Mascot 5HTT KO;
also introducing Mitzi and Maxi
Brain Regions Amygdala, Prefrontal Cortex
ANXIETY indicators Rarely Sometimes Often
I'm easily startled o o o
I'm a worrier o o o
I keep my opinions to myself o o o
Are you that partygoer who neglects the stuffed mushrooms because you're a little freaked out by that guy scowling alone on the sofa? Or perhaps you avoid the mushrooms because you're worried that other people will see you pigging out. Perhaps you just aren't hungry, the party is a disappointment, and you wish you were at home in bed. Maybe you're the partygoer who does eat the stuffed mushrooms, about half of them, because once you start you just can't stop. If any of these sound like you, congratulations! You could have a Neurotic personality!
Neuroticism is about avoidance. Neuroticism is about anticipating the worst and retreating. It's about being the first person to come in out of the rain, and the last to believe the storm has passed. A Neurotic brain is attracted to angry faces, to shouts of alarm, to catastrophic headlines. It commits life's harshest lessons to memory and does not forget them.
For a strongly Neurotic person life is not a bowl of cherries. A Neurotic brain is more upset by stressful events than a less Neurotic brain would be. A person with a Neurotic personality is inclined to be moody and emotional, at best. At worst Neurotic people have a higher chance of sliding into a full-blown anxiety disorder or depression. Neuroticism is a bit of a burden.
But somebody has to be the doubter. We can't all just laugh and play the days away. Someone has to look gift horses in the mouth. Someone has to interrogate the charming stranger before we throw open the gates. Someone has to look past the sunbeams and notice the gathering thunderheads. People with Neurotic brains are our watchdogs. They notice signs of trouble first, they remember every disaster that ever happened, and they're always on guard against new ones.
Serotonin is the signature brain chemical of Neuroticism. This chemical helps information move through our (and every animal's) nervous system. If you have the normal amount of serotonin lubricating your brain, you've got a shot at serenity. But if your serotonin is either too low or too high, Neuroticism may cast its shadow over your picnic.
The amygdala is the mascot brain region of the Neurotic personality. Named after an almond, and tucked deep between your ears, it's an ancient emergency control center. This little nut has the power to dismiss your fancy intellect when circumstances call for action instead of analysis. When the amygdala detects an emergency it prepares you to run, fight, scream, or overturn a vehicle in order to protect life and limb. In a person with a Neurotic personality the amygdala is set on "supersensitive." It's jumpy. It's trigger-happy. It's an emergency center that would rather issue a false alarm than be caught off guard. In fact, the more stress you throw at a Neurotic amygdala, the more watchful it becomes.
But Neuroticism does more than keep us all safe from lightning and spiders and mayonnaise left out overnight. A recent study found that anxious children are less likely to die in stupid accidents-the "Hey, watch this" accidents that claim carefree kids who ride skateboards down stairs or play with loaded guns. The Neurotic personality also appears to convey a certain blessing of intelligence, particularly the planning variety that helps a person to avoid surprises.
The anxiety and depression facets of Neuroticism are heavyweights in human happiness. If you score relatively high for those, that doesn't mean you're destined for the psychiatric ward. But a personality that's high in anxiety or depression does have an elevated risk of developing mental illness. These personalities are poised to skid right off the Neuroticism personality scale and plunge into the pit of psychiatric disorders. Anxiety disorders and serious depression are painful conditions. So science hunts for a cure. And in the process, science reveals a lot about personality, both disordered and normal.
This gives you a quick look at where you land on this facet. If your answers tend toward the "often" side, you're higher in that facet.
Anxiety is the quintessential "avoid" emotion. When it rises up, it's instructing you to step away from the edge of the cliff, back away from the spider, run away from the man with the axe. Everyone's brain monitors her environment for danger. Some brains shrug off most of the omens and portents as meaningless, and others duck and cover for every passing sparrow.
The father of serotonin, Klaus-Peter Lesch, resides in Germany. On a bleak November day I travel to Bavaria to make his acquaintance. And to meet the mouse version of myself that he has created. My train rushes into a hilly eastern quadrant of Germany I've never seen before. The leaves have fallen, but ivy and other creeping things keep the woods green, and under spitting clouds the farmland looks mossy. Then we wend into a river valley with steep golden hills on either side, and I've arrived in Würzburg, home to the anxious mouse.
