The Upward Spiral: Using Neuroscience to Reverse the Course of Depression, One Small Change at a Time

by Alex Korb

Sometimes everything just feels difficult and pointless. It’s a feeling we all get from time to time, and it’s simply a natural by-product of our complex brain circuitry. And for most people, it’s just a fleeting feeling, gone like a whisper. But due to slight differences in neurobiology, some people get stuck.

Fortunately, the studies described above—and dozens of others—beautifully illustrate how small life changes actually change the activity and chemistry in specific circuits. We know the circuits that contribute to depression, and we know how to modify those circuits. As brain activity and chemistry begin to change, so does the course of depression.

People often think depression is just being sad all the time, but it’s far more than that. In fact, people with depression do not necessarily feel sad—they often feel numb, like an emptiness where emotion should be. Hopeless and helpless. Things that used to be enjoyable aren’t fun anymore: food, friends, hobbies. Energy plummets. Everything feels difficult, and it’s hard to explain why, because it shouldn’t be. Nothing seems worth the effort it requires. It’s hard to fall asleep and to stay asleep. Aches and pains are felt more deeply. It’s hard to concentrate, and you feel anxious, ashamed, and alone.

The big problem with the downward spiral of depression is that it doesn’t just get you down, it keeps you down. Depression is a very stable state—your brain tends to think and act in ways that keep you depressed. All the life changes that could help your depression just seem too difficult. Exercise would help, but you don’t feel like exercising. Getting a good night’s sleep would help, but you’ve got insomnia. Doing something fun with friends would help, but nothing seems fun, and you don’t feel like bothering people. Your brain is stuck—depression pulls it downward, relentless as gravity. Your mood becomes like a marble sitting at the bottom of a bowl: whichever way you push it, it always rolls back down.

For example, exercise changes the electrical activity in your brain during sleep, which then reduces anxiety, improves mood, and gives you more energy to exercise. Similarly, expressing gratitude activates serotonin production, which improves your mood and allows you to overcome bad habits, giving you more to be grateful for. Any tiny change can be just the push your brain needs to start spiraling upward.

Depressed mood, such as feeling sad or empty or even constantly irritable Decreased interest or pleasure in all—or almost all—activities Significant (and unintentional) weight loss, weight gain, or decrease or increase in appetite Insomnia or increased desire to sleep Either restlessness or slowed behavior that can be observed by others Fatigue or loss of energy Feelings of worthlessness, or excessive or inappropriate guilt Trouble thinking, concentrating, or making decisions Recurrent thoughts of death or suicide1

Whereas most diseases are defined by their cause (for example, cancer, cirrhosis of the liver), the disorder of depression is currently defined by a collection of symptoms. You feel crappy most of the time. Nothing seems interesting, and everything seems overwhelming. You have trouble with sleep. You feel guilty and anxious and have thoughts that life isn’t worth living. These are the signs that your brain circuits are caught in the downward spiral of depression. And if you’ve got enough symptoms, you’re diagnosed with depression. There’s no lab test, no MRI scan; it’s just the symptoms.

The same is true of your brain. In depression, there’s nothing fundamentally wrong with the brain. It’s simply that the particular tuning of the neural circuits creates the tendency toward a pattern of depression. It has to do with the way the brain deals with stress, planning, habits, decision making, and a dozen other things—the dynamic interaction of all those circuits. And once the pattern starts to form, it causes dozens of tiny changes throughout the brain that create a downward spiral.

Serotonin—improves willpower, motivation, and mood Norepinephrine—enhances thinking, focus, and dealing with stress Dopamine—increases enjoyment and is necessary for changing bad habits Oxytocin—promotes feelings of trust, love, and connection, and reduces anxiety GABA—increases feelings of relaxation and reduces anxiety Melatonin—enhances the quality of sleep Endorphins—provide pain relief and feelings of elation Endocannabinoids—improve your appetite and increase feelings of peacefulness and well-being

This is an oversimplification, but in general, each neurotransmitter contributes to a different depressive symptom. A dysfunctional serotonin system is responsible for the lack of willpower and motivation. The difficulty in concentration and thinking is probably due to problems with norepinephrine. Dysfunction in the dopamine system leads to bad habits and lack of enjoyment. All of these neurotransmitters are necessary for proper functioning of dozens of circuits throughout the brain, and to make things more complicated, they all interact. Unfortunately, depression is not just a matter of not having enough norepinephrine, serotonin, and dopamine, and thus it’s not solved by simply increasing the levels of these neurotransmitters. But that is part of the solution. Boosting serotonin leads to a better mood and a greater ability to set goals and avoid bad habits. Increasing norepinephrine means better concentration and lower stress. And more dopamine generally means more enjoyment.

