Cerebrum Article

Brainsick: A Physician’s Journey to the Brink

During the past 10 years, progress has been notable in erasing the stigma of mental illnesses, which we have come to understand are diseases of the brain. But however much we may accept a poet who is manic, a businessman who is anxious, even a politician who is depressed, we still want to think that our scientists and physicians—especially those with long, illustrious careers—are immune. They are not. Leon E. Rosenberg, M.D., former dean of the Yale School of Medicine, former head of pharmaceutical research for Bristol-Meyers Squibb, now professor of molecular biology at Princeton University, describes his harrowing journey to the brink and back. It is past time that he and his affected colleagues speak out, he declares.

Published: October 1, 2002

More than four years ago—on May 26, 1998, to be exact—I awakened during another restless, dreadful night. The clock read 4:15 a.m., so I closed my eyes and tried to be calm. It didn’t work. I got out of bed. “This must end, today,” I thought. “I can’t sleep. I can’t eat. I can’t teach. I can’t even read or write.”

After taking a walk around our farm, I brewed coffee for my wife, Diane, and me, and then helped get our 16-year-old daughter, Alexa, off to high school. Diane asked if she should cancel her appointment to go horseback riding. “No,” I said. “I’m a little less depressed, and you can’t just sit around here day after day and take care of me like I’m a baby. By the time I get a haircut, you’ll be back.”

As soon as she had driven away, I put all the antidepressants and sleeping pills I had into a small satchel, added a full quart bottle of vodka, and headed my car toward Highway 95. I didn’t know where I was going, but it certainly was not to the barber.  As I crossed the bridge into Pennsylvania, I vaguely remember seeing the sign for Highway 32, and I exited. The sun was shimmering on the Delaware River, which only made keeping my eyes on the road more difficult. I saw a sign for New Hope (or was it No Hope?) and drove into town. I wandered up one street and down another until I saw a sign for the Wedgewood Inn.  I had never been there before, but I was too agitated to look further. The Wedgewood it would be.

The proprietress looked askance at the luggage I carried but showed me to a small room anyway. “This will be fine,” I think I said and closed the door. I sat down on the double bed with its chenille spread and put the pills and the vodka on the bedside table. Slowly, almost ritually, I took one or two pills at a time, washed down with a generous swig of vodka. By the time all the pills and more than half the vodka were gone, I started to feel less wired—even quiet.  As I lay down and sank toward what I believed would be death, I found myself thinking of a relative who had committed suicide this way some years earlier. Perhaps I connected with him because my jumbled brain thought he, and only he, might comprehend what I was doing.

I woke up 12 hours later with a headache, dizziness, nausea, and hiccups. I stumbled out to my car in the darkness, and called my wife from the cell phone. I remember being so relieved to hear her voice. “We’ve been looking all over for you,” she said, “where are you?” I told her what I had done, where I was, and that I wanted to come home. “Stay right where you are,” she said.

About 30 minutes later, a Pennsylvania state policeman pulled his car into the parking lot. I got into the backseat and was told we were going to New Jersey. A short while later, we rendezvoused with Diane’s car on the Jersey side of the river. “Thank you, Officer,” I muttered as I changed cars. We drove in silence for a time. Then Diane asked in a strained, calm voice, “Why did you do it, dear?” I replied with my usual professorial certitude, “I thought it would be best for everyone. I couldn’t go on the way I was.”

Once home, I proclaimed to Diane and Alexa that I loved them very much, that they needed to do a better job of looking after each other, and that each of us must figure out how to take better care of ourselves. They laughed at the incongruity of this advice. “That’s it!” they said in unison, and whisked me to the emergency room of the Princeton Medical Center.

For the next couple of hours, I was subjected to the usual pre-admission process. My height, weight, blood pressure, and insurance status were checked. Samples of blood and urine were collected. Finally, I was taken to the psychiatric service, called Princeton House, and admitted to the highest security wing. I exchanged my clothes and toilet kit for a robe and flimsy flip-flops.  The shame I felt on surrendering my belt, shoelaces, and razor is still palpable. Equally wrenching was being shown to my room and encountering my roommate. He was a grizzled, paunchy man in his sixties whose hypnotic-assisted, foghorn-loud snoring would make sleep impossible. Weeks later, Diane said that leaving me in the hospital that way was the hardest thing she had ever done and that she had barely resisted the impulse to take me home—whatever the risk.

The next morning I met some of the other patients. They ranged in age from about 16 to 76, with diagnoses ranging from acute drug overdose to chronic alcoholism, from panic attacks to paranoid schizophrenia. I recall best an elderly woman who must have called her family 20 times a day on the only available pay phone, telling them it was time to come and take her home. Subsequently, I learned that this was her pattern during each of many hospitalizations for depressive episodes ending in suicide attempts.