Wait, steep golden hills? What is that gold stuff? Grapevines? Seriously? Just my luck! Normally I am a traveler whose road stories detour into descriptions of the ceviche, or the curry, or the smoldering chestnut liqueur. Approaching Germany I steeled myself for the würsts of many colors, but I neglected to review the beverage category beyond a quick nose-wrinkle regarding beer. Now here I stood in the cloying, the unbearably sweet, heart of Riesling country. Riesling is the wine I love to hate. This far north, a grape's growth is retarded by the low temperature, allowing sugar and acid to accumulate under its skin. If the wine's fermentation ceases before that sugar is converted to booze, then achtung, baby! Sticky wine warning! Oh, well. This is work, not play.
In the morning I walk across town to find Lesch, who works in a building complex among the vineyards. "Nervenkliniken," the sign on the guardhouse reads. This I find charming. Technically, it means "neural clinics." But it reminds me of the olden-days term for people like me: I'm "nervous." I've got "weak nerves." I must "take the cure at a Nervenklinik." It occurs to me that the standard olden-days medicine for a case of nerves-alcohol-was squeezed from the grapes now being displaced by the Nervenkliniken. Times change, cures change.
My goodness, it is a nice Nervenklinik. It's airy, and tropical plants crowd every window. And let me just say two things for the record, two things that may be applied to every German academic office I enter in the course of this book. First, they're so nice. The paint is fresh, the carpeting-carpeting!-stands proud, the furniture is neither rusty nor peeling. Second, they're tidy. I've been studying scientists for twenty years, and I've never seen so many bare desks! A more typical academic habitat contains so many research papers and journals and books that the floor (scuffed linoleum, usually) is visible only in little trails the resident treads between the piles. Here in Germany an office will have a wall of closed bookcases and file drawers, leaving the entire floor and desk surfaces exposed! I swear I'm not falling for the cliché regarding German orderliness. It is a truly striking difference in the culture of academic shelter.
The tenant of the proverbial corner office is a towering specimen with graying hair a few millimeters longer than a crew cut, and a wide, tight smile. Among the requisite plants on the windowsill are photographs of his blond family. Lesch is a psychiatrist with one hiking boot in the human world and the other in mousedom. He ministers to human patients who battle their depression in an adjoining hospital. And in a nearby laboratory, he alters the genes of mice to create animals prone to depression. By studying the mice, he hopes to find a cure he can transfer to those humans in the hospital.
"Coffee?" he asks, hoisting his long frame away from the computer and toward the coffee table. "No? No coffee? We drink a lot of coffee around here!"
With my first question, he lurches back to the computer to print off a research paper. Then returns. On the occasion of my third question he retrieves a laptop and starts flipping through PowerPoint presentations. "It's easier to describe if I have a few slides [tap tap]?.?.?.?a talk I just gave in London . . ."
But here's the short story: Back in 1996 Lesch discovered what one colleague has described as a needle in a haystack-he found a serotonin gene that caused measurable differences in personality.
He wasn't searching randomly. Scientists already knew serotonin probably had a role in anxiety and depression. And they knew where to find some of the genes that operate the serotonin system.
Serotonin is an ancient chemical, found in every living thing endowed with a nervous system. (It shows up in plants, too, but as far as we know does not make them moody when it malfunctions.) The stuff is made in special cells originating in that gnarled old tree trunk of the brain, the brain stem. Most serotonin neurons stretch their axon arms down the spinal cord, to service the gut and other humble functions. But a few meander up into the brain, twisting and branching like morning glory vines. And like a morning glory vine, each axon is studded all over with buds, called spines, from which serotonin ultimately flows to work its magic.
Most simply, a serotonin molecule is a key. Its job is to linger in the intersection between two nerve cells, ready to help messages cross. When a message arrives, serotonin opens a locked gate on the next nerve cell so that messages can travel smoothly through the brain. Imagine the synapse as an intersection where three streets meet, each blocked by a gate. Two of the streets are axons that help move your arms. The third street is the spine of a serotonin cell. Way out on the front of your head, your nose itches. The neurons of your brain start to pass a message, fire-brigade style, with the goal of raising your hand to your nose. When the message reaches our three- way intersection, it pauses for a split second. It can jump across only if serotonin has already opened a gate across the way.
So if the serotonin isn't flowing at the right speed?.?.?.?the message?.?.?.?
stops?.?.?.?moving. Brain?.?.?.?must find a work-around. Start a new?.?.?.?message. Things move slowly. You, from the outside, could almost look?.?.?.?