The prefrontal cortex is the most recently evolved part of the cortex, and humans have more of it than any other animal. Our big prefrontal cortex gives us a huge evolutionary advantage, but it can also cause problems. In depression, it is responsible for worrying, guilt, shame, problems with thinking clearly, and indecisiveness. Changing activity in the prefrontal cortex can help with these problems, and it can change bad habits and improve willpower.

Pretty much the whole prefrontal cortex is affected by depression.3 Not feeling any motivation? It’s likely the fault of reduced serotonin in the ventromedial prefrontal cortex. Finding it difficult to make plans or think clearly? It’s probably disrupted activity in your dorsolateral prefrontal cortex. However, most problems, like difficulty in following through with plans, cannot always be pinpointed to one region or neurotransmitter system and often result from the communication between several of them.

Lastly, the cingulate cortex controls focus and attention, which is of huge importance in depression, because what you focus on, whether by automatic habit or willful choice, makes a huge difference to your mood.

Anxiety isn’t always obvious, but increased anxiety, in one form or another, is a symptom of depression. Anxiety is primarily mediated by the amygdala, an ancient structure deep in the brain, which is closely connected to the hypothalamus and is a central part of the emotional limbic system. People with depression often have higher amygdala reactivity, so reducing that can help lower anxiety and relieve depression.4

When was the last time you were truly happy? People with depression often have trouble remembering happier times but have no problem recalling sad events. This memory bias can be blamed on the hippocampus, which sits deep in the brain, adjacent to the amygdala; it also has strong connections to the hypothalamus. The primary job of the hippocampus is turning short-term memories into long-term ones, like hitting “Save” on a new document to store it on your computer’s hard drive. The hippocampus is the “save” button; without it, you couldn’t form new memories. It particularly likes to save emotional memories (like building your first snowman, the embarrassing thing you said to your crush in middle school, that great ski trip you took last year). That’s somewhat problematic in depression, because the new memories your hippocampus forms will skew to the negative.

However, the hippocampus does much more. It is also central to context-dependent memory, which is the fact that it’s easier to remember things that relate closely to your current situation.5 For example, it’s easier to recall memories from your undergraduate days if you’re visiting your old college campus, because the context is the same. Unfortunately, in depression, there is a large downside to context-dependent memory. Because the “context” is depression, all those happy memories that are easy to recall when you’re in a good mood suddenly evaporate. Meanwhile, all the tragedies in your life become too easy to remember.

Think of happy memories. Happy memories boost serotonin in the anterior cingulate (chapter 8). Try to think of one happy memory before you go to sleep—write it in a journal or just reflect on it.

Depression is often accompanied by bad habits such as impulsiveness, poor coping skills, addiction, and procrastination. That can also include feeling fatigued and unmotivated. These bad habits are primarily caused by disrupted activity in the striatum, which is an ancient subcortical region deep below the surface that we inherited from the dinosaurs. The striatum has two main parts that are particularly important in depression: the upper part, known simply as the dorsal striatum, and the lower part, called the nucleus accumbens. Both parts rely heavily on the neurotransmitter dopamine to function properly.

Make a decision. Anxiety and worrying are provoked by possibility, not certainty. In fact, many people are less happy when they have more choices, because they have more to worry about.1 When everything is up in the air, the amygdala becomes more reactive.2 So if you tend to worry, reduce your options and make quick decisions whenever possible. As soon as you make a decision, however small, everything starts to feel more manageable—we’ll

Worrying and anxiety are distinct but related concepts—you can have worrying without anxiety and anxiety without worrying.6 Worrying is mostly thought based, whereas anxiety has more to do with physical components like bodily sensations (such as an upset stomach) or associated actions (like avoiding a situation). Worrying involves the prefrontal cortex and its interactions with the limbic system, particularly the anterior cingulate, while anxiety involves only the limbic system, mostly interactions between the amygdala, hippocampus, and hypothalamus. In essence, worrying is thinking about a potential problem, and anxiety is feeling it.

