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

by Alex Korb

The disease of depression is a pattern of activity that arises from the interactions of all these circuits.

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.

What it's like to be depressed.

depression generally involves a problem with how the thinking and feeling circuits in the brain get out of whack. While your brain can be divided into dozens of regions, the circuits that cause depression rely on relatively few. Two parts of the brain in particular are to blame: the prefrontal cortex and the limbic system. To simplify, the prefrontal cortex is basically the thinking part of the brain, and the limbic system is the feeling part. In depression, something is off with the way these regions act and communicate with each other. The thinking prefrontal cortex is supposed to help regulate the feeling limbic system, but it’s not doing a good job.

Depressed mood, such as feeling sad or empty or even constantly irritable Decreased interest or pleasure in all—or almost all—activities

Do you have depression? If you have five or more of the following symptoms nearly every day for two weeks, then you may have Major Depressive Disorder (but only a mental health professional can make an accurate diagnosis). If you have fewer symptoms, you may have low-level depression. Either way, you can still benefit from the upward spiral.

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

Do you have depression? If you have five or more of the following symptoms nearly every day for two weeks, then you may have Major Depressive Disorder (but only a mental health professional can make an accurate diagnosis). If you have fewer symptoms, you may have low-level depression. Either way, you can still benefit from the upward spiral.

Serotonin—improves willpower, motivation, and mood

Norepinephrine—enhances thinking, focus, and dealing with stress

Dopamine—increases enjoyment and is necessary for ch...

Oxytocin—promotes feelings of trust, love, and connection, ...

GABA—increases feelings of relaxation and ...

Melatonin—enhances the quali...

Endorphins—provide pain relief and feeli...

Endocannabinoids—improve your appetite and incr...

...peacefulness and well-being.

Bright sunlight helps boost the production of serotonin. It also improves the release of melatonin, which helps you get a better night’s sleep (chapter 7). So if you’re stuck inside, make an effort to go outside for at least a few minutes in the middle of the day. Go for a walk, listen to some music, or just soak in the sun.

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.

brain-derived neurotrophic factor (BDNF) aids in the growth of new neurons and overall brain health.

depression is primarily a result of poor communication between the thinking prefrontal cortex and the emotional limbic system.

The prefrontal cortex gets its name from the fact that it is the front-most part of your brain. Basically, it is the whole surface of the front third of your brain, sitting just behind your forehead. It is the CEO of the brain—the center of your planning and decision-making circuits. It is also responsible for controlling impulses and motivation.

In depression, it is responsible for worrying, guilt, shame, problems with thinking clearly, and indecisiveness.

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.

The hypothalamus controls stress. The amygdala is the key to reducing anxiety, fear, and other negative emotions. The hippocampus is responsible for creating long-term memories, and because its neurons are very sensitive to stress, it often acts as the canary in the coal mine of depression. 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.

Finding ways to calm the hypothalamus is therefore one of the best ways to reduce stress.

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

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.

The dorsal striatum is the brain’s habit circuit;

Because your habits are behaviors you do automatically, without thinking, once you create a good habit it has the power to change your life without conscious thought.

depression, reduced dopamine activity in the nucleus accumbens explains why nothing seems enjoyable.

The insula is part of the cortex that folds inward a couple inches from your ears, sitting close to the amygdala and hippocampus. It’s one of the main regions in the pain circuit and contributes more generally to bodily awareness. In people with depression, the insula shows elevated activity,10 because it is more highly tuned to notice pain, elevated heart rate, breathing troubles, and other bodily problems.

“My life has been full of terrible misfortunes, most of which never happened.”

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.

Take a deep breath. Taking a slow, deep breath—inhaling and then exhaling slowly—actually calms down the sympathetic nervous system and reduces stress (as discussed in more depth in chapter 9).

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.