July 1, 2008
By GINA KOLATA
On Dec. 18, 2005, Ariel Sharon, then Israel’s prime minister, was taken to a Jerusalem hospital with symptoms of a stroke, unable to speak or understand what others were saying.
Over the next 36 hours, his doctors found themselves in a quandary. Mr. Sharon had two conditions that might lead to a new and devastating stroke. And treating one condition could make the other one worse.
First, he was susceptible to blood clots that could be swept from his heart to his brain, causing a major stroke. Anticlotting drugs might protect him.
But his brain scans showed microbleeds, pinpoint drops of blood that leaked from blood vessels in the brain. The fear was that an anticlotting drug might turn a new microbleed into a life-threatening, incapacitating hemorrhagic stroke.
Until recently, microbleeds were all but unknown. Now, with improved scans, they are turning up constantly; one recent study found them in the brains of 1 out of 5 people age 60 and older. And they are leading to a classic conundrum of modern medicine: Just because something turns up on an M.R.I. scan, is it significant? And if it may or may not be significant, what to do about it?
With strokes, the stakes can be life or death. Or, as happened with Mr. Sharon, somewhere in between.
His doctors decided that blood clots were his biggest risk, so they gave him heparin, an anticlotting drug. Two weeks later, he had a major bleeding stroke. Mr. Sharon remains in a persistent vegetative state to this day, awake but not aware, unable to respond, unable to communicate, able to breathe but unable to think.
It can never be proved that an anticlotting drug caused a stroke in an individual case. But it is known that when patients taking such drugs have hemorrhagic strokes, the strokes are much worse, with double the normal fatality rate.
The microbleed story began when neurologists, using newer magnetic resonance imaging techniques, began seeing them in patients who had symptoms of a stroke or, in some cases, signs of an electrical disturbance in the brain. A patient might have numbness or tingling in part of the face that then migrated to a hand and went away.
On scans, neurologists would see a few drops of blood in the patient’s brain, smaller than the tip of a pen. Or they would see tiny drops in routine scans in patients with dementia, or in patients who had had a serious stroke.
Now, neurologists are seeing microbleeds even in some patients who seemed free of neurological problems — people who were given a scan because of a blow to the head, or memory problems, or headaches.
“They clearly are being picked up more often,” said Dr. Steven M. Greenberg, a neurologist at Massachusetts General Hospital who studies microbleeds. “That’s one reason why we all get nervous about getting scans on people who don’t necessarily need them. You have to be able to deal with the consequences.”
With microbleeds, that can be difficult. At a loss as to what to do, doctors call specialists like Dr. Greenberg, asking for advice.
“I get a lot of calls I didn’t used to get,” Dr. Greenberg says. “And they mostly involve questions I can’t answer.”
When the bleeds are on the outer surface of the brain, they often seem associated with a condition in which blood vessels are damaged by the protein amyloid. This is the same protein that piles up in the brains of patients with Alzheimer’s disease; microbleeds from amyloid can be associated with dementia.
Other times, the microbleeds are deep in the brain and may be linked to high blood pressure, a leading cause of strokes. But it is not clear whether microbleeds, especially those deep in the brain, are of any real consequence. Until recently, no one asked how often they turn up in healthy people, nor whether they predict strokes or other serious brain damage.
That changed when Dr. Monique M. B. Breteler, a neuroepidemiologist at Erasmus University in Rotterdam, the Netherlands, decided to look for microbleeds among residents of her city.
“If there were more than we knew of in the general population, that might — and I want to stress might — have important consequences,” Dr. Breteler said. “That is why we started to look for them.”
For more than a decade, Dr. Breteler and her colleagues have followed a group of Rotterdam residents age 45 and older. The goal is to do repeated brain scans on 8,000 people; so far they have scanned nearly 4,000 and are analyzing those data.
“What we found came as a big surprise,” Dr. Breteler said. Previous estimates were that 5 to 7 percent of healthy older people had microbleeds. The Rotterdam study found them in more than 20 percent. And the older the person, the more likely the microbleeds. They were present in 18 percent of 60-year-olds and nearly 40 percent of those over 80.
“We now know that these changes are there and that they are frequent,” Dr. Breteler said. “But we don’t know yet what their clinical impact is, what their prognosis is.”
Still, she and other experts say, there is reason for concern.
Dr. Greenberg has found that if the microbleed is near the brain’s surface, where it might be associated with amyloid, then anticlotting drugs are more likely to precipitate a brain hemorrhage. But sometimes a patient is at such grave risk of a stroke that the balance tips in favor of an anticlotting drug anyway, he says.
If the microbleed is deep in the brain, it is not clear whether anticlotting drugs are dangerous.
Even patients who come in with symptoms that might be caused by microbleeds can pose a problem.
Edward Reynolds, 74, of Beverly, Mass., was referred to Dr. Greenberg after an episode in which part of his face went numb, then his hand, and then the numbness faded and he felt fine. He had an abnormal heart rhythm, which meant that anticlotting drugs might help him avoid a stroke caused by blood clots in his heart.
But an M.R.I. scan found microbleeds on the surface of his brain, which meant they were probably associated with amyloid. And that meant powerful anticlotting drugs like warfarin could be dangerous for him.
“Here’s a guy on a knife edge of being anticoagulated or not,” Dr. Greenberg said. “There really are major risks on both sides. You can see bad things happening either way.”
Dr. Greenberg decided in the end that the risk from drug like warfarin was not justified. He advised Mr. Reynolds to take baby aspirin, with its mild anticlotting properties.
“It’s only one decision, but it’s a big one,” Dr. Greenberg said.
So far, Mr. Reynolds has done well, with no recurrence of the numbness and no signs of a stroke.
“I’m feeling pretty good,” he said.
Monday, June 30, 2008
Sunday, May 25, 2008
Welcome to Max’s World (Growing up with Bipolar disorder)
Bipolar disorder is a mystery and a subject of medical debate. But for the Blakes, it's just reality.
Mary Carmichael
NEWSWEEK
Updated: 3:48 PM ET May 17, 2008
Max Blake was 7 the first time he tried to kill himself. He wrote a four-page will bequeathing his toys to his friends and jumped out his ground-floor bedroom window, falling six feet into his backyard, bruised but in one piece. Children don't really know what death is, as the last page of Max's will made clear: "If I'm still alive when I have grandchildren," it began. But they know what unhappiness is and what it means to suffer. On a recent Monday afternoon, Max, now 10,
was supposed to come home on the schoolbus, but a counselor summoned his mother at 2:15. When Amy Blake arrived at school, her son gave her the note that had prompted the call. "Dear Mommy & Daddy," it read, "I am really feeling sad and depressed and lousy about myself. I love you but I still feel like I want to kill myself. I am really sad but I just want help to feel happy again. The reason I feel so bad is because I can't sleep at night. And dad yells at me to just sleep at night. But, I can't control it. It is not me that does control it. I don't know what controls it, but it is not me. I really really need some help, love Max!!!!! I Love you Mommy I Love you Daddy."
This is the story of a family: a mother, a father and a son. It is, in many ways, a horror story. Terrible things happen. People scream and cry and hurt each other; they say and do things that they later wish they hadn't. The source of their pain is bipolar disorder, a mental illness that results in recurring bouts of mania and depression. It is an elusive disease that no parent fully understands, that some doctors do not believe exists in children, that almost everyone stigmatizes. But this is also a love story. Good things happen. A couple sticks together, a child tries to do better, teachers and doctors and friends help out. Max Blake and his parents may not have much in common with other families. They are a family nonetheless. That is what has
mattered most to Amy and Richie Blake since Oct. 31, 1997, the day
their son took his first ragged breath.
Max came into the world with a hole in his heart. Struggling to be born, he lost oxygen, and doctors performed an emergency C-section. Recovering from the operation, Amy feared her infant son would need surgery, too, but the doctors said the hole would close with time.
Four days later the Blakes wrapped their baby in a blanket and brought him home to their little house in Peabody, Mass. Richie, a former Marine, was working as a county corrections officer. Amy was a promising divorce lawyer at a firm in nearby Boston. As children, both Richie and Amy had watched their parents split up, but they had found a comfortable routine in each other: he played straight man to her comic. Marriage suited them. Amy hung a large, sunny wedding portrait in the living room. Starting a family would not be easy: there were no grandparents living nearby, and Amy could take only three months of maternity leave. Still, she thought, this was a stable home, one where Max would be safe and happy.
The mothers of bipolar kids often say their babies are born screaming. These are children who live at the extremes: so giddy they can't speak in sentences, so low they refuse to speak at all. Unlike bipolar adults, they flit rapidly between emotions; sometimes they seem to
feel everything at once. At least 800,000 children in the United States have been diagnosed as bipolar, no doubt some of them wrongly. The disease is hard to pin down. The bipolar brain is miswired, but no one knows why it develops that way. There are many drugs, but it's
unclear how they work. Often, they don't work at all, and they may interfere with normal brain growth. There are no studies on their long-term effects in children. Yet untreated bipolar disorder can be disastrous; 10 percent of sufferers commit suicide. Parents must choose between two wrenching options: treat their children and risk a bad outcome, or don't treat and risk a worse one. No matter what they do, they are in for uncertainty and pain.
Amy knew none of this when Max was born. She did know new motherhood was tough. Max never slept through the night, and neither did she. He cried for hours at a time. He banged his head against his crib and screamed until his face burned red. Nursing, cuddling, pacifiers—none
of them helped. At 2 a.m., at 3, at 4 and 5 and 6, Amy cradled her son, trying to believe this was typical infant irritability, the kind her friends with kids had warned her about. It must be colic or gas, she thought, as Max howled another day into being. Exhausted, mystified, she made jokes—he was born on Halloween, she ate too many spicy chicken wings before delivery—trying to explain how a baby too young to hold up his head could raise such hell.
After a year, the jokes gave way to worry. Max was reaching and surpassing his milestones, walking by 10 months and talking in sentences by age 1, but he wasn't like the babies in parenting books. Richie carried his son to the backyard and tried to put him down, but
Max shrank back in his father's arms; he hated the feel of the grass beneath his small bare feet. Amy gave Max a bath and turned on the exhaust fan; he put his hands over his ears and screamed. At 13 months, he lined up dozens of Hot Wheels in the same direction, and
when Amy nudged one out of order, he shrieked "like you'd just cut his arm off." At day care, he terrorized his teachers and playmates. He wasn't the biggest kid in the class, but he attacked without provocation or warning, biting hard enough to leave teeth marks. Every day, he hit and kicked and spat. Worries became guilt. Amy had been overweight and dehydrated in pregnancy. Was Max so explosive because she had done something wrong?
By 18 months, the day-care facility was threatening to throw Max out, and the Blakes were desperate. Richie, the drill sergeant, tried the strict discipline he'd grown up with—he said no, he withheld TV and dessert, he spanked. It didn't work. Amy, the lawyer, tried bargaining
with her toddler. That didn't work either. Amy and Richie started to fight about how to raise their son. The family's pediatrician had been treating kids for decades—he had once been Amy's doctor—but he had no answers. All he could say was that this wasn't the terrible twos come
early. It was bigger than anything he could fix, and if the Blakes wanted help, they would have to look for it 20 miles down the road.