After breakfast I had an awkward encounter with my primary care internist, Dr. Andrew Costin, who had been one of my students at the Yale University School of Medicine. As he was examining me in his usual thorough and thoughtful way, he blurted out, “No one will believe that you, of all people, would try to take your own life.” Then he asked if I understood that my family had made frantic efforts to find me after I disappeared, and that he had as well. I apologized. He shook my hand and left, looking as bewildered as I felt.

Next came a visit from a psychiatrist I had already been seeing, Dr. Philippe Khouri, who, it seemed to me, always spoke softly and unemotionally lest he disturb me. He was accompanied by a third year student from Robert Wood Johnson Medical School. Dr. Khouri asked me to tell the student what had brought me to the hospital and how I was feeling at that moment. For someone who had spent much of his career teaching medical students at the bedside of sick people—young and old—being both patient and teacher under these circumstances was more than I could bear, and I wept.

Shame, Sorrow, and Stigma

The list of writers who have described their suicidal attempts and suicidal thoughts is long and illustrious—Alvarez, Lowell, Melville, Plath, Poe, Ruskin, Sexton, Styron, Woolf, to mention but a few. Yet physicians and scientists, who commit and attempt suicide at least as often as artists, writers, politicians, and business leaders, have been remarkably silent. The taboo signifies dread about losing those very qualities upon which professional authority and reputation are built: trust, credibility, reliability, control. For physicians, it also reflects, in part, fear of losing one’s license. I understand all these reasons to hide and, until recently, found them personally compelling. But not any longer.

Now that I feel reasonably safe from attempting suicide again, I wish to join Kay Redfield Jamison and Lewis Wolpert as scientists bearing witness. I now understand that I was brainsick (“diseased of the brain or mind”) when I tried to kill myself. I view my suicide attempt as the end result of mental illness in the same way I view a heart attack as the end result of coronary artery disease. Both are potentially lethal, both have known risk factors, both are major public health problems, both are treatable and preventable, and both generate fear and grief. But the shame associated with them differs greatly. Heart attack victims are consoled (“Isn’t that a pity?”); suicide victims are cursed (“How could he?”).

In her definitive and evocative book on suicide, Night Falls Fast, Kay Redfield Jamison tells us about the history, epidemiology, antecedents, and sociology of killing oneself. She reminds us that the taking of one’s own life is mentioned several times in the Old and New Testaments of the Bible and in the writings of such Greek and Roman philosophers as Aristotle, Pythagoras, and Seneca. In fact, the stigma attached to suicide can be traced to these early discourses. Aristotle and Pythagoras reviled self-murderers as cowards. Roman law forbade suicide. This abhorrence of suicide is found, as well, among the teachings of the great religions. Roman Catholics who kill themselves are subject to excommunication; orthodox Jewish suicides may be denied usual funeral rites; Islamic law considers suicide a crime worse than homicide.

Despite the shame, sorrow, and stigma associated with suicide, a surprisingly large number of people kill themselves, or try to. An estimated 30,000 Americans will commit suicide this year—about one every 20 minutes. Suicide is the eighth leading cause of death in our country, accounting for many more deaths than homicides, AIDS, or leukemia. Its toll among the young is even more frightening. Worldwide, among those between the ages of 15 and 44, suicide is the second leading cause of death among females and the fourth in males.

But the public health problem posed by suicide goes far beyond these grim statistics. For every American who “completes” a suicide, another 50 to 100 attempt it and “fail.” This means that one to three million people will attempt suicide in our country this year. Imagine the grief, anger, confusion, and guilt set loose by this desperate desire to die.

Caught in an Inexplicable Tide

Mental illness is the underlying cause of most suicides and suicide attempts, probably figuring in at least 90 percent of them. Mood disorders such as major depression and manic-depression are the most common antecedents, followed by schizophrenia, alcohol and substance abuse, pervasive anxiety, and personality disorders. These conditions differ from one another in many ways: in the significance of genetic risk factors, in age of onset, in clinical manifestations, and in the means to treat them. They all predispose some of their victims to suicide, but we do not know why.

After we tick off the regions of the brain that are affected in these disorders, after we point out that depression and schizophrenia are associated with perturbations in the brain’s chemical messengers (such as serotonin and dopamine), after we applaud the insights being gained about brain metabolism from new brain imaging techniques—we still must admit that we don’t begin to fathom what happens when a person reaches (usually impulsively, as in my case) for death rather than life. Answering this question is as important, in my view, as explaining in neurobiological terms such other enormous brain mysteries as love, hate, courage, and denial.

I have the typical risk profile for a suicide victim, if one can use such a banal expression for so terrible an action. By “typical,” I mean that I’m white, male, over age 65, and I suffer from a mood disorder. Yet as I write this memoir, I can barely believe that, not very long ago, I was so filled with psychic pain that I temporarily “crossed over” from sanity to insanity, and nearly took my life in the process. My suicide attempt was not a gesture or a cry for help; there was neither revenge nor logic in my action. I was oriented and conscious, and I remember the critical events with startling clarity. Somehow, some inexplicable how, pain pulled up the heavy anchor forged of wife, children, friends, and work, then grabbed the tiller and pointed my lifeboat toward death.

