The Real Happy Pill Read online

  While the objective of these tests was to see if depression could be treated with physical activity, it was not to find the causes of depression. To discover that reason, we need to look at the substances in the brain that control how we feel: dopamine, serotonin, and noradrenaline.

  The brain is not a chemical soup

  Serotonin, noradrenaline, and dopamine are substances in the brain that transmit signals between the brain cells—in scientific parlance they’re referred to as neurotransmitters—and they influence how we feel. Lack of all three neurotransmitters has been connected to depression, and many antidepressant medications are effective by increasing the levels of those neurotransmitters. Selective serotonin reuptake inhibitors (SSRIs), the world’s most widely prescribed type of antidepressant medication, raise the level of serotonin; there are also drugs that boost levels of dopamine and noradrenaline. Serotonin, noradrenaline, and dopamine do a lot more than make you feel depressed, or not. They are also essential to the makeup of your personality and important for your cognitive abilities, such as concentration, motivation, and decision making.

  THE DRUGS DO WORK

  It’s important to emphasize that antidepressant medications do work. They have saved many lives and eased the suffering of millions of people. Anyone who suffers from depression should consider taking medication and seek out professional help.

  This is not about using either pharmaceuticals or training, and it is not advisable for you to discontinue your medication simply because you run or bike on a regular basis. The best effect is achieved if you combine both approaches, since the combination of medication and training is especially powerful. For those who find that medication does not work for them, training might be a good alternative to drugs. Training can also be a good option for people who experience strong side effects of medication.

  I want to stress that this book’s purpose is not to slam medication, but to show what happens in the brain when we exercise. I’m not in the least worried that there won’t be enough people praising the benefits of pharmaceuticals. However, I believe that the effects achieved by exercise and training get way too little attention—and that’s why I wrote this book.

  Serotonin has an inhibitory effect, which modulates the brain’s activities. Serotonin calms overactive brain cells and suppresses activity in the entire brain so that worries and anxiety recede. Serotonin creates calm, harmony, and a feeling of inner strength. A lack of serotonin can make you feel fretful and anxious.

  Noradrenaline affects how alert, attentive, and focused you are. Low levels of noradrenaline can make you feel tired and down, while too much of it can make you feel keyed up, hyperactive, and unable to settle.

  Dopamine is central to the brain’s reward system and affects your motivation and your drive. Good food, social interaction, and sex raises dopamine levels, which in turn influences you to try to get more of it. Every little “like” on social media releases a small kick of dopamine, which makes you want to check your cell phone again to see if you’ve gotten more “likes.” All addictive drugs, such as amphetamines, cocaine, and nicotine, raise dopamine levels. Dopamine is also important for concentration and decision making—as you’ve read in the chapter Improved concentration.

  It would be very cool if we could draw the conclusion that anyone who is depressed lacks serotonin, noradrenaline, and/or dopamine and replaces what is missing with pills. Sadly, it’s not that simple. The image of the brain as a kind of “chemical soup” containing the ingredients serotonin, noradrenaline, and dopamine—in which a lack of one or several causes us to suffer from depression—is too simplistic. There’s no way to say for sure if someone is lacking in serotonin, noradrenaline, or dopamine.

  One reason is that these substances are interconnected in a larger system of the brain where they don’t just affect one another; they also influence a slew of other substances that are pivotal to our well-being. This system is so complex that we have a long way to go before we can fully grasp the extent of it. We should see the brain as an advanced network where activities in different areas mutually affect one another, rather than as a soup of poorly measured ingredients.

  Regardless of their complexity, there is no doubt that serotonin, noradrenaline, and dopamine are all central to our feelings—and pharmaceuticals and physical training can raise their levels. The effects of exercise are typically felt after a workout and can last anywhere from one to a few hours. If you continue to exercise regularly, these levels will increase over time, not just after training but over the next twenty-four hours. Physical activity can increase serotonin, noradrenaline, and dopamine the same way antidepressant pharmaceuticals do.

  THE BRAIN’S MIRACLE MATTER

  A great mystery surrounds antidepressant medication. When they’re administered to a depressed person, serotonin and dopamine levels usually rise immediately, but without the person feeling any better. It often takes weeks for depression to clear, and the same applies to the effects of physical training. Levels of dopamine and serotonin increase as soon as the first run, but the antidepressant effects don’t kick in until after several weeks of regular running.

  If serotonin and dopamine play such important roles in how we feel, we should notice their effects immediately, but that’s not the case. Perhaps the increase of the two substances, whether by medication or training, is just the first step toward something else that’s taking place in the brain, with this “something else” being what makes us feel better in the end. What could it be, then? In neurological research, more and more scientists are looking at what has been dubbed a miracle matter for the brain. Its name is brain-derived neurotrophic factor (BDNF).

  BDNF is a protein that the brain creates in, among other places, the cerebral cortex (the brain’s outer layer) and the hippocampus. We need to be careful when calling something a “miracle,” especially in medical research, but the fact is BDNF has such a positive impact on the brain that its moniker is well deserved.

