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Found This Article - When Memories Are Scars

Discussion in 'General' started by GR-ass, Dec 4, 2006.

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  1. GR-ass

    GR-ass Well-Known Member

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    Roger Pitman, M.D., hunts nightmares for a living. Not the vivid phantasmagoria populated by zombies or disembodied skulls, or even the nude-at-the-podium orations that leave us blushing in our sleep. He's after the nonfiction variety, the indelible, enduring flashbacks that stick in our heads after reality goes awry: a saw blade meeting flesh, say, or an improvised explosive device overturning a Humvee.

    I'm in Dr. Pitman's lab in Boston, watching him track down a particularly vivid figment, a stab wound to the neck that's been plaguing 43-year-old carpenter Al Carney for 2 months now. "We're about to put him back in the most horrifying moment of his life," says the Harvard psychiatrist, peeling back the top sheet on a thick medical file labeled Patient 102. In the room next door, the stout laborer sits, eyes closed, headphones on, wired with a battery of biofeedback equipment: electrodes affixed to his chest to monitor his heart rate; a forehead sensor scanning for tension; and a tiny pad on the inside of his palm measuring how much sweat seeps through his skin.

    "It's 8:30 a.m. on Thursday, March 30," a narrator begins to read over the headphones. "Noticing Peter Bowman standing there, you become tense all over. He says he's here to collect a check. Feeling jittery, you tell him he needs to fix several things before you pay him any more. As the argument becomes heated, your heart beats faster. Peter becomes physically aggressive, and you feel a blow to your neck. You fall to the ground. Several people pull him off you. . . . After you're separated, you realize that you're bleeding profusely from several knife wounds."

    Fade Away


    Carney's vital signs ebb and flow on a flat-screen monitor in the corner of the room as he reimagines the assault. They spike when he's "stabbed" by Bowman. But I don't need whirring telemetry machines to tell me the narrative has struck a nerve: Carney starts fidgeting, and he taps his scuffed gym shoes together at the toes. Even though he's been asked to sit still, his head twitches back and forth against the recliner's headrest. Later, Dr. Pitman will compare Carney's physiological responses with the results from previous sessions, as well as his reactions to positive scripts used as controls—the birth of his first child, a transcendent round of golf.

    Carney is one of dozens of accident victims that Dr. Pitman and his team have culled from Boston emergency rooms to study a drug called propranolol. The study is double-blind—no one, least of all Carney, knows whether the pill he took was a placebo or propranolol. But the contractor hopes he'll get lucky and will be able to stop the spiral of substance abuse, irritability, and insomnia that started with the stabbing at the construction site.

    Dr. Pitman's study is leading a new wave of research that promises to curtail the harmful psychological effects of extreme stress, especially posttraumatic stress disorder (PTSD). Today's most common treatment, cognitive-behavior therapy coupled with drugs such as Prozac, fails at least as often as it succeeds. Dr. Pitman hopes that defusing horrible memories—that high-school car crash, the abusing babysitter—could within 5 years become less difficult with the help of propranolol.

    "Posttraumatic stress disorder is just a memory that has its volume set too loud," Dr. Pitman observes, thumbing through a thick sheaf of case histories. "Something turned up the switch. We're trying to turn it back down again."

    Surviving Trauma

    We all have things we'd like to forget. And some of us have things we can't bear to remember. According to the National Center for Post-Traumatic Stress Disorder, 61 percent of American men will be exposed to a traumatic event in their lifetimes. And, according to the National Comorbidity Survey, 5 percent of men nationwide will develop PTSD at some point in their lives. These men include 9/11 survivors, Hurricane Katrina victims, and, increasingly, military veterans: According to a 2005 study published in the New England Journal of Medicine, 17 percent of Iraq war veterans suffer from PTSD, anxiety, or depression.

    But the disorder also hits closer to home. Domestic disputes, burglaries, accidents, and even surgeries can engrave malignant memories on the brain. One recent study suggests that more than 15 percent of heart-attack victims suffer from PTSD, slowing recovery and increasing chances of a second attack.

    Not every man who falls victim to atraumatic event develops PTSD, of course. To be diagnosed, you must experience a laundry list of symptoms for more than a month. Some people, inexplicably, shrug off serious trauma without a second thought. Carney is somewhere in between the two extremes: While the past has become an inescapable drag on the present, it is a nagging presence, not an overriding one.

