C H A P T E R 1

BRAVE NEW BRAINConfronting the Burden

of Mental Illness

O, wonder!

How many goodly creatures are there here!

How beauteous mankind is! O brave new world,

That has such people in't!

—William Shakespeare

The Tempest, v,i, 182-186

uman beings are wondrous, goodly, and beautiful creatures, as

Miranda observed in Shakespeare's magical final play, TheTempest. This play was his farewell to London theater. Shakespeare wroteit in his late forties and then walked away forever, retiring to a quiet life inStratford-on-Avon.We do not know why. In this last play that he wouldever write, he must have wanted to give the world a message that he con-sidered very important. Just as Romeo and Juliet is a great play for teen-agers, The Tempest is a great play for grown-ups. It is about lofty and fun-damental themes, such as conquering evil with goodness and ignorancewith wisdom. It is about love and hope. Because it is both wise and affir-mative, it is my favorite play.

Miranda speaks these lines when she sees other human beings for thefirst time, after a tempest wrecks a ship and the survivors struggle ashore.She has grown up on an isolated island, surrounded only by nonhumancreatures such as the ethereal spirit Ariel and the primal Caliban. Herfather, Prospero, is the only human being she has ever seen. By a twist offate, the survivors include Prospero's brother, Antonio, who betrayed himand banished him from Milan many years ago. Also among them is ahandsome young man, Ferdinand, with whom Miranda falls in love.(Even at almost fifty, Shakespeare still understood the nature of being inlove.) Miranda suddenly envisions a brave new world, filled with beauti-ful and goodly people. The play is about the reconciliation between theestranged brothers and the love that develops between Miranda and Fer-dinand.

Despite the fundamental optimism of his final play, Shakespeare alsoknew that human beings can be very troubled creatures. The Tempest rec-

4 BROKEN BRAINS AND TROUBLED MINDS

ognizes that there are many dark forces around us and within us: misun-derstanding, betrayal, cruelty, hatred, and evil. We murder one another. Welie to one another. Our loved ones develop illnesses, suffer, and die. Weourselves also become ill, suffer, and die. The Tempest is a play that con-fronts such darkness with a seasoned and realistic eye ... and counters itwith light. Optimism based on a foundation of realism is the only truepath to a "brave new world."

Like The Tempest, this book looks at pain and suffering and expressesthe conviction that they can be conquered through enlightenment andknowledge.This book is about building a "brave new brain" It is aboutone group of illnesses that human flesh is heir to: the illnesses that arisefrom the brain and are expressed through the mind. Mental illnesses. It isabout the people who develop them, the friends and relatives who sharetheir suffering, the physicians who treat them, and the scientists whostudy them so that causes can be discovered and better treatments can befound. Ultimately, it is about how the powerful tools of genetics and neu-roscience will be combined during the next several decades to buildhealthier, better, braver brains and minds. To achieve that goal, however,we must first confront the facts of illness, pain, and suffering. As in TheTempest, our optimism must be built on the solid foundation of reality, noton the ephemeral foundation of naivete.

Mental illnesses are often ignored, misunderstood, or stigmatized.Confronting any serious illness makes us feel charged with emotion andfear. It makes those of us who have a capacity for empathy or introspec-tion recognize that we too are vulnerable, and that we too could sufferthe same fate, as could any of our loved ones. We speak the names of ill-nesses—"cancer" . . . "heart attack"—in a hushed and respectful voice.Mental illnesses probably produce the most intense reaction of all, sincethey are the least well understood among the many human illnesses. Ourintuitive reaction, when confronted on the sidewalk with a mumblingand disheveled person suffering from a mental illness, is to look away.Even when a close friend has a problem that requires hospitalization, weare reluctant to visit her. (The excuse is often, "I don't want to embarrassher." Or, "I wouldn't know what to talk about.")

There are many important reasons why we cannot afford to ignoremental illnesses.

First, they are very common. Almost anyone who picks up this bookhas a friend with mental illness, or a family member, or suffers from onehimself or herself. Mental illnesses are among the most common diseasesthat afflict human beings. Schizophrenia affects I% of the population,

5 BRAVE NEW BRAIN

manic-depression another 1%, major depression another 10-20%, andAlzheimer's disease 15% of people over 65. And that is only mentioningthe most severe illnesses.

