Judy Foreman

Nationally Sindicated Fitness, Health, and Medicine Columnist

Good night? Good luck.

by

As the economy sinks, insomnia increases and America searches for a good night’s sleep

Chris Dalto is an affable fellow, a happily married father of two and a lawyer-turned-financial planner. Normally, he sleeps like a baby.

But last fall, when Lehman Brothers tanked and the stock market fell apart, Dalto began waking up at 3 a.m. “You take on the clients’ stress, which made it impossible to get back to sleep,” he says. He would spend the wee hours fretting and checking on the already-open Asian markets. Then, come 6 a.m., it was off to work again.

Even in normal times, an estimated 40 million Americans have trouble sleeping, according to the National Institutes of Health. Sleep troubles are more prevalent now because of the economy, some psychologists and psychiatrists say. A third of all Americans are losing sleep worrying about money, according to a poll done last fall and released last week by the National Sleep Foundation, a nonprofit research organization.

Uncertainty – and especially the fear of job loss – are precisely the kind of worries that makes for sleepless nights, says Carol Kauffman a McLean Hospital psychologist. “A hypothetical emergency is often harder to deal with, and can cause more insomnia, than an actual one,” she says; the worst place to be is “in limbo, waiting for the other shoe to drop, and there’s a millipede up there raining shoes.”

So what are the stressed out masses supposed to do to get some sleep? Sleeping pills, once frowned upon by doctors, are now increasingly prescribed if non-drug treatments don’t help.

Stress management, meditation, exercise, nighttime habits more conducive to sleep, and, of course, talk therapy, should be tried first, says psychologist Cynthia Dorsey, director of behavioral sleep medicine at the Sleep Health Centers, a for-profit network of sleep disorder clinics

But for those who need more – and many do; doctors wrote more than 56 million prescriptions in 2008, according to IMS Health, a healthcare information company – sleeping pills are an acceptable alternative.

What changed? For one thing, it’s clearer that extended use of some sleeping pills can be safe. Until relatively recently, doctors advised patients to take sleeping pills for no more than two weeks, partly out of the “concern that nightly use of sleeping pills would lead to ‘tolerance’ – the need to increase doses to get the desired effect,” says Dr. John Winkelman, medical director of the Sleep Health Center affiliated with Brigham and Women’s Hospital.

But then a study, funded by the makers of Lunesta, showed that the sleeping pill was just as effective at six months as at day one, suggesting that people did not become tolerant, and thus would not be inclined to boost their dosage. The US Food and Drug Administration approved Lunesta in 2004 for long-term use. Ambien CR and Rozerem are also now approved for long-term use, although there is less data on whether patients develop tolerance to these drugs.

The other change was in attitude. There is now “more acceptance of the fact that sleep disorders are very disturbing to the individual who has them,” says Winkelman. Thus, the medical community sees more value in correcting the problem, which can harm both mental and physical health, says Winkelman, a consultant to several companies that make sleeping pills.

A new study from Carnegie Mellon University illustrates the health risk of insomnia. It links poor sleep “efficiency” (the percentage of time in bed actually asleep) and shorter duration of sleep to a higher risk of coming down with a cold. People who slept fewer than 7 hours were 3 times more likely to get sick than people, equally exposed to the cold virus, who slept 8 hours or more.

Still, many people view sleeping pills with suspicion. A common worry is that stopping sleeping pills use will cause withdrawal symptoms, including worse sleep. This can happen, but is often preventable if a person tapers off a drug gradually, rather than stopping abruptly.

People also worry that sleeping pills will make them do strange things in the middle of the night. Bizarre side effects are rare, but people on Ambien have reported cooking, eating, talking on the phone, even having sex – with no memory of such things the next day.

Still others fear that sleeping pills will make them groggy the next day, which can occur if the dose is too high or taken too late into the night.

On the plus side, having a sleeping pill handy may help – even if you don’t take it, says Kauffman, the McLean Hospital psychologist. Much of the problem in insomnia is not worrying about a real fear – such as losing a job – but is the “secondary anxiety” about losing sleep. Just knowing you can take a sleeping pill if you really need it can allay this secondary fear.

As for Chris Dalto – the sleep-deprived accountant worried about his clients, me among them – he never turned to sleeping pills. Nor did he seek therapy or change his sleep habits.

What he did do was to figure out what he could, and what he could not, control. The larger economy, clearly, was out of his hands. So he focused intently on managing his clients’ portfolios – more bonds, fewer stocks – to reduce the inevitable losses of a bad market. It worked.

“Gradually,” he says, “I started to string together two, three, four normal nights’ sleep. Now, I’m sleeping like a baby.”

Social Support Shields Spouse from Damage of Caregiving

by

Yolanda Spencer is eternally grateful for the weekly visits from fellow members of the Bethel AME Church in Jamaica Plain. Without them, she’s not sure how she would have survived the last eight years, since her husband Vincent, now 62, fell off a ladder and became a quadriplegic.

An accident like Vincent’s “is such a devastating thing to happen to a family,” said Yolanda, adding that both of their relatives live far away. Having church members nearby “has been really really supportive.”

A pair of recent studies show just how detrimental such caregiving can be for the health of a spouse. And also, how close social connections like the ones the Spencers, who are black, have with friends from church can offset some of this risk.

Although marriage is generally good for health, the stress of caring for a spouse with a disabling illness can shorten the life of a caregiving spouse, a Harvard Medical School physician and sociologist Dr. Nicholas Christakis showed in a major study published late last month. How well one spouse fares after the death of the other hinges in large part on race, Christakis found in a separate, large study also published a few weeks ago.

While whites married to whites suffer a “large and enduring widowhood effect” when one spouse dies, blacks married to blacks don’t, probably because they have stronger social ties — to church and to extended family — that offset the trauma of losing a spouse, Christakis said.

Actually, it’s the wife’s race that really counts, according to the study, of 410,272 older couples, published in the American Sociological Review. A black man married to a white woman suffers from being widowed just as much as if he were white because her kin might reject him after her death, Christakis suggested. But if a man, black or white, is married to a black woman, he is buffered from the widowhood effect because her black kin accept him as part of the family and continue to provide social and emotional support.

In other words, Christakis said, one of the many things a black wife does is connect her husband with her kin, putting him in a “supportive context” that continues even after her death.

“When you marry someone, you really do marry their family,” said Gail Wyatt, a professor in the department of psychiatry at the David Geffen School of Medicine at UCLA who was not part of the study. “It’s marriage in the context of other people that is the protective thing.”

Many blacks and immigrant families are used to communal caregiving of the very old and the very young, Wyatt said. As immigrants adapt to American ways, however, they tend to “shift toward the white model.”