Pay attention to what you can control. If the future were completely under our control—or at least predictable—there would be nothing to be anxious about. Feeling in control reduces anxiety, worrying, and even pain.7 These effects are mediated by the dorsolateral prefrontal cortex, so strengthening dorsolateral activity helps create an upward spiral.8 You can do this by simply paying more attention to what is in your control, which helps modulate your brain activity and quickly reduces anxiety.

Whatever their differences, worrying and anxiety can both get in the way of living a good life. When you’re using your planning and problem-solving circuitry to worry, you can’t use that part of your brain for more important things, like excelling at your job or organizing a dinner party. It keeps you from focusing on what you’re doing and often makes it harder to connect with other people. Most importantly, it ca...

Go for good enough. Worrying is often triggered by wanting to make the perfect choice or by trying to maximize everything. When buying a used car, you want one that is cheap, reliable, safe, sexy, the right color, and fuel efficient. Unfortunately, no single option is likely to be the best in all those dimensions. If you try to have the best of everything, you’re likely to be paralyzed by indecision or dissatisfied with your choice. In fact, this kind of “maximizing” has been proven to increase depression.9 So don’t try to make the most amazing dinner; start out by just making a good dinner. Don’t try to be the perfect parent; just be a good one. Don’t try to be your happiest; just be happy.

Anxiety doesn’t always have a conscious, thinking component; it can simply be a sensation, like an upset stomach or shortness of breath. Often when you think you’re sick, it’s actually the physical manifestation of anxiety.

Avoid catastrophizing. Anxiety is exacerbated by envisioning the worst possible scenario—a process known as “catastrophizing” (for example, your friend doesn’t call back immediately, so you conclude he or she doesn’t like you anymore). It usually starts with a perfectly reasonable worry, and then, through an incorrect assumption, it snowballs out of control. Well, you can’t control noticing the “alarm” in the first place, but you can reduce its negative impact. First, remind yourself of the more likely (and better) outcomes (“Maybe my friend is busy right now”). Second, whether or not the worst-case scenario is actually likely, make a plan to deal with it (for example, “If my friend doesn’t call me back in three days, I’ll just call again,” or even “If my friend doesn’t like me anymore, then I’ll hang out with another friend”). Planning your response to stressful situations can increase prefrontal norepinephrine, and calm the limbic system, helping you feel more in control.12

Putting emotions into words—however hokey that sounds—actually rewires your brain circuits and makes you feel better.

All of this means that to be happy in our daily lives, we need a high ratio of positive to negative. And it turns out, after considerable study, that ratio is three to one. We need three positive comments from a friend for every negative one, three wins at work for every loss.12 Of course, not everyone is the same. That three-to-one ratio is just an average. Some people might need only a two-to-one ratio and be fine, but others—people who feel losses and disappointments more deeply—might need a higher ratio. On top of that, if your brain simply ignores the positive events that happen to you—as is often the case with depression—you might need an even higher ratio.

“Life is a train of moods like a string of beads; and as we pass through them they prove to be many colored lenses, which paint the world their own hue.” The poet Ralph Waldo Emerson understood how moods can change perception—a process called the mood congruent attentional bias. It turns out that when your mood gets worse, so does your brain’s negative bias. Feeling down means you’re more likely to notice negative things about the world and about yourself. This includes context-dependent memory, mentioned in chapter 1, which, in certain contexts, makes you less likely to remember happy events and more likely to remember sad ones.

Of course, as described above, this bias is even worse in people with depression. They tend to pay more attention to negative events and emotions22 and to notice more sadness in the world.23 Having depression is like being tuned to the six o’clock news all the time. If that was all you watched, you’d start to think the whole world was full of nothing but political scandals, weather disasters, and horrific crimes. If you could only change the channel, you’d see everything else that’s out there—but you can’t.

Notice what you notice. You can’t control the random bits of information that pop into your head. But you can start to notice your biases. When you get annoyed that you’re stuck at a red light think, Oh, that’s interesting. I noticed this red light, but I didn’t notice the last green light I made. In short, try practicing nonjudgmental awareness. Nonjudgmental awareness is a form of mindfulness that simply means noticing without reacting emotionally, even when things don’t turn out as you expected. Awareness does not require emotion, because emotion and awareness are mediated by different brain regions. Noticing a mistake might automatically trigger the emotional amygdala, but becoming aware of your own reaction activates the prefrontal cortex, which calms the amygdala.

