What follows is a piece I started during BreakFast over at CCC. It’s my attempt to reconcile what I know about neurobiology, neurochemistry, and depression with some ideas on how to treat what is an incredibly complex and devious disease. Being a person who every so often gets trapped in a downward spiral, and having experienced so many brilliant, capable, utterly valuable people go hurtling down into a deep dark hole I want to share my thoughts and see if I can shed any light on the situation.

I’m an active reader of neurobiology. I’ve had an intense interest in it for nearly ten years, now, but am in no way a neurobiologist or practicing scientist. I’m an armchair reader trying to piece this together, share what I know, and spread my love of science. If you’re an expert in the field and find fault in my logic or terminology, please let me know. I’m always eager to hone my understanding of the meat that makes us think.

You can find part 2 of this article here.

So, here are two entirely unfortunate facts. Depression, serious clinical depression, is the most common disability in the United States [1, 2] and stress related disease (heart attack, chronic high blood pressure, hypertension, anxiety disorder) accounts for much of the remainder.

Stress, depression, and disease have a pervasive and infuriatingly close relationship. They are horsemen of the apocalypse, if the apocalypse included spending several weeks in your bathrobe, sitting on top of a pile of unfolded laundry, watching the Princess Bride for the twelfth time.

What isn’t commonly understood, and is perhaps most cruel to depression’s sufferers, is that it is not a disease of mindset. If a traumatic event happens, say your cat goes missing, you will feel depressed. You will likely be sad, remember all the good times you had, perseverate on all the ways you could have kept your sweet Mr. Muffins from escaping, and generally be a drag on all of your friends for a while. However, the mourning process will eventually lose its grip on you and you’ll return to normal, healthy life.

When one suffers from chronic, clinical depression, the story takes on a more sinister shape. Depression is a stressful affair. One measures stress commonly as the expression of Glucocorticoids in the spinal fluid. Essentially, the brain doses itself with this particular neurotransmitter in times of stress. In the short term this is a huge advantage: it improves memory, reflex time, mental acuity, endurance, and a host of other factors that would have been vital in, say, running from a lion. However, its effect is not linear with time. As it is continually pumped out, i.e. the stress continues, it has an incredibly negative effect on all of these same factors. Initially dendridic spines, chemical receptors used for picking up certain neurotransmitters, are grown between the neurons in response to an influx of Glucocorticoids, but this effect eventually reverses. These spines will retract, taking other spines with them. In the long term the effect is neurotoxic, killing whole neurons beneath a wave of stress.

Another amazing property of the human brain is that calling to mind a traumatic event, or a former love, or the feel of skydiving, replicates with startling precision the chemical interaction of the actual event. Thus, reliving trauma, recalling depressing memories, feeling generally crap, has the tendency to dose the brain in wave after wave of these deleterious neurotransmitters.

What’s striking about the method in which we learn, lay down new memories, and adjust to changes in the state of our bodies (e.g. losing a limb), is that it’s tied to the frequency and intensity by which we travel the connections between neurons. Neurons have remarkably accurate mechanisms for filtering out junk signals. Every neuron in the brain has a baseline level of random signaling. If they weren’t able to distinguish between each of their neighbors winking randomly on and off and genuinely passing along data, we’d have a cascade of strange contradictory signalling running the brain at all times.

Neurons use a few methods for distinguishing meaningful signals from noise. They need to take a summation of the signals hitting them from all sides and produce a meaningful response. One is to pass on identical signals coming in from multiple neurons simultaneously, or spatial summation. Another is passing along signals that a single neuron repeats rapidly over a short span of time, or temporal summation.

Once a neuron has passed on a certain flavor of signal from a certain source, it will take much less energy to get that same signal passed along. Essentially once a neuron trusts the data that it’s getting, it’s eager to move that data along. This is called long term potentiation or LTP. It’s significant that, over time, the pathways between neurons become not only strengthened, but refined. As you may have experienced learning to decipher a gestalt illusion, once something has been learned each subsequent foray into that pathway becomes easier and more fluid. Once you’ve learned to see both the old lady and the young lady, flipping back and forth between them becomes trivial. In some ways it also becomes impossible to return to the state you occupied before you learned this trick.

The point I’m driving at in describing these mechanisms is what it implies for how your brain alters in reaction to a long term depression. It seems very possible that returning to depressing memories, poor moods, and morbid fantasies sets up a vicious cycle, repeatedly reinforcing the pathways to those experiences, and continuously dosing out those stress hormones.

Your response might well be “Lighten up, Buttercup. It’s only depression. Surely you’re indulging yourself. Surely you can let it go.” This sentiment belies the true meathook nature of depression. As the disease rips through the brain, it eventually shapes its host into a perfect vessel. Depression literally reshapes your brain to suit a continual, long, depressive slide.

Wow. Writing this has left me a bit depressed. Tune next week for the conclusion. I’m going to pick up on this thread to talk about the Nash Equilibrium, why Viking adoptions produce fantastic data, and the cure for anhedonia.