Back from the Brink

After giving me time to regain whatever was substituting for composure at that moment, Dr. Khouri said that the depression that had nearly taken my life must be treated at once. “Prozac hasn’t worked,” he said, “and there isn’t time to start other antidepressant medications.”

“What do you recommend?” I asked. “Electroconvulsive treatment,” he replied. “It acts quickly and there is about an 85 percent chance that it will lift your depression in less than one month.”

However groggy I still was, I registered surprise. I thought that ECT had been abandoned years before. As a medical student at the University of Wisconsin in the 1950s, I had watched a patient with schizophrenia being given ECT. It wasn’t a pretty sight—like watching Jack Nicholson in One Flew Over the Cuckoo’s Nest. This negative image, so widely shared by the public, was reinforced by my early years at Yale. At that time the department of psychiatry was a bastion of psychoanalytic theory and practice. Drugs were rarely used; forget ECT.

Dr. Khouri knew what I was thinking. “ECT isn’t anything like it used to be. I have spent the last fifteen years learning how to do it correctly,” he said. He went on to tell me that he was treating more than 50 patients with ECT each year, that treatments were given under general anesthesia, that use of muscle relaxants eliminated muscle contraction everywhere but in one foot, that the seizure would be monitored by EEG and would last between 30 and 60 seconds, and that treatment would be on only one side of the brain. “Please discuss this with your wife,” he said. “We have a good videotape on ECT if you want to look at it.”

I shuffled back to the pay phone, waited my turn, and asked Diane to come soon. We sat in the cold, cavernous, patients’ lounge, equipped with a Ping-Pong table and numerous groupings of upholstered chairs, couches, and tables. I expressed my fear that ECT would incapacitate me permanently, yet both of us allowed that my situation was perilous. Diane reminded me that she had recently read an article about ECT that corroborated Dr. Khouri’s description. So it didn’t take us long to decide to go along with it. We watched the video with the ECT nurse coordinator, and were reassured by her sympathetic answers to our questions. I signed the permission forms and was scheduled for my first treatment a day and a half later.

During the remainder of the day, I spoke to each of my four children. Their responses to my predicament ranged from silence, to disbelief, to a simple “I love you.” They must have wondered where their pater familias had gone. My older daughter, Diana, insisted on coming from Vermont, and this was a big help to Diane, Alexa, and me. I told my sons, Bob and David, who were much farther away, that we would stay in touch by phone.

I now had a new roommate, an affable 16-year-old boy whose problem was drugs and alcohol. We played cards and talked about sports. Even so, time passed slowly. Sometimes he and I ate in our room—off plastic trays, on plastic dishes, and with soft plastic utensils, of course. Whenever possible, I ate in the patients’ cafeteria, chaperoned by my wife and daughters. The food was better there, better than my appetite. As the nurses gained confidence in my behavior, I was given a private room and permission to take walks outdoors with my family and our white standard poodle named Tatum (after the Nobel Laureate Edward Lawrie Tatum).

Friday morning finally came, and with it my first ECT. A motley group of us, all dressed in our loose-fitting pajamas and robes, was driven to the Princeton Medical Center in a van. I felt like a character in a prison movie. After being ushered into a waiting room with lockers for our clothes, we waited our turn, then entered a large ambulatory surgical suite with eight gurneys, each surrounded by assorted electronic paraphernalia and stainless steel poles. A nurse who knew this was my first ECT tried to put me at ease by telling me again what was going to happen. An intravenous line was placed in my left arm. Then Dr. Khouri and an anesthesiologist appeared and described the procedure, again, in great detail.

Electrodes were attached to my head, an EKG to my chest, a blood pressure cuff to my arm, and a blood oxygen-measuring device to my finger. The anesthesiologist injected Brevital, a very short-acting barbiturate, into a vein, and I promptly lost consciousness. Five minutes later, I woke up to find that the treatment was over, and  was told I could sit up whenever I felt ready.  Shortly thereafter, I walked back to the waiting room and sat there until all of us were ready to be transported back to Princeton House. The only “side effect” I remember was the sticky electrode paste in my scalp hair, which washed out with a shower. I asked Diane to check my recent and not-so-recent memory with particular questions—all of which I answered correctly, to our shared relief.

The weekend passed slowly. My younger brother, Irv, a member of the Tufts University Medical School faculty, visited. He seemed relieved that I was able to “talk shop” about academic medicine, as is our custom. I took walks with Diane, Alexa, and Tatum but failed in several tries to absorb an Agatha Christie mystery.  We lobbied Dr. Khouri to discharge me. I remember him shaking his head and saying, “Please allow me to treat you like I would anyone else.” After the second ECT treatment on Monday morning, which went as well as the first, he agreed to let me go home provided I continue ECT three times weekly for up to twelve treatments.

