David's Inferno (16 page)

As far as depression goes, the most famous and prolific neurotransmitter is
serotonin. Norepinephrine
and
dopamine
also get a lot of play. A little
GABA
and
glutamate
come in handy. And then there's
acetylcholine
, which, for some reason, you don't hear about as much—probably 'cause it's even harder to pronounce than the others.

Neurons shoot these and other neurotransmitting molecules out of hairs at the end of an umbilical-like cable called an
axon
.

The rest of the neuron is covered with little receptive filaments
called
dendrites
. You'd think dendrites would be the end of the line, size-wise. But each one features even tinier
receptors
. They also come in a variety of sizes and shapes, which bear a suspicious similarity to the different sizes and shapes of the neurotransmitters. This ensures that only certain kinds of neurotransmitters can hook up with certain kinds of receptors to transmit certain kinds of signals.

There are, for example, about 13 or 14 subtypes of receptors for serotonin alone. The scientists can't seem to decide. And each one is part of a specific neural pathway that's responsible for relaying certain types of messages. That's why the activity of a single neurotransmitter or type of receptor can affect so many different aspects of your life. And, in turn, why everyone responds a little differently to meds that increase synaptic levels.

Once a neurotransmitter finds a compatible receptor, it settles in for a quickie, and gives the “target” cell a charge. Some scientists call this neurotransmitter-receptor relationship a lock-and-key kind of thing. Seems more like kamikaze speed-dating to me. Especially since, as soon as an individual neurotransmitting molecule has made its point, it skedaddles. Which it quickly lives to regret because (like drone bees who mate with the queen), once it's done, it gets eaten up by an
enzyme
which breaks it into smaller molecules. They, in turn, become the raw materials for more neurotransmitters. Elegant, huh?

This complex dance doesn't happen one synapse at a time. Every axon of every neuron has ±1000 synaptic endings spewing out neurotransmitters like there's no tomorrow; as well as ±1000 of those dendrites which are receiving those messenger molecules from other neurons. Axons can be up to 12 feet long, so we're not exactly talking a bucket brigade. More like a switching station that would blow even Bill Gates' mind. Fortunately, most of those axons and dendrites know what they're doing. So, with minimal, if any, conscious help from you, they usually do a good job of helping you digest your food, type on your laptop, or try to explain something inexplicable.

Put a few of those puppies together, do a little algebra, and you realize that one little neuron can share synapses with tens of thousands of other neurons. Move on up to Algebra II, add all those billion or so brain cells, and we're talking like a quadrillion synapses in all—give or take a trillion every second (or less). What a racket! Pretty amazing when you think of it. Which, hopefully, you can, even if one of those neural pathways is slow on the uptake.

What's even more amazing is that your brain is able to assemble this unceasing barrage of synapses into experiences and thoughts such as: “I'm happy.” “I'm sad.” “I'm starving.” “I'm full.” “I want a beer.” “I'm freaked out.” “I can't wait to get to work.” “I can't wake up.” “Ouch, that hurts.” “Mmmm, that feels good.” “I need to buy 1,000 copies of this book and give it to all my friends.”

When you feel “off” in any which way, one or more of the following things is probably happening:

You might be wondering why, instead of taking little pills, we don't just flash flood our brains with neurotransmitting molecules
and hope for the best—i.e., take a pill filled with a balanced combination of neurotransmitters themselves instead of something that inhibits their reuptake or their ultimate demise. Unfortunately, in the “How-to-Make-a-Human” manual, they put in something called the “blood-brain” barrier. Only neurons have the right stuff to make neurotransmitters. We can eat or drink more of the ingredients they need to make them. But
they
have to do the work.

Dealing with the blood-brain barrier is the
raison d'être
for a lot of natural/dietary treatments for depression. Supplements like tryptophan, SAM-e, and 5-HTP
can
get through the blood-brain barrier. And they're just what a productive neuron needs to make more neurotransmitters. Although even supplements with the best of intentions might get detoured into some other job on their way to your brain, or throw something else out of balance.

Things like alcohol, nicotine, and heroin are
really
good at messing around with receptors and encouraging your neurons to release more neurotransmitters. This can make neurons kind of lazy, because they figure it's only a matter of time before you give them another hit. That's one reason withdrawal can really suck.

