Freud suggested that in both mourning and its pathological cousin, melancholia, when an object of love is lost, the ego re-creates an image of the loved one inside the self. Thus, the lost love object lives on in the ego in what Freud compared to a shadow. This identification, or “shadow,” is not fully integrated into the personality, thereby enabling part of the ego to “split off” and observe. In this “ego splitting” a part of the ego may sit in judgment on the rest of the ego, criticizing it, attacking it, even condemning it to death. Suicide is the ultimate expression of this dynamic. In other words suicide originates in the wish to kill someone whom the suicide has loved or identified with; because he cannot kill this person, he “kills” him by destroying the internalized image of him. Psychologically, suicide is thus a kind of inverted murder or, as psychologist Edwin Shneidman has put it, “murder in the 180th degree.”
At the time he wrote Mourning and Melancholia, Freud believed that all aggression had a sexual origin. In 1920 he proposed the existence of another primal drive. “After long hesitancies and vacillations we have decided to assume the existence of only two basic instincts, Eros and the destructive instinct,” he later wrote. “The aim of the first of these basic instincts is to establish ever greater unities and to preserve them thus—in short, to bind together; the aim of the second is, on the contrary, to undo connections and so to destroy things. In the case of the destructive instinct we may suppose that its final aim is to lead what is living into an inorganic state. For this reason we also call it the death instinct.” Most aspects of human behavior, Freud believed, could be understood as the product of the struggle between the sexual drive and the death instinct, Eros and Thanatos, love and hate.
While Freud’s primary purpose in proposing the death instinct was to explain the phenomenon of masochism, it also provided an explanation for suicide. While the death instinct exists in everybody, Freud said, in suicidal people it prevails over their instincts for love and life. “We find that the excessively strong super-ego which has obtained a hold upon consciousness rages against the ego with merciless violence,” he wrote in The Ego and the Id. “What is now holding sway in the super-ego is, as it were, a pure culture of the death instinct, and in fact it often enough succeeds in driving the ego into death.” Ten years after adjourning the Vienna Psychoanalytic Society’s special session on suicide, Freud had devised a theory that, in part, suggested that every death is, to an extent, psychological self-murder.
V
FAITH, HOPELESSNESS,
AND 5HIAA
NEARLY A CENTURY LATER, a growing number of people believe that the key to the enigma of suicide may lie in a glassy, contemporary six-story building overlooking the Hudson River in Upper Manhattan, where, in the second-floor neuroanatomy laboratories of the New York State Psychiatric Institute, twenty-seven stainless-steel deep freezers preserve, at minus eighty degrees centigrade, some two hundred brains. Although harvested from people of various ages, sexes, and ethnicities, these brains have one thing in common: they all come from people who killed themselves. Psychiatrist John Mann and neurobiologists Victoria Arango and Mark Underwood, of the NYSPI’s Mental Health Clinical Research Center for the Study of Suicidal Behavior, are studying these brains to find out what else they have in common, and how they might differ from the brains of those who die by other causes.
Donated by grieving families in hopes that their tragedies might benefit others, these brains are said to constitute the country’s finest collection of specimens from suicide victims. They are, therefore, treated as gingerly as Tiffany diamonds. Each freezer is equipped with a computerized warning system so that if its interior temperature rises to minus sixty degrees centigrade, liquid carbon dioxide will automatically be discharged to cool its contents. Each freezer is also linked to Arango’s cell phone, to her home, and to the home of a technician who lives near the institute so that someone will know immediately if anything goes wrong. Until a few years ago, the specimens were donated by families in Pittsburgh, where Arango, Underwood, and Mann previously worked, and in New York City. When, for political and bureaucratic reasons, it became impossible to collect in New York, NYPSI found another collaborator, and recent additions to the collection have all been imported, oddly enough, from upper Macedonia. Several times a year, NYSPI pathologist Andrew Dwork travels to southeastern Europe to pick them up. The specimens must be obtained and flash-frozen within twenty-four hours of death (otherwise they deteriorate); the donors must have died suddenly (a prolonged death increases the brain’s acidity and makes it harder to study); and they must not have been taking medications (the chemical complications would confound the findings). Each brain is accompanied by a “psychological autopsy,” a collection of interviews with friends and family, in an attempt to gather information—method used, clues left behind, previous attempts, history of aggressive behavior, and so on—that may shed light on the physical evidence, as well as provide the basis for a psychiatric diagnosis.