Home had never felt so good. From then on, my improvement was dramatic. After the fourth ECT, I was noticeably less depressed. My appetite returned, as did my ability to sleep. After eight treatments, my mood was fully restored. I experienced no confusion, memory loss, headache, or any other symptom sometimes attributed to ECT. I felt so well that, with some trepidation, I prepared to go back to work at Princeton University.

Although the spring semester was over, I had a pressing assignment to complete. For the previous five months I had chaired a committee of the Institute of Medicine (IOM) that had been charged by Congress to assess the priority-setting process at the National Institutes of Health (NIH). This was the most difficult committee assignment I had ever had, and being depressed almost the whole time had made it agony. The committee was fractious, the NIH leadership less than cooperative, the Congress more than a little aggressive, and the report review process of the IOM poisonous. Nonetheless, the committee had made 12 recommendations, and I felt it was my job to defend the group’s work. On July 7, just six weeks after my suicide attempt, I took the train to Washington, DC, and presented the committee’s report to NIH Director Harold Varmus, then to Sen. William Frist (the only physician in the Senate), and finally to the press. My comments were well received, and the committee’s work was lauded. I am quite certain that none of the people I addressed that day knew that I had recently lost and then retrieved my mind.

Treatments: Old, New, and Revisited

ECT was the first treatment that was lifesaving for me. The second was lithium. Based on my history of recurrent depressions and on a compelling family history (an older brother with confirmed manic-depression responsive to lithium, several of my children, a niece, and a nephew with clinical depression, paternal aunts and cousins with mental illness of undefined type), Dr. Khouri made a presumptive diagnosis of manic depression (also known as bipolar disorder) and put me on a low dose of lithium, the drug of choice for this condition. For the past four and a half years I have taken lithium carbonate daily and have not experienced a single instance of depression—the first time in more than 30 years that I have been free of this curse for that length of time.

There is no blood test for depression, as there is for diabetes; no X-ray for bipolar disorder, as there is for pneumonia. So psychiatrists have used their experience to compile a list of signs or symptoms that accompany the diseases. For depression, these include persistent sadness, sleep disturbance, decreased appetite, irritability, social withdrawal, inability to experience pleasure, hopelessness, helplessness, suicidal ideation. When a large number of these manifestations exist for a month or more, psychiatrists call the depression “major” or “clinical.” The term “mild depression” is used when fewer of the symptoms exist, and for a shorter time.

Not surprisingly, the treatment of depression varies widely. Most mild depression responds to the “tincture of time” and support from family and friends. But major depression is a serious medical problem because it can be both debilitating and, as my case history demonstrates, potentially lethal. There are three general categories of treatment options for major depression: pharmacologic (drugs), behavioral (psychotherapy), and electrical (ECT). They are not mutually exclusive, two or more often being used at the same time.

Four different classes of drugs are used in the treatment of major depression: tricyclics; monoamine oxidase (MAO) inhibitors; selective serotonin reuptake inhibitors (SSRI); and “atypical” drugs (meaning they act on the brain’s chemical messengers in ways different from any of the previously mentioned classes). Today, the SSRIs are the most widely used. Unfortunately, all of these drugs share three drawbacks. First, they act slowly—beneficial effects are usually observed only after three to six weeks of continued dosing. Second, only 50 to 60 percent of patients who receive any one of these medicines will derive benefit. Third, all have unpleasant side effects, which, as you will see, may be catastrophic.

One of several reasons I left Yale in 1991 to become chief scientific officer of the Bristol-Myers Squibb Company was my desire to make a contribution to the discovery and development of drugs for disorders of the nervous system. The first of the SSRIs, Prozac, had been marketed only three years earlier by the Lilly Company and was quickly becoming a blockbuster. Bristol-Myers Squibb needed to compete in this arena. There were huge unmet medical needs for such burdensome health problems as Alzheimer’s disease, schizophrenia, multiple sclerosis— and depression. Initially, I did not appreciate how difficult it would be to create a successful pharmaceutical “franchise” in this area, where the mechanisms of the disorders were unknown, the preclinical assays in mice and rats unreliable, and the clinical trial data marked by larger placebo effects than those seen for any other class of disorders. But we persevered, and as a result, the atypical antidepressant Serzone is on the market today.  It has proven useful for many patients because of its efficacy and its mild side effects.

How ironic, then, that I should end up taking our competitor’s antidepressant, Prozac, as part of my suicide cocktail. I had taken it as prescribed for only two weeks—too short a time for it to have done me any good, but long enough to have likely done me harm. A small fraction of patients (especially those with manic-depression) react to Prozac and other antidepressants with agitation, hyperactivity, a worsening of their sleep disturbances, even frank mania. I will never know with absolute certainty whether the agitation and restlessness I felt soon after starting Prozac were a result of the drug or a manifestation of my severe depression, but I do not intend to take Prozac ever again.