Second, they are incredibly costly, both economically and psychologi-cally. Worldwide, the cost runs to billions of dollars. In 1990 the WorldHealth Organization did a survey of the cost of medical illness throughoutthe world. The results were recently summarized in a book called TheGlobal Burden of Disease. If asked, many people would guess that the great-est costs are from cancer or heart disease. Wrong. Mental illnesses cost usmore than any other general class of disease.There are many ways to sum-marize the economic burden of disease, but they consistently lead to theconclusion that mental illnesses should be given a high priority for treat-ment and research because of the many ways that they are costly to society.

Table 1-1 shows the figures for the costs due to disability for peoplewho are between 15 and 44 years old. The costs are expressed in a unit ofmeasurement developed by the Harvard researchers who wrote TheGlobal Burden of Disease, known as Disability-Adjusted Life Years(DALYs).This is a composite measure of time lost due to premature mor-tality and the time lived with the disability. A loss of one DALY is equiva-lent to the loss of one year for one person. Among people in the prime oflife, depression costs society more than any other disease, and four mentalillnesses are in the top ten. Self-inflicted injuries (usually suicide as a con-sequence of a mental illness) are also in the top ten. In this age-groupmental illnesses cause us to lose millions of years of potentially productivelife.

TABLE 1-1

The Ten Leading Causes of Disability in the World

Type of Disability Cost (in DALYs)

Unipolar major depression 42,972

Tuberculosis 19,673

Road traffic accidents 191625

Alcohol use 14,848

Self-inflicted injuries 14,645

Manic-depressive illness 13,189

War 13,134

Violence 12,955

Schizophrenia 12,542

Iron deficiency anemia 12,511

6 BROKEN BRAINS AND TROUBLED MINDS

Mental illnesses are not just economically costly. They also take a cruelpsychological toll and are unfortunately often fatal. Suicide claimsapproximately 10% of people with schizophrenia and 10% of people withdepression. Suicide rates are inexorably rising in our most valued nationaland international asset: our children. Losing a child by suicide may be themost painful experience a person can have. But observing how schizo-phrenia invades the personality and mental skills of an adolescent oryoung adult also causes nearly unbearable pain to both the young personand his family. Watching a parent or a spouse die a slow death fromAlzheimer's disease is heartbreaking.

In fact, if we confront reality honestly, we realize that mental illnessesstand out from other human diseases as both special and frightening.They affect the most important organ in our bodies and the most impor-tant capacities that we have. They affect the brain and its product, themind. Modern medicine has taught us that we do not die when our heartstops or when we stop breathing. We die when our brains die, when theystop producing the characteristic electrical rhythms that indicate that ournerve cells are firing. We feel ourselves truly alive when our brains aremost active, when we play (or even excitedly watch) a basketball game,when we read an interesting book, when we listen to a particularlyengaging song or a symphony. What we fear most is not being paralyzedin an accident or even a sudden death by a heart attack, although eitherwould be cruel. We fear losing our minds.

Mental illnesses are that 600—pound gorilla, hidden in the closet, thatwe fear to confront. But we must confront them. They are importantnow, and they will only become more important as the next severaldecades pass by. The global burden of mental illness will continue toincrease, until or unless we proactively identify ways to improve treat-ments or implement preventive measures. Several demographic trendscreate this situation. First, our country is aging, with the consequencethat the number of elderly will increase and will develop the most impor-tant mental illness that affects the elderly: Alzheimer's disease. Second, thebaby boomers are aging. This particular cohort already has higher levelsof depressive and anxiety disorders than previous generations. As thislarge group moves into their sixties, they will also swell the ranks of thosewith Alzheimer's disease. Unless we do something, our children will beleft holding a heavy bag of responsibility and suffering.

The reality of mental illness is painful on many fronts. No wonder wewould like to ignore it.