The Blakes started calling doctors in Boston. After three months of trying, they got through to Joseph Jankowski, chief of child psychiatry at Tufts-New England Medical Center, and scheduled an appointment for Nov. 18, just after Max's 2nd birthday. Jankowski ran several lab tests, but they showed little except for slightly high levels of a metabolic enzyme. He ordered a brain scan and sat down with his interns to watch his new patient. Max behaved as usual: he screamed and bit Amy, then gathered up pieces of paper to draw on, only to rip them to shreds. After an hour, Jankowski said he thought Max might have bipolar disorder. He told the Blakes little else.
To the Blakes, bipolar disorder was as foreign as dengue fever. Amy had heard of "manic-depression," but that was a serious illness, one that didn't strike children. Although the National Institute of Mental Health (NIMH) estimates that 5.7 million American adults are affected by the disorder, most doctors, then as now, consider it impossible to diagnose in toddlers. There are still those who joke that every child is "bipolar": up, down, at the mercy of emotion. Amy had her doubts as well. She sat in Jankowski's office and wondered if she should get a second opinion. Worn down, she looked at the degrees on his wall, at the name embroidered on his white coat. "Well," she thought, "I hope he knows what he's talking about."
Jankowski wanted to put Max on a low dose of Depakote, a drug used for seizures, migraines and bipolar disorder. Amy was used to migraine medications—she'd had the headaches for years—and she and some of her family members had taken antidepressants. Richie was more wary. Like many people, he didn't think children should be on powerful psychoactive meds. He worried about side effects, a concern that would dog him and Amy for years to come. Max lasted on Depakote for just three weeks. He wasn't eating and couldn't sleep. Jankowski tried Zyprexa, an antipsychotic. Within days, Max started eating again. For the first time Amy could remember, he slept like the baby he was. "Good," Amy thought. "We'll keep him on this for a few weeks, like an antibiotic. Then he'll get well and we'll move on."
On Feb. 4, Jankowski said he had a diagnosis. Amy was hoping for something with a cure—"something like a brain tumor, even, something we could read about and understand and fix." Most likely, she thought, it would be attention-deficit/hyperactivity disorder; her friends'
kids all had that. Richie thought that whatever Max had, he might grow out of it, the way the hole in his heart had healed on its own. But Jankowski had little comfort for the Blakes. Their son's problem was serious and incurable: a life sentence. Jankowski's first impression
had been borne out. Max was bipolar. Amy and Richie took their son home, and Amy started writing in a notebook that would become a complete log of Max's medical history: "dx: Bipolar Disorder, Hyperactivity." Then she closed the notebook. Max was screaming again.
There was one good thing about this strange diagnosis, she thought: at least it meant she wasn't a bad mother.
At the time, pediatric bipolar disorder was obscure, even within child psychiatry. Doctors at Massachusetts General Hospital (MGH) fully described the disorder just four years before Max's diagnosis. In 1995, child psychiatrist Joseph Biederman and his protégée Janet Wozniak reported that 16 percent of the kids in their clinic had a form of the illness. "Back then it was considered so rare in children that you might see one in your entire career," says Wozniak. "But we'd been blind to children who were right in front of us." Doctors had missed the fact that their young patients were bouncing between pathological highs and lows, she says: if they saw kids on the upswing, they diagnosed hyperactivity, and if they saw the down side, they diagnosed depression. The MGH team's ideas left many doctors skeptical, but other psychiatrists followed them closely.
Scientists now know that bipolar children have too much activity in a part of the brain called the amygdala, which regulates emotions, and not enough in the prefrontal cortex, the seat of rational thought. "They get so emotional that they can't think," says Mani Pavuluri, a child psychiatrist at the University of Illinois at Chicago. More than the rest of us, a bipolar child perceives the world as a dramatic and dangerous place. If he is shown a picture of a neutral face, he may see it as angry. Show him one that really is angry, and his prefrontal cortex will shut down while his amygdala lights up like a firecracker. The typical result: a fury that feeds on itself. Neurological research has its limits, though, and bipolar disorder still cannot be identified based on brain scans. Diagnosing it is more art than science. Many psychiatrists think that in the years since Max's diagnosis, doctors have erred on the side of seeing it everywhere, mislabeling kids and creating a lucrative market for drug companies. Even one of Max's docs says he thinks nine out of 10 kids with the bipolar label have been wrongly classified. But this sort of debate doesn't much interest Amy. "I don't care what diagnosis Max has," she says. "To me, the concern is, what are we going to do about it?"
In the months after his diagnosis, Max's med log filled up with drug after drug, but he didn't get any better. His private day care kicked him out at 28 months, and the Blakes transferred him to their best remaining option, a public-school special education program. Now he was surrounded by children with physical or serious learning disabilities, in the care of people who were neither trained nor able to handle such a small, angry bull. Amy would drop him off in the morning, only to arrive at her Boston office and find a message from a teacher telling her to drive back to Peabody and pick him up. There were whole months when he was suspended and the Blakes were stuck at home. Something had to change.
Amy had never stopped thinking about a second opinion. Through a friend, she heard of Jean Frazier, a child psychiatrist at McLean Hospital in Belmont, Mass., who was interested in behavioral therapies as well as drugs. On Dec. 19, 2000—a year, a month and a day after
Max's first visit with Jankowski—the Blakes took their 3-year-old to Frazier's office. Max started off in good spirits, but as the appointment wore on, he began to fidget. He refused to look at Frazier when she asked him questions. He tried to bite Richie. He told Amy he wanted to go home. Instead, the Blakes stayed, and Frazier started asking questions again, this time in a whisper. Now Max paid attention, and Frazier realized something: he had been irritated by
the sound of her voice. Max couldn't tolerate normal volumes of speech. In her notes, she wrote that he was "a handsome young man with dark hair and a twinkle in his eye." She agreed that he had classic symptoms of bipolar disorder, but she ordered a fresh round of brain scans and blood tests. She told the Blakes she wanted to streamline some of Max's meds. They asked about play therapy, which Jankowski had discouraged. She gave them a referral. More important, she gave them hope.
Max was still adrift in the public schools' special-ed program, and soon he would need to go to kindergarten. Under state and federal disability laws, the district had to pay for him to attend private school if it couldn't meet his needs. Hoping to keep Max in the public-school system, Peabody administrators designed a special curriculum for him. He lasted six weeks, punching and cursing and vandalizing the walls, before they gave up and agreed to send him to the Manville School, part of the Judge Baker Children's Center in Boston, at a cost of $64,000 a year. Manville looked like a regular school, with desks and chairs and a brightly colored mural in the
lobby, but it was staffed by social workers and psychologists. It had three teachers for every eight students and almost as many timeout rooms as classrooms. Amy bought a huge three-ring binder where she kept every teacher's note about her son's school-day behavior, the way
another mother might save book reports and drawings of dinosaurs. She also found a babysitter, Jenny Mellor, who could watch Max in the afternoons. Richie arranged to spend more time at home, too. He became a firefighter; he had to sleep at the firehouse two nights a week, but that meant he could spend the following days with his son.
For all the support he was getting, Max's life was still a series of upheavals. In the space of one year, he tried eight psychoactive medications. Despite all the meds—and in part, because of them—he was an emotional wreck. Amy learned to recognize a look in his eyes. When she saw it, she'd think, "Here comes the devil." In January 2002, 4-year-old Max said he wanted to "freeze to death." In June, he ran away; Amy found him hiding under a neighbor's car. Max seemed to think his imaginary friends were real. His parents wondered if he was hearing voices. In the grocery store, he heard a woman laughing in the next aisle and broke down—he thought she was laughing at him.
By now, Amy and Richie were feeling stranded. Max couldn't go to birthday parties, so Amy quietly tossed the invitations in the trash. Some of the Blakes' friends stopped calling. Amy's mother started e-mailing her "cures" for bipolar disorder she'd found on the Web. Amy
wondered if Max's own relatives thought he was "damaged goods." Strangers were no more understanding. One afternoon at the mall, Max threw a fit, and a woman walked up to Amy and told her people like her shouldn't be allowed to have children.
Even at home, Amy and Richie weren't safe from judgment. At their most strained, they turned on each other. Richie had been a patient person before Max came along, but now his patience was worn "as thin as a sheet of paper." Bipolar disorder runs strongly in families, so in the
heat of their arguments, Amy and Richie both yelled the worst thing they could think of: "He's your kid! It's your fault!"
The Blakes had always planned on having another child. During the times when Max was stable—and there were some—Amy found herself thinking about that second baby. She and Richie feared their own genes now, but maybe they could adopt. She started looking at agencies. The next day, Max threw a tantrum, as if to announce that he knew what she was up to. That was when the Blakes decided their first child would be their last. Later, Max started to ask why he didn't have any siblings. At times, Amy said she didn't want him to have to share his toys, or
that "Mommy and Daddy wanted one perfect child, and we got him." There were other times when her patience, like Richie's, was thin, and she felt that Max was sturdy enough to take a joke. Those were the times when she answered his question. "Look in the mirror," she'd say,
half-smiling. "That's why."
By 7½, Max was on so many different drugs that Frazier and his parents could no longer tell if they were helping or hurting him. He was suffering from tics, blinking his eyes, clearing his throat and "pulling his clothes like he wanted to get out of his skin," says Richie. In February 2005, under Frazier's supervision, the Blakes took Max off all his meds. With the chemicals out of his system, Max was not the same child he had been at 2. He was worse. Bipolar disorder
often gets more serious with age. The brain also reacts to some drugs by remodeling itself, and its dopamine receptors end up naked and sensitive. When the drugs are removed, it's a shock. Off his meds, Max became delusional and paranoid. He imagined Amy was poisoning him and
refused to eat anything she cooked. He talked about death constantly and slept little more than two hours a night. Within a month Frazier had put him back on medication, but with a caveat: she wanted to place him in a short-term bed in a child psych ward.
This move did not sit well with the Blakes. They visited Max every day in the hospital but were disturbed to find that many parents with kids on the ward didn't do likewise. They also worried that Max wasn't getting proper treatment. Doctors couldn't check his med levels because he wouldn't sit still for blood tests. Finally, after three weeks, Amy and Richie held him down, and the resulting test showed his levels of lithium were indeed too low to do any good. Against
Frazier's advice, they pulled Max out of the hospital and vowed never to send him away again. Two months later he jumped out his bedroom window.
Today, Max's med log is jammed full of papers: prescription sheets, printouts from Web sites, business cards from doctors. At 10, he has been on 38 different psychoactive drugs. The meds have serious side effects. They have made Max gain weight, and because he's still growing, they frequently need to be changed. The Blakes are aware that many people think their child—any child—should not be on so many drugs. They aren't always happy about it either. But to some degree, they have made their peace with medication.
Max's prognosis has also grown more complex in the seven and a half years since Jankowski first labeled him as bipolar and hyperactive. "He's oppositional defiant, he's dyslexic, he's ADHD, he's OCD," says Amy. "Give me an initial and he has it." Bipolar children, especially those diagnosed early, often have such a litany of disorders. The bipolar brain tries to compensate for its weak prefrontal cortex by roping in other areas to help; these areas may now become dysfunctional, too. Child psychiatrists thus face an enormous practical challenge: they often can't treat one disorder without affecting another one. "It's like a balloon where you push on one side and the other side pops out," says Wozniak, the MGH psychiatrist who helped define childhood bipolar disorder. With kids like Max, she adds, parents often have to settle for "just having one part of the symptoms reduced."