  When the brain cells receive BDNF, they acquire protection from things that would otherwise damage or kill them. If we subject brain cells to an oxygen deficit, low blood sugar, an attack of free radicals, or other toxic substances, it typically leads to cell damage or cell death; however, they will be shielded if they get some BDNF first. If someone suffers brain damage—by having a stroke, or taking a hard blow to the head, for instance—the brain seems to pump out BDNF, probably in the effort to save itself. The substance is sent out as a type of brain rescue squad to limit the damage, much like when our white blood cells produce antibodies to fight an infection or when blood platelets coagulate at the site of an injury.

  That’s how BDNF protects the brain cells. In addition, it oversees the creation of new brain cells and helps these newly formed cells survive their vulnerable early stage. BDNF strengthens the connection between brain cells, which is important for learning and memory. BDNF also makes the brain more flexible and slows the aging of the cells. The list of its benefits is so long it’s almost ridiculous. BDNF is, in short, the brain’s natural fertilizer. It is as important for the brain’s health whether we are children, adults, or elderly.

  What does this have to do with depression? Well, BDNF levels appear to be low in people who suffer from depression; this phenomenon has also been observed in the brains of those who have committed suicide. If a sufferer is treated with antidepressants, his or her level of BDNF increases. And the better you feel when recovering from depression, the more BDNF you seem to build up. But that’s not all. Levels of BDNF aren’t just connected to depression; they also seem to affect our personality traits, as well. Low levels of BDNF appear to be more common in more neurotic people!

  Run up the fertilizer levels

  Now for the big question: How can we get more of this miraculous product? Can we swallow it in a pill? Unfortunately, no, because it would be destroyed by the acid in our stomach. Even if it were possible to protect the BDNF from our stomach acid, it would not make it through the blood-br
ain barrier. The same would happen if we injected BDNF directly into our bloodstream—the substance would not pass through the blood-brain barrier. Theoretically, one could drill a hole in the skull and inject the BDNF right into it, but who would agree to do that?

  However, there is a way to raise the levels of BDNF in a natural way, and it is—drumroll, please—exercise! There is nothing as effective as physical activity to get the brain to make BDNF. We’ve seen in animal experiments that the brain immediately starts making this substance when they’re physically active, and it continues to do so for a few hours after they have stopped. A great deal of BDNF seems to be generated when the heart’s rate is properly elevated. It’s also worth keeping up regular training even if the brain starts producing BDNF right after the initial workout, because an identical dose of exercise appears to generate more BDNF per workout as the regimen progresses over time. Let’s say you run for thirty minutes twice a week; your brain will slowly produce more and more BDNF with each run, without you having to run longer or faster. If you quit training, the raised levels of BDNF will last for up to two weeks before they start to fall. This means that, from the standpoint of BDNF alone, you don’t have to be physically active every single day.

  Cardiovascular training is responsible for increased BDNF levels, while strength training doesn’t appear to have the same effect. You’ll need to exercise aerobically, using interval training, preferably regularly and vigorously, if you wish to generate more BDNF. Elevating the heart rate is important—if not always, then at least from time to time.

  Do all roads lead to BDNF?

  There are many reasons for becoming depressed or feeling low. Someone might be going through a traumatic event, such as a divorce or a death. Perhaps someone is being subjected to long-term stress. If you walk around for extended periods with high levels of cortisol (the stress hormone) in your body, your risk of becoming depressed rises. Likewise, you can become depressed after a short burst of stress caused by an extremely intense, perhaps life-threatening, event.

  But a lot of depression seems to come out of nowhere, and this is something that’s being closely monitored today in the effort to understand what might be the root cause. It appears that there could be other reasons for depression besides exterior factors—it could stem from the brain. Somehow, it seems to start from within the body and emerges from unexpected sources. Among other things, being overweight or obese increases one’s risk of suffering from depression—not only because the person feels stigmatized or stared at because of their appearance (although this, of course, can be a contributing factor), but also due to something on a purely biological level. One possibility is the fat tissue releases a substance that affects the brain, which can in turn lead to depression. There are several substances under suspicion. Fatty tissue is not just a passive source of energy; it constantly sends signals to the rest of the body to report on existing stocks. These signals are sent with the assistance of different substances, several of which can affect our brain and how we feel.

  We’re also aware that people with hormonal imbalances, such as the levels of the female hormone estrogen, are at greater risk for depression. Besides, we have a constant, low-grade inflammation in the body, and that too can increase our likelihood of becoming depressed. Some medications inhibit inflammation—anti-inflammatory drugs—appearing to have an effect against depression.