In general, research shows that marriage benefits a person’s health, especially if that person happens to be male. Married men, on average, live seven years longer than single guys, and married women, two years longer than their single sisters. Married people have better mental health than never-marrieds, too, though, again, it’s men who benefit more from marriage.

But the emerging view of the link between marriage and health is more subtle than that — that “marriage is good for you, except when it isn’t,” as Janice Kiecolt-Glaser, a professor of psychiatry at Ohio State University, put it, only half in jest. In her own work, Kiecolt-Glaser has shown that wounds heal more slowly than normal in caregivers of spouses with dementia, a sign that the stress of caregiving impacts the immune system.

Researchers have long known that the death of one spouse raises, at least temporarily, the risk of death for the surviving spouse. What Christakis’ team showed in the other new study was that it’s not just being widowed that can ruin the health of the healthier spouse, but the stress of caregiving as well. The causes of excess death in the caretaking spouse include accidents, suicides, heart attacks, infections, lung disease and diabetes, according to the study of 518,240 couples aged 65 and older.

In the first 30 days after a spouse’s hospitalization — a marker for the time of diagnosis — the risk of death for the partner was almost as great as it would be if the spouse had died. After a husband’s hospitalization, a wife faces a 44 percent higher risk of death than if her husband were well, the study found. A husband faces a 35 percent increased risk.

Perhaps even more startling, a woman taking care of a husband with dementia or psychiatric illness was at greater risk of dying than if she were actually widowed. Taking care of a spouse with cancer, on the other hand, was much less deleterious to the healthier spouse, probably Christakis said, because cancer, while potentially lethal, is often not as disabling day-to-day.

Suzanne Mintz has been taking care of her husband for 30-plus years, since he was diagnosed with multiple sclerosis. Over the years, she has suffered four bouts of serious depression, in part because of her husband’s illness, and the couple separated twice. They are now back together — with more support, including home health aides. She said she co-founded the National Family Caregivers Association (nfcacares.org), a non-profit advocacy organization in Kensington, MD., in part to help caregivers get the kind of support she needed.

The moral of the story is clear. Get — and stay — married if you can find someone to love.

Take good care of each other. If one of you gets sick or disabled, don’t try to manage alone.

Get help — and social contact — from as many sources as you can, including churches, community groups and social service agencies.

And if you do become widowed, try to maintain the family and community ties you had when you were married. It could be a matter of life or death.

Some comfort for the grieving: There’s no wrong way to do it

by

Grieving used to be seen as a very straightforward process: You cried at the funeral, were sad for a few months, then you had some “closure,” and got on with your life.

Psychologists — both pop and professional — thought that anyone who didn’t cry at the funeral or were still crying a year later was either heartless or overly emotional.

But, mercifully, the emerging view among mental health experts is that grieving for a lost loved one is really a disorderly, highly idiosyncratic process — that there are no set stages to go through and no “normal” or “right” way to do it.

For Lynn Osborn, 48, who lost her husband to Lou Gehrig’s disease four years ago after a slow, awful decline, the grieving process “has been very personal, and it’s still not over yet,” she said. “Fortunately, it never occurred to me that there was a “right” way to grieve.”

Osborn, a vivacious woman with a passion for rowing and ballet who is the mother of two sets of twins, now aged 8 and 11, has become something of an expert on grief. She lost her father suddenly to a car crash 16 years ago (“I had had breakfast with him that morning. I came home to a phone call saying he had been killed.”).

Though she had much more time to prepare herself for her husband’s death, it was no less terrible when it actually came than her father’s had been, she said.

As the disease slowly robbed her husband Charley, also a rower, of his ability to pick up his children, feed himself, talk and, toward the end, even blink and smile, Lynn spoke with a psychiatrist at Mass General. “I told him I felt there was a freight train coming. He said, ‘There IS a freight train coming. And there is nothing you can do to prepare for it.'”

Osborn said that insight proved liberating — and very different from the kind of counseling someone in her position might have received in the past.

In the old days, following (or perhaps twisting) the advice of Dr. Sigmund Freud, there was a virtual commandment for people to “process” their grief intensely, then “let go” and, as soon as possible, “move on,” experts said.

But newer research has shown that there is no right way to grieve.

Some people get depressed when a loved one dies. Some don’t. Some move on reasonably quickly. Others maintain a relationship with the deceased that — new research shows — is healthy, not depressing.

“The idea that grief is necessarily a debilitating experience is not true. We cope much better than our social expectations say we will,” said psychologist George Bonanno of Columbia University Teachers College, who has shown that among a group of “normal, everyday people,” only about half will get depressed at any point during their grieving process.

Maintaining a “continuing bond” with the person who has died is also normal. That doesn’t mean living in the past, but honoring the ways in which the relationship, in a sense, still goes on, said Phyllis R. Silverman, an associate in the department of psychiatry at Massachusetts General Hospital and author of the 2004 book “Widow to Widow.” The relationship with the dead person “is a part of who we are. So, much of our life is still connected to that person.”

It’s also very common — and not crazy — for bereaved people to talk to the person they have lost, said Roxane Cohen Silver of the University of California, Irvine: “There is no sign that is unhealthy.”

It is also normal to feel distressed when you realize you are moving on, said Silver, citing the case of a patient who had lost a child. “One of the worst days of her life was when she realized she had gone 15 minutes without thinking about her baby. She realized she was feeling better, but that also got her upset.”

Although there’s no way to fully prepare emotionally for the expected death of a loved one and no “right” way to grieve afterward, there are a few things that can help, said Dr. John Rolland, a psychiatrist and co-director of the Center for Family Health at the University of Chicago.

In a couple, if the husband has a potentially fatal disease and the couple has had traditional gender roles, it may help to begin to “re-organize” these roles while the husband is relatively healthy. The wife may want to look for a job, said Rolland. If she doesn’t know how to balance the checkbook, he could teach her. “You can’t wait until the person is lowered into the ground.”

It also helps, he said, to do some “re-prioritizing so that life goals are focused on the here and now, rather than 30 years later.”

Researchers used to think that grieving before a loved one’s death necessarily made things easier later. But many people are still “shocked by how intense the grief is because they figured they had already done this,” said behavioral scientist Kathleen R. Gilbert at Indiana University in Bloomington.

Osborn has some suggestions, too.

  • One is to “record your loved one’s voice. I didn’t figure that out with Charley. But I will do that for my children.”

  • The other is to treasure the time you do — and did — have with the person you love.

“I don’t mean to be a Pollyanna, but I had 20 wonderful years with that man,” she said. “There are people who don’t have one day as happy as I had.