In New York, each brain is prepared for study by being divided into its left and right hemispheres, each of which is then subdivided into ten or twelve blocks. Using a microtome, a machine that looks and works something like a meat slicer in a butcher shop—but with infinitesimal precision—a technician can pare a slice thinner than a piece of paper. Transferred to a glass slide, the tissue is examined using autoradiography, which maps chemical alterations in brain regions. It is then compared to a similar sample from the brain of a person of the same age and sex who had no psychiatric disorders and who died suddenly of a cause other than suicide. By reassembling the slides by computer, researchers can also construct a virtual model of how those chemical alterations might interact to affect mood or behavior.
Since the 1970s, researchers have been exploring the link between depression and serotonin, one of the more than a hundred kinds of neurotransmitters identified thus far. Neurotransmitters are the brain’s chemical messengers—molecules that jump the narrow gaps known as synapses between neurons to carry information from the signal-sending (presynaptic) neuron to the receiving (postsynaptic) neuron. Receptors on the postsynaptic neurons bind to the serotonin and register biochemical changes in the neuron. The presynaptic neurons eventually reabsorb the serotonin using molecular sponges called transporters. (The antidepressants known as SSRIs work by binding to serotonin transporters and preventing presynaptic neurons from reabsorbing the secreted serotonin too quickly, allowing it to linger in the synapse.)
Neurobiologists have long been aware that serotonin seems to exert a soothing effect on the mind. Over the years, low serotonin levels in the brain have been linked to depression, aggressive behavior, and impulsivity. At the NYSPI—as at several other cutting-edge laboratories in this country and in Europe—Mann, Underwood, and Arango, who have worked together since 1985, have been homing in on how serotonin may more specifically be involved in suicide. Studies at the NYSPI and elsewhere of people who attempt suicide have found evidence of serotonin depletion in the cerebrospinal fluid—the liquid that bathes the brain and spinal cord. Postmortem studies of completed suicides have found lower-than-normal levels of serotonin in the brain. That the low serotonin levels in suicide victims is similar in degree regardless of psychiatric diagnosis suggests that the serotonin deficit is associated with the suicidal behavior and not with the psychiatric disorder.
Over time, the NYSPI researchers have zeroed in on the frontal cortex. Using autoradiography, they have found that in depressed patients, serotonin activity is reduced throughout the frontal cortex, whereas in patients who have attempted suicide, the reduced serotonin activity is confined to the orbital prefrontal cortex, the portion of the brain that sits immediately above the eyes and is the source of our ability to control our impulses—“the emotional seat belt,” as Mann has described it. (“Depression affects more parts of the brain,” observes Arango. “Suicide appears to be more local.”) Postmortem studies, too, have suggested that not enough serotonin seems to be reaching this key par
t of the brain.
Arango assumed that the reason there was less serotonin in the cortexes of suicide victims was that they had fewer serotonin neurons. But when Underwood, using a video-based computer imaging system attached to a microscope, manually identified, counted, and analyzed every serotonin-synthesizing neuron—some tens of thousands—in the brain stem, he found that the brains of suicide victims had more serotonin neurons than did control brains. Arango and her colleagues narrowed it down still further. The prefrontal cortex has two parts; the upper part (the dorsal prefrontal cortex) appears to be more affected in depression, while the lower part (the orbital prefrontal cortex) appears to be more affected in suicide. In 2001, Arango found that the brains of completed suicides contained fewer neurons in the orbital prefrontal cortex than control brains did, but a normal number in the dorsal prefrontal cortex. Furthermore, the orbital prefrontal cortex had one-third the number of presynaptic serotonin transporter sites than that of control brains, but some 30 percent more postsynaptic serotonin receptors, suggesting that the brains of people who kill themselves are trying to make the most of what serotonin they have, by attempting to increase their ability to receive serotonin while decreasing the number of transporters that reabsorb it.