Pharmacologic treatment of manic-depression has been available longer than that for major depression. An Australian psychiatrist named John Cade discovered serendipitously in 1948 that lithium salts were effective in reversing manic attacks in manic-depression. After a number of studies during the 1950s and 60s confirmed this, lithium became the drug of choice for this condition and, with refinements over the years, remains so today. In Europe, lithium is also being used increasingly for the treatment of recurrent depression unassociated with mania. Lithium also has its detractors, because it does not benefit everyone and has unpleasant dose-related side effects, including tremor and behavioral changes. It is often discontinued—unwisely—by manic-depressive patients who are unwilling to give up the high of mania and the sense of power and creativity that goes with it. This is dangerous, because stopping lithium is often followed by a depression of suicidal proportions. Recently, a number of anticonvulsants have proved efficacious in patients with manic-depression. I feel fortunate to have responded extremely well to a low dose of lithium. I have had neither depression nor side effects since beginning it in 1998, and, equally important, I have not felt that my professional productivity or creative energy has diminished.

Psychotherapy, short- or long-term, is commonly sought by depressed patients. Psychoanalytic approaches have given way to cognitive ones. Many therapists believe that using drugs and psychotherapy together is more effective than using either by itself. Psychotherapy cannot be undertaken in individuals who are suicidal, however. In this state, psychiatric intervention must focus on preventing patients from harming themselves. My thought processes in the weeks immediately preceding my suicide attempt were so erratic and scattered that cognitive therapy would have had no chance of success. Wisely or unwisely, I have not sought psychotherapy since recovering.

Because ECT is offered at a relatively small number of hospitals, I find myself wondering what would have happened to me had I not been referred to one of them.

Dr. Khouri is convinced that I would have rejected ECT if I hadn’t been so ill, that the frightful images of ECT would have poisoned my already compromised mind to this option. Fortunately, a brave band of psychiatrists have resurrected ECT by changing it, just as heart transplantation was resurrected by a small group of courageous cardiovascular surgeons. Today, more than 100,000 severely depressed patients are treated with ECT annually in the U.S. Of these, 70 to 90 percent get prompt benefit, usually within two weeks.

Transient loss of short- or long-term memory is said to be a common enough side effect of ECT to scare off many patients. How much this depends on the expertise of the person administering the treatment is not clear. What is clear is that there is a high relapse rate after ECT; perhaps as many as 50 percent of patients initially helped by ECT suffer another bout of depression within a year. Fortunately, this relapse rate can be reduced markedly by using lithium or antidepressants after the initial course of ECT.  Based on my experience, I have little doubt that ECT will be used more widely in the future than it is now.  It is simply too beneficial to be used as a last resort.

The Last, the Worst

The depression that precipitated my suicide attempt crept up on me in early March 1998, around my 65th birthday.  This was an unwelcome milestone that forced me to accept becoming a full-fledged, Medicare-eligible senior citizen. I had to leave Bristol-Myers Squibb, because the company had a mandatory retirement age of 65 years for its officers. I believed secretly that an exception would be made for me, but when it became clear that those in charge found me eminently replaceable, my bruised ego and I prepared for the unwanted transition. Retirement implied several negative things to me—boredom, uselessness, infirmity. I “celebrated” with a birthday party at which many friends from Yale, Princeton, and Bristol-Myers Squibb joined members of my immediate and extended family. Each time I was asked what I was going to do after retirement, I said, “I’m not retiring.  I’m joining the faculty at Princeton and embarking on a new career.” Whether that bravado convinced others I don’t know, but it must not have convinced me.

I moved into my office at the university, hired an excellent assistant, and began teaching a course in the Woodrow Wilson School of Public and International Affairs dealing with medical research policy. But the “blahs” overtook me anyway.  I no longer woke up in the morning with excitement about work and optimism about life. Everything seemed slow. Nothing seemed important. I felt numb. I would find myself staring out my office window wondering why the hours took so long to pass. My assistant later told me that she felt the “negative energy.”

Nights soon became worse than days. Sleep was hard to find and harder to keep, punctuated by black dreams, early awakening, and a fearful loneliness. Sleep deprivation ushered in irritability and inability to distinguish little things from big ones. My wife’s quirky sense of humor, which usually amused me, now annoyed me. Laughter disappeared and, interestingly, so did tears. I felt sad, but I couldn’t cry. Everything was out of focus. But I had been in this dark place many times before and expected that, after some weeks, this fog, too, would lift and I would recover.

March gave way to April, and April to May, without relief. I was finding it harder to concentrate on my work. This had not happened during my earlier depressions and was particularly scary because I had so highly prized my intellectual acuity throughout my life. Finally, my wife told me that she didn’t think either of us could stand this much longer and insisted I see a psychiatrist.

