Alex Korb Ph.D.

PreFrontal Nudity

The Mysterious Fog

Observations on the depressed brain

Posted Jun 26, 2012

Just as a warning, this post has a more somber tone than my previous posts. Perhaps a better writer would convey that more subtly through diction or sentence structure, but you get what you get. 

The ultimate team stretching in the fog.

I met Chip in 2003 when I began coaching the UCLA women’s Ultimate Frisbee team. Her name was Mandy then, but everyone on the team soon got a nickname. She was a freshman with short blonde hair, and cheeks that turned red after a hard run. She had a great sense of humor, but maybe I’m just saying that because she laughed at all the terribly lame jokes I made. Although, she did laugh a lot in general, and made others laugh, often through animal noises.

She had never played Ultimate before, but she picked it up pretty quick. She was a great athlete – fast, strong and aggressive – but she got sick a lot. At practice she ran hard through the drills, and then after an hour would often amble over to me and say she was feeling sick and needed to stop practicing. Or sometimes during the scrimmage at the end of practice she just sat by herself on the sideline. I would ask if she was ok. She would smile and take a deep breath, and say she was fine, just a little sick.

Some days she skipped practice entirely. I got little annoyed because I had egocentric visions of winning a college Ultimate Frisbee national championship, and I felt she should be able to play through her frequent colds, or whatever was making her sick. It was confusing to me because she never seemed hampered by anything on the field, but I figured that was just a testament to her athleticism. It turned out that she had a deeper illness that she carried around, and ultimately it took her life.

One night at a tournament about halfway through the season she finally revealed her secret. She had depression. She’d been depressed ever since middle school. There was no precipitating cause. There was no “reason” for it. She’d never been abused, or gone through traumatic events. She had loving parents. Her life was pretty good. She just felt terrible almost all the time.

I didn’t really understand depression then. In fact though, most people don’t have a good understanding, even though it is the most common mental illness, and as many as 1 in 6 people will get depressed in their lifetime. But at least after studying it in grad school for five years, I have a better idea.

In standard usage the words “depression” and “sadness” are mostly synonymous, but medically there is something fundamentally different about the two. Depression is not just being sad, or even really sad. In fact people with depression do not necessarily feel sad all the time. When you’re depressed you often feel numb, like an emptiness where emotion should be. You feel hopeless. You feel helpless. Things that you used to enjoy aren’t fun anymore: food, people, sports. Even if things were enjoyable, you don’t have the energy to do them. Everything feels really difficult, and you can’t explain to people why it feels difficult, because it shouldn’t be. Nothing seems worth the effort it requires.You can even have problems falling asleep, or staying asleep. It’s hard to concentrate. You worry a lot.

Depending on the severity of the depression, it might not be like that all the time, but that doesn’t make it much better. Moods are like fog. They can roll in unexpectedly and obscure the brightness of life, making everything gray and dark and difficult. And you might stumble through it for hours, or days, or months. And then all of a sudden with a gust of wind, or beam of light it dissipates, and the world brightens, and you don’t understand why it didn’t look that way the whole time. But the times you feel good can be somewhat random and short-lived, and that can make the heaviness all the more unbearable when it returns.

Chip couldn’t finish all the drills because she just didn’t have enough energy. And she couldn’t come to tournaments sometimes because everyone would be having so much fun, and she couldn’t bear the thought that she might ruin it. And she couldn’t make it out to practice sometimes because … she just couldn’t.

This may surprise you, as it did me, but no one really knows exactly what’s going wrong with the brain in depression. For Parkinson’s we can point to the death of dopaminergic cells in the substania nigra. For Alzheimer’s we understand it is caused by the growth of amyloid plaques and neurofibrillary tangles. But we don’t understand depression in the same way. I summed it up nicely in my dissertation (if I do say so myself): “While no specific neurobiological cause has been identified, [depression] is generally believed to involve dysfunction in frontal-limbic circuitry.” So we kind of know the brain regions involved, but we don’t understand what causes it, or how to fix it.

In the above description, “frontal” is easy to understand. It just means the front part of your brain (N.B. “pre-frontal” is part of “frontal”, just even more to the front). The limbic regions of the brain are the parts that deal with emotion. Technically the limbic regions are all closely tied with the hypothalamus, which controls the fight-or-flight response, hunger, thirst, and various hormonal changes. In depression something seems to be messed up with the way these regions operate and interact with each other.

The prefrontal cortex and limbic regions communicate with each other, and other brain regions, through various neurotransmitters. Doctors and scientists used to think depression was simply a matter of having too little of the neurotransmitter norepinephrine. Then the theory changed to too little serotonin. Now we know it’s much more complicated.