    "We all have stress hormones, and we're all affected by them," says Deane Aikins, Ph.D., a Yale psychologist who heads up the cognitive neuroscience wing of the National Center for PTSD. "We're just now beginning to understand why some of us are inherently more resilient to the stress, and how maladaptive behaviors learned at an early age can impact us for the rest of our lives."

    Just as cancer researchers have made countless discoveries about how normal cells live and die, so have PTSD researchers used their unique niche to shine a broader spotlight on the delicate interaction between the brain and the body. And what they've learned has implications far beyond PTSD. It could change how we think about stress altogether.

    All in a Day's Work

    "I should never have even been at the mill," says Terrell Kyle, a 43-year-old cabinetmaker from Caribou, Maine. "That's what really gets me."

    Kyle is the sort of solitary woodworker who'd rather fashion the occasional cabinet in his garage workshop than work behind the big-mill, big-money lumber machines that churn thousands of logs into millions of planks each day. But in the winter of 2005, his family short on cash, he went back to the mill, reluctant but resolute.

    About 3 months in, and just 25 minutes before the end of a brutal graveyard shift, the conveyor belt of lumber under Kyle's watch jammed. He walked over to do the usual routine: Hit the kill switch, clear the board, restart the saw. And that's how it might have gone, in fact, if he'd been more familiar with the equipment, if it hadn't been his 10th machine of the day, or if he hadn't been working at high speed for 11 hours and 35 minutes among some very sharp, very dangerous, very finicky machinery. As it happened, he dislodged the board, his hand kicked back into 24 inches of whirring steel, and, in a flurry of blood and blade, Kyle lost all the fingers and the thumb on his left hand.

    "I keep coming back to that moment," he says. "I know I was screaming. But here's the thing: I don't ever remember looking at my hand. That moment is just lost. My supervisor came over, and I told him I had lost all of my fingers, so I'm sure I knew. But I just walked out of the mill and had a cigarette."

    The orthopedic surgeon at the nearest hospital decided Kyle's injuries were beyond his reach, so the carpenter was helicoptered, along with a plastic bag containing four of his fingers breaded in sawdust, to Massachusetts General Hospital. There, he met an on-call member of Dr. Pitman's team and was administered a pill—either propranolol or a placebo—and underwent reattachment surgery.

    The Role of Adrenaline

    Kyle's hand rejected the fingers soon after, and months later, he still can't erase the painful memories. "Sometimes I wonder if I would have been better off as an automobile-accident victim with amnesia," he says. "The memory just seemed to impregnate itself so that it's there, all the time, like static, on the fringes of my mind, finding a way to intrude on my other thoughts. Anything going around fast creates this clenching feeling inside my chest. A snowblower. An airplane propeller. Car wheels. I often think I'm having a heart attack. I mean, consciously I know I'm not in any danger. But subconsciously, it makes me want to run, to get away, to not look, to plug my ears."

    Kyle's psychological symptoms—blackouts, flashbacks, depression, anxiety, insomnia, irritability, and hypervigilance—aren't the only tolls paid by PTSD sufferers. In a 2006 study, researchers in Switzerland found that the syndrome significantly raises the levels of a key blood-clotting agent, promoting arteriosclerosis and, by extension, increasing the risk of heart disease. Traumatic stress has also been linked to immune system, gut, and muscle disorders, such as hemorrhaging and ulcers.

    Posttraumatic stress amounts to a spectacular breakdown of what is normally a very helpful mechanism. Bundling an emotional component with a memory dovetails with Darwin's theory of natural selection, says Dr. Pitman. "If you, as a Paleolithic man, happen to be taking a new route to the watering hole one day and encounter a crocodile, you'd better remember that crocodile," he says. "If you don't, you'll be eliminated from the gene pool. Adrenaline not only helps you escape, but strengthens that emotional component to make sure you won't forget."

    But extremely traumatic events can unleash a torrent of stress hormones, searing the memory into the brain. That's where propranolol enters the picture. It blunts the impact of stress hormones on the amygdala, the small, emotional control center in the middle of your brain. As a result, the brain is able to encode the traumatic memory as a factual event, a garden-variety horrible memory, rather than a world-changing, panic-inducing schism in consciousness. It's like removing the crescendo of violins from the climax of an action movie: You still know what's happening, but you're able to focus on just the facts.