On May 11, Diane and I went to the office of Dr. Khouri, who came highly recommended by the chair of Yale’s psychiatry department. He was immediately concerned by the length and depth of my depression and by the difficulty I had in speaking loud enough to be heard (called hypophonia). He referred to my emotional state as “totally depleted” and prescribed Prozac—emphasizing that I couldn’t expect any improvement for at least three weeks, but that things would likely improve considerably thereafter. Soon after starting Prozac, though, I began to feel jittery, hyperactive, and agitated. Thoughts raced to nowhere. Rest and sleep evaporated.

Then depression gave way to despondency. I began to catalog the pros and cons of various means of self-destruction, even as I told myself that I was not suicidal. I remember being surprised that I could behave in this irrationally rational way, almost as if my brain belonged to two occupants. I would walk past the tallest building on the Princeton campus, appraise it as a place to jump from, then discard the idea because I could see no way to get to its precipice and because it seemed cruel to inflict myself on the students who might see me fall. In like fashion, I imagined filling the pockets of my raincoat with rocks and drowning myself in our swimming pool (á la Virginia Woolf in the river), but shuddered at the monstrous effect that would have on Diane and Alexa when they found me. I didn’t own a gun and rejected a knife.  So, leaning on my medical training and my experience in the pharmaceutical industry, I decided that if worst came to worst, a fatal dose would be my choice.

But May brought several travel commitments that I dreaded but refused to cancel: a visit to Bethesda, Maryland, where my students presented their policy recommendations to Harold Varmus (who was particularly kind and generous to them); a trip to my alma mater, the University of Wisconsin, to chair a committee of medical school alumni; a meeting in Baltimore convened by the Lasker Foundation to honor prominent scientists at Johns Hopkins. I spoke at each of these events—haltingly, it seemed to me, yet no one asked if anything was wrong. It seemed that I could still disguise the black mood that was stalking me.

The Baltimore trip was the worst. After the dinner celebration on May 20, held at the historic Peabody Library, I felt too exhausted to chat with anyone and hurried back to the hotel. I craved sleep, but was given none. I was so wired that I could not lie down or close my eyes. I pictured myself sliding out the narrow, slotted windows eight floors above the ground, but they were locked.

The next morning I was in a sorry state, and called my wife who literally “talked me” out of the hotel and onto the train. We went  directly from the railroad station in Trenton  to Dr. Khouri’s office. He asked me if I was  suicidal. My wife remembers that it took a long time for me to say “no.” Then he asked whether I thought I’d be better off dead. Again, my answer was “no.” I was not suicidal at that moment, and I guess I parsed the answer in some legalistic, Clintonesque way. Dr. Khouri wishes now that he hadn’t believed me, but he did, and I went home for the long Memorial Day weekend.

Diane rented The Full Monty and was aghast that I could see no humor in it. I was unable to watch television, read the newspaper, or listen to music. This progressive, profound loss of cognitive function was the last straw. I became convinced that death would be preferable to being brain dead, that my family would be better off without me as a vegetable, and that remembering me in my prime would be better than watching me disintegrate further. My wife wrapped me in a blanket, hoping that swaddling me would bring some warmth and comfort. She asked me repeatedly if I was suicidal, but I continued to say no—not realizing until much later that this was the ultimate lie in a relationship built on truth and trust.

The holiday weekend, replete with graduations and outdoor picnics, came and went. Every event was an ordeal, every motion slow motion, every smile an effort. On Tuesday morning, I lied for the last time and reached for death rather than the grim facsimile that my life had become.

A Healer Who Rejected Healing

My “great depression” of 1998 was only the latest (and most harrowing) such sojourn in my adult life. I recall first being clinically depressed in 1959, at the age of 26. After finishing two years of residency training in internal medicine at Columbia-Presbyterian Medical Center in New York, my first wife and I moved to Bethesda, Maryland, with our four-year-old son, Bob, and our one-year-old daughter, Diana. I had been accepted as a fellow at the National Cancer Institute and was eager to find out if I had the “right stuff” for a career in research.

Anticipation quickly turned to disappointment. My supervisor asked me to analyze data that he and his associates had collected on cancer patients over 10 years. As we sat in what was supposed to be my office, he pointed to several bookshelves filled with green-covered hardback notebooks. “You won’t have to do any experiments,” he said. “Just figure out what all these observations mean.”  I was horrified. I thought to myself, “If this guy doesn’t know why he’s been collecting samples of blood, urine, and stool for a decade, why does he think I’ll be able to find out?”

That night I decided I would request a transfer to some other part of the Public Health Service, perhaps the Indian Health Service, where I would at least be sure that I was doing something useful. Fortunately, the chief of the department said I should find another supervisor. Some months later, under the tutelage of Dr. Stanton Segal, I conceived, conducted, and analyzed an experiment that asked how the kidney transports amino acids. Though hardly earthshaking in retrospect, this experience of discovery was so thrilling that I knew I must pursue a career in medical research, and so I did.