This is a huge oversimplification, but in general the various neurotransmitters contribute to different depressive symptoms. A dysfunctional serotonin system is responsible for the lack of willpower and motivation in depression. The difficulty in concentration and thinking in depression is probably due to problems with norepinephrine. Dopamine is also involved. In a healthy brain dopamine is responsible for the enjoyable aspects of behaviors, including eating, sex, earning money, or even checking an item off your to-do list (e.g. cleaning the kitchen, buying milk). Dysfunction in the dopamine system leads to lack of enjoyment. All of these neurotransmitters are necessary for proper functioning of both limbic and frontal regions, 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 available levels of these neurotransmitters.

In addition to not knowing exactly what depression is in a neurobiological sense, we also don’t know why it happens to some people and not others. Fortunately, we do at least know many of the factors that increase the likelihood of developing it. Genetics and early childhood experiences shape the development of the brain and affect how it gets wired and how sensitive it is to various neurotransmitters, like dopamine and serotonin (see my posts here and here).  Thus your genes and your early experiences in life can place you at higher risk for developing depression. Then in your current life, stressful events (like losing your job or a loved one), or even just general life stress, can further increase your risk. It is important to note here that two people can experience the same event, like getting in a car accident, and experience vastly different levels of stress. Lastly, close friends and family are protective against depression, so if they’re absent your risk increases.

Even knowing the risk factors it’s not clear why Chip was depressed. She was gay, so that was likely a large life stressor, even though her friends and family were very supportive. It didn’t seem to cause her that much stress though. But my lack of clarity just illustrates a key point about clinical depression: people with major depression are not usually depressed about something specific, or because of something specific. It might start out that way, or be triggered by an event, but it evolves into a general depressed state. In fact it doesn’t need a trigger. Sometimes it just happens.

While Chip was deeply depressed, she did a great job of putting on a happy face. She did it because she cared so much about the people around her. She didn’t want to infect them with her mood. She told me once, “Just because I felt shitty, doesn’t mean everyone else has to.”

Her sophomore year I saw less of her, though she would still come out to practice from time to time. I encouraged her to come to practice more often, because exercise is helpful for depression, so is having friends. She agreed, but it didn’t really get her out to practice more. At least she was seeing a psychiatrist, and living with her best friend, and a school psychologist lived just down the hall. She was also on lithium, which is sometimes regarded as the most potent preventer of suicide. She seemed to be doing so much better. But, just as I couldn’t see the depression in the first place, perhaps there were more signs I missed.  It is hard to know the depths of someone’s secret despair.

A few months into her sophomore year I got a late night call from one of the team captains. Her roommate had found her in her dorm room…

No event in my life has shattered me more. I cried a lot. Then for a brief period I was incredibly angry. Not at her per se, just in general. Then I went back to crying a lot. That lasted for a few weeks, and slowly diminished over months. But if I played certain songs on the guitar I would cry, or just some nights falling asleep thinking about life, or even in the shower where it felt safe that no one could hear me.

Fortunately mourning is not depression. But as I struggled to understand how Chip had felt I began to realize that I had sometimes felt hints of it myself creeping into my life – brief periods where nothing seemed to matter. For example, my senior year of college I had a crisis of not knowing what I was going to do with my life. That uncertainty and anxiety soon seeped into all parts of my life. I just felt a heaviness around everything I tried to do, like the air was too viscous, or like I was wearing that thick pad the x-ray technician puts over you at the dentist’s office. I tended to overthink everything and worry that my best wouldn’t be good enough. Nothing seemed worth doing because it wouldn’t turn out the right way. I felt paralyzed. I remember trying to explain it to my girlfriend at the time, but lacking the ability to put it into words. Talking about it was too difficult. I just wanted to ignore it. She didn’t understand why I couldn’t snap out of it.

I don’t pretend that it was anywhere near as bad as what Chip had, but it gave me a glimpse of what she carried around for years and years. The struggle Chip went through was expressed well by one of her friend’s at her memorial service: “She fought a battle everyday, and she lost that battle once.” Even though it was terrible, it was comforting to begin to understand what she was feeling. It was somehow better to know that in the depths of her suffering it at least had made sense to her, even though to everyone else it was senseless. I still felt helpless though, and to combat that feeling I ended up in a PhD program in neuroscience doing research on depression.

When people find out I study depression they often ask me, “why can’t depressed people just snap out of it?” Well, if they could do something about it they would. Depression takes away your hope, your confidence, your energy. It can even take away your ability to feel close to other people. It basically takes away the ability to do anything that would help you feel better. It is a very self-stabilizing state.

Just as when you are not depressed it is difficult to understand depression, when you are depressed it is difficult to remember what it’s like to not be depressed. This phenomenon is known as state-dependent recall, and is quite insidious. Often when people are feeling really depressed they say that they can’t remember ever feeling truly happy. In Chip’s dark loneliness in her dorm room she could maybe remember flashes of joy, but she thought she could see the thin line of depression drawn through them. And it was always tugging at her, and the future just held more of the same.

