’s usually just cloaked in the white-coat authority of a physician.

For those of us who want to get a head start on health, who want to live with a little more purpose and precision, then a DNA scan is a great place to start.

Making Penicillin

In 1928, Alexander Fleming discovered penicillin through an equal mix of scientific rigor and serendipity.  Still, doctors spent the better part of the 1930’s one step behind infections that had no regard for human life.   Penicillin was simply too expensive and difficult to produce in large quantities, and the drug was tucked away on a laboratory shelf until the outbreak of WWII in 1939. The US government used the need to treat battlefield infections to seize control of penicillin production, along with the intellectual property and patents behind the drug.  But Uncle Sam’s questionable tactics paid off: from 1939 to 1944, penicillin went from an expensive laboratory experiment to a battlefield staple in every soldier’s medic kit.

Having lost their patents and potential financial gain to the government, drug companies began the quest to develop other types of drugs that were similar to penicillin, thereby launching a billion dollar antibiotic development industry.

NPR had a segment on ‘All Things Considered’ this week discussing the full story of bringing penicillin to market, which appears in a new book, ‘A Fierce Radiance’, by Lauren Belfer.

PepsiCo at ScienceBlogs

ScienceBlogs.com -- one of the most well-known and highly-cited blog sites -- caused quite the hullabaloo on Twitter and the blogosphere today when they announced their newest contributor: PepsiCo. For quite some time, SEED Media (the parent company behind ScienceBlogs.com) has sold advertising space on contributors' sites.  But as PalMD describes in his post, the center panel of each site is always under the direct control of the author.  With the launch of the PepsiCo blog, SEED Media is in grave danger of blurring the line between advertising and content.

I don't think there is anything inherently wrong with selling ad space on the periphery of popular blog platforms.  Everyone has to pay the bills, and SEED Media needs a revenue stream to distribute and market its content.  But I'm not exactly sure how PepsiCo will use its newly launched blog, now that it has control of that valuable "center panel".  Only time will tell whether the PepsiCo blog will become a PR platform for the food conglomerate, or whether they'll actually contribute to scientific discourse.

Whether we like it or not, the prepared food industry will be a major player in our food supply in the near future.  We need to find novel ways to engage these companies to improve health and nutrition in society.  Hopefully, PepsiCo takes this opportunity to contribute in the exchange of scientific information, and doesn't just focus on improving sales.

I'll be watching this site very closely over the next few months, and I'll report on what I find.

Time to Make a Dopamine Run

It's 6am and my alarm clock is buzzing, but I don't hear it. I don't even move. But the incessant noise wakes my wife, and her gentle nudges (read: elbows) and soft whispers (read: expletives) eventually convince me to get out of bed. It seemed like a great idea: Run in the morning before work, to free up countless evening hours. “Think of all you'll get done at night if you don't have to run after work”, I said to myself. “For once you'll actually hit your goal of blogging multiple posts per week! Maybe even finish some of those half-read books lining the shelves.” But two days into the new regime, I'm having second thoughts.

It's freaking early. I mean, I've gotten up at the crack of dawn to work on blog posts, but going out for a 6-mile run requires a bit more activation energy than typing away on the computer.

To make matters worse, I just don't feel like running today. It's cold and raining. I can hear the wind blowing from inside my apartment. My warm bed is calling to me, but I muster the will to put on my running clothes, and step outside.

I trod along, slower than usual, because my legs are still tight. A few minutes into the workout, a homeless man approaches me on a rickety bike. He rides close by, taunting me. “You keep running, boy”, he says. “Gonna run yourself right into the grave!” Living in San Francisco, I’ve grown moderately accustomed to such neighborhood friends. But today, instead of being a minor annoyance I shrug off, this guy truly sounds like the voice of reason.

We talk a lot on this blog about ways to drive healthy behavior change: Self-tracking and the Hawthorne effect. Competition and group dynamics. But no way around it, rewards are the heart of behavior change, thanks to the way our brains respond to the molecule dopamine, which differentiates what you have to do, from what you want to do. Dopamine turns a chore into a hobby.

The clearest example of the dopamine reward system in action is the now-famous experiments of Ivan Pavlov. In the early 1900’s, Pavlov noticed that when dogs saw food coming, they began to salivate. The dog's brains were moving faster than their bodies, already anticipating the sweet reward of food before a morsel even hit their mouths. So Pavlov wondered what would happen when he paired a food reward with a random stimulus, such as a bell, whistle, or electric shock. We all know how the story ends: After training, Pavlov's dogs salivated when they heard they bell, regardless if they got a food reward or not.

Pavlov's experiment unlocked our understanding of classical conditioning: Pair a random stimulus close enough to a reward, and soon the stimulus itself tells the brain to get ready for the big payout.

With brains wired for immediate reward in a world of instant gratification, it’s easy to see why we struggle when starting a new exercise routine. The stimulus (the act of running) is so far separated from the reward (the endorphin kick, the runner’s high, or even improvements in our health and fitness).

So how can we ever be expected to change a behavior unless we get an instant payout for our actions? A hand-waiving explanation would be we’ve simply trained our brains to wait longer and longer for the reward. On the other hand, consider this: If you talk to enough runners, they'll tell you they don't “feel right” when they haven’t gone for a run in a few days. They feel “off” if they don’t get their fix. I’m certainly not the first to wonder if chronic exercise somehow primes the dopamine reward system to make us crave the activity, the old “exercise addiction” theory. But the similarities between the two are striking. Could we one day use what we know about addiction to drugs to reveal new ways to get people hooked on positive behavior changes? I’m still funneling through the scientific literature regarding exercise addiction, so I’ll give you updates as the ideas surface.