“It took me six months after Charley died to realize that that feeling will never go away. It’s like the Grand Canyon. There’s this big hole, and it hurts like hell, but it’s beautiful.”

Eat Fish, Be Happy

by

Feeling depressed? Ask not what your parents did or didn’t do when you were a child. Ask yourself what you had for dinner last night, and the night before, and the night before that.

For half a dozen years now, the evidence has been growing that omega-3 fatty acids, the kind found in fatty fish like salmon, sardines and tuna, can help prevent and treat depression.

Rich in EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), these are among the “good” oils that have long been known to reduce the risk of heart attacks and strokes. They are also the oils that, in recent decades, in tandem with rising depression rates, Americans have not been getting enough of.

The case for linking low omega-3 levels to depression is strong, though not yet a slam-dunk. But there is little risk -and significant benefit – to following the American Heart Association recommendation to eat fish at least twice a week and, if you already have heart disease, taking at least 1 gram a day of supplements containing EPA and DHA. Unlike omega-6 fatty acids (from corn and safflower oils), which most of us overindulge in, omega-3s combat auto-immune diseases like rheumatoid arthritis , reduce cardiac arrhythmias and are crucial to the development of the spinal cord, brain and retina in infants and to healthy brain functioning in adults as well.

The latest evidence for the role of omega-3 fatty acids and depression came several weeks ago last month, when researchers from McLean Hospital in Belmont, reported that omega-3 fatty acids, plus uridine, another substance found commonly in food, prevented depression in rats just as well as antidepressant drugs. The effect of uridine was immediate, said Bill [cq] Carlezon [cq], director of the behavioral genetics lab at McLean. It took 30 days for omega-3 to kick in. But combining the two made omega-3 effective three times faster.

“There is something to this story,” said Dr. Andrew Leuchter [cq], vice chair of psychiatry at the Neuropsychiatric Institute at UCLA. “I have seen enough patients who treat themselves with omega-3 fatty acids to think these substances may have, at least in some individuals, potent effects on mood.”

No one knows exactly why omega-3s might protect against depression, but theories abound. One is that depression may, in part, be an inflammatory problem, which omega-3s can damp down, said Dr. Andrew Stoll, [cq], director of psychopharmacology at McLean. Another is that the oils keep cell membranes more fluid, making it easier for receptors to respond to neurotransmitters like serotonin, which is often deficient in depression. Another is that omega-3s may boost levels of serotonin.

Whatever the underlying mechanism, “the epidemiological evidence is huge,” Stoll said, that omega-3s can protect against depression.

Overall, major depression is 60 times more prevalent in countries where little fish is eaten, said Dr. Joseph R. Hibbeln [cq], senior clinical investigator at the National Institute on Alcohol Abuse and Alcoholism.

 In 1998, Hibbeln and others showed that high fish-eating countries like Japan and Taiwan have very low rates of depression, while low fish-eating countries like Germany and the United States have high rates. “When you compare rates of depression across populations, there is a consistent finding of strikingly lower rates of major depression, bipolar depression, seasonal affective disorder and postpartum depression in countries where people eat more seafood.”

A 2002 double-blind, placebo-controlled study of 20 people in Israel, for instance, showed that adding EPA to standard antidepressants significantly decreased depression after three weeks. A 2002 Scottish study of 60 people came to similar conclusions when patients added a 1-gram daily supplement of EPA to their standard treatment. (Interestingly, higher doses did not work as well.) A 2002 Taiwanese study of 28 people using both EPA and DHA also found significant improvement in depression scores, compared to placebo.

But not all studies support this. A New Zealand team studied 77 mildly depressed people and randomly assigned them to add 8 grams a day of fish oil or a placebo (olive oil) to standard antidepressant therapy. Mood improved in both groups.

A Finnish study that asked nearly 30,000 men to recall their fish oil consumption over the years also found no link between omega-3 fatty acids and depression or suicide, although studies based on recall are notoriously inaccurate. And a double-blind, placebo-controlled study of 35 people at Baylor College of Medicine in Houston found no improvement in depression when they gave patients only DHA, not EPA.

In the plus column, bi-polar depression, too, also known as manic-depression, also seems to be helped by omega-3 fatty acids. A study comparing 10 countries showed that higher fish consumption correlated with lower rates of bi-polar disorder. A 1999 study by Stoll of McLean showed that giving fish oil supplements to people with bi-polar disorder reduced episodes of depression and mania.

Omega-3 fatty acids also appear to reduce hostility and homicide. Several studies have found that low intake of fish and omega-3s correlates with higher rates of hostility, which is often associated with depression in males. A 36-country study showed lower rates of homicide in countries where people ate more fish.

And postpartum depression also appears linked to omega-3 levels. A study of women in 23 countries showed that women who ate less seafood and had lower rates of DHA in their breast milk were more likely to suffer postpartum depression. Pilot studies by Dr. Marlene Freeman [cq], director of the Women’s Mental Health Program at the University of Arizona, suggest taking DHA and EPA can reduce post-partum depression by 50 percent.

(Many pregnant women and nursing mothers, added Freeman, have been frightened about eating any kind of fish because of government warnings of particularly high mercury levels in a few species, king mackerel, shark, swordfish and tilefish. The Center for Science in the Public Interest, a nutrition advocacy group, says that sardines and salmon contain little mercury; women of reproductive age should probably limit their consumption of canned tuna to one can of white or two cans of light per week.)

Even borderline personality disorder, characterized by volatile interpersonal relationships and impulsivity, seems to respond to omega-3 treatment. Yet another McLean study of 30 patients found that EPA, without any other medication, improved symptoms of borderline personality.

That’s more than enough evidence for me. Given the longstanding overall health benefits of omega-3 fatty acids and the newly-emerging psychiatric benefits, the conclusion is a no-brainer. Eat fish three times a week. And if you hate fish (as I do), take at least one gram a day of a supplement with EPA and DHA.     

Biology May be to Blame for Panic Attacks

by

Carol Brown  is 54 now, healthy and happy. But until her early 40s, her life was one panic attack after another.

The first occurred when she was 16, in an elevator. Out of the blue, said Brown, who lives in Belmont, “my heart started racing, my hands were sweating, my breathing was shallow. I thought I was going to die. I didn’t tell anybody. I thought I was losing my mind. It lasted maybe a minute, maybe a minute and a half, but it was enough to begin the pattern of events.”

That pattern is horribly familiar to the 2.4 million Americans who get panic attacks.