Max's life has improved in some ways since his early childhood. Manville has given him a social life. He still has violent tantrums at school, but he also has a best friend, a sweet blond boy with a mild anxiety disorder. Last year he won a "Welcome Wagon" award after teachers noticed he was always the first to show new students around. When his classmates have outbursts of their own, he talks them down. "He'll say that maybe they need to take some space, take a deep
breath, leave the classroom," says his teacher, Julie Higgins. He has not, however, figured out how to talk himself down, and for all he has progressed as a classmate, he struggles as a student. Technically, Max is in fourth grade—Manville does not separate grade levels—but he is behind in some subjects. He loves science and art, but he has a hard time reading, and although he is creative, he can't put his ideas in a coherent order. Even holding a pencil for more than a few minutes can be a challenge. "Sometimes you can look at him and you know his disorder has captured him," says the school's director, Jim Prince. "But we can't abandon him. We have to be able to hold on to him, sometimes literally, but also emotionally, to help him come out on the
other side."
Max also finds it hard to describe his feelings, deep and strong though they are. Jean Frazier, now at Cambridge (Mass.) Health Alliance, has him sketch his worries on a whiteboard. At a recent appointment Max drew a crab: insomnia was making him "crabby." His other therapist, Stuart Ablon, a clinical psychologist at MGH, tries to reach him through play. Max brings Power Ranger action figures to his sessions. "He likes to demonstrate with the characters that there
is good and evil, and evil usually triumphs," Ablon says. "He is greatly worried that the evil parts of himself will always get thebetter of his good side. But you can't ask him about that directly.
It's too raw." Once, Ablon tried. Max whipped a toy at him, cutting his leg. "As soon as I started to bleed," Ablon says, "he felt ashamed and shut down."
Max's feelings often move faster than his thoughts. Riding home after he wrote his most recent suicide note, he sobbed, "Please don't send me to the hospital." By the time he had walked through the door he was indignant: he had written the note because his teacher had "treated
him unfairly as pre-sual," he said, sending him to timeout. Then he was ashamed for getting in trouble in the first place. "I was scared of disappointing you and Dad because I didn't finish the day at school," he told Amy, knitting his fingers together. "I was sad and scared. I felt like everyone was out to get me." A minute later he was laughing, romping with the family's pet bull mastiff as if he'd never been scared of anything.
Team sports are out of the question; Max is too volatile. But he is learning self-control through therapeutic horseback riding at Challenge Unlimited in Andover, Mass. "We have to teach kids like him to relax," his instructor, Linda Goss, said one recent afternoon as Max rode around an indoor ring. "The trick is to give him choices while also giving him clear directions. He gets a little frustrated, and the horse picks up on that." On cue, Max's horse galloped toward a pair of jumping poles that weren't set up yet. Linda ran, telling him not to jump, but it was too late. The horse made the leap. "I'm sorry," Max said. "I don't have control." But he stayed on long enough
to do a few fancy tricks. Last year he won two bronze medals in the state Special Olympics. He wore them for weeks and wanted to keep them on in the shower.
Karate is helping with his self-esteem, although there have been bumps along the way. At a dojo he used to attend, a teacher tried to toughen him up by calling him a crybaby, and Max quit on the spot. Five months ago he restarted karate at Cervizzi's Martial Arts Academy in North
Reading, Mass., which makes a point of accommodating special-needs kids. He has already earned his yellow belt. "Sometimes he just assumes he's wrong when he isn't," says Kris Smith, his sensei. "He may need extra encouragement at times. But he knows the blocks, kicks
and punches."
It is strange to hear that Max Blake is punching and kicking, phrased as if it's a good thing. He has never acted out in karate class, but he still attacks the people he loves. Jenny Mellor, his babysitter, had a son of her own three years ago, and when she comes over, she brings little Jackson with her. Max is almost always gentle with him. Almost. Last summer, the three of them went swimming in the Blakes' backyard pool, and Jenny found a dead rodent in the filter. Max had heard a lot about rabies at school, and he tore out of the water. Jenny and Jackson kept swimming. Max got angry, hyperventilating and screaming over and over, "Nobody listens to me!" Eventually Jenny became alarmed. She climbed out, went inside and locked herself and
her toddler in the family's home office. Max charged the door,shattering a mirror hung on the back of it. Jenny sat behind the locked door, shaking, and dialed a neighbor for help. She was scared for herself and her son, but, she says, she was "crying for Max." She very nearly quit. But she came back two weeks later, and she has been coming back ever since.
Amy is still figuring out how best to discipline her son. He needs boundaries, but she admits she's a sucker. She used to reward his good behavior with toys, and it seemed to work until she realized it was bribery and also that it was about to bankrupt her. "I started to feel like I had a Toys 'R' Us annex in my house," she says. So, with Ablon's guidance, she is trying to learn a new way to raise Max, using techniques outlined in the book "Treating Explosive Kids."
Richie hasn't read the book. He has too much Marine in him to apply its methods, which focus on the child's concerns and discourage parents from imposing their will. When he was growing up, he says, a kid like Max would have gotten "smacked around a little. Not everybody was touchy-feely and politically correct." He admits he sometimes eggs Max on. "I'm trying to teach him in my own way," he says. It has been tough for Richie to accept that his son is not like other people's
sons. "When I was Max's age, I was playing hockey and baseball. I was athletic," he says. "Max is 10 years old and he can't ride a bicycle, and that bums me out. He can't do a lot of things kids his age can do. But maybe as he gets older—you know, Tom Brady didn't start playing
football until he was 12. There's still hope."
Richie comes from a long line of stoics. There is mental illness in his family tree, but it is not discussed. His brother took his own life at 21; no one knows why. "My father's not going to talk to me about it," says Richie, "because that's the way he is—he doesn't talk about anything." Like his father, Richie is no fan of talking. He also wrestles with some of the same issues as his son: he has a temper, and Amy calls him "inflexible." Richie counters that he's "stern, and she's Caspar Milquetoast." He says he has never been to therapy. But late last year, Amy demanded that the two of them see a marriage counselor. Richie agreed. They went a few times, but there were
"scheduling issues," says Richie, and they haven't gone back. For the moment, they are getting help from the same people who help Max. Anything that makes his life easier makes theirs easier, too.
Max's life, of course, is rarely easy. During a recent appointment at Frazier's office, he went into full-fledged mania. Laughing wildly, he rolled on the floor, then crawled over to his parents and grabbed an empty medication bottle, yelling, "Drugs! I've got drugs! It's child safety!" Richie grabbed it back, Max screamed, Richie threw the bottle across the room, as if playing fetch. Max squealed and dove for it, then began to sing into the neck of the bottle: "Booorn to be wiiiiild
…" Amy rolled her eyes: "Two kids." And then: "It's hard not to laugh."
It was. And it was hard to look at Max, who has borne so much, and remember that the grin on his face was not a sign of childish goofiness but a symptom of an illness. Sadness and anger can be
pathological; anyone can see that. It's harder to see happiness that way. As Amy guided Max out of the office, she asked him if he was OK. Max cocked his head. It took him a few seconds to come up with his answer: "Apparently, yes." On this rare occasion, he'd described himself perfectly.
Max will never truly be OK. In a few years, he will hit puberty, and at that point things will get even more complicated. Teenage rebellion is one thing; a bipolar teenager's rebellion can end in tragedy. "What happens the first time he says to me, 'I'm not taking my pills'?" says Amy. "I can't put them down his throat." She also worries about the end of 10th grade, which is as far as the Manville School goes. Amy doesn't think Max will go back to public school in Peabody, which
means he'll have to find another special school or he'll never go to college. Max hasn't processed that yet; he wants to be an animator and has already set his sights on the Massachusetts College of Art and Design. Amy hasn't really processed it either. Every year she puts money in a college account, although she knows the money almost certainly won't be used for tuition. "I want to believe that Max will have this great normal life, but I don't know what's going to happen,"
she says. "I wouldn't be able to get up in the morning if I thought about it. So I don't anymore."
There are scientists who have thought about the future of children like Max in great depth. Many still think bipolar disorder is vastly overdiagnosed, but they agree that those who have it face a long, rough road. Two years ago the NIMH released findings from a large study of kids diagnosed between 7 and 17. The ones who fared badly had an early onset of the disorder, as well as psychosis, anxiety, ADHD and a tendency to switch quickly between mania and depression. Max has all these. His chances do not look good.
For now, though, his 18th birthday is a long way off. The Blakes are focusing on making it to his 11th. They have found things to look forward to. "We have Max for better or worse, and there's a lot of worse, but there's a lot of better, too," Amy says. "I'm really lucky because I have a kid who can hug me and tell me he loves me, and there are a lot of autistic kids at Manville whose parents never get that. Through all the tears and the hitting and the 'I hate you,' I get to
hear 'I love you'."
There was a night last month when Max was calm, and after he finished his homework, he curled up in an easy chair with Amy. She was reading him a book, and although it was only 7:45 his eyelids were fluttering. Eventually he began to whine, and Amy asked him if he was about to
start a fight. "Probably," he said. "Let's just get it over with." But he didn't fight. Instead, he was quiet for a few minutes, then he looked at her and said, "Your heart is the size of the world." What he may not realize now, although he surely will someday, is that it has to be.
URL: http://www.newsweek.com/id/137517
Mary Carmichael
NEWSWEEK
Updated: 3:48 PM ET May 17, 2008
Max Blake was 7 the first time he tried to kill himself. He wrote a four-page will bequeathing his toys to his friends and jumped out his ground-floor bedroom window, falling six feet into his backyard, bruised but in one piece. Children don't really know what death is, as the last page of Max's will made clear: "If I'm still alive when I have grandchildren," it began. But they know what unhappiness is and what it means to suffer. On a recent Monday afternoon, Max, now 10,
was supposed to come home on the schoolbus, but a counselor summoned his mother at 2:15. When Amy Blake arrived at school, her son gave her the note that had prompted the call. "Dear Mommy & Daddy," it read, "I am really feeling sad and depressed and lousy about myself. I love you but I still feel like I want to kill myself. I am really sad but I just want help to feel happy again. The reason I feel so bad is because I can't sleep at night. And dad yells at me to just sleep at night. But, I can't control it. It is not me that does control it. I don't know what controls it, but it is not me. I really really need some help, love Max!!!!! I Love you Mommy I Love you Daddy."
This is the story of a family: a mother, a father and a son. It is, in many ways, a horror story. Terrible things happen. People scream and cry and hurt each other; they say and do things that they later wish they hadn't. The source of their pain is bipolar disorder, a mental illness that results in recurring bouts of mania and depression. It is an elusive disease that no parent fully understands, that some doctors do not believe exists in children, that almost everyone stigmatizes. But this is also a love story. Good things happen. A couple sticks together, a child tries to do better, teachers and doctors and friends help out. Max Blake and his parents may not have much in common with other families. They are a family nonetheless. That is what has
mattered most to Amy and Richie Blake since Oct. 31, 1997, the day
their son took his first ragged breath.