When people with depression were told they were going to be shown negative pictures, they had more activation in the insula and the ventrolateral prefrontal cortex, indicating more visceral and emotional processing than nondepressed people would have.27 Surprisingly, when they weren’t told about the type of picture, their brains still reacted as if expecting a negative picture. In the face of uncertainty, their brains assumed the worst. On top of that, when they were uncertain, depressed people also had more worried dorsolateral prefrontal activity, as well as more self-focused emotional processing in the medial prefrontal cortex. This response to uncertainty can explain why people with depression are more likely to be pessimistic—the past was negative, so the future must be too.28

Similarly, during actual painful stimulation, people with depression had greater increases in amygdala activity than nondepressed people. Their brains had a more emotional response to the pain. And the more helpless they felt, the greater the brain’s emotional response. Furthermore, they had decreased activation in the region of the brainstem that produces painkilling endorphins, so their brains did not try to suppress the pain as much. They also had decreased activity in the ventral anterior cingulate and prefrontal cortex, which meant that the pain had a greater impact on their optimism circuitry and lowered their ability to think rationally about the situation. Thus, if a depressed person and a nondepressed person both burn their hand on the stove, the depressed person is more affected by the pain. The brain’s response to pain is one reason that people with chronic pain are more likely to develop depression, and vice versa.

Lastly, you might think your happy memories are safe from the mood bias, but unfortunately, old memories aren’t retrieved like an old email; they’re reconstructed from bits and pieces every time you remember them. Your negative mood influences that reconstruction so that you add a bit more darkness and sadness to them. Recognizing that you’re viewing your own past through the sunglasses of your current depression can help you realize that your life hasn’t always been this bad.

How to increase norepinephrine. Surprisingly simple things can help increase norepinephrine—and thus decrease the negative bias—such as exercise, a good night’s sleep, and even getting a massage.

To combat pessimism, you can strengthen the brain circuits responsible for optimism. The first step is to simply imagine the possibility of positive future events. You don’t have to believe they will happen, just that they could happen. It’s possible you could find true love tomorrow. It’s possible that you could find a better job. It’s possible that things won’t turn out in the worst conceivable way. Recognizing that good things are possible activates the lower (ventral) anterior cingulate.35 Importantly, the ventral anterior cingulate helps regulate the amygdala, so admitting the possibility of good things helps control the brain’s negative bias.

Habits are, by definition, hard to change. And some habits are so deeply ingrained that we don’t believe they can be changed. Fortunately, the first step to accomplishing change is simple awareness, and the second step is believing it to be possible. Which it is. You might need therapy or medication, or you may simply need to perform some of the activities described in this book. But first and foremost, you need an understanding of how your brain creates and controls your habits.

Everyone has coping habits; they are some of the deepest, most ingrained routines we have. They make us feel better, at least for the time being, by reducing amygdala activity and the body’s stress response. Good coping habits can pull you out of an impending downward spiral, because the dorsal striatum takes over and sets your life back on course. But bad coping habits don’t stabilize your mood in the long term, so acting them out just creates more stress later on, and down the rabbit hole you go.

Ultimately, it comes down to the most clichéd but scientifically true maxim: practice, practice, practice. To create new, good habits, you have to repeat them over and over again until your brain rewires itself. At the end of the day, repeating actions is the only way to get them encoded into the dorsal striatum. It may take a lot of time and patience, but once you train your dorsal striatum, it’ll start working for you instead of against you; we’ll cover that more in chapter 8. And it’s pretty amazing that it’s possible—no matter how old you are, you still have the power to change your brain and improve your life.

But there’s good news. Your brain is not set in stone. Life changes cause brain changes—you can willfully change the activity, chemistry, and wiring of the regions and circuits in your brain that lead to depression. Like upgrading your computer, you can change not only the software but also the hardware. The changes are not always big, but they add up—each one pushing the brain toward an upward spiral.

We all know how important exercise is for your body, but what I didn’t realize then is how important exercise is for your brain.