But the trauma of the initial encounter tipped me over. Although I was functioning, my sense of self-worth evaporated. I cried over nothing and lost pleasure in my family. When this funk lasted for several weeks, my parents became concerned enough to drive from Wisconsin to visit. Things slowly improved, and after about six weeks I had fully recovered. The next episode of depression occurred when I moved to Yale from NIH in 1965. I worked my way out of that downturn, too, just as I would with many subsequent depressions.

I began to wonder why major professional moves precipitated my down moods, and what other patterns, if any, I could recognize. Two insights emerged. One trigger was Christmas. I always got cranky and sour in December. My parents were devout immigrant Jews who felt that it was sacrilegious for their sons to join in the Christmas celebration in any way.  We weren’t allowed to sing carols in school assemblies, being told instead to sit or stand silently—or leave the room. Not surprisingly, I learned to feel like an outsider, a feeling accentuated as I grew to adulthood and subjected my children to some of the same seasonal insults. When we were living in New York, I got into an elevator with my three-year-old son, Bob, a couple of weeks before Christmas. A woman smiled and asked him what Santa was going to bring him for Christmas. “Santa Claus doesn’t come to our house,” he said. The woman reproached me with her eyes, and I may have reproached her back.

The other trip wire was spring. I was always at my best in fall and winter. These were the school seasons, after all, and I loved school—any and every school from kindergarten through medical school. I enjoyed studying and learning. I enjoyed even more the praise and adulation I received from my parents and teachers for my academic prowess. Maybe that explains why spring, which signaled that school would soon be out, became a season to endure. Maybe the fact that my birthday occurred in March—reminding me that age only went in one direction—accentuated the weight of spring on my fragile mood structure.

Some of my depressive bouts would last a month, others hung on for two or three. I felt like everything—movement, thought, speech—took more energy. I had trouble connecting with either my family or my associates. I had to push harder to get started in the morning and to keep going during the day. Jogging and playing tennis helped, as did travel and, of course, work.

Flirting helped too, until it metamorphosed into a love affair. I was 36 and an associate professor; she was 29, beautiful, and a gifted laboratory technician. We collaborated on what is surely the most innovative science of my career, but the scientific collaboration slowly became more than that. Work and love reinforced each other, until little else mattered. We behaved in ways that put us and others at risk, but I could not imagine doing anything else. After nearly a year I remember finally understanding that I could not live two lives at once and trying to sever this powerful bond. The ensuing battle between narcissistic gratification on one side and familial responsibility on the other led ultimately to the loss of both my lover and my marriage, and to a particularly knee-buckling depression.

I spent six months in psychotherapy with an able psychoanalyst who led me back to my family origins and psychological roots. I suppose I was helped by this approach, but not for very long. When my older brother suffered major depression and then clear mania following the death of our father, I was not willing to admit that both he and I had manic-depression. Even his good response to lithium was not convincing. “Gil may need lithium,” I thought, “but I don’t.”

Subsequently, in 1980, I consulted a young biologically oriented psychiatrist at Yale who was interested in pharmacologic approaches to the treatment of mental illness. I asked whether I was a candidate for drug treatment. He said something like this: “Your depressions are self-limiting; the medications now available have lots of side effects and are of limited efficacy; and I’m not sure you want to be labeled as having clinical depression.” Perhaps I followed this advice rather than getting a second opinion because it is what I wanted to hear. In any case, I accepted depression as my private albatross to be coped with—but not treated. I was a healer who rejected healing.

I liked the way my mind worked during the long intervals when I wasn’t depressed. I could work 16 to 18 hours daily, write papers quickly, make original scientific connections, speak articulately, and interact with associates and family pleasurably. Was this hypomanic (i.e., mildly manic) behavior or merely positive energy? In the absence of any boundary markers that distinguish between healthy exuberance and unhealthy hypomania, I simply don’t know.

Becoming a Scientist-Witness

The first person who suggested I write this account was Dr. Khouri, who believed that I could help destigmatize both mental illness and ECT by “going public.” My friend and fellow sufferer, Kay Redfield Jamison, was sure that describing my struggle with manic-depression would be seen by young scientists and physicians as a testament that mental illness was compatible with professional success. Other friends and colleagues, including Steve Bunney, Yale’s psychiatry chair, and Steve Hyman, the former director of the National Institute of Mental Health, echoed these sentiments.

So I began to tell my story. Two years ago, I presented my own case history orally to a class of 100 second-year medical students at the Robert Wood Johnson Medical School. Some cried, others looked stricken, a few shook their heads. Their interest, sympathy, and gratitude reinforced the encouragement I was receiving from my wife and several colleagues to step forward. Yet I was still not ready to “come out” completely. My reluctance reflected my concern that the public good I might do by telling my story would be less than the resulting harm to my professional standing. Scientists are prone to focus more on their competitors’ mistakes or frailties than on their contributions or strengths. I worried that I would be making myself vulnerable in a way I had never done before, even though my good name in medical science would be hard to take away from me.