In a panic attack, a person feels a rush of fear or distress with no sense of its cause. This is often accompanied by heart palpitations, shortness of breath or “air hunger,” numbness or tingling, lightheadedness, fear of going crazy, depersonalization (feeling like you are not really there), flushes ,chills, nausea, sweating, trembling or shaking. Many people rush to the hospital emergency room, fearful they are having a heart attack.

The first attack often makes a person so afraid of another that she – and women do get panic attacks more than men – soon avoids anything associated with it.

For Brown, who now works as director of program and resource development at the Jonathan O. Cole Mental Health Consumer Resource Center at McLean Hospital, that meant elevators. Then, after an attack on the highway, driving. Then the supermarket. Then agoraphobia, the fear of being trapped in any situation or place where a panic attack might happen, even situations where no attack has occurred before.

Years ago, doctors might have attributed panic attacks like Brown’s to some deep psychological problem. Now, they suspect biology.

“The biological hypotheses for panic disorders are based on several observations,” said

Dr. Srini  Pillay , director of the panic disorders research program at McLean.

“Pharmacologic medications can stop panic attacks and panic attacks can be induced by various compounds,” he said. Panic attacks also occur “out of the blue, suggesting some sudden alteration in chemistry.” They can also occur when a person is not anxious, and even occur during sleep, “suggesting panic attacks may be tied to biological rhythms.”

Family history plays a role, too, he noted. If you have a parent or sibling with panic attacks, you have four to eight times the normal risk of getting them, too.

In laboratory experiments, for instance, researchers have shown that panic attacks can be induced by sodium lactate or carbon dioxide, which change the acid-base balance in the brain, triggering shortness of breath, one of the hallmarks of panic attacks.

And panic attacks respond extremely well to medications likes Paxil, an SSRI, or selective serotonin reuptake inhibitor, which boosts the efficacy of serotonin. Indeed, while SSRIs are  about 60 percent effective against depression, they are effective 80 to 90 percent of the time in panic disorder, noted Dr. Alexander Neumeister, an associate professor at the Yale University School of Medicine. Carol Brown can vouch for that:  When she began taking Paxil 12 years ago, her panic attacks vanished.

Panic attacks also seem to occur in people who have overly sensitive “suffocation alarm” systems that cause the brain to perceive a shortage of oxygen when there is none.

These alarm signals, generated in the brain and in special receptors called carotid bodies in the large arteries in the neck, have a “periodic tendency to get fired off too easily and to misinterpret ordinary fluctuations as signals of suffocation,” said Dr. Donald Klein , a professor of psychiatry at Columbia University Medical Center who coined the term “panic attack” more than 40 years ago.

“In panic attacks,” he said, “there is this acute sense of ‘air hunger,’ of struggling to breathe, which is not part of normal fear.”

Moreover, scientists are closing in on the brain regions that may be involved in panic attacks. In a study published earlier this year, researchers showed for the first time, using PET scanning technology, that people who get panic attacks have one third fewer of a certain kind of serotonin receptor in their brains. Serotonin is a key regulator of mood.

In people with panic attacks, but not in normal controls, five areas of the brain showed up as deficient in serotonin receptors, said the leader of that study, Neumeister of Yale. “I think that people are born with this reduction” in receptors, he said, and that other factors subsequently “contribute to the fact that they develop symptoms.”

The good news is that, terrifying as they are, panic attacks are not in themselves harmful and rarely last more than a few minutes, although they can lead to dysfunctional behavior such as drinking, avoiding normal life activities and unnecessary visits to the ER.

 “Anywhere from 60 to 80 percent of people with panic attacks are vastly improved by cognitive behavioral therapy or medications or both,” said Dr.Chris  Hayward , an associate professor of behavioral sciences and psychiatry at Stanford University School of Medicine.

And some therapists, like Kamila  White , director of the behavioral medicine program at  Boston University’s Center for Anxiety and Related Disorders, argue that as many as 80 percent of people who have panic attacks, with or without agoraphobia, can be helped with behavioral treatment alone.

At BU’s center, people with panic attacks are taught to deliberately induce feelings of panic and distress – making themselves dizzy by spinning in a chair or breathless by breathing for several minutes through a straw. The goal, said White, is to learn that feelings of panic can be lived through, and that “even when you have extreme symptoms at the highest levels, you don’t lose control.”

But perhaps the best strategy is to combine medication and behavioral therapy, said Dr. Joe  Bienvenu , a psychiatrist at Johns Hopkins University School of Medicine. Even after panic attacks are controlled by drugs, people often “have not learned that they will not have more,” he said. “This really requires going there and dealing with this anticipatory fear.”

Alcoholism a Disease or a Moral Failing

by

In the old days, people used to debate whether alcoholism was a disease or a moral failing. Now it is abundantly clear that not only is it a disease, but one with a strong genetic component.

At least 50 percent of the vulnerability to alcoholism is now believed to be triggered by genetics, and the other 50 percent by environment, such as living in a culture where heavy drinking is endemic.

What’s also increasingly clear is that many genes play a role and that genes work both ways — with some protecting people against alcoholism and others greatly raising the risk, said Dr. Mary-Anne Enoch, a research physician at the National Institute of Alcohol Abuse and Alcoholism.

Certain groups of people, for instance, like many Japanese, Chinese and Jews, carry genes that protect against alcoholism by raising levels of particular liver enzymes so that it’s unpleasant to keep drinking because of nausea, flushing and rapid heart beat.

Others, including many Caucasians, carry genes that act in the brain rather than the liver and raise the risk of becoming an alcoholic, although if people with these genes never touch a drop, they will never become alcoholics. Overall, those with a parent or sibling who is alcoholic, are at three to four times the normal risk.

Even with no genetic predisposition, people can become alcoholic by constant exposure to alcohol, which turns on genes in brain cells “that set up a vicious cycle of wanting or needing more and more alcohol,” said Bill Carlezon Director of the Behavioral Genetics Laboratory at McLean Hospital in Belmont.

The goal of this genetics research is to better understand alcoholism in order to design better drugs to protect people from it.

The latest statistics, released in August by the government, show that alcohol problems are on the rise. An estimated 17.6 million American adults — 8.5 percent of the population — now fit the diagnostic criteria for having an alcohol use disorder. Definitions vary, but alcohol abuse is often defined as recurrent drinking that disrupts work, school or home life and/or occurs in hazardous situations; alcohol dependence, also known as alcoholism, is defined as impaired control over drinking, preoccupation with drinking, withdrawal symptoms and/or high tolerance to alcohol.

For several years now, researchers have suspected that heavy drinkers drink as a form of self-medication — to calm overactive circuits in the brain.

Several months ago, researchers at Indiana University School of  Medicine reported findings on a study of 1,547 families that support this theory.

