Plumbing the Depths Of Depression

"I applied my heart to know wisdom, and to know madness and folly. I perceived that this also was a chasing after wind. For in much wisdom is much grief; and he who increases knowledge increases sorrow."

Playwright Eugene Ionesco:

"No society has been able to abolish human sadness, no political system can deliver us from the pain of living, from our fear of death, our thirst for the absolute. It is the human condition that directs the social condition, not vice versa."

The true genius of the disease, of course, is that it is a cognitive disorder that makes clear thinking impossible -- and yet requires insightful self-analysis in order to report the problem to a physician. You have to admit that is pretty ingenious.

Freud revolutionized the psychiatric field and the study of depression with his study of dreams, the taxonomy of id, ego, superego and the unresolved formulations of childhood trauma. Also, sex. You've got Jung, of course, and later the persuasive theory of Aaron T. Beck, the father of cognitive psychotherapy, who argues that depression twists the thinking process into increasingly negative avenues that repeat, over and over again.

And, about the same time as the Beatles, you had scientists voicing the theory that little chemicals ran around in our brains and made us do things that we'd rather not, Freud be damned. This was of great help to the novels of Kurt Vonnegut if nothing else. Brain biology: being utterly unable to get out of bed, running into the yard pronouncing yourself to be the risen Christ or pulling a shotgun out of the hall closet and looking down the barrel. You could take a pill, man. You could still be just as repressed as you ever were, with your mother who had beaten you with a curtain rod, but you just didn't care so much.

Wasn't that great?

It was like pulling a centuries-old dragon into daylight, where you found out it liked fresh hay and a nice barn. The beast could be tamed.

It happened like this: Doctors studying high blood pressure, or tuberculosis, discovered the medications they were using alleviated (or caused) great changes in their patient's moods. One of the main researchers was Rockville's own Julius Axelrod, who spent most of the 1960s learning how a neurotransmitter named noradrenaline works in the brain. (A scientist at the NIH, he won the Nobel Prize in 1970.)

His big idea was something called the catecholamine hypothesis, and it continues to the granddaddy of all psycho-pharmacology.

The thrust of his studies was the role of norepinephrine, a tiny messenger that goes between one neuron in the brain and the next, in depression. It turns out that a lack of that little messenger in the synapses, the spaces between neurons, tends to result in depression, because it can't tell the next neuron to slow down in whatever it is doing. So that neuron has a tiny crash, a little molecular runaway train, and that results in depression.

The first round of medications focused on norepinephrine, and the next generation focused on another messenger called serotonin. That's what Prozac and friends target -- they're called selective serotonin reuptake inhibitors, because they prevent the serotonin from being sucked back ("reuptaking") into the first neuron, and thus keeps them out there in the happy synapses, which results in a sort of mental sunshine.