    Erasing Memories from the Hard Drive

    Propranolol is part of a class of drugs called beta-blockers already being used to treat real-time anxiety disorders, such as performance anxiety in public speakers. Dr. Pitman's study hinges on administering the drug within 6 hours of a traumatic event. And other researchers have been stretching the window even further—uncovering new revelations about how memories are made and stored in the brain. "The old story was that once memories are stored, they're stored forever," says Karim Nader, Ph.D., a researcher at McGill University, in Montreal. Nader specializes in the relatively new field of memory "reconsolidation," the subsequent revision of a memory after it's already been transferred into long-term storage. "But what I found is that once you access a memory, you have to restore it. It's kind of like taking a file off the hard drive and putting it into RAM—you have to save it to the hard drive all over again, or parts of it can get lost."

    Nader and his researchers have found an ingenious way to induce just such a memory loss—even in patients more than 3 decades removed from a traumatic event. First, he administers propranolol, effectively hitting the emotional mute button. Then he uses the same sort of prerecorded narration that Dr. Pitman (a co-researcher on the project) does to bring the memory into RAM. Finally, he moves on to other memories, and the patient's brain naturally "reconsolidates" the traumatic one with much less drama. Nader is now expanding the study in an attempt to corroborate his results with a larger group of subjects.

    "Nobody knows when they're going to be in a car accident, or be raped, or be kidnapped, so trying to give them a pill within 6 hours of the trauma is difficult," he says. "But we can control the memory now, bringing it back to the point of sensitivity no matter when it occurred. This could have implications for all kinds of problems: drug addiction, obsessive-compulsive disorder, or anything where you need to change the wiring in the brain."

    As visceral as they may be, traumatic events—explosions, stabbings, car crashes—may be less to blame for PTSD than the brains of the sufferers themselves. That's the lesson from as-yet-unpublished research on the army's 10th Mountain Division, a light-infantry, rapid-deployment force that has been dispatched into active duty more frequently than any other army division over the past decade.

    Stress Resistance

    What's unique about these soldiers, beyond their combat training and high stress levels, is their uniformity: They're all healthy, they're all screened often to eliminate psychological maladies and substance abusers, and, most important, they're all willing to let Deane Aikins, the Yale psychologist, scan their brains, drain their blood, and shock them with a small probe, all in the name of science.

    Aikins, a soft-spoken researcher charged with helping the Department of Veterans Affairs plan its approach to treating the waves of soldiers returning from Iraq, designed an experiment to compare how the soldiers would react to two different stimuli: an innocuous pulse of light, and a pulse of light paired with a slight electrical shock. He found that soldiers who overreacted to the innocuous stimulus were more likely to develop PTSD in Iraq if exposed to a traumatic event (95 percent of active-duty members are) than the cool-hand Lukes in the crowd. What could the key physiological difference be? A chemical called neuropeptide Y.

    "In another study, we found that stress-resilient guys were under the same amount of combat stress as the PTSD guys, and indeed some of them were from the same unit," says Aikins, who plans to publish his research this fall. "But there's an explosion, somebody dies, a Humvee flips, and then one guy gets PTSD and another guy from the same unit doesn't. Why? Lo and behold, we're finding that the men who are unflappable may also have lower levels of cortisol and higher levels of neuropeptide Y."

    Neuropeptide Y is one of hundreds of compounds involved in the complicated braiding of stress signals and memory. It isn't easily administered or synthesized, and so Aikins's research is valuable largely for prescreening for PTSD susceptibility, rather than as a means of treatment. But it's proof positive that the way we react to any stress—even a slight shock and an annoying flash of light—dictates the way we're likely to react to the most extreme stressors.

    Flight-or-Flight Response

    Beneath all the bells and whistles, behind all the high-level cognition—calculus, poetry, Sudoku—the brain is just a fancy system for detecting and avoiding stress. Nobel Prize-winning researcher Eric Kandel demonstrated this more than 50 years ago by analyzing the nervous system of a simple sea snail, called aplysia. The snail's nervous system, Kandel found, would change at the synaptic level when it "learned," strengthening the connection between nerve cells that carry out a particular behavior (gill retraction) and sensory nerve cells that react to a stimulus (mechanical probe). It was a seminal discovery: Actual physical changes, both in how the neurons connect to one another and within the chemical gateways that govern the firing of each neuron itself, underlie learning and memory.

    The consequence of having a brain tuned to change with even minor stress, however, is that it's extra-sensitive to overload by extreme stress. Over the past decade, molecular biologists have begun to unravel how this happens at the cellular level.