One of the latest theories for why it can take a while for meds to work is that they're actually not directly affecting the synaptic success rate of neurotransmitters, they're actually cajoling your brain into making more neurons. Either theory implies a third: that antidepressants cause significant changes in your brain's electro-vibrational frequency. I never had electro-shock treatment, but that clearly affects the connections between neurons, and definitely helps some people. Ditto for, say, acupuncture. And, perhaps, even homeopathy.

All these theories don't matter a whole lot as far as we head-cases are concerned, except as a reminder that most know-it-alls don't.

Let's not forget about hormones. In the midst of my
extremis
, a friend who was in the process of setting the world record for
hot flashes, wrote: “Have you thought about how your mental state might have a relationship to your hormones?” This was and is a really good question. Particularly when discussing a 53-year-old guy having a nervous breakdown … not to mention a mother dealing with postpartum depression, an anorexic teenager, or hyperactive child.

I wasn't exactly thrilled with the idea that my fragile mental states were being exacerbated by a virulent case of rapidly vanishing testosterone, but I figured I might as well man up and do more research.

Both hormonal and neurotransmitting molecules pass messages between cells. The difference is that, instead of being created in neurons and leaping across a synaptic divide like neurotransmitters, hormones are created in glands and
travel through your bloodstream
in search of receptive cells.

Norepinephrine, for example, tends to be attracted to cells that deal with stress. So, if your neurons do a better job of making norepinephrines, and give them a good swift kick across the synapse, they might help you get out of that catatonic funk. However, norepinephrine is also synthesized in the adrenals and travels through your bloodstream, in which case it's considered a hormone.
Those
norepinephrine molecules know how to spread the word that you need to increase your heart rate and blood flow. This helps you leap into action whenever you feel threatened: like when a car is heading right at you or—if you're in the state I was in—you can't find the top to the yogurt container.

This hormonal/neurotransmitter connection explains why adolescence and menopause in particular can trigger big-time mood changes in both men and women. It also makes you wonder how people could question the diagnosis of “postpartum depression.” Telling a new mother—whose hormonal system is thinking, “What the heck just happened?”—that she'll get over it seems remarkably insensitive considering that “it” can last months or years. Just as with any depression, there are numerous options for treating it—although paying attention to the warnings and caveats
would seem particularly important in that case, especially if you're nursing.

Bottom line: It's a real good idea to tell your psychiatrist if you just had your first period, are starting to grow your first beard, are pregnant, nursing, showing signs of male or female menopause, or are in the middle of a sex change procedure.

Y
OU
'
VE DECIDED
to take the plunge. Actually, you've already taken the plunge and you're in way over your head.

So you've finally gone to see someone with an M.D. or N.P. tacked on their name who, thankfully, appears to have heard most of it before. And, more important, appears to have a reasonable idea how to deal with it. They've taken their notes. They've handed you Kleenex. They've looked in their big books to check on potential interactions. And then … then … they get out the pad and start scribbling. Yes!

They hand you the piece of paper with an expression that combines concern and optimism: “This should work. Remember, you
might
feel something right away, but it could take a couple of weeks. Don't worry. We'll figure this out. Make an appointment for next Wednesday. Try to get some rest.”

“Rest?” You say with a pitiful choking sigh.

And then … then … they get out the pad and start scribbling again! Yes!

You walk out and go back to the receptionist's window. He or she sees folks like you all day, and struggles between sympathy and
professionalism, with a hint of job fatigue. You make the appointment. A reminder card? Well, sure. But there ain't no way you're going to forget
this
appointment. For the next week, it's going to be a faint lighthouse of hope. On the way from the doctor's office to downtown, you clutch those two pieces of paper like lottery tickets with a winning number.

You take the first pill as soon as you leave the drugstore—unless you are dissuaded by those warnings that say not to drive until you see if you have side effects. In that case, you rush home. Or to the office if you
have
to go back there. Get some water. And swallow. Full stomach. Empty stomach. Whatever.

And then, in spite of all the warnings that it could take weeks for the drug to be effective, you sit down and wait to “get off.” The same way you'd wait, and expect, an ibuprofen to take away pain.

After a while, you accept that it's really not going to work right away, and reluctantly go about doing whatever it is you do. Later that evening, you tell your spouse, partner, or friends what happened at your appointment and what drug(s) you're taking. There's a good chance you go online and read everything you possibly can about those drugs.

At the end of the day, you get into bed and reach for the other bottle (remember that second slip of paper?) and take one. With any luck, you get some sleep.