By the time Lesch was groping for his needle in a haystack, science already knew serotonin was implicated in depression and anxiety. In the 1950s scientists noticed that a family of heart and lung drugs was making patients unexpectedly cheerful. Initially they dismissed this as a side effect: Who wouldn't be happy to recover from tuberculosis or heart disease? But in a human, an increase in happiness is a transient phenomenon. It lasts a day, a week, maybe a month, then the human reverts to the old baseline. These patients were staying happy much longer than they should. The best guess was that the drugs were increasing the amount of serotonin in their synapses.
Since then we've learned that this chemical has a central role in human personality. And monkey personality. And, yes, mouse personality.
Lesch's big breakthrough came in the form of a gene-or rather, two variations of the same gene, SLC6A4. This gene helps to manufacture a street-sweeper molecule that collects serotonin from the intersections in your brain. The serotonin neuron steadily dumps serotonin into the street; the street-sweeping molecule, or transporter, steadily collects it and returns it to the neuron for reuse. Lesch's street-sweeper gene contains a paragraph of DNA dictating how hard the gene itself shall work at making street sweepers. The long version of the paragraph makes a lot; the short version of the paragraph makes fewer. Each of us gets two copies of this gene from our parents, for a total of three combinations: long- long; long-short; short-short.
Lesch's discovery was that those people who inherited the short version of this gene from one or both of their parents ranked higher than normal on tests of Neuroticism. It was a reassuring confirmation that a balanced serotonin system is crucial to your happiness.
For me, reading Lesch's study was more confusing than reassuring. I had understood that we humans who suffer from depression and anxiety don't have enough serotonin sloshing around in our synapses. We take drugs that actually sabotage the street sweepers so that serotonin lingers longer in the intersections. Now Lesch is saying just the opposite: Too much serotonin in the synapse can also spoil your mood.
Researching on my own, I had furrowed my brow at this paradox until my brows ached. In Lesch's office, I aired my grievance: A lot of research says that too little serotonin messes you up. But other research says too much messes you up. So which is it?
"Both," he said, looking a little aggrieved himself. He's standing now, as though he is physically unable to be still. My father used to pace like this. I wonder if Lesch is a bit anxious. "You want just the right amount, and you want it in the right place," he says with a grimace. He thinks maybe an imbalance between the serotonin that's inside a neuron and out in the synapse-just that imbalance-creates an anxious personality.
When I got past my confusion, I realized this wouldn't be a novel arrangement. You could say the same thing for salt. If you don't have enough salt in your body, your nervous system sputters and stalls. But too much salt sucks water out of your cells, and then chews up your kidneys on the way out of your body. There's a happy medium where your nerves hum and your kidneys whistle and all is right with the world. And ditto for thyroid hormone: Too little and your metabolism burns too slowly, leaving you chilly, weary, and teary. Too much and you become hot, jittery, and hungry.
And so it seems with serotonin. In the correct amount it produces a calm animal who can tolerate her neighbors. When it's out of balance, both mouse and man are at risk for negative emotions: anxiety, depression, aggression, obsession, or all of the above.
In a stressful environment like our stimulating culture, a small imbalance in your serotonin can grow into a big problem. The Neurotic personality can easily become a clinically depressed personality, or a socially anxious personality. And then the serotonin-modulating drugs can become a multi-billion-dollar industry.
That's where the mice come in. You can't go around popping experimental pills into depressed and anxious humans. You can't take samples of human brain tissue to see if your pills altered serotonin distribution. I don't know about you, but even when I'm anxious, I still prefer to have my brain nearby. So the early testing of drugs rests entirely on the backs of mice.
Since his pivotal discovery Lesch has gone on to create mouse strains whose serotonin system is altered in a variety of ways. When he disabled the street-sweeper gene completely, he made a mouse who behaves, well, like me. Like someone who looks gift horses in the mouth, and peers through the sunbeams in search of thunderheads.
Lesch isn't the kind of guy who can abandon his multi-million-dollar research empire to make introductions between anxious humans and anxious mice. But he is the kind of guy who's surrounded by two dozen fellow geniuses. A postdoctoral student, Thomas Wultsch, draws the short straw. To visit the mice he leads me on a path through the vineyards. Crows turn like black leaves against the clouds. A student on a bicycle whispers past on damp pavement. Wultsch excuses his boss's absence.
Excerpted from Quirk by Hannah Holmes. Copyright © 2011 by Hannah Holmes. Excerpted by permission of Random House, a division of Random House LLC. All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.