Max came into the world with a hole in his heart. Struggling to be born, he lost oxygen, and doctors performed an emergency C-section. Recovering from the operation, Amy feared her infant son would need surgery, too, but the doctors said the hole would close with time.
Four days later the Blakes wrapped their baby in a blanket and brought him home to their little house in Peabody, Mass. Richie, a former Marine, was working as a county corrections officer. Amy was a promising divorce lawyer at a firm in nearby Boston. As children, both Richie and Amy had watched their parents split up, but they had found a comfortable routine in each other: he played straight man to her comic. Marriage suited them. Amy hung a large, sunny wedding portrait in the living room. Starting a family would not be easy: there were no grandparents living nearby, and Amy could take only three months of maternity leave. Still, she thought, this was a stable home, one where Max would be safe and happy.
The mothers of bipolar kids often say their babies are born screaming. These are children who live at the extremes: so giddy they can't speak in sentences, so low they refuse to speak at all. Unlike bipolar adults, they flit rapidly between emotions; sometimes they seem to
feel everything at once. At least 800,000 children in the United States have been diagnosed as bipolar, no doubt some of them wrongly. The disease is hard to pin down. The bipolar brain is miswired, but no one knows why it develops that way. There are many drugs, but it's
unclear how they work. Often, they don't work at all, and they may interfere with normal brain growth. There are no studies on their long-term effects in children. Yet untreated bipolar disorder can be disastrous; 10 percent of sufferers commit suicide. Parents must choose between two wrenching options: treat their children and risk a bad outcome, or don't treat and risk a worse one. No matter what they do, they are in for uncertainty and pain.
Amy knew none of this when Max was born. She did know new motherhood was tough. Max never slept through the night, and neither did she. He cried for hours at a time. He banged his head against his crib and screamed until his face burned red. Nursing, cuddling, pacifiers—none
of them helped. At 2 a.m., at 3, at 4 and 5 and 6, Amy cradled her son, trying to believe this was typical infant irritability, the kind her friends with kids had warned her about. It must be colic or gas, she thought, as Max howled another day into being. Exhausted, mystified, she made jokes—he was born on Halloween, she ate too many spicy chicken wings before delivery—trying to explain how a baby too young to hold up his head could raise such hell.
After a year, the jokes gave way to worry. Max was reaching and surpassing his milestones, walking by 10 months and talking in sentences by age 1, but he wasn't like the babies in parenting books. Richie carried his son to the backyard and tried to put him down, but
Max shrank back in his father's arms; he hated the feel of the grass beneath his small bare feet. Amy gave Max a bath and turned on the exhaust fan; he put his hands over his ears and screamed. At 13 months, he lined up dozens of Hot Wheels in the same direction, and
when Amy nudged one out of order, he shrieked "like you'd just cut his arm off." At day care, he terrorized his teachers and playmates. He wasn't the biggest kid in the class, but he attacked without provocation or warning, biting hard enough to leave teeth marks. Every day, he hit and kicked and spat. Worries became guilt. Amy had been overweight and dehydrated in pregnancy. Was Max so explosive because she had done something wrong?
By 18 months, the day-care facility was threatening to throw Max out, and the Blakes were desperate. Richie, the drill sergeant, tried the strict discipline he'd grown up with—he said no, he withheld TV and dessert, he spanked. It didn't work. Amy, the lawyer, tried bargaining
with her toddler. That didn't work either. Amy and Richie started to fight about how to raise their son. The family's pediatrician had been treating kids for decades—he had once been Amy's doctor—but he had no answers. All he could say was that this wasn't the terrible twos come
early. It was bigger than anything he could fix, and if the Blakes wanted help, they would have to look for it 20 miles down the road.
The Blakes started calling doctors in Boston. After three months of trying, they got through to Joseph Jankowski, chief of child psychiatry at Tufts-New England Medical Center, and scheduled an appointment for Nov. 18, just after Max's 2nd birthday. Jankowski ran several lab tests, but they showed little except for slightly high levels of a metabolic enzyme. He ordered a brain scan and sat down with his interns to watch his new patient. Max behaved as usual: he screamed and bit Amy, then gathered up pieces of paper to draw on, only to rip them to shreds. After an hour, Jankowski said he thought Max might have bipolar disorder. He told the Blakes little else.
To the Blakes, bipolar disorder was as foreign as dengue fever. Amy had heard of "manic-depression," but that was a serious illness, one that didn't strike children. Although the National Institute of Mental Health (NIMH) estimates that 5.7 million American adults are affected by the disorder, most doctors, then as now, consider it impossible to diagnose in toddlers. There are still those who joke that every child is "bipolar": up, down, at the mercy of emotion. Amy had her doubts as well. She sat in Jankowski's office and wondered if she should get a second opinion. Worn down, she looked at the degrees on his wall, at the name embroidered on his white coat. "Well," she thought, "I hope he knows what he's talking about."
Jankowski wanted to put Max on a low dose of Depakote, a drug used for seizures, migraines and bipolar disorder. Amy was used to migraine medications—she'd had the headaches for years—and she and some of her family members had taken antidepressants. Richie was more wary. Like many people, he didn't think children should be on powerful psychoactive meds. He worried about side effects, a concern that would dog him and Amy for years to come. Max lasted on Depakote for just three weeks. He wasn't eating and couldn't sleep. Jankowski tried Zyprexa, an antipsychotic. Within days, Max started eating again. For the first time Amy could remember, he slept like the baby he was. "Good," Amy thought. "We'll keep him on this for a few weeks, like an antibiotic. Then he'll get well and we'll move on."
On Feb. 4, Jankowski said he had a diagnosis. Amy was hoping for something with a cure—"something like a brain tumor, even, something we could read about and understand and fix." Most likely, she thought, it would be attention-deficit/hyperactivity disorder; her friends'
kids all had that. Richie thought that whatever Max had, he might grow out of it, the way the hole in his heart had healed on its own. But Jankowski had little comfort for the Blakes. Their son's problem was serious and incurable: a life sentence. Jankowski's first impression
had been borne out. Max was bipolar. Amy and Richie took their son home, and Amy started writing in a notebook that would become a complete log of Max's medical history: "dx: Bipolar Disorder, Hyperactivity." Then she closed the notebook. Max was screaming again.
There was one good thing about this strange diagnosis, she thought: at least it meant she wasn't a bad mother.
At the time, pediatric bipolar disorder was obscure, even within child psychiatry. Doctors at Massachusetts General Hospital (MGH) fully described the disorder just four years before Max's diagnosis. In 1995, child psychiatrist Joseph Biederman and his protégée Janet Wozniak reported that 16 percent of the kids in their clinic had a form of the illness. "Back then it was considered so rare in children that you might see one in your entire career," says Wozniak. "But we'd been blind to children who were right in front of us." Doctors had missed the fact that their young patients were bouncing between pathological highs and lows, she says: if they saw kids on the upswing, they diagnosed hyperactivity, and if they saw the down side, they diagnosed depression. The MGH team's ideas left many doctors skeptical, but other psychiatrists followed them closely.
Scientists now know that bipolar children have too much activity in a part of the brain called the amygdala, which regulates emotions, and not enough in the prefrontal cortex, the seat of rational thought. "They get so emotional that they can't think," says Mani Pavuluri, a child psychiatrist at the University of Illinois at Chicago. More than the rest of us, a bipolar child perceives the world as a dramatic and dangerous place. If he is shown a picture of a neutral face, he may see it as angry. Show him one that really is angry, and his prefrontal cortex will shut down while his amygdala lights up like a firecracker. The typical result: a fury that feeds on itself. Neurological research has its limits, though, and bipolar disorder still cannot be identified based on brain scans. Diagnosing it is more art than science. Many psychiatrists think that in the years since Max's diagnosis, doctors have erred on the side of seeing it everywhere, mislabeling kids and creating a lucrative market for drug companies. Even one of Max's docs says he thinks nine out of 10 kids with the bipolar label have been wrongly classified. But this sort of debate doesn't much interest Amy. "I don't care what diagnosis Max has," she says. "To me, the concern is, what are we going to do about it?"
In the months after his diagnosis, Max's med log filled up with drug after drug, but he didn't get any better. His private day care kicked him out at 28 months, and the Blakes transferred him to their best remaining option, a public-school special education program. Now he was surrounded by children with physical or serious learning disabilities, in the care of people who were neither trained nor able to handle such a small, angry bull. Amy would drop him off in the morning, only to arrive at her Boston office and find a message from a teacher telling her to drive back to Peabody and pick him up. There were whole months when he was suspended and the Blakes were stuck at home. Something had to change.
Amy had never stopped thinking about a second opinion. Through a friend, she heard of Jean Frazier, a child psychiatrist at McLean Hospital in Belmont, Mass., who was interested in behavioral therapies as well as drugs. On Dec. 19, 2000—a year, a month and a day after
Max's first visit with Jankowski—the Blakes took their 3-year-old to Frazier's office. Max started off in good spirits, but as the appointment wore on, he began to fidget. He refused to look at Frazier when she asked him questions. He tried to bite Richie. He told Amy he wanted to go home. Instead, the Blakes stayed, and Frazier started asking questions again, this time in a whisper. Now Max paid attention, and Frazier realized something: he had been irritated by
the sound of her voice. Max couldn't tolerate normal volumes of speech. In her notes, she wrote that he was "a handsome young man with dark hair and a twinkle in his eye." She agreed that he had classic symptoms of bipolar disorder, but she ordered a fresh round of brain scans and blood tests. She told the Blakes she wanted to streamline some of Max's meds. They asked about play therapy, which Jankowski had discouraged. She gave them a referral. More important, she gave them hope.
Max was still adrift in the public schools' special-ed program, and soon he would need to go to kindergarten. Under state and federal disability laws, the district had to pay for him to attend private school if it couldn't meet his needs. Hoping to keep Max in the public-school system, Peabody administrators designed a special curriculum for him. He lasted six weeks, punching and cursing and vandalizing the walls, before they gave up and agreed to send him to the Manville School, part of the Judge Baker Children's Center in Boston, at a cost of $64,000 a year. Manville looked like a regular school, with desks and chairs and a brightly colored mural in the
lobby, but it was staffed by social workers and psychologists. It had three teachers for every eight students and almost as many timeout rooms as classrooms. Amy bought a huge three-ring binder where she kept every teacher's note about her son's school-day behavior, the way
another mother might save book reports and drawings of dinosaurs. She also found a babysitter, Jenny Mellor, who could watch Max in the afternoons. Richie arranged to spend more time at home, too. He became a firefighter; he had to sleep at the firehouse two nights a week, but that meant he could spend the following days with his son.
For all the support he was getting, Max's life was still a series of upheavals. In the space of one year, he tried eight psychoactive medications. Despite all the meds—and in part, because of them—he was an emotional wreck. Amy learned to recognize a look in his eyes. When she saw it, she'd think, "Here comes the devil." In January 2002, 4-year-old Max said he wanted to "freeze to death." In June, he ran away; Amy found him hiding under a neighbor's car. Max seemed to think his imaginary friends were real. His parents wondered if he was hearing voices. In the grocery store, he heard a woman laughing in the next aisle and broke down—he thought she was laughing at him.