The researchers, led by Howard J. Edenberg, a professor of biochemistry, molecular biology and molecular genetics, found that variations in one gene raise the risk of alcoholism. This gene acts on GABA, one of the brain’s chief inhibitory neurotransmitters whose job is to slow down — or calm — the firing of certain brain nerves. Tranquilizing drugs like Valium and alcohol increase the ability of GABA to calm neural circuits.

People with a “high risk” variant of the GABA gene are at 40 percent increased risk of becoming alcohol-dependent.

According to researchers at University of California, San Diego, another GABA gene also seems to raise the risk of alcoholism, in this case by programming people to have a weak response to alcohol.  These people need to drink large quantities of alcohol to get the same effect other people would get from less, said Dr. Marc Schuckit, a professor of psychiatry at the San Diego VA Hospital and UCSD medical school. This trait is common in some Native Americans and Koreans.         

On the flip side, the genetic protection against alcoholism only goes so far — it can be overridden if a person persistently drinks heavily, Dr. Deborah Hasin, a professor of clinical public health at Columbia University, has shown.

Hasin studied Jews with the protective gene who had grown up in Israel and those who had emigrated to Israel from Russia, where heavy drinking is common. The Russian Jews were more likely to be alcoholics, said Hasin, showing that both genetics and environment clearly play a role.

That finding was also supported by a study by Christina Barr, a research fellow at the National Institute on Alcohol Abuse. She found that female monkeys who were separated from their mothers in childhood AND had a high risk gene were more likely to become alcoholics than monkeys with just the gene or just the unpleasant history.

The bottom line? So far, there are no genetic tests to tell if you’re predisposed to alcohol problems. But if you’re worried, talk to your doctor or drop in on an Alcoholics Anonymous meeting.

Some drugs may also help if your drinking is serious. Naltrexone can help reduce the craving for alcohol. Ondansetron can help reduce relapse in some alcoholics. Antabuse (disulfiram) helps by making people feel sick if they drink. And acamprosate (Campral), widely used in Europe but not yet available here, helps reduce alcohol craving.

Brain Scanning and OCD

by

The sophisticated science of brain scanning may be on the brink of revolutionizing the intuitive art of psychiatry, one of the few domains left in medicine in which a doctor’s educated guess is still the most common way to figure out what’s wrong

To be sure, brain scanning is still too young a science to be used for routine diagnosis of the most common psychiatric ills. But it is already proving invaluable in understanding the underlying abnormalities in a wide range of psychiatric disorders including obsessive compulsive disorder (OCD), schizophrenia, anxiety and depression.

Obsessive-compulsive disorder, for instance, which strikes roughly 8 million Americans, is a potentially disabling condition in which recurrent fears, images or impulses cause severe anxiety and drive people to repetitive behaviors such as compulsive hand-washing, arranging, checking or hoarding.

At the University of California, Los Angeles, doctors are experimenting with PET (positron emission tomography) scanning to predict which patients with OCD or major depression will respond to the anti-depressant drug, Paxil, and which won’t.  (In PET scans, patients are given a radioactive form of the sugar, glucose; the color-coded images show, in real time, which areas of the brain are using the most glucose and are working hardest.)

One patient in the UCLA study, Marc Pincus, is a 41-year old office manager who used to wake up at night and feel he had to turn his head toward the clock exactly 19 times (once for each family member) within one minute to protect them from disaster. “If, by chance, the clock changed, I had to start again. So I didn’t get a lot of sleep,” recalls Pincus, who knew this was not protecting anyone but felt he had to do it anyway.

Just as Pincus’ initial PET scan predicted, he had a good response to Paxil. A second PET scan after several months on the drug showed the characteristic changes of a good response to the drug.

The lead researcher, Dr. Sanjaya Saxena, an associate professor at the UCLA Neuropsychiatric Institute, says that PET scans have “the potential to be used for identifying patterns of brain activity that predict response” to therapy for both OCD and depression, even though the scans confirmed that the underlying brain abnormalities in OCD and depression are different.

At Massachusetts General Hospital in Boston, Dr. Scott Rauch, director of psychiatric neuroimaging, has long been using PET and other scans in psychiatric illnesses. In OCD, he and his colleagues scan patients first, while they are resting, then they touch them with feared objects that induce obsessions.

 “You see the circuitry light up,” says Rauch, noting that the abnormal brain circuits involve nerve pathways from the orbitofrontal cortex (behind the eyes) to the caudate nucleus (part of the basal ganglia) and thalamus, which lie deep within the brain.

Rauch and his colleagues have also shown that abnormal neural activity in the anterior cingulate portion of the OCD pathway can predict how well people with severe, intractable OCD respond to surgery in which doctors interrupt the pathways through tiny cuts.

Armed with patients’ scans, brain surgeons are now  trying a potentially better approach – implanting permanent electrodes (brain pacemakers) into the abnormal brain tissue to modulate the abnormal electrical activity, a technique, called deep brain stimulation, already being used to treat Parkinson’s disease.

More than 15 patients with severe OCD have received the implants from doctors in a multi-center study based at the Cleveland Clinic in Ohio, Butler Hospital in Providence, R.I. and the University of Leuven in Belgium.  The electrodes, made by Medtronic, Inc., can be turned up or down by the doctor, making the procedure is reversible – unlike traditional neurosurgery.

Dr. Ali Rezai, director of functional neurosurgery at the Cleveland Clinic, says patients who have had the electrodes implanted show an average 35.7 percent improvement in OCD symptoms.  At Butler Hospital, Dr. Benjamin Greenberg, who heads the brain stimulation work in OCD, says that while longer follow up is needed, initial results seem “promising.” The researchers are also trying deep brain stimulation for intractable depression.

Elsewhere, researchers are using other types of scans to probe other psychiatric afflictions. At the National Institute of Mental Health, researchers have used MRI, or magnetic resonance imaging, to study ADHD, or attention deficit hyperactivity disorder in children. (In MRI, a magnet induces chemicals in the body to emit characteristic radio signals. These signals are converted into 3-D images that show the anatomical structure of the brain. No radioactive drugs are needed.)  They found their brains to be 3 to 4 percent smaller than those of normal children.

Other researchers are using a variant of MRI called fMRI, or functional MRI, to study brain abnormalities in schizophrenia and other disorders. (Functional MRI provides a real-time image of the brain’s functions, not just structure, by tracking blood flow.) 