This wrestling match between altruism and pride ended definitively two days after the terrible events of September 11, 2001. Diane and I were in Germany attending the grand opening of the Jewish Museum of Berlin. The celebration was splendid and the architecture of the museum so brilliant that my lifelong ambivalence toward all things German—born of being an heir of Holocaust victims—was diminishing. The terrorist attacks on the World Trade Center and the Pentagon ended that bonhomie. It was impossible to get home. Sightseeing was unthinkable. Our days were spent watching CNN, walking the streets, and feeling the empathy of passers by, clerks, and restaurant workers.

On September 13, while discussing how lucky we were that our family had been spared, Diane and I confronted a painful reality of our own—that we had been taking each other for granted, that the emotional distance between us had been widening for months, and that other “friends” were ready to move into the vacuum we had created. Undistracted by work or family, we reaffirmed our commitment to each another, and fell in love again.

Among the first things Diane said to me during this renaissance of feelings and actions was that she had realized only recently how terribly hurt and angry she had been about my suicide attempt. Her words hit me like a slap in the face. “I can’t believe you didn’t love me or your children enough not to try to kill yourself. How can it be that we didn’t make life worth living, even if your all-important career was declining? And, by the way, you didn’t even care enough to leave a note so everyone would know you didn’t commit suicide because of me.” Here was my sophisticated wife—the person who more than anyone else had helped me recover from my attempt to end my life—saying that she understood intellectually that the impulse to kill myself was evidence of temporary insanity, but that she hadn’t forgiven me emotionally for an action that, if “successful,” would have, in her words, “created a huge hole in my life and in the lives of your children, grandchildren, brothers, and beyond.”  

I realized instantly that I had not made peace with her or the rest of my family about either my suicide attempt or the longstanding mood disorder that predisposed me to it. I recalled that Jamison devoted an entire chapter in Night Falls Fast to the devastating effect of suicide on surviving family members and friends. Now I realized that the families of those who had attempted, but not completed, suicide suffered some of the same pain, confusion, and grief. But these families have one additional horror. They must deal, on a daily basis, with the person who had tried to die. They must decide whether they are willing to risk future commitment and trust.

So I was propelled to write—to describe, to analyze, and, I hope, to understand. Both of my sons had a negative reaction to an early version of this article. They thought I was “letting myself off the hook” by saying that my suicide attempt was a manifestation of temporary madness. “You’re copping out,” Bob said. “What about all the years you knew you had a mood disorder and didn’t get treatment?  If you had started taking lithium thirty-five years ago, you very likely would not have become so depressed as to become suicidal.” I had no rejoinder.

My older children, who had grown up in the shadow of my mood disorder and the disfiguring divorce between their mother and me, needed me to think about what my mental illness had cost them, as well as Diane and Alexa. So I have. I have asked for, and received, their forgiveness. I have asked myself new and old questions—some that have answers, others that don’t, still others whose answers seem contradictory.

It Is Time

At the end of all this questioning, there are some things I have come to know and need to tell. The condition I have, manic-depression, is a remarkably common illness, probably affecting nearly five million Americans, yet most people with manic-depression go undiagnosed and untreated, and 20 percent of the latter group commits suicide. It makes no sense to allow stigma, whose underlying premise is that people with mental illness are weak, to cow affected people into being unwilling to be diagnosed. It is time that I and other physicians say so.

Manic-depression is among the leading causes of morbidity and mortality in our country and the world, with huge economic and human costs, and it is time that I and my colleagues in the world of health policy say so.

Manic-depression runs in families, but we remain woefully ignorant about the genes that underlie it or the relative importance of them compared to environmental factors. It is time that I and my colleagues in genetics say so.

Manic-depression responds well to treatment with lithium and anticonvulsants, but SSRIs must be used with caution, and it is time that psychiatrists say so.

Manic-depression is compatible with a fulfilling career in medicine and science (as well as other occupations), and it is time that I and my many affected colleagues say so.

Finally, manic-depression and other mental illnesses—regardless of their biological basis and their chemical nature—are not like disorders of the heart or lung or kidney, because the brain is unlike any other organ. The human brain is the organ that validates our being at the top of the hierarchy of species. It enables us to create, to contemplate, and to communicate. It helps us make sense out of life. When any other organ gets sick, it is the brain, and its Janus-like other half, the mind, that manifests our fear, concern, dread, or relief. But when we become brainsick, the brain’s ability to be a mind is diminished, and we become mindsick as well.

Attempting suicide is a “brainquake,” in that it signifies that this remarkably complicated organ, with its 10 billion neurons, has failed in a profound way. Although I feel intense remorse for my suicide attempt, I feel no guilt because I know I was temporarily mad. But that doesn’t absolve me from culpability for the anguish my dark morning and its long antecedents heaped on those closest to me. Nor does insanity absolve me from the awful responsibility of being a suicide survivor, a responsibility I must face for the rest of my life—my natural life. And it is time—past time—that I say so.