By now, Amy and Richie were feeling stranded. Max couldn't go to birthday parties, so Amy quietly tossed the invitations in the trash. Some of the Blakes' friends stopped calling. Amy's mother started e-mailing her "cures" for bipolar disorder she'd found on the Web. Amy
wondered if Max's own relatives thought he was "damaged goods." Strangers were no more understanding. One afternoon at the mall, Max threw a fit, and a woman walked up to Amy and told her people like her shouldn't be allowed to have children.
Even at home, Amy and Richie weren't safe from judgment. At their most strained, they turned on each other. Richie had been a patient person before Max came along, but now his patience was worn "as thin as a sheet of paper." Bipolar disorder runs strongly in families, so in the
heat of their arguments, Amy and Richie both yelled the worst thing they could think of: "He's your kid! It's your fault!"
The Blakes had always planned on having another child. During the times when Max was stable—and there were some—Amy found herself thinking about that second baby. She and Richie feared their own genes now, but maybe they could adopt. She started looking at agencies. The next day, Max threw a tantrum, as if to announce that he knew what she was up to. That was when the Blakes decided their first child would be their last. Later, Max started to ask why he didn't have any siblings. At times, Amy said she didn't want him to have to share his toys, or
that "Mommy and Daddy wanted one perfect child, and we got him." There were other times when her patience, like Richie's, was thin, and she felt that Max was sturdy enough to take a joke. Those were the times when she answered his question. "Look in the mirror," she'd say,
half-smiling. "That's why."
By 7½, Max was on so many different drugs that Frazier and his parents could no longer tell if they were helping or hurting him. He was suffering from tics, blinking his eyes, clearing his throat and "pulling his clothes like he wanted to get out of his skin," says Richie. In February 2005, under Frazier's supervision, the Blakes took Max off all his meds. With the chemicals out of his system, Max was not the same child he had been at 2. He was worse. Bipolar disorder
often gets more serious with age. The brain also reacts to some drugs by remodeling itself, and its dopamine receptors end up naked and sensitive. When the drugs are removed, it's a shock. Off his meds, Max became delusional and paranoid. He imagined Amy was poisoning him and
refused to eat anything she cooked. He talked about death constantly and slept little more than two hours a night. Within a month Frazier had put him back on medication, but with a caveat: she wanted to place him in a short-term bed in a child psych ward.
This move did not sit well with the Blakes. They visited Max every day in the hospital but were disturbed to find that many parents with kids on the ward didn't do likewise. They also worried that Max wasn't getting proper treatment. Doctors couldn't check his med levels because he wouldn't sit still for blood tests. Finally, after three weeks, Amy and Richie held him down, and the resulting test showed his levels of lithium were indeed too low to do any good. Against
Frazier's advice, they pulled Max out of the hospital and vowed never to send him away again. Two months later he jumped out his bedroom window.
Today, Max's med log is jammed full of papers: prescription sheets, printouts from Web sites, business cards from doctors. At 10, he has been on 38 different psychoactive drugs. The meds have serious side effects. They have made Max gain weight, and because he's still growing, they frequently need to be changed. The Blakes are aware that many people think their child—any child—should not be on so many drugs. They aren't always happy about it either. But to some degree, they have made their peace with medication.
Max's prognosis has also grown more complex in the seven and a half years since Jankowski first labeled him as bipolar and hyperactive. "He's oppositional defiant, he's dyslexic, he's ADHD, he's OCD," says Amy. "Give me an initial and he has it." Bipolar children, especially those diagnosed early, often have such a litany of disorders. The bipolar brain tries to compensate for its weak prefrontal cortex by roping in other areas to help; these areas may now become dysfunctional, too. Child psychiatrists thus face an enormous practical challenge: they often can't treat one disorder without affecting another one. "It's like a balloon where you push on one side and the other side pops out," says Wozniak, the MGH psychiatrist who helped define childhood bipolar disorder. With kids like Max, she adds, parents often have to settle for "just having one part of the symptoms reduced."
Max's life has improved in some ways since his early childhood. Manville has given him a social life. He still has violent tantrums at school, but he also has a best friend, a sweet blond boy with a mild anxiety disorder. Last year he won a "Welcome Wagon" award after teachers noticed he was always the first to show new students around. When his classmates have outbursts of their own, he talks them down. "He'll say that maybe they need to take some space, take a deep
breath, leave the classroom," says his teacher, Julie Higgins. He has not, however, figured out how to talk himself down, and for all he has progressed as a classmate, he struggles as a student. Technically, Max is in fourth grade—Manville does not separate grade levels—but he is behind in some subjects. He loves science and art, but he has a hard time reading, and although he is creative, he can't put his ideas in a coherent order. Even holding a pencil for more than a few minutes can be a challenge. "Sometimes you can look at him and you know his disorder has captured him," says the school's director, Jim Prince. "But we can't abandon him. We have to be able to hold on to him, sometimes literally, but also emotionally, to help him come out on the
other side."
Max also finds it hard to describe his feelings, deep and strong though they are. Jean Frazier, now at Cambridge (Mass.) Health Alliance, has him sketch his worries on a whiteboard. At a recent appointment Max drew a crab: insomnia was making him "crabby." His other therapist, Stuart Ablon, a clinical psychologist at MGH, tries to reach him through play. Max brings Power Ranger action figures to his sessions. "He likes to demonstrate with the characters that there
is good and evil, and evil usually triumphs," Ablon says. "He is greatly worried that the evil parts of himself will always get thebetter of his good side. But you can't ask him about that directly.
It's too raw." Once, Ablon tried. Max whipped a toy at him, cutting his leg. "As soon as I started to bleed," Ablon says, "he felt ashamed and shut down."
Max's feelings often move faster than his thoughts. Riding home after he wrote his most recent suicide note, he sobbed, "Please don't send me to the hospital." By the time he had walked through the door he was indignant: he had written the note because his teacher had "treated
him unfairly as pre-sual," he said, sending him to timeout. Then he was ashamed for getting in trouble in the first place. "I was scared of disappointing you and Dad because I didn't finish the day at school," he told Amy, knitting his fingers together. "I was sad and scared. I felt like everyone was out to get me." A minute later he was laughing, romping with the family's pet bull mastiff as if he'd never been scared of anything.
Team sports are out of the question; Max is too volatile. But he is learning self-control through therapeutic horseback riding at Challenge Unlimited in Andover, Mass. "We have to teach kids like him to relax," his instructor, Linda Goss, said one recent afternoon as Max rode around an indoor ring. "The trick is to give him choices while also giving him clear directions. He gets a little frustrated, and the horse picks up on that." On cue, Max's horse galloped toward a pair of jumping poles that weren't set up yet. Linda ran, telling him not to jump, but it was too late. The horse made the leap. "I'm sorry," Max said. "I don't have control." But he stayed on long enough
to do a few fancy tricks. Last year he won two bronze medals in the state Special Olympics. He wore them for weeks and wanted to keep them on in the shower.
Karate is helping with his self-esteem, although there have been bumps along the way. At a dojo he used to attend, a teacher tried to toughen him up by calling him a crybaby, and Max quit on the spot. Five months ago he restarted karate at Cervizzi's Martial Arts Academy in North
Reading, Mass., which makes a point of accommodating special-needs kids. He has already earned his yellow belt. "Sometimes he just assumes he's wrong when he isn't," says Kris Smith, his sensei. "He may need extra encouragement at times. But he knows the blocks, kicks
and punches."
It is strange to hear that Max Blake is punching and kicking, phrased as if it's a good thing. He has never acted out in karate class, but he still attacks the people he loves. Jenny Mellor, his babysitter, had a son of her own three years ago, and when she comes over, she brings little Jackson with her. Max is almost always gentle with him. Almost. Last summer, the three of them went swimming in the Blakes' backyard pool, and Jenny found a dead rodent in the filter. Max had heard a lot about rabies at school, and he tore out of the water. Jenny and Jackson kept swimming. Max got angry, hyperventilating and screaming over and over, "Nobody listens to me!" Eventually Jenny became alarmed. She climbed out, went inside and locked herself and
her toddler in the family's home office. Max charged the door,shattering a mirror hung on the back of it. Jenny sat behind the locked door, shaking, and dialed a neighbor for help. She was scared for herself and her son, but, she says, she was "crying for Max." She very nearly quit. But she came back two weeks later, and she has been coming back ever since.
Amy is still figuring out how best to discipline her son. He needs boundaries, but she admits she's a sucker. She used to reward his good behavior with toys, and it seemed to work until she realized it was bribery and also that it was about to bankrupt her. "I started to feel like I had a Toys 'R' Us annex in my house," she says. So, with Ablon's guidance, she is trying to learn a new way to raise Max, using techniques outlined in the book "Treating Explosive Kids."
Richie hasn't read the book. He has too much Marine in him to apply its methods, which focus on the child's concerns and discourage parents from imposing their will. When he was growing up, he says, a kid like Max would have gotten "smacked around a little. Not everybody was touchy-feely and politically correct." He admits he sometimes eggs Max on. "I'm trying to teach him in my own way," he says. It has been tough for Richie to accept that his son is not like other people's
sons. "When I was Max's age, I was playing hockey and baseball. I was athletic," he says. "Max is 10 years old and he can't ride a bicycle, and that bums me out. He can't do a lot of things kids his age can do. But maybe as he gets older—you know, Tom Brady didn't start playing
football until he was 12. There's still hope."
Richie comes from a long line of stoics. There is mental illness in his family tree, but it is not discussed. His brother took his own life at 21; no one knows why. "My father's not going to talk to me about it," says Richie, "because that's the way he is—he doesn't talk about anything." Like his father, Richie is no fan of talking. He also wrestles with some of the same issues as his son: he has a temper, and Amy calls him "inflexible." Richie counters that he's "stern, and she's Caspar Milquetoast." He says he has never been to therapy. But late last year, Amy demanded that the two of them see a marriage counselor. Richie agreed. They went a few times, but there were
"scheduling issues," says Richie, and they haven't gone back. For the moment, they are getting help from the same people who help Max. Anything that makes his life easier makes theirs easier, too.
Max's life, of course, is rarely easy. During a recent appointment at Frazier's office, he went into full-fledged mania. Laughing wildly, he rolled on the floor, then crawled over to his parents and grabbed an empty medication bottle, yelling, "Drugs! I've got drugs! It's child safety!" Richie grabbed it back, Max screamed, Richie threw the bottle across the room, as if playing fetch. Max squealed and dove for it, then began to sing into the neck of the bottle: "Booorn to be wiiiiild
…" Amy rolled her eyes: "Two kids." And then: "It's hard not to laugh."
It was. And it was hard to look at Max, who has borne so much, and remember that the grin on his face was not a sign of childish goofiness but a symptom of an illness. Sadness and anger can be
pathological; anyone can see that. It's harder to see happiness that way. As Amy guided Max out of the office, she asked him if he was OK. Max cocked his head. It took him a few seconds to come up with his answer: "Apparently, yes." On this rare occasion, he'd described himself perfectly.