    "The brain is like a collection of mobile phone networks," says Hermona Soreq, Ph.D., a Jerusalem-based neurobiologist who has developed a drug to block PTSD at the DNA level. "They all communicate within themselves, but also within each other. We know that when there is a big disaster, like the recent missile attacks, the network crashes. That's posttraumatic stress for you. That's what we see in the shelters and streets every day."

    Soreq's motivation for beating PTSD is anything but academic: I spoke with her the day before the UN-proposed cease-fire went into effect in the Israeli-Lebanese conflict, as she feared for the safety of her son, a soldier, and as both sides bombed and strafed to try to claim victory with the deadline looming.

    Threats of any kind—especially life-threatening ones—trigger the release of the fight-or-flight neurotransmitter acetylcholine. Add more and the neurons fire faster and more efficiently, speeding up the network. Take it away—this is what chemical-warfare agents like Sarin or Zyklon B do—and you essentially shut down the network. To keep us on an even keel, the brain releases certain chemicals to help tone down this fight-or-flight response after the threat has passed. But if we keep seeing Dr. Pitman's crocodiles, even just in our heads, these compounds can permanently alter the structure of our brain, disrupting our neurochemical balance and leading to PTSD-like problems.

    Playing God with the Brain

    Soreq's drug, called Monarsen (after her nickname, Mona), stops the unbalancing by blocking production of one of these buffering compounds, a persistent, fast-moving version that appears only during stressful situations. Monarsen effectively handcuffs the compound's DNA blueprint, or gene, from being turned into a biologically active protein, cutting the problem off at the source.

    "What we do in present-day therapy, with drugs such as Prozac or propranolol, is the least economical approach," says Soreq. "We try to block the bottom of the gene-expression pyramid—the proteins, the stress hormones such as cortisol or adrenaline," she says. "But you have one gene at the top of the pyramid controlling everything, so why not aim there?"

    Monarsen, then, is the equivalent of using a laser-guided missile to target an enemy's headquarters instead of razing the entire town. That precision enables it to be administered in smaller doses, with fewer side effects. And because acetylcholine impacts cellular signaling throughout the body, from the immune system to the red blood cells, it may prevent an even wider range of stress-caused symptoms.

    "Our goal is to prevent changes in the brain that have the potential to ruin the life of a child who spends 4 weeks in a bomb shelter, or the victims of 9/11," she says. "Or the soldiers now fighting in Iraq."

    "That's like playing god with the brain," says Barry Romo, a national coordinator with a Vietnam-veterans antiwar group. "One of the things that keeps us from remaking mistakes is looking back and having regret, as opposed to thinking, Well, shit, that was a close shave, but at least I'm okay."

    Romo, one of a small but very vocal group of critics of Soreq's and Dr. Pitman's research, worries that the way we interpret memories, whether terrifyingly vivid or naive and nostalgic, is part of who we are as individuals. To tinker with that is to step onto unsteady ethical ground.

    Avoiding Abuse

    "I think people have a right to have medication, if they need it, but I have to wonder what these drugs will be used for in the hands of police or the military or someone who doesn't deserve them," he says. "We don't want to create a bunch of storm troopers who can do anything they want without having to worry about the repercussions."

    Dr. Pitman, for his part, says that's overstating what such drugs can do—at least for now. "I think it's far-fetched, but it's possible that something like that will be found. I don't think it's going to be with propranolol, but it's possible," he says. "But then you get into the question of 'Do we hold back a drug from people it can help simply to prevent others from abusing it?' If we practiced that, then nobody in the hospital would be able to get morphine for their pain. When you're talking about people who are dying of cancer, it's not really a tough decision."

    Cabinetmaker Terrell Kyle won't know for another year whether he received the placebo or the active drug in Pitman's double-blind study. But simply learning about the biology of his disorder has helped Kyle deal with the flashbacks and panic attacks, rein in his rage around the house, and reconnect with his daughter, who, he says, bore the brunt of his mood swings. The prosthetic he's been given is too clumsy for detailed woodworking, but Kyle hopes that someday he might even be able to fire up some of the new tools that now sit in his garage gathering dust.

    "Some people go through years and years of torture," he says. "Should we mess with their memories? Should we be able to take those thoughts away? Absolutely. We want to act as though nothing happened, but it's never that easy."

    "It's not about playing God," Kyle goes on. "It's about finding a way to feel human again."

    Source: MSN Health
     
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