  So, depression seems to have many causes. Does this mean there is a common link between obesity, disturbed estrogen levels, inflammation, and the stress hormone cortisol? It looks increasingly like that might be the case, and it boils down to four letters: BDNF. In fact, it seems these disorders can affect BDNF. Stress leads almost immediately to a drop in the production of BDNF. Even carrying too much weight/being overweight, having impaired estrogen levels, and inflammation can lead to low levels of BDNF, which can make us feel depressed. In other words, BDNF seems to play a central, maybe even pivotal, role in the development of a depression—regardless of its root cause. Knowing this, we should make sure to increase our BDNF levels, and we can do that by exercising. It will help no matter what the cause of the depression.

  THE MIRACULOUS BACKSTORY OF MIRACLE MATTER

  The foundation for the discovery of the brain creating its own fertilizer was laid in the 1930s by the Italian physician and researcher Rita Levi-Montalcini. Being Jewish, she was barred from conducting research by Italy’s Fascist regime and lost her position as scientist at the University of Turin. She had to flee several times during WWII, but she never gave up her research. Even though she had neither a position nor a laboratory, she continued her work in her bedroom, at home, using items from her sewing kit as tools.

  She used chicken embryos as test subjects for her research into the nervous system. One day, she discovered that something odd had happened in the presence of tumor cells from mice. The nerve cells in the chicken embryo grew at a record pace and in places where they had no place growing at all, such as in blood vessels. The only reasonable explanation for this was that the tumor cells must have secreted a substance that caused rampant growth of the nerve cells. It wasn’t until the 1950s that, together with the German professor Viktor Hamburger, she solved the puzzle of the small protein released by the tumor cells: nerve growth factor (NGF).

  Levi-Montacini soon realized that NGF didn’t make all types of nerve cells grow and concluded that there must be several similar substances that could stimulate nerve growth. In the 1980s, another such substance, which showed itself to be closely related to NGF, was discovered. It was given the name BDNF—brain-derived neurotrophic factor.

  If quick recognition for advances in the field is what you seek, don’t go into research. It wasn’t until 1986 that Levi-Montalcini was awarded the Nobel Prize in Medicine, in acknowledgement for her great contributions. Rita Levi-Montalcini kept on working every day up into her nineties. She died in 2012 at 103 years of age, and was at the time the oldest living Nobel Prize winner.

  A disposition that leans toward depression can be partly blamed on genetics, so if a parent has suffered from it, the chances of his or her offspring having it increases. But if some people carry an increased genetic risk, how does that square up with BDNF? Perfectly well, it turns out! BDNF can look a bit different from person to person, and a certain genetic variation is more common among people who suffer from depression. In fact, BDNF is one of the few genes that would be interesting to examine if we want to find the answer as to whether an individual has a genetic predisposition for depression or not.

  New brain cells fight depression

  The brain tends to shrink a little in a person who suffers from depression. Actually, this happens to everyone. From around the age of twenty-five, the brain’s size decreases by about 0.5 percent per year, but it seems to happen more quickly in someone with depression. It is tied to, among other things, the fact that not enough new brain cells are being created. Now we know for sure that new brain cells are created even in adulthood (more about this in the chapter Jog your memory), but regeneration is inhibited in someone who suffers from depression.

  The current thinking among some scientists is that depression is caused by not having enough new brain cells being generated. Not that the creation of new brain cells is less vigorous due to depression—but that the lack of creation is in fact the reason for the depression. Much points to this hypothesis. If rats are given antidepressants, the amount of newly created brain cells in the hippocampus increases by 50 percent. This doesn’t happen overnight; it takes a few weeks for the new cells to form. This is the same amount of time it takes someone who is on antidepressant medication to begin feeling better. Is this a coincidence? If there is a correlation here, and many things indicate there might be one, it means that antidepressant drugs kick-start the formation of new brain cells and clear the depression.

  Medication is not the only thing that can help generate new brain cells; exercise can jump-start the production of new cells in the hippocampus, too. Few thin
gs, if any, are as good at firing up the regeneration of brain cells as physical activity. New brain cells aren’t just good for those who are depressed; they also play an important role in the brain regardless of how we feel. Even those who are not depressed will benefit from the new cells. So, which substance is responsible for the brain’s cell regeneration? You’ve guessed it: it’s BDNF.

  Your self-efficacy can cure you

  Thus, several things happen in the brain when we become depressed: levels of dopamine, serotonin, noradrenaline, and BDNF fall. Fewer new brain cells are created. Never mind which one of these is the most relevant—we don’t know this yet (it’s more than likely that they’re all linked), but we do know that physical exercise helps.

  Aside from the biological impact on the newly created brain cells and on molecules such as dopamine and BDNF, there are other reasons why physical training is a good treatment for depression. One, just like my female patient in the ER, you yourself can get a handle on the situation. You’re actively doing something to get well; in my case, the patient started to exercise. In the research community, we talk about self-efficacy, which basically means “belief in one’s own ability to complete a task or reach a goal.” Self-efficacy may sound a bit hollow, but it is in fact an established psychological concept. You increase your self-efficacy with regular training, and you are pleased with yourself. This goes for kids, as well.