Max will never truly be OK. In a few years, he will hit puberty, and at that point things will get even more complicated. Teenage rebellion is one thing; a bipolar teenager's rebellion can end in tragedy. "What happens the first time he says to me, 'I'm not taking my pills'?" says Amy. "I can't put them down his throat." She also worries about the end of 10th grade, which is as far as the Manville School goes. Amy doesn't think Max will go back to public school in Peabody, which
means he'll have to find another special school or he'll never go to college. Max hasn't processed that yet; he wants to be an animator and has already set his sights on the Massachusetts College of Art and Design. Amy hasn't really processed it either. Every year she puts money in a college account, although she knows the money almost certainly won't be used for tuition. "I want to believe that Max will have this great normal life, but I don't know what's going to happen,"
she says. "I wouldn't be able to get up in the morning if I thought about it. So I don't anymore."
There are scientists who have thought about the future of children like Max in great depth. Many still think bipolar disorder is vastly overdiagnosed, but they agree that those who have it face a long, rough road. Two years ago the NIMH released findings from a large study of kids diagnosed between 7 and 17. The ones who fared badly had an early onset of the disorder, as well as psychosis, anxiety, ADHD and a tendency to switch quickly between mania and depression. Max has all these. His chances do not look good.
For now, though, his 18th birthday is a long way off. The Blakes are focusing on making it to his 11th. They have found things to look forward to. "We have Max for better or worse, and there's a lot of worse, but there's a lot of better, too," Amy says. "I'm really lucky because I have a kid who can hug me and tell me he loves me, and there are a lot of autistic kids at Manville whose parents never get that. Through all the tears and the hitting and the 'I hate you,' I get to
hear 'I love you'."
There was a night last month when Max was calm, and after he finished his homework, he curled up in an easy chair with Amy. She was reading him a book, and although it was only 7:45 his eyelids were fluttering. Eventually he began to whine, and Amy asked him if he was about to
start a fight. "Probably," he said. "Let's just get it over with." But he didn't fight. Instead, he was quiet for a few minutes, then he looked at her and said, "Your heart is the size of the world." What he may not realize now, although he surely will someday, is that it has to be.
URL: http://www.newsweek.com/id/137517
Thursday, May 8, 2008
Can a Lack of Sleep Cause Psychiatric Disorders?
Study shows that sleep deprivation leads to a rewiring of the brain's emotional circuitry
By Nikhil Swaminathan
There's no question that people need their sleep: studies have linked a lack of shut-eye to everything from disruptions in the immune system to cognitive deficits to weight control.
In fact, psychologist Matthew Walker of the University of California, Berkeley, says that "almost all psychiatric disorders show some problems with sleep.'' But, he says that scientists previously believed the psychiatric problems triggered the sleep issues. New research from his lab, however, suggests the reverse is the case; that is, a lack of shut-eye is causing some psychological disturbances.
Walker's team and collaborators from Harvard Medical School reached their conclusions, published in Current Biology, after studying 26 healthy students aged 24 to 31 after either an all-nighter or a full night's sleep.
Fourteen subjects spent 35 straight hours without getting a wink before being rolled into a functional magnetic resonance imaging (fMRI) scanners where their brains were observed while they viewed a set of 100 photos that became increasingly disturbing as they progressed. Early slides were snapshots of an empty wicker basket on a table; the scenes changed as the series progressed, however, to more shocking settings, such as a tarantula on a person's shoulder and finally pictures of burn victims and other traumatic portraits.
The researchers mainly monitored the amygdala, a midbrain structure that decodes emotion, and observed that both sets of volunteers had a similar baseline of activity when shown the innocuous images. But, when the scenes became more gruesome, the amygdalae of the sleep-deprived participants kicked up, showing 60 percent more activity relative to the normal population's response. In addition, the researchers noticed that more than five times more neurons in the area were transmitting impulses in the sleep-deprived brains.
Walker described the heightened emotional response in the weary as "profound," noting, "We've never seen a magnitude of increase between two groups that big in any of our studies before."
The team also checked the fMRI readings to determine whether any other brain regions had a similar pattern of activity, which would indicate that the brain networks were communicating with one another. In normal participants, the amygdala seemed to be talking to the medial prefrontal cortex, an outer layer of the brain that, Walker says, helps to contextualize experiences and emotions. But, in the sleep-deprived brain, the amygdala seemed to be "rewired," coupling instead with a brain stem area called the locus coeruleus, which secretes norepinephrine, a precursor of the hormone adrenaline that triggers fight-or-flight type reactions.
"Medial prefrontal cortex is the policeman of the emotional brain," Walker says. "It makes us more rational. That top-down, inhibitory connection is severed in the condition of sleep deprivation. … The amygdala seems to be able to run amok." People in this state seem to experience a pendulum of emotions, going from upset and annoyed to giddy in moments, he says.
"There seems to be a causal relationship between impaired sleep and some of the psychiatric symptomatology and disorders that we're seeing," says Robert Stickgold, an associate professor of psychiatry at Harvard Medical School who was not involved in this study. He cites research linking sleep apnea, in which breathing is disrupted, to attention deficit hyperactivity disorder and the evidence of a connection between depression and insomnia as examples. "It might be that those medial frontal regions tell the rest of the brain, 'You can chill,'" he says. "Those circuits become exhausted or altered after a lack of sleep."
Walker says the team now plans to examine the effects of disruption of certain types of sleep, such as REM sleep or slow-wave sleep. "I think we may start to think about a new potential function for sleep," says Walker. "It does actually prepare our emotional brains for next-day social and emotional interactions."
Friday, April 4, 2008
First Gene for Schizophrenia Discovered
By Kristin Leutwyler
No single genetic mutation can ever account for the complex range of symptoms that arise in devastating neuropsychiatric disorders such as schizophrenia. But scientists from the Julius-Maximilians-University of Wuerzburg in Germany have zeroed in on one mutation of a gene on chromosome 22 that appears to play an important role in catatonic schizophrenia particularly severe form of the disease characterized by acute psychotic breaks and disturbed body movements. They will describe their finding, based on an analysis of a large pedigree, in an upcoming issue of Molecular Psychiatry.
Earlier linkage studies lead the team of geneticists, psychiatrists and neuroscientists to examine chromosome 22 more closely and in particular, they focused on a gene encoding a protein called WKL1. This protein appears to share many features with ion channels, complexes that straddle a cell's membrane and help transport electric currents along neurons. (Mutations in one remotely related ion channel, the potassium channel KCNA1 cause a rare movement disorder called episodic ataxia.) Of significance, the researchers found the WKL1 gene transcript exclusively in brain tissue.
Further study is needed to determine if the same WKL1 mutation occurs in other families with a history of schizophrenia, or in uniherited cases of the disease. Still, the scientists are hopeful that their discovery may help elucidate some of the biological mechanisms behind schizophrenia and ultimately one day lead to better treatment options.
No single genetic mutation can ever account for the complex range of symptoms that arise in devastating neuropsychiatric disorders such as schizophrenia. But scientists from the Julius-Maximilians-University of Wuerzburg in Germany have zeroed in on one mutation of a gene on chromosome 22 that appears to play an important role in catatonic schizophrenia particularly severe form of the disease characterized by acute psychotic breaks and disturbed body movements. They will describe their finding, based on an analysis of a large pedigree, in an upcoming issue of Molecular Psychiatry.
Earlier linkage studies lead the team of geneticists, psychiatrists and neuroscientists to examine chromosome 22 more closely and in particular, they focused on a gene encoding a protein called WKL1. This protein appears to share many features with ion channels, complexes that straddle a cell's membrane and help transport electric currents along neurons. (Mutations in one remotely related ion channel, the potassium channel KCNA1 cause a rare movement disorder called episodic ataxia.) Of significance, the researchers found the WKL1 gene transcript exclusively in brain tissue.
Further study is needed to determine if the same WKL1 mutation occurs in other families with a history of schizophrenia, or in uniherited cases of the disease. Still, the scientists are hopeful that their discovery may help elucidate some of the biological mechanisms behind schizophrenia and ultimately one day lead to better treatment options.
Tuesday, April 1, 2008
Instant Expert: The Human Brain
Instant Expert: The Human Brain
• NewScientist.com news service
• Helen Philips
The Human Brain - With one hundred billion nerve cells, the complexity is mind-boggling. Learn more in our cutting edge special report. The brain is the most complex organ in the human body. It produces our every thought, action, memory, feeling and experience of the world.
This jelly-like mass of tissue, weighing in at around 1.4 kilograms, contains a staggering one hundred billion nerve cells, or neurons. The complexity of the connectivity between these cells is mind-boggling. Each neuron can make contact with thousands or even tens of thousands of others, via tiny structures called synapses.
Our brains form a million new connections for every second of our lives. The pattern and strength of the connections is constantly changing and no two brains are alike. It is in these changing connections that memories are stored, habits learned and personalities shaped, by reinforcing certain patterns of brain activity, and losing others.
Grey matter
While people often speak of their "grey matter", the brain also contains white matter. The grey matter is the cell bodies of the neurons, while the white matter is the branching network of thread-like tendrils - called dendrites and axons - that spread out from the cell bodies to connect to other neurons.
But the brain also has another, even more numerous type of cell, called glial cells. These outnumber neurons ten times over. Once thought to be support cells, they are now known to amplify neural signals and to be as important as neurons in mental calculations. There are many different types of neuron, only one of which is unique to humans and the other great apes, the so called spindle cells.
Brain structure is shaped partly by genes, but largely by experience. Only relatively recently it was discovered that new brain cells are being born throughout our lives - a process called neurogenesis. The brain has bursts of growth and then periods of consolidation, when excess connections are pruned.
The most notable bursts are in the first two or three years of life, during puberty, and also a final burst in young adulthood. How a brain ages also depends on genes and lifestyle too. Exercising the brain and giving it the right diet can be just as important as it is for the rest of the body.
Chemical messengers
The neurons in our brains communicate in a variety of ways. Signals pass between them by the release and capture of neurotransmitter and neuromodulator chemicals, such as glutamate, dopamine, acetylcholine, noradrenalin, serotonin and endorphins.
Some neurochemicals work in the synapse, passing specific messages from release sites to collection sites, called receptors. Others also spread their influence more widely, like a radio signal, making whole brain regions more or less sensitive.
These neurochemicals are so important that deficiencies in them are linked to certain diseases.
For example, a loss of dopamine in the basal ganglia, which control movements, leads to Parkinson’s disease. It can also increase susceptibility to addiction because it mediates our sensations of reward and pleasure.
Similarly, a deficiency in serotonin, used by regions involved in emotion, can be linked to depression or mood disorders, and the loss of acetylcholine in the cerebral cortex is characteristic of Alzheimer’s disease.
Brain scanning
Within individual neurons, signals are formed by electrochemical pulses. Collectively, this electrical activity can be detected outside the scalp by an electroencephalogram (EEG).
These signals have wave-like patterns, which scientists classify from alpha (common while we are relaxing or sleeping), through to gamma (active thought). When this activity goes awry, it is called a seizure. Some researchers think that synchronizing the activity in different brain regions is important in perception.