For any new runners out there looking for pearls of wisdom about what to do when the going gets tough, I leave you with this: I know that even experienced runners lack motivation at times. In fact, I don't know that it ever gets easier to plunge into the first few steps of a run on days you’re dealing with bad weather, a busy schedule, or belligerent guys on bikes. But hang in there, your body and brain will thank you (hopefullly sooner than) later.

What Did the NIH Report on Lifestyle Modification/Alzheimer's Really Say?

My inbox flooded with links to the report released by NIH (and evangelized by TIME) stating that lifestyle interventions (diet, physical activity, mental exercises, etc.) may not be that effective in preventing Alzheimer's Disease. Before I mount my full counterattack, I need to carefully read through the studies the meta-analysis cites.  Still, a quick glance at the exclusion criteria of the meta-analysis reveals the authors limited their review to studies using patients over the age of fifty.  So really, these results imply that lifestyle modifications may not prevent, delay, or treat Alzheimer's Disease if you start these changes later in life.

My second point is that all lifestyle modifications are not created equal.  Scientific evidence in animal studies suggests that of all interventions, aerobic exercise is our best chance of staving off cognitive decline.  In fact, this meta-analysis also found some correlation between exercise and preserving or improving cognitive ability.

There's a good article in The Economist that discusses the failures of the drug industry to find a solution to treating Alzheimer's Disease.  One particular quote resonates with my feelings on the NIH report:

Another fundamental problem is that, whatever is causing the damage, treatment is starting too late. By the time someone presents behavioural symptoms, such as forgetfulness, his brain is already in a significant state of disrepair. Even a “cure” is unlikely to restore lost function.

Internet: Good or Bad for the Brain?

I was fairly quiet on the blogs and Twitter the latter part of last week, because I spent Thursday and Friday at the Health Horizons Conference, sponsored by the Institute for the Future (IFTF). I’ll post some reflections soon, but first I want to comment on an interesting discussion that was brewing last week. Over at Neuron Culture, David Dobbs has some nice insight into the ongoing debate between renowned science/tech writers Stephen Pinker and Nicholas Carr.

Carr apparently states in his new book, The Shallows, (which I have not read), that the internet might be killing our brains with increasing distractions. Pinker, on the other hand, thinks that while many people are initially panicked by new media technology, one day society will see the internet for what it truly is: a way of richly organizing the ever-increasing abyss of information.

A second showdown, this time between writers Jonah Lehrer and Clay Shirky, tackles the question: Is the internet better for creating a ‘Cognitive Surplus’ than television? Shirky believes the era of the mindless television sitcom moved us away from social interaction and deep thought, but the advent of online social exchange – even in the form of inane material such as the lolcats at icanhascheezburger.com – is once again bolstering our feeble brains. Lehrer fires back, saying that television and internet alike can fuel passionate offline discussions and detailed analysis.

From a neuroscience perspective: Is the never-ending online information flow good or bad for our brains? (Or, for that matter, is technology good for our brains?) Is one technology (television) better or worse than another (the internet)?

Just like all aspects of life, I suspect brain growth is all about balance. For me, Twitter serves as a filter for my information stream. I follow people whose insight and opinion I respect (whether I agree with them or not doesn’t matter). But sitting down to write a blog post takes me away from the cacophony of Twitter for a moment to think critically about a particular topic. Often I engage my colleagues and friends in a discussion, either in person or over email/chat, regarding the ideas in my head long before I publish anything online. I balance the real-time information flow with real-life conversations.

One could argue that any information stream – be it reading a book, watching a movie, or surfing the net could deaden our brain if we don’t pause for reflection. Intelligently analyzing, as opposed to passively experiencing, the information that enters our brains is no doubt one of the distinguishing factors that makes us human. So don’t be afraid of technology, and don’t quibble over which technologies are good or bad. Rather, simply use technology to augment human social interaction.

Big News, Big Changes

Two-and-a-half years ago, I met Thomas as a burned-out postdoc contemplating a career change.  On our first meeting, I asked him what sort of job existed for a someone who loved science but didn’t want to work in the lab, had a deep interest in writing and communication, and wanted to be a part of building tools to disseminate scientific information to the public.  I finally found the answer to my question. At the end of the month, I'll be moving out of the lab (once and for all) and headed over to the Public Library of Science (PLoS) as the new Community Manager of PLoS Hubs.  I am thrilled about the new opportunity, and very much looking forward to working with the super talented team at PLoS.

Several people have asked me what exactly I’ll be doing as Community Manager.  PLoS has an exciting new post-publication product launching in a few months called Hubs, which will aggregate the most relevant research and discussion around particular topics.  As Community Manager, I’ll help build and maintain these communities, stay abreast of new developments, and work with other members of the team to develop new features and tools.

My apologies for the limited posts here at The Decision Tree and sporadic updates on Twitter over the past few months.  Disentangling myself from my lab work took much more time and effort than I expected.  Rest assured, I have some good posts in store, and I hope to expand the breadth of topics I cover as I dive into the world of open access publishing and scientific community.