Your mood actually changes what details your brain perceives about the world. Interestingly, there is even evidence that depressed people perceive the world more accurately than the rest of us, and everyone else just floats on a cloud of self-delusional optimism. When you’re depressed you cannot see the bright side of things. Maybe you can understand “the bright side” abstractly, but it doesn’t feel like anything. That’s part of the dysfunction in frontal-limbic circuitry. The thinking frontal lobe can conceptualize positive ideas, but there’s no resulting positive emotion in the limbic system. The circuit is disconnected.

Asking why depressed people don’t just snap out of it is a bit like asking, “Why don’t poor people just make more money?” Depressive symptoms are sort of like income. They are something that can be influenced by the choices you make in life, and how hard you work at it, but they are not completely determined by it. With income, sure the choices you make and how hard you work can have a large effect. But, where you were born, the type of upbringing you had, the resources available to you, your innate abilities, and random luck, all have a strong impact (probably stronger than your personal choices) on how much money you make.  So too with depression. The choices you make can help you feel better, but ultimately they may not be enough to overcome to impact of genetics, early childhood experiences, current life circumstances, and random luck.

Although that analogy can fall short, perhaps, if you think that poor people are just lazy. So another way to look at it is to compare the depressed brain to a traffic jam (yes, I live in Los Angeles). Thus, asking why depressed people don’t just “snap out of it” is like asking, “why can’t we solve traffic jams by telling everyone to just drive faster?” In a traffic jam it’s not just that this Camry needs to drive faster, and that Explorer, and that Prius. It’s not any individual car. It has to do with the system. The cars all influence each other. The whole system is dysfunctional, so just changing one piece wouldn’t help. And similarly with depression, it is not just this piece of prefrontal cortex that needs to be fixed, or that bit of the limbic system, or even this squirt of serotonin or that dab of dopamine; it is in the dynamic interaction of numerous brain regions and neurotransmitters. It is a “dysfunction in frontal-limbic circuitry”.

To understand how fortunate you are not to have depression, you have to understand that depression is just an alternate functioning of a brain network that is in all of us. Perhaps you get a flitting feeling from time to time that your life is pointless, and you don’t have any real friends. But your brain allows you to escape that feeling after a while. Your neural roads are quicker at dissipating traffic.You may be fortunate to have a brain that is wired to make happiness more accessible, but if you don’t recognize yourself as fortunate, then you run the risk of being judgmental of people who don’t have the same advantages.  

A few months after Chip’s death I came across a poem written by the poet Sergei Esenin, who wrote it in his own blood before his suicide. Despite the gruesome context, I felt better when I read it. I suppose it was comforting because it offered more insight into how she was feeling. The poem is sweet and thoughtful, though you can feel the heaviness of the words being written.

Good-bye my friend without handshake and words,

Do not grieve and sadden your brow,

For in this life there’s nothing new in dying,

But nor, of course, is living any newer.

To a normally functioning brain there’s something exciting to be alive, even if there’s heartache, even if there’s mourning. Imagine what it would be like if the spark were gone from everything, if you were just trapped in the static traffic of your mind.

I got stuck for a bit while writing this post, and I almost didn’t write it. I wanted it to be beautiful and meaningful and insightful. It started out ok, but things got difficult along the way. I felt a sense of dread seeping in. I thought, “If it’s not good, then what’s the point?” I tried to tell myself, “just do your best”. But what if my best isn’t good enough?

Eight years after her death I feel like I should have done something amazing to honor her memory. I thought in grad school I might discover some miracle breakthrough in the treatment of depression. I didn’t. I thought I would coach the UCLA ultimate team to a national championship. I didn’t. And I wanted this post to be moving, and really say something unique about depression. I’m not sure I did that either.

I realized the difficulty I had in writing this post was because I wanted it to reflect well on me. I wanted to say that there was this girl nicknamed Chip, and she was killed by the weight of the world, and that tragedy inspired me to do great things. But I think that is what has kept me stuck; worrying about whether the things I do are great enough, worrying about whether my best is good enough, worrying about how it will look.

There’s a bit of darkness tugging at me, and I think it’s there in all of us. Even though part of me wants to dwell on what I didn’t do, I can escape it. I can feel the bright side.

I earned a PhD in neuroscience. I shed some light on a small corner of our understanding of depression. I coached a team of girls to believe they could do anything, and hopefully that extends into the rest of their lives. Chip’s memory still moves me, and I try to honor it. I did my best I think, in research, in coaching, in writing. I didn’t get what I was after per se, but I can see I’m fortunate to get what I got. It might sound like a cop out, but I suppose your best is all you can do. No use worrying about it though. It’s either enough, or it’s not enough; it’s just what it is.

If you want to learn more about the brain in depression then check out my book The Upward Spiral: Using Neuroscience to Reverse the Course of Depression, One Small Change at a Time (Now available on kindle, audiobook and in bookstores everywhere).

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