Other ways of imaging brain activity are indirect. Functional magnetic resonance imaging (fMRI) or positron emission tomography (PET) monitor blood flow. MRI scans, computed tomography (CT) scans and diffusion tensor images (DTI) use the magnetic signatures of different tissues, X-ray absorption, or the movement of water molecules in those tissues, to image the brain.
These scanning techniques have revealed which parts of the brain are associated with which functions. Examples include activity related to sensations, movement, libido, choices, regrets, motivations and even racism. However, some experts argue that we put too much trust in these results and that they raise privacy issues.
Before scanning techniques were common, researchers relied on patients with brain damage caused by strokes, head injuries or illnesses, to determine which brain areas are required for certain functions. This approach exposed the regions connected to emotions, dreams, memory, language and perception and to even more enigmatic events, such as religious or "paranormal" experiences.
One famous example was the case of Phineas Gage, a 19th century railroad worker who lost part of the front of his brain when a 1-metre-long iron pole was blasted through his head during an explosion. He recovered physically, but was left with permanent changes to his personality, showing for the first time that specific brain regions are linked to different processes.
Structure in mind
The most obvious anatomical feature of our brains is the undulating surfac of the cerebrum - the deep clefts are known as sulci and its folds are gyri. The cerebrum is the largest part of our brain and is largely made up of the two cerebral hemispheres. It is the most evolutionarily recent brain structure, dealing with more complex cognitive brain activities.
It is often said that the right hemisphere is more creative and emotional and the left deals with logic, but the reality is more complex. Nonetheless, the sides do have some specialisations, with the left dealing with speech and language, the right with spatial and body awareness.
See our Interactive Graphic for more on brain structure
Further anatomical divisions of the cerebral hemispheres are the occipital lobe at the back, devoted to vision, and the parietal lobe above that, dealing with movement, position, orientation and calculation.
Behind the ears and temples lie the temporal lobes, dealing with sound and speech comprehension and some aspects of memory. And to the fore are the frontal and prefrontal lobes, often considered the most highly developed and most "human" of regions, dealing with the most complex thought, decision making, planning, conceptualising, attention control and working memory.
They also deal with complex social emotions such as regret, morality and empathy.
Another way to classify the regions is as sensory cortex and motor cortex, controlling incoming information, and outgoing behaviour respectively.
Below the cerebral hemispheres, but still referred to as part of the forebrain, is the cingulate cortex, which deals with directing behaviour and pain. And beneath this lies the corpus callosum, which connects the two sides of the brain. Other important areas of the forebrain are the basal ganglia, responsible for movement, motivation and reward.
Urges and appetites
Beneath the forebrain lie more primitive brain regions. The limbic system, common to all mammals, deals with urges and appetites. Emotions are most closely linked with structures called the amygdala, caudate nucleus and putamen. Also in the limbic brain are the hippocampus - vital for forming new memories; the thalamus - a kind of sensory relay station; and the hypothalamus, which regulates bodily functions via hormone release from the pituitary gland.
The back of the brain has a highly convoluted and folded swelling called the cerebellum, which stores patterns of movement, habits and repeated tasks - things we can do without thinking about them.
The most primitive parts, the midbrain and brain stem, control the bodily functions we have no conscious control of, such as breathing, heart rate, blood pressure, sleep patterns, and so on. They also control signals that pass between the brain and the rest of the body, through the spinal cord.
Though we have discovered an enormous amount about the brain, huge and crucial mysteries remain. One of the most important is how does the brain produces our conscious experiences?
The vast majority of the brain’s activity is subconscious. But our conscious thoughts, sensations and perceptions - what define us as humans - cannot yet be explained in terms of brain activity.
• NewScientist.com news service
• Helen Philips
The Human Brain - With one hundred billion nerve cells, the complexity is mind-boggling. Learn more in our cutting edge special report. The brain is the most complex organ in the human body. It produces our every thought, action, memory, feeling and experience of the world.
This jelly-like mass of tissue, weighing in at around 1.4 kilograms, contains a staggering one hundred billion nerve cells, or neurons. The complexity of the connectivity between these cells is mind-boggling. Each neuron can make contact with thousands or even tens of thousands of others, via tiny structures called synapses.
Our brains form a million new connections for every second of our lives. The pattern and strength of the connections is constantly changing and no two brains are alike. It is in these changing connections that memories are stored, habits learned and personalities shaped, by reinforcing certain patterns of brain activity, and losing others.
Grey matter
While people often speak of their "grey matter", the brain also contains white matter. The grey matter is the cell bodies of the neurons, while the white matter is the branching network of thread-like tendrils - called dendrites and axons - that spread out from the cell bodies to connect to other neurons.
But the brain also has another, even more numerous type of cell, called glial cells. These outnumber neurons ten times over. Once thought to be support cells, they are now known to amplify neural signals and to be as important as neurons in mental calculations. There are many different types of neuron, only one of which is unique to humans and the other great apes, the so called spindle cells.
Brain structure is shaped partly by genes, but largely by experience. Only relatively recently it was discovered that new brain cells are being born throughout our lives - a process called neurogenesis. The brain has bursts of growth and then periods of consolidation, when excess connections are pruned.
The most notable bursts are in the first two or three years of life, during puberty, and also a final burst in young adulthood. How a brain ages also depends on genes and lifestyle too. Exercising the brain and giving it the right diet can be just as important as it is for the rest of the body.
Chemical messengers
The neurons in our brains communicate in a variety of ways. Signals pass between them by the release and capture of neurotransmitter and neuromodulator chemicals, such as glutamate, dopamine, acetylcholine, noradrenalin, serotonin and endorphins.
Some neurochemicals work in the synapse, passing specific messages from release sites to collection sites, called receptors. Others also spread their influence more widely, like a radio signal, making whole brain regions more or less sensitive.
These neurochemicals are so important that deficiencies in them are linked to certain diseases.
For example, a loss of dopamine in the basal ganglia, which control movements, leads to Parkinson’s disease. It can also increase susceptibility to addiction because it mediates our sensations of reward and pleasure.
Similarly, a deficiency in serotonin, used by regions involved in emotion, can be linked to depression or mood disorders, and the loss of acetylcholine in the cerebral cortex is characteristic of Alzheimer’s disease.
Brain scanning
Within individual neurons, signals are formed by electrochemical pulses. Collectively, this electrical activity can be detected outside the scalp by an electroencephalogram (EEG).
These signals have wave-like patterns, which scientists classify from alpha (common while we are relaxing or sleeping), through to gamma (active thought). When this activity goes awry, it is called a seizure. Some researchers think that synchronizing the activity in different brain regions is important in perception.
Other ways of imaging brain activity are indirect. Functional magnetic resonance imaging (fMRI) or positron emission tomography (PET) monitor blood flow. MRI scans, computed tomography (CT) scans and diffusion tensor images (DTI) use the magnetic signatures of different tissues, X-ray absorption, or the movement of water molecules in those tissues, to image the brain.
These scanning techniques have revealed which parts of the brain are associated with which functions. Examples include activity related to sensations, movement, libido, choices, regrets, motivations and even racism. However, some experts argue that we put too much trust in these results and that they raise privacy issues.
Before scanning techniques were common, researchers relied on patients with brain damage caused by strokes, head injuries or illnesses, to determine which brain areas are required for certain functions. This approach exposed the regions connected to emotions, dreams, memory, language and perception and to even more enigmatic events, such as religious or "paranormal" experiences.
One famous example was the case of Phineas Gage, a 19th century railroad worker who lost part of the front of his brain when a 1-metre-long iron pole was blasted through his head during an explosion. He recovered physically, but was left with permanent changes to his personality, showing for the first time that specific brain regions are linked to different processes.
Structure in mind
The most obvious anatomical feature of our brains is the undulating surfac of the cerebrum - the deep clefts are known as sulci and its folds are gyri. The cerebrum is the largest part of our brain and is largely made up of the two cerebral hemispheres. It is the most evolutionarily recent brain structure, dealing with more complex cognitive brain activities.
It is often said that the right hemisphere is more creative and emotional and the left deals with logic, but the reality is more complex. Nonetheless, the sides do have some specialisations, with the left dealing with speech and language, the right with spatial and body awareness.
See our Interactive Graphic for more on brain structure
Further anatomical divisions of the cerebral hemispheres are the occipital lobe at the back, devoted to vision, and the parietal lobe above that, dealing with movement, position, orientation and calculation.
Behind the ears and temples lie the temporal lobes, dealing with sound and speech comprehension and some aspects of memory. And to the fore are the frontal and prefrontal lobes, often considered the most highly developed and most "human" of regions, dealing with the most complex thought, decision making, planning, conceptualising, attention control and working memory.
They also deal with complex social emotions such as regret, morality and empathy.
Another way to classify the regions is as sensory cortex and motor cortex, controlling incoming information, and outgoing behaviour respectively.
Below the cerebral hemispheres, but still referred to as part of the forebrain, is the cingulate cortex, which deals with directing behaviour and pain. And beneath this lies the corpus callosum, which connects the two sides of the brain. Other important areas of the forebrain are the basal ganglia, responsible for movement, motivation and reward.
Urges and appetites
Beneath the forebrain lie more primitive brain regions. The limbic system, common to all mammals, deals with urges and appetites. Emotions are most closely linked with structures called the amygdala, caudate nucleus and putamen. Also in the limbic brain are the hippocampus - vital for forming new memories; the thalamus - a kind of sensory relay station; and the hypothalamus, which regulates bodily functions via hormone release from the pituitary gland.
The back of the brain has a highly convoluted and folded swelling called the cerebellum, which stores patterns of movement, habits and repeated tasks - things we can do without thinking about them.
The most primitive parts, the midbrain and brain stem, control the bodily functions we have no conscious control of, such as breathing, heart rate, blood pressure, sleep patterns, and so on. They also control signals that pass between the brain and the rest of the body, through the spinal cord.
Though we have discovered an enormous amount about the brain, huge and crucial mysteries remain. One of the most important is how does the brain produces our conscious experiences?
The vast majority of the brain’s activity is subconscious. But our conscious thoughts, sensations and perceptions - what define us as humans - cannot yet be explained in terms of brain activity.
Sunday, March 30, 2008
A new study points to rare gene duplications and deletions that are believed to play a significant role in the psychological disorder
By Nikhil Swaminathan
A new study indicates that the genetic culprits behind schizophrenia may be much less common than previously believed. Researchers report this week in Science that a rare but devastating change in one of several different genes may dramatically increase the risk of developing the debilitating brain disorder affecting 1 percent of the world's population and marked by psychotic behavior, hallucinations and delusions. Until now, most scientists believed that it was likely
that a cluster of relatively common genetic mutations was to blame.
"We're not saying that our results themselves are irrefutable proof that schizophrenia is all rare mutations," says study co-author Jonathan Sebat, a geneticist at Cold Spring Harbor Laboratory in Long Island, N.Y. "But, rare mutations are an important part of the story, and it's this type of risk factors that tend to have the strongest effects."
Until recently, researchers trying to unravel the mysterious disease searched the genomes of schizophrenia patients for flaws not present in the genes of healthy people. Their probes turned up a few possible genetic suspects, but the findings were contradicted by those from other studies. In addition, candidate mutations typically only showed up in no more than 10 percent of schizophrenia sufferers sampled. The new study identifies more than 20 genes that may trigger the disease. If researchers can positively link any or all of these genes to the disease, it would set the stage for development of new therapies.