At Johns Hopkins University, Dr. Rudolf Hoehn-Saric, a professor emeritus of psychiatry, is using fMRI to compare the brains of normal and anxious people. In tests involving listening to recordings of personal worries, people with generalized anxiety disorder, his research shows, have increases in activation in parts of the prefrontal cortex (the thinking part of the brain) and in parts of the emotional brain, or limbic system, including the hippocampus.  But after seven weeks on the medication Celexa, an anti-depressant, the patients’ scans improved considerably, says Hoehn-Saric.

In fact, many of the drugs, like Celexa, that were originally designed to combat depression also seem to work for anxiety, which raises a question the imaging scientists haven’t quite answered yet.

 “We know that anxiety and depression, while distinct syndromes, have certain common clinical features and both respond to similar drugs,” says Dr. Helen Mayberg, chair of neuropsychiatry at the Rotman Research Institute at the University of Toronto. “Interestingly, when we get to scanning, we can see at the brain level what might account for some of these similarities and differences.”

In other words, brain scans may never substitute for intuitive guesswork by a good psychiatrist. Nor should they.  But they will undoubtedly be increasingly useful in helping doctors figure out which patients with severe psychiatric illnesses are most likely to respond to treatments.

Meditation and the Brain ….?

by

For decades, open-minded Westerners – patients and doctors alike – have been touting the medical benefits of meditation, an ancient Eastern practice that comes in hundreds if not thousands of different flavors but consists basically of quieting the mind through moment-to-moment nonjudgmental awareness.

Considerable research suggests that regular meditation, or even just 10-20 minutes a day practising the “relaxation response” long promoted by Dr. Herbert Benson, president of the Mind/Body Medical Institute and associate professor of medicine at Harvard Medical School, can reverse many of the ill effects of stress.

Meditation, or the relaxation response, has been shown to lower blood pressure, heart rate and respiration; to reduce anxiety, anger, hostility and mild to moderate depression; to help alleviate insomnia, premenstrual syndrome, hot flashes and infertility; and to relieve some types of pain, most notably tension headaches.  

What nobody, until now, has even come close to explaining is how meditation may work. That is, what mechanisms within the brain might explain why changing one’s mental focus can have such large effects on mood and metabolism. Nor has there been until now, much collaboration between experts in meditation such as Buddhist monks and neuroscientists.

All that is changing – fast.

A new study, accepted for publication soon in Psychosomatic Medicine, is a significant first step in understanding what goes on in the brain during meditation. The study was led by Richard Davidson, director of the laboratory for affective neuroscience at the University of Wisconsin, and Jon Kabat-Zinn, founding director of the Stress Reduction Clinic and Center for Mindfulness at the University of Massachusetts Medical School.

The underlying theory is that in people who are stressed, anxious or depressed, the right frontal cortex of the brain is overactive and the left frontal cortex, underactive. Such people also show heightened activation of the amygdala, a key center for processing fear.

By contrast, people who are habitually calm and happy typically show greater activity in the left frontal cortex relative to the right. These lucky folks pump out less of the stress hormone cortisol, recover faster from negative events and have higher levels of natural killer cells, a measure of immune system function.

Each person has a natural “set point,” a baseline frontal cortex activity level that is characteristically tipped left or right and around which daily fluctuations of mood swirl. What meditation may do is nudge this balance in the favorable direction.

To find out, they recruited stressed-out volunteers from the Promega Corp, a high tech firm in Madison, Wisc. At the outset, all volunteers were tested with EEGs (electro-encephalographs), in which electrodes were placed on the scalp to collect brain wave information. The volunteers were then randomized into one of two groups – 25 in the meditation group and 16 into the control group.

The meditators took an 8-week course developed by Kabat-Zinn. At the end of 8 weeks, both meditators and controls were again given EEG tests and a flu shot. They also got blood tests to check for antibody response to the flu shots. Four months later, all got EEG tests again.

By the end of the study, the meditators’ brains showed a pronounced shift toward the left frontal lobe, while the nonmeditators’ brains did not, suggesting that meditation may have shifted the “set point” to the left. (The nonmeditators actually got slightly worse, perhaps because they were cranky from making several trips to the lab without the payoff of learning to meditate.) The meditators also had more robust responses to the flu shots. Indeed, the bigger the mood effect, the bigger the immune response.

The Wisconsin study fits with a smaller study published in May, 2000 by Sara Lazar, a neurobiologist at Massachusetts General Hospital, Benson and others that looked at 5 Sikh meditators using a brain scanning technique called functional MRI. It found a shift in blood flow in the brain during meditation.

The new meditation work also fits with data suggesting that certain drugs produce meditation-like effects on the brain, says Dr. Solomon Snyder, director of the department of neuroscience at  Johns Hopkins Medical School. Synder. “It’s reasonable to assume,”: he says, that meditation may increase serotonin, a calming neurotransmitter, in the brain.

No one has been more fascinated by this kind of  research than the Dalai Lama himself,  the leader (in exile) of Tibetan Buddhism.

The Dalai Lama spent 5 days in March, 2000 meeting with other Buddhis monks, philosophers and Western neuroscientists at a retreat in Daramsala, India that is chronicled in a new book called “Destructive Emotions” by Daniel Goleman, author of  “Emotional Intelligence.”

In addition to lots of esoteric debate, the conference had a practice outcome. One participant, Paul Ekman, professor of psychology at the University of California, San Francisco, School of Medicine, went on to study several monks in his California lab.

Ekman had previously developed a way to measure the facial expression of emotions and found that most people don’t do well when asked to decipher rapid changes in facial expression. But the monks were near-perfect decoders of facial expression. And one meditator, a 60-year old French intellectual who has been a monk for nearly 30 years

Appeared able to suppress the startle reflex while meditating – a stunning display of control over a basic, biological response.

None of this, of course, means that meditation is a cure-all.  As Barrie Cassileth, chief of the integrative medical service at Memorial Sloan-Kettering Cancer Center in New York, puts it, meditation is a wonderful tool “but it’s not going to let you fly to Europe on your own without a plane.”

But it is, as Ekman says cautiously, “an exercise for the brain that could be of some benefit.”

So, what does it all mean? Obviously, a few studies on several dozen amateur meditators and a handful of pros is not the final answer on how meditation acts on the brain to produce changes in mood and basic, biological functions.

Though it’s “a wonderful tool,” no one should expect meditation to work miracles, cautions psychologist-medical sociologist Barrie Cassileth, chief of the integrative medicine service at Memorial Sloan-Kettering Cancer Center in New York. It  “cannot bring about levitation. It cannot control cellular activity in the sense of getting rid of disease. …It’s not going to let you fly to Europe on your own without a plane.” 

But what these very preliminary studies do suggest is that, at long last, the subtleties of mind long known subjectively to proficient meditators may prove capable of being understood objectively as well.