Arango has turned her attention to the brain stem, the part of the brain that leads to the spinal cord, where serotonin is made and subsequently projected to the rest of the brain. Doing more “neuron counting,” Arango has found that there is more of the enzyme that makes serotonin in the brain stems of completed suicides than in control brains. “So the problem is not in the brain stem,” she says. “There seems to be a disconnect between the brain stem and the prefrontal cortex. The cortex is behaving as if it doesn’t have enough serotonin. The brain stem is working overtime to make up the deficit, trying to make more serotonin, but somehow it is getting lost on its way to the cortex.” Arango and her colleagues are now studying the middleman, so to speak—the amygdala, an almond-shaped part of the brain located in the anterior portion of the temporal lobe and associated with fear and aggression.
The idea that suicide is rooted in the brain dates as far back as the fifth century BC when Hippocrates suggested that an excess of black bile led to a condition whose symptoms included “sadness, anxiety, moral dejection, tendency to suicide,” and which was treatable with mandrake root and hellebores, a plant whose leaves contain a toxic alkaloid. The link between suicide and the brain, however, would, for the most part, lie dormant during the following two millennia, as suicide was blamed on the devil, the weather, and civilization, among other scapegoats. In the eighteenth and nineteenth centuries, with the rise of “scientific” medicine, physicians once again turned to the brain; some pathologists claimed to find organic lesions in the brains of completed suicides, others an excess of phosphorus. Although the shadows of Durkheim and Freud dominated the discussion of suicide through the first half of the twentieth century, the suspicion persisted that depression and other forms of mental illness could be traced to physical aberrations in the brain. This was reflected in a variety of treatments: insulin coma therapy, in which patients were deliberately put into a coma up to sixty times over two months; Metrazol convulsive therapy, in which injections of a synthetic preparation of camphor induced explosive seizures; electroconvulsive therapy, in which patients were strapped to a table and shocked with 125 volts; and prefrontal lobotomies, in which two holes were drilled through the skull and a dozen or more nerve fibers were severed in the frontal lobes. These treatments, which worked by damaging the brain, were—among physicians, at least—wildly popular. A 1937 New York Times article extolling the virtues of the lobotomy pronounced it to be “surgery of the soul.”
In Mad in America, journalist Robert Whitaker cites some of the less mainstream somatic “treatments” inflicted on mentally ill patients during the first half of the twentieth century. They were injected with malaria-infected blood, arsenic, manganese, cesium, horse serum, and extracts from animal ovaries, testicles, pituitaries, and thyroids. They wore “blankets” coated by refrigerant, which dropped their body temperatures into the seventies and kept them in “hibernation” for up to three days. They were forced into ice-packed cabinets and refrigerated for a day or two. Their teeth were pulled one by one (in the belief that insanity could be cured by removing potential hiding places for bacteria), and if that didn’t work, their tonsils, colon, gallbladder, appendix, uterus, ovaries, cervix, and seminal vesicles were removed (in that order) until they were sane or dead. (Forty-three percent of patients given what was called the “thorough treatment” died.) In the course of these therapies, which were often administered without the patient’s consent and often without warning, many patients died, many more were irreparably damaged, and some were said to be cured—which usually meant they had been dulled into a state of bovine tractability.
Then, in the early 1950s, a number of tubercular patients at the Sea View Sanatorium in Staten Island were treated with a new compound called iproniazid, which was intended to help them breathe more easily. Although iproniazid proved to be a red herring in the treatment of tuberculosis—it not only failed to ease breathing but caused jaundice—the drug had an unexpected and fortuitous side effect: despite their grim medical prognosis, the patients grew surprisingly animated, even happy. (A 1953 newspaper photograph shows a semicircle of Sea View patients clapping hands as two residents dance.) The compound, which evolved into imipramine, was quickly pressed into service as the first modern antidepressant.