As in The Tempest, however, we can counter the reality of suffering with

7 BRAVE NEW BRAIN

the reality of hope. During the last two decades of the twentieth century,both psychiatrists and their patients have steadily recognized that mentalillnesses are diseases of the brain that can be understood and treated usingestablished scientific tools. The last decade of the twentieth century wasdesignated by Congress as "The Decade of the Brain."We are at present inthe midst of a golden age of biomedical research.We are currently engagedin two of the most important endeavors in the history of science and med-icine. We are simultaneously mapping the human brain and the humangenome. Each of these is a daunting task. The brain contains billions ofneurons—most estimates are around 10I2.The human genome containsfar fewer genes. Most estimates are around 80,000, or maybe even fewer.Not all are active ("expressed") in all parts of the body—only around20—30,000 in the liver, for example. But most are active in the brain. Themapping of the brain is made possible by a variety of new technologiesthat permit us to understand things on a large scale, a scale that neuroscien-tists refer to as the "level of systems," by which they mean functions of themind such as memory and attention. The mapping of the genome is madepossible by spectacular advances in the technology of molecular geneticsand molecular biology, which work on a very small scale at the level of themolecule.The achievements of these two endeavors are described in detailin chapters 4 through 6 of this book.

The achievements occurring on these two levels will meet oneanother some time within the next decade or perhaps two. When theydo, the payoff will be impressive. We will understand how the cells in ourbrains go bad when their molecules go bad, and we will understand howthis is expressed at the level of systems such as attention and memory sothat human beings develop diseases such as schizophrenia and depression.

Once mind and molecule meet, prevention is possible. Improvementsin treatment are certain.

This book is a travel guide to the future, written to help the curiousunderstand how better treatments and preventive measures will be cre-ated or identified. Part 2, "From Mind to Molecule" (chapters 4-6), intro-duces readers to the scientific foundations of modern psychiatry: thestudy of brain and mind, and the study of genetics and molecular biology.Part 3, "The Burden of Mental Illnesses" (chapters 7—11), gives readerscutting-edge information about what we have learned so far about thediagnosis, mechanisms, and treatment of four major groups of mental ill-nesses: schizophrenia, mood disorders, dementias, and anxiety disorders.

The readers of this book will be sitting in the theater during the firstdecades of the twenty-first century, watching as the hope of conquering

8 BROKEN BRAINS AND TROUBLED MINDS

mental illnesses gradually turns to reality. Perhaps for the first time in his-tory, we can be optimistic about mental illnesses, which have previouslybeen a dreaded scourge. It is an exciting time.

The lights are going down. The first act in this drama begins with areal story about real people, people who suddenly find themselves deal-ing with mental illness, in a world that is still ill-prepared to look at itand see it.

Let's begin with the painful reality. Let's see how mental illness canaffect the lives of ordinary people like you and me.

C H A P T E R 2

A WAKING NIGHTMARE

Mental Illness

and Ordinary People

O the mind, mind has mountains; cliffs of fall

Frightful, sheer, no-man-fathomed. Hold them cheap

May who ne'er hung there. Nor does long our small

Durance deal with that steep or deep.

—Gerard Manley Hopkins

No Worst, There Is None

ary was concerned. She had known Jim for eleven years andhad been married to him for six. He was as solid as a rock.

She could always count on him. Now, suddenly, he seemed to be fallingapart, for no apparent reason. Her rock was turning into a pile of pebblesright before her astonished—and increasingly frightened—eyes. Whatcould be going on?

It started about four months ago.

Jesus, what is wrong with me??Jim fixed a vacant stare on the Alka Seltzer as the bubbles

swarmed about the tablet before rising in the glass.I can't do it. I just CAN'T do this. I can't work all day and try to study

all night. Why did I let myself get into this trap? Mary would be better offwithout me.

The knot in his stomach tightened. He reached for his tooth-brush and knocked the Alka Seltzer glass shattering to the floor. Hesank down to the cool tile floor and held a smooth piece of glass tohis forehead as if to chill the worried thoughts that kept boiling tothe surface. He tried to remember when he began feeling so terri-ble. He tried to think of a reason for the pained feeling in his stom-ach that seemed to poison his concentration and sap away his usualspirit. He could think of no reason. His wife Mary was the joy of hislife. She'd been contentedly supporting his return to business schoolso that he could move on from his construction work to a betterlife. He was only one semester away from taking his place in theworld of boardrooms and laptops. He ought to have it made. So