Sleep and Memory – Are they Intertwined?

by

In July, researchers led by Robert Stickgold, an assistant professor of psychiatry at Harvard Medical School, reported that a full eight hours’ sleep after learning a motor task boosts performance by 20 percent the next day.

Even a one-hour nap can improve scores on a simple visual task, others reported in May.

Perhaps even more compelling, Belgian researchers, using a brain imaging technique called PET scanning, reported two years ago that when people perform reaction time tests, certain areas of the brain become activated. These same areas “light up” again when the people experience REM (rapid eye movement, or dreaming) sleep, as if their brains were actively rehearsing what had been learned.

Over the years, researchers have found tantalizing evidence that sleep may enhance learning and memory. Some have showed that infants who learn a head-turning response have more REM sleep than those who failed to learn the response. Others, that people given 90 minutes of training in Morse code showed an increase in REM sleep. Still others, that people who did well learning French increased their REM sleep, while poorer learners did not – and that the sooner the good learners started dreaming in French, the higher their scores on French tests. (The poor learners never did dream in French.)

Case clinched, right? Sleep, particularly REM sleep, seems to boost memory, just as many scientists – and mothers – have been saying for years.

Would that it were that simple.

“Everybody knows sleep has something to do with memory – except people who study sleep and memory,” says Stickgold.

Brain researchers would like nothing better than to come up with a neat paradigm of how sleep affects memory.

It would go something like this: Learning creates chemical changes in specific cells in specific parts of the brain. When a person sleeps shortly after learning, and perhaps especially when she dreams that night, the brain takes these fragile, new memories, shuffles them around into a more permanent home, or at least a more permanent set of neural circuits. And  – Presto! – the memories would be firmly “consolidated” by morning.

There are two main reasons why confidence in such a nice, simple scenario is impossible, as least for now: At the electrical and biochemical level, sleep itself is devilishly complicated. Memory, arguably, is even more so.

A night’s sleep typically goes from light (Stages 1 and 2 sleep to deeper stages 3 and 4, known as slow wave sleep). All of these are called non-REM sleep. Non-REM sleep alternates with REM, or dreaming sleep, with REM periods getting longer and non-REM periods getting shorter as the night progresses.

One reason for thinking that REM sleep may be involved in memory consolidation is that the brain behaves differently during slow wave and REM sleep. During deep sleep, the brain is relatively inactive, and electrical patterns are slow and synchronized; during REM, it is extremely active, and desynchronized..

Brain chemistry changes, too. During REM, some neurotransmitters, or chemical  messengers, especially norepinephrine and serotonin  are virtually shut off while others, notably acetylcholine, believed to be a memory booster, go up.

Memory is even trickier. Scientists divide memory into two basic categories, declarative and procedural. That’s the difference between “knowing that” and “knowing how,” notes psychologist Carlyle Smith of Trent University in Peterborough, Ontario.

Declarative memory involves learning facts – knowing that the French Revolution began in 1789. Knowing how is knowing, often without knowing that you know, how to turn the key in the ignition to start the car. Declarative memory is “explicit,” and usually consciously acquired; procedural memory is “implicit,” often unconsciously acquired.

The trouble is, although declarative memory is what most of us mean when we talk about memory, most of what researchers study is procedural memory – the less juicy stuff like learning finger-tapping exercises.

For declarative memory, there is little evidence that sleep, even REM sleep, has any effect, says Smith of Trent University.

“No matter what I have done – I have deprived people of sleep, I have deprived people of REM sleep, I have deprived them of non-REM sleep –  and I have never seen any difference [in declarative memory] between people who got a good night’s sleep and those who didn’t,” says Smith of Trent University.

Dr. Jerome Siegel, professor of psychiatry at the David Geffen School of Medicine at UCLA and chief of neurobiology research at the VA Greater Los Angeles Healthcare System Sepulveda, agrees, noting in a paper in Science in 2001 that the evidence for such a link is “weak and contradictory.”

And a link between sleep and procedural memory? That’s stronger.

In 1991, researchers studied people learning trampolining, which required  new, complex motor skills. The best learners showed increases in REM sleep (and no differences in non-REM sleep); those in control groups who expended the same number of calories but didn’t learn new motor skills showed no difference in either REM or non-REM sleep.

REM and some non-REM sleep may help with a different type of procedural task – visual learning. In a paper published in 2000, Stickgold and his team found that improvement on a visual task increased with stage 3 and 4 slow wave sleep in the first part of the night, and with REM later in the night. The real payoff, he finds, is with REM sleep in the final two hours of an 8-hour sleep.

In a sequel to Stickgold’s studies, doctoral student Sara Mednick wanted “to see if napping had the same effect as a night’s sleep.” To find out, she used the same visual memory task and tested volunteers on it at four points in the same day. They all got worse as the day went on.

So she let some volunteers take a half-hour nap between the second and third session and others, an hour nap. The half-hour nappers were able to stop the decline in performance. The hour-nappers not only stopped the decline but performed as well as they had first thing in the morning. The long nappers, by the way, exhibited both slow wave sleep and some REM sleep as well.

The bottom line in all this? There is still much that remains a mystery. Someday, maybe they’ll figure it all out. For now, “the simple answer is that we don’t know,” says Stickgold of  Harvard. “You  push this system just a bit and you stumble onto complete ignorance.

New Drug for Narcolepsy

by

Mary Rourke, a 55-year old teacher from Salem, N.H., used to nod off all the time as a child, but people just shrugged and said, “Oh, she must be very tired,” she recalls.

Then, as an adult, she began having attacks in which her muscles would lose tone and she’d fall- every time she laughed or felt any strong emotion. “I was constantly falling,” she says. “If you told me a joke, I’d flip. I couldn’t be around people.”

In Massachusetts, a 49-year old nurse from Norwood who asked that her name not be published also used to crash helplessly to the floor whenever she laughed or got angry, a fact her children quickly learned to exploit. “I couldn’t yell at my kids when they were younger because if I got too mad, I couldn’t stand up,” she says.

Things were even worse for Bob Cloud, a 58-year old lawyer from Cincinnati, Ohio. It was bad enough falling asleep talking to judges, he says, but one day he went limp while swimming and had to be rescued.

At least, he says, that provided a “great educational opportunity” to tell stunned onlookers what was really wrong: A brain disorder called narcolepsy, characterized by extreme daytime sleepiness and caused by low levels of a brain chemical called hypocretin. In many cases, low hypocretin levels also cause cataplexy, sudden loss of muscle tone due to the intrusion of dreaming (REM) sleep in the waking state.