If altering brain chemicals was part of the solution to depression, it stood to reason that brain chemicals were part of the problem. Working backward, researchers learned that the drug was effective because it inhibited the action of monoamine oxidase, an enzyme that inactivates the neurotransmitters serotonin, norepinephrine, and dopamine after they have been released into the nerve synapses. It gradually became clear that the proper functioning of certain neurotransmitters was vital to the expression and regulation of mood. When something went wrong in this communication system, certain forms of depression might occur. Over the following decades, researchers focused their attention on one of those neurotransmitters, serotonin. When serotonin levels were low, depression was more likely; when serotonin levels were elevated, depression in many patients was relieved. Many disorders once regarded as purely psychological were now thought to be caused by chemical imbalances.
The connection between suicide and serotonin was made almost by happenstance. In the early 1970s, a Swedish psychiatrist named Marie Åsberg and her associates at the Karolinska Institute in Stockholm were searching for chemical markers in the cerebrospinal fluid of severely depressed patients. By identifying some of the markers, they hoped to describe some of the subgroups of depression. One thing they found was that about a third of the sixty-eight patients in the study had especially low levels of a chemical called 5-hydroxyindoleacetic acid—5HIAA for short—a metabolite, or “breakdown product,” of serotonin.
In 1975, Åsberg’s research team learned that one of the depressed patients in the study had completed suicide by taking an overdose of his antidepressant medication. When told the news, one psychiatrist remarked, “All these low 5HIAA patients kill themselves.” She explained that not only had this man had a low level of 5HIAA in his cerebrospinal fluid, but so had another recent suicide, a woman who had drowned herself in a lake. When Åsberg checked the case records, she found low 5HIAA among more than two-thirds of those who had attempted or completed suicide. Furthermore, many of the low 5HIAA suicides had chosen violent methods.
Åsberg organized a study of forty-six suicide attempters, sixteen of whom suffered from severe depression, the rest from a variety of psychiatric illnesses. Although some had normal levels of 5HIAA in their spinal fluid, the group as a whole had an abnormally low level—an average of 3.5 nanograms (a nanogram is one billionth of a gram) per milliliter less than the forty-five healthy volunteers in the control group. Within one year, six people in the study had committed
suicide. All of them belonged to the low 5HIAA group.
Since then, some two dozen studies have confirmed an association between suicide risk and low serotonin. Whether suicidal patients suffered from depression, schizophrenia, alcoholism, or personality disorders, low serotonin, or its metabolite, seemed to be a common denominator in those who had made suicide attempts or who had completed suicide. Low serotonin may predispose people to act impulsively, aggressively, and perhaps violently while under stress or in emotional turmoil. Indeed, in 2003, the NYSPI’s John Mann, in a study of attempted suicide, reported that those attempters who had used the most lethal means had the least serotonin-based activity in their cerebrospinal fluid—“the more lethal the suicide attempt, the bigger the abnormality,” he observed.
The link between serotonin function and aggressive and impulsive behavior has been reinforced by animal research. Mice with low serotonin attack faster and acquire addiction more readily; rats with low serotonin are more likely to attack and kill other rats; monkeys with low serotonin are more likely to attack other monkeys, to increase their alcohol intake, to take risks, to be ostracized by their peers, and to die a violent death. If levels of serotonin are increased in these animals, their aggressive and impulsive behaviors decrease. Although low serotonin is believed to be heritable, it may also be affected by environment: a strong maternal influence can improve serotonin functioning in rhesus monkeys, as can a rise in group status. But when monkeys are isolated in cages, their serotonin level drops by 50 percent. It has been suggested that with humans, too, a stressful event—the death of a family member, the loss of a job, physical or sexual abuse—may disrupt the serotonergic system and increase the chances of depression and, possibly, suicide. Substance abuse, stress, and even low cholesterol may lower serotonin levels. On average, men have lower serotonin levels than women, which may be a clue to why they are statistically far more likely to complete suicide, although many more women attempt.
November of the Soul Page 29