In this study, researchers combed the genomes of 150 schizophrenia sufferers and 268 healthy individuals for never-before-seen copy number variations (CNVs)—mutations that result in large swaths of DNA encompassing multiple genes either being deleted or duplicated. Some
such mutations have been found to be benign, but others have been implicated in ailments such as autism and cancer. The team of scientists, from research facilities across the U.S., found novel gene alterations in 5 percent of the healthy volunteers and 15 percent of the schizophrenia patients; new CNVs showed up in 20 percent of those subjects who developed symptoms at or before the age of 18.
"What we prove is that, collectively, there is a threefold effect in schizophrenia and a fourfold effect in the childhood-onset disorder," says Mary-Claire King, a geneticist at the University of Washington School of Medicine and another co-author, referring to the incidence of these rare variants between the groups.
The researchers determined which affected genes were likely to cause damage—and where in the body that damage that might occur. The flawed genes in the schizophrenia patients were overwhelmingly linked to changes in pathways responsible for communication between and within nerve cells. In fact, one gene, ERBB4, is known to code for a receptor that interacts with neuregulin 1, a protein that's been associated with the illness for a decade. "The silver lining is that these new findings show us … that we were already on the right track," Sebat says.
Daniel R. Weinberger, director of the Genes, Cognition and Psychosis Program at the National Institute of Mental Health in Bethesda, Md., agrees that CNVs likely play a role. But he doesn't believe the new study demonstrates that they operate alone.
King says the next step is to screen the 20 suspect genes to pinpoint specific defects common among large groups of schizophrenia patients. Sebat acknowledges that the data presented is merely consistent with the rare mutation gene model and not direct proof of it. "It's premature to say that these findings have diagnostic value [right now]," he says. "But, that's exactly where we're headed."
A new study indicates that the genetic culprits behind schizophrenia may be much less common than previously believed. Researchers report this week in Science that a rare but devastating change in one of several different genes may dramatically increase the risk of developing the debilitating brain disorder affecting 1 percent of the world's population and marked by psychotic behavior, hallucinations and delusions. Until now, most scientists believed that it was likely
that a cluster of relatively common genetic mutations was to blame.
"We're not saying that our results themselves are irrefutable proof that schizophrenia is all rare mutations," says study co-author Jonathan Sebat, a geneticist at Cold Spring Harbor Laboratory in Long Island, N.Y. "But, rare mutations are an important part of the story, and it's this type of risk factors that tend to have the strongest effects."
Until recently, researchers trying to unravel the mysterious disease searched the genomes of schizophrenia patients for flaws not present in the genes of healthy people. Their probes turned up a few possible genetic suspects, but the findings were contradicted by those from other studies. In addition, candidate mutations typically only showed up in no more than 10 percent of schizophrenia sufferers sampled. The new study identifies more than 20 genes that may trigger the disease. If researchers can positively link any or all of these genes to the disease, it would set the stage for development of new therapies.
In this study, researchers combed the genomes of 150 schizophrenia sufferers and 268 healthy individuals for never-before-seen copy number variations (CNVs)—mutations that result in large swaths of DNA encompassing multiple genes either being deleted or duplicated. Some
such mutations have been found to be benign, but others have been implicated in ailments such as autism and cancer. The team of scientists, from research facilities across the U.S., found novel gene alterations in 5 percent of the healthy volunteers and 15 percent of the schizophrenia patients; new CNVs showed up in 20 percent of those subjects who developed symptoms at or before the age of 18.
"What we prove is that, collectively, there is a threefold effect in schizophrenia and a fourfold effect in the childhood-onset disorder," says Mary-Claire King, a geneticist at the University of Washington School of Medicine and another co-author, referring to the incidence of these rare variants between the groups.
The researchers determined which affected genes were likely to cause damage—and where in the body that damage that might occur. The flawed genes in the schizophrenia patients were overwhelmingly linked to changes in pathways responsible for communication between and within nerve cells. In fact, one gene, ERBB4, is known to code for a receptor that interacts with neuregulin 1, a protein that's been associated with the illness for a decade. "The silver lining is that these new findings show us … that we were already on the right track," Sebat says.
Daniel R. Weinberger, director of the Genes, Cognition and Psychosis Program at the National Institute of Mental Health in Bethesda, Md., agrees that CNVs likely play a role. But he doesn't believe the new study demonstrates that they operate alone.
King says the next step is to screen the 20 suspect genes to pinpoint specific defects common among large groups of schizophrenia patients. Sebat acknowledges that the data presented is merely consistent with the rare mutation gene model and not direct proof of it. "It's premature to say that these findings have diagnostic value [right now]," he says. "But, that's exactly where we're headed."
Thursday, March 27, 2008
Brain map project set to revolutionize neuroscience
March 2008
NewScientist News Service
By: Peter Aldhous
Take the most complex organ in the human body, superimpose the legacy of biology’s biggest research project, and what have you got? An unprecedented brain map that is set to transform studies of neuroscience and brain disease.
The Allen Institute for Brain Science in Seattle, Washington, US, is today launching a four-year, $55-million effort to build a three-dimensional map documenting the levels of activity of some 20,000 different genes across the human brain.
“The Human Genome Project was the ‘what’, and our project is the ‘where’,” says Allan Jones, the institute’s chief scientific officer.
Established in 2003 with a $100-million gift from Microsoft co-founder Paul Allen, the Allen institute has already created a similar atlas of the mouse brain, unveiled in December 2006.
By revealing patterns of gene activity, the mouse atlas has allowed neuroscientists to identify functionally important regions that were invisible simply by looking at the brain’s anatomy.
Evolution insights
“That’s why the brain is such a unique structure,” says Greg Foltz, a neurosurgeon at the Swedish Neuroscience Institute, also in Seattle. “Its function is very much embedded in its anatomy.”
Foltz’s team has also used the mouse atlas to help home in on two genes, known as BEX1 and BEX2, which seem to be silenced in a form of brain cancer called glioma. An atlas of the human brain should be an even more powerful tool in identifying what goes wrong at the gene level in cancer and other diseases, he says.
For instance, some neuroscientists suspect that autism may be linked to abnormalities in a paired structure called the amygdala, involved in processing emotional information. The genes likely to be involved could be narrowed down by looking in the atlas for those that are active in the amygdala. Researchers could then compare the brains of autism patients with those from people without the condition, matched for age and gender, studying the activity of these candidate genes.
Comparisons between the mouse and human brain atlases should also yield insights into the evolution of our advanced cognitive abilities, suggests David Anderson, a neuroscientist at the California Institute of Technology in Pasadena, and one of the Allen institute’s scientific advisers. “Are there fundamental differences in the organisation of the brain?” he asks.
Huge task
The sheer size of the human brain will make the new project a much bigger challenge.
The mouse atlas was produced using a method called “in situ hybridisation”, in which thin slices of brain tissue are bathed in a solution containing molecular probes that bind to messenger RNA sequences produced by each gene. This gives a very detailed map of gene activity, down to the level of individual cells.
Trying to repeat this effort for all 20,000 genes across an organ about 2000 times larger than the mouse brain is impractical, for now. So Allen institute scientists will instead divide the human brain into between 500 and 2000 anatomical regions, and study gene activity in each by washing extracts from tissues in these regions across “gene chips” that can record which messenger RNA is present.
Once results from this initial phase of the project are in, which will take about two years, the institute’s scientists will perform in situ hybridisation across the whole brain for up to 500 genes with the most interesting patterns of activity.
As well as launching the human brain atlas, the Allen institute is starting two further projects. The first, costing around $15 million over the next two years, will look at the activity of around 4000 mouse genes at different stages in embryological and juvenile development.
A second project, taking about a year to complete at a cost of $2 million, will make an atlas of gene activity in the mouse spinal cord.
The Human Brain - With one hundred billion nerve cells, the complexity is mind-boggling. Learn more in our cutting edge special report.
NewScientist News Service
By: Peter Aldhous
Take the most complex organ in the human body, superimpose the legacy of biology’s biggest research project, and what have you got? An unprecedented brain map that is set to transform studies of neuroscience and brain disease.
The Allen Institute for Brain Science in Seattle, Washington, US, is today launching a four-year, $55-million effort to build a three-dimensional map documenting the levels of activity of some 20,000 different genes across the human brain.
“The Human Genome Project was the ‘what’, and our project is the ‘where’,” says Allan Jones, the institute’s chief scientific officer.
Established in 2003 with a $100-million gift from Microsoft co-founder Paul Allen, the Allen institute has already created a similar atlas of the mouse brain, unveiled in December 2006.
By revealing patterns of gene activity, the mouse atlas has allowed neuroscientists to identify functionally important regions that were invisible simply by looking at the brain’s anatomy.
Evolution insights
“That’s why the brain is such a unique structure,” says Greg Foltz, a neurosurgeon at the Swedish Neuroscience Institute, also in Seattle. “Its function is very much embedded in its anatomy.”
Foltz’s team has also used the mouse atlas to help home in on two genes, known as BEX1 and BEX2, which seem to be silenced in a form of brain cancer called glioma. An atlas of the human brain should be an even more powerful tool in identifying what goes wrong at the gene level in cancer and other diseases, he says.
For instance, some neuroscientists suspect that autism may be linked to abnormalities in a paired structure called the amygdala, involved in processing emotional information. The genes likely to be involved could be narrowed down by looking in the atlas for those that are active in the amygdala. Researchers could then compare the brains of autism patients with those from people without the condition, matched for age and gender, studying the activity of these candidate genes.
Comparisons between the mouse and human brain atlases should also yield insights into the evolution of our advanced cognitive abilities, suggests David Anderson, a neuroscientist at the California Institute of Technology in Pasadena, and one of the Allen institute’s scientific advisers. “Are there fundamental differences in the organisation of the brain?” he asks.
Huge task
The sheer size of the human brain will make the new project a much bigger challenge.
The mouse atlas was produced using a method called “in situ hybridisation”, in which thin slices of brain tissue are bathed in a solution containing molecular probes that bind to messenger RNA sequences produced by each gene. This gives a very detailed map of gene activity, down to the level of individual cells.
Trying to repeat this effort for all 20,000 genes across an organ about 2000 times larger than the mouse brain is impractical, for now. So Allen institute scientists will instead divide the human brain into between 500 and 2000 anatomical regions, and study gene activity in each by washing extracts from tissues in these regions across “gene chips” that can record which messenger RNA is present.
Once results from this initial phase of the project are in, which will take about two years, the institute’s scientists will perform in situ hybridisation across the whole brain for up to 500 genes with the most interesting patterns of activity.
As well as launching the human brain atlas, the Allen institute is starting two further projects. The first, costing around $15 million over the next two years, will look at the activity of around 4000 mouse genes at different stages in embryological and juvenile development.
A second project, taking about a year to complete at a cost of $2 million, will make an atlas of gene activity in the mouse spinal cord.
The Human Brain - With one hundred billion nerve cells, the complexity is mind-boggling. Learn more in our cutting edge special report.
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