Though the true numbers are probably higher because many people go undiagnosed for years, narcolepsy is believed to affect at least 140,000 Americans and 3 million people worldwide – more than are affected by some better-known diseases like cystic fibrosis and muscular dystrophy.

Yet stunning brain research in the last three years, along with the hoped-for approval this spring of a controversial new cataplexy drug called Xyrem – known on the street as the date-rape drug, GHB – are catapulting this once-hidden condition into the limelight.

With luck, the research on narcolepsy and cataplexy – essentially, disruptions in the body’s normal sleep-wake cycles – may lead to novel treatments for insomnia and depression as well.

And there’s another reason for the limelight: A remarkable degree of cooperation on the Xyrem/GHB issue by Congress, the US Food and Drug Administration and law enforcement officials that shows that it is possible to treat the same substance as both legitimately needed by desperate patients and subject to criminal penalties when abused.  

In the illicit street form, GHB (gamma hydroxybutyrate), has been blamed for dozens of deaths and countless sexual assaults. The colorless, odorless liquid can be slipped into someone’s drink. It is so simple to concoct at home that “a 9-year old can make it,” says Bob Gagne, a public affairs consultant for Orphan Medical. “I stumbled upon a crockpot recipe” for one form of the drug on the Internet, he notes. Some people also drink industrial chemicals such as GBL (gamma butyrolactone) for their GHB-like effects.

Because GHB is also believed to promote the body’s production of growth hormone, some body builders take illicit forms of the drug to increase muscle bulk.

All in all, a dicey substance for a pharmaceutical company to pursue. But in the early 1990s, Congress, concerned that big, profit-minded pharmaceutical companies were showing little interest in making drugs for so-called “orphan diseases” passed legislation encouraging companies to make such drugs. (Orphan diseases are those that affect 200,000 or fewer people – a small market.)

So Orphan Medical, Inc. of Minnetonka, Minn. began researching Xyrem. It’s still not quite clear how it works, though it may act through a brain chemical called dopamine. It is clear that Xyrem seems to reduce cataplexy attacks, and restore restful sleep for narcoleptics, who, despite overpowering sleepiness during the day, wake up frequently at night. Indeed, Mary Rourke, Bob Cloud and the Massachusetts nurse have all taken Xyrem under research protocols – and all say it has significantly improved their lives.

Though GHB was classified in March, 2000 as a Schedule I (most restricted) controlled substance, its potential as the prescription drug Xyrem for cataplexy (but not narcolepsy) meant that it was recommended as “approvable” last summer by an advisory committee to the FDA. The agency usually follows the recommendations of such committees. To make sure it does not get into the wrong hands, Orphan Medical is setting up a special distribution system so that all prescriptions will be filled by one central pharmacy.

To be sure, there are skeptics. Dr. John Winkelman, medical director of the sleep health center at Boston’s Brigham and Women’s Hospital, says, “I think the jury is still out on Xyrem because of concerns about potential abuse.”

But other doctors are as positive as patients. “Many people are transformed by it,” says Dr. Emmanuel Mignot, a professor of psychiatry and behavioral science at Stanford University Medical School.

Some people with cataplexy have as many as 15 to 20 falls a day, says Dr. Michael Biber, medical director of Neurocare, Inc. in Newton. “People are unbelievably disabled.” Yet on Xyrem, which he has tried on three patients so far,  people can become “almost completely free of symptoms.”

But just as important as the advent of Xyrem is the remarkable confluence of brain research on the triggers for narcolepsy, notes Dr. Jerome Siegel, professor of psychiatry and behavioral sciences at UCLA and chief of neurobiology research at the Sepulveda VA Medical Center in Los Angeles.

“What is extraordinary is that everything has been done in the last three years,” adds Mignot, the Stanford narcolepsy researcher.

In 1998, while looking for brain chemicals believed to control appetite,  two independent teams – one in San Diego, one in Dallas – discovered a neurotransmitter in a part of the brain called the hypothalamus. It quickly acquired two names – hypocretin and orexin – and it is made by only by a few cells in the hypothalamus. Significantly, hypocretin-producing cells in the hypothalamus connect to other parts of the brain and brainstem that control arousal and muscle tone.

Curious, the Texas team went on to see what would happen if they deleted, or “knocked out,” the gene for hypocretin in mice. To their surprise, mice with the missing hypocretin gene seemed to wander around normally, then suddenly drop in their tracks, just like narcoleptics with cataplexy. Also like narcoleptics, the knock-out mice began their night’s sleep abnormally – with REM, instead of non-REM sleep.

Meanwhile, unaware of this work, Mignot’s team at Stanford University was trying to figure out the genetic causes of narcolepsy in dogs.

Within weeks of each other in 1999, the Stanford and Texas teams reported work that dovetailed perfectly. The Stanford team found that dogs with narcolepsy have a mutation in the gene for the hypocretin receptor. The Texas team found that mice missing the gene for hypocretin itself showed behavior remarkably similar to narcolepsy.

“It was quite amazing and convincing,” says Siegel of UCLA. The cause of narcolepsy suddenly seemed obvious: lack of hypocretin, or its receptor.

In early January, 2000, Mignot’s team reported that human narcolepsy patients had low levels of hypocretin in the fluid that bathes the brain and spinal cord. Another key clue.

But an important step remained. So both Mignot’s group at Stanford and Siegel’s at UCLA obtained brain tissue from narcoleptics who had died and they, too, published their findings in the fall of 2000 within weeks of each other. Both teams found that almost all of the hypocretin-producing cells in the hypothalamus of people with narcolepsy were missing.

Moreover, Siegel’s group found that there was scar tissue where hypocretin-producing cells should have been, a clue that (unlike dogs, in whom narcolepsy is often hereditary) people who develop narcolepsy are born normal and subsequently suffer damage to these cells, most likely because of a misguided attack on these cells by the immune system.

It’s still not clear why many people with narcolepsy also have cataplexy while others don’t. But a number of companies are now scrambling to make narcolepsy drugs that mimic hypocretin to restore normal levels.

In the meantime, prescription stimulants such as Provigil, Ritalin and Dexedrine often help people with narcolepsy stay awake during the day. And anti-depressants such as Tofranil and Prozac can partially control cataplexy. If Xyrem is approved, it may prove a valuable addition to the medical arsenal.

Longterm sufferers like Mary Rourke are crossing their fingers. Because she participated in a research study on Xyrem, Rouke has been allowed to take the drug, even though her participation in the study is over. She says it has changed her life.

Recently, she was standing in her classroom when a student snuck up behind her and said, “Boo!”

“If I hadn’t been taking this drug,” she says, “I would have gone right down.”