And by “exercise,” I just mean moving around. It doesn’t mean you need to go to the gym or buy fancy workout clothes; you just need to move your body more and not be so sedentary.

Have fun (a.k.a. don’t “exercise”). When you don’t think of it as “exercise” but rather as “being active” or “having fun,” you’re more likely to do it, and it will have a bigger emotional benefit. If you bike to work three days a week or play Frisbee with friends in the park, it won’t feel like you’re exercising, but it’ll add up to a lot of activity.

Exercise is possibly the most straightforward and powerful way to start an upward spiral. Not only is it easy to understand, but exercise also has many of the same effects on the brain as antidepressant medications and even mimics the buzz of recreational drugs. Yet exercise is natural, it causes more nuanced...

Almost everything that depression causes can be combatted by exercise. For example: Physically Depression makes you lethargic and tired, but exercise gives you more energy and vitality. Depression often messes up your sleep patterns, but exercise improves your sleep, making it more restorative for your brain (chapter 7). Depression wreaks havoc on your appetite, so you either eat too little or chow down on junk food (in fact, people who eat lots of processed foods are at higher risk for depression1). Exercise improves your appetite, leading to more enjoyable eating and better health. Mentally Depression can make it hard to concentrate, but exercise makes you mentally sharper and better at planning and decision making.2 Depression makes you…well…depressed, but exercise improves your mood.3 It also reduces anxiety,4 decreases stress,5 and boosts self-esteem. Socially Depression usually keeps you isolated and alone, but exercise tends to bring you out into the world. Furthermore, all of these effects make it more likely that you’ll engage in other activities and thought processes that also reverse the course of depression. For example, exercise improves sleep, which then reduces pain, improves mood, and increases energy and alertness. Then reduced pain makes you more likely to exercise and increases your enjoyment of exercise. Having more energy also makes it more likely that you’ll exercise. The take-home message is that all these causes and effects intermingle and build on ...

Enjoy the view. Exercising in pleasant environments, whether urban or rural—or while looking at images of pleasant environments—boosts the benefits of exercise.8 In fact, irrespective of exercise, being in nature or even just looking at views of trees or lakes can have a big impact on your mood and can reduce depressive symptoms.9 So try going for a run in a park, or pick a treadmill near a window.

Think about what’s important to you. When you connect your exercise to a long-term goal, it helps your brain overlook momentary discomfort and makes your exercise more satisfying (chapter 6). In my case, I reminded myself that being in better shape made playing sports more fun. Maybe you’ll do it for your kids. Maybe you’ll do it because you value hard work. Only you know what’s most important to you.

The difficulties with concentration and deep thinking that often accompany depression are mainly the fault of a lagging norepinephrine system, which is why, next to serotonin, norepinephrine’s the neurotransmitter most commonly targeted by antidepressant medications. Fortunately, exercise increases norepinephrine as well.15 A study in Germany had subjects either rest, jog slowly, or sprint at high speed. While all exercise increased norepinephrine, intense exercise was particularly helpful. So if you can find the energy to push yourself, your brain will make it worth your while.

Dopamine is your brain’s version of methamphetamines. The dopamine circuit in the brain controls aspects of pleasure, decision making, and focus. It’s the primary neurotransmitter behind addiction. All those addictive drugs called “uppers,” like crystal meth or cocaine, are basically jacking up your dopamine. In fact, any addiction—not just to drugs, but also to risk taking, emotional drama, or whatever turns you on—simply hijacks the brain’s natural capacity to enjoy things. Dysfunctional dopamine explains the lack of enjoyment that often accompanies depression. Fortunately—you guessed it—the dopamine system is also positively affected by exercise.16

Exercise before you reward yourself. Let’s face it: you’re going to watch television. You’re going to eat ice cream. You’re going to waste time on Facebook. No big deal. But the next time you do, make it a reward for something. Exercise beforehand. Walk up and down the stairs twice. Do ten sit-ups. Jog around the block. You were going to have the reward anyway, so just insert a little activity into your inactivity. And when you feel that you earned that television show or that ice cream, it’s even more enjoyable.

Endorphin release is highest during intense exercise.19 So if you can manage to push yourself through a hard workout, you’ll get a bigger endorphin boost. But if you can’t get the runner’s high, it’s fine to settle for the walker’s buzz.