Authors: D. F. Swaab
The anatomical terms, for enthusiasts (
fig. 18
): Memory information is transmitted from the hippocampus via the fornix (1) to the mammillary bodies (2) at the rear of the hypothalamus. (These structures had been removed in the operation.) The information is then routed to the thalamus (3). The suprachiasmatic nucleus (4) is the biological clock. Thermoregulation and sexual activity are governed by the preoptic region (5). The memory and concentration disorders were caused not only by the loss of the mammillary bodies but also by damage to the tuberomammillary nucleus (6), the only place in the brain where histamine is produced, which is important for focusing our attention. The areas that regulate appetite and metabolism are the infundibular (or arcuate) nucleus (7) and paraventricular nucleus (8). An MRI of the patient described in this chapter showed that the hypothalamus had in fact been entirely removed. An endoscopic fenestration (keyhole surgery at the base of the brain) confirmed the damage. Given the loss of the mammillary bodies, the input of the fornix, which could still be seen on the MRI scan, wouldn't have been much use to the patient. Moreover, the base of the hypothalamus, the infundibulum, or tuber cinereum, was entirely missing.
The truth lay in this, that life had no meaning for me. Every day of life, every step in it, brought me nearer the edge of a precipice, whence I saw clearly the final ruin before me. To stop, to go back, were alike impossible; nor could I shut my eyes so as not to see the suffering that alone awaited me, the death of all in me, even to annihilation. Thus I, a healthy and a happy man, was brought to feel that I could live no longer, that an irresistible force was dragging me down into the grave.
Leo Tolstoy
All those who have become eminent in philosophy or politics or poetry or the arts are clearly melancholics.
Aristotle
Many creative minds and famous politicians suffered from depression. Some famous examples are Goethe, Isaac Newton, Ludwig van Beethoven, Robert Schumann, Charles Dickens, Christiaan Huygens, Vincent van Gogh, Charles de Gaulle, Willy Brandt, and Menachem Begin. From his early youth, Abraham Lincoln suffered from severe mood disorders. He's even credited with the authorship of a poem called “The Suicide's Soliloquy,” published in 1838.
A doctor must be aware that depression can also be an early symptom of a tumor, an infectious or autoimmune disease, or a hormonal or metabolic disorder. This has led to the theory that in the case of physical illness, depression might confer an evolutionary advantage. The theory goes that when you are depressed, you withdraw, you eat less, you lose interest in everything, and you avoid activity so that all your energy can be devoted to physical recovery. Depression is thought to have another possible evolutionary advantage, being a potentially beneficial response when someone with a dominant status is forced to occupy a lower place in the pecking order. Behavior such as avoiding eye contact or sexual contact would reduce the likelihood of attack by more dominant individuals. Whatever the case, bodily diseases can provoke depression, so you need to start by giving someone with depression a proper physical examination.
Brain disorders, like Alzheimer's, can also start with depression. Prince Claus, the Dutch king's late father, was treated for depression for many years in expensive Swiss clinics before it emerged that his depression was an early symptom of Parkinson's disease. Depression is also often commonly linked to other psychiatric conditions like eating disorders and borderline personality disorder. Patients with schizophrenia often suffer from depression, sometimes committing suicide. But depression does arise as a condition in its own right.
Causes
In the Netherlands, around five hundred thousand people are diagnosed with depression every year. It can be triggered by a very stressful event, like the death of a partner or failing an exam. In many cases, however, it's impossible to find a clear cause. Some individuals develop a strong predisposition for depression very early on. Others are able to rise above the most terrible events with apparent ease. The memoirs of the former Dutch cabinet minister Marcel van Dam clearly show how much adversity some people can take without suffering depression:
The war broke out and in 1943, when I was five years old, we were warned that the officers of the
Sicherheitsdienst
were on their way to arrest my father. He had been one of the organizers of an uprising by the police in Utrecht against the arrest of Jews. The entire family had to flee instantly, and I ended up living with a farmer and his family who I didn't know at all. My sister wasn't able to escape in time and was put in a concentration camp. I was told, probably for fear of me revealing something, that my father was dead. In 1944, my mother and the younger children were reunited, but my younger brother Leo died shortly afterward, probably of meningitis. My mother's distress was heartrending, and was made worse because my father, who turned out to be alive after all, couldn't be at the funeral. The Germans were waiting to intercept him at the cemetery. When the Netherlands was liberated, it seemed as if we were making a fresh start. Until my brother Wim, who was 12 years old at the time, went with me to the Galgenwaard Stadium in Utrecht to retrieve fire extinguishers from the tanks and army trucks parked there. When we set off for home, he ran across the street without looking and was knocked down and killed in front of my eyes.â¦Â I've relived all these memories many times.â¦Â It never disrupted my life. None of these events ever gave me any
nightmares. I never became depressed, never disproportionately fearful.â¦Â Why was that? Why do some people become traumatized after what would seem to be much less extreme experiences?
The answer to Van Dam's question lies in a combination of genetic factors and development in the womb and early childhood, which program the activity of the stress system for the rest of our lives. There are different forms and subforms of depression, but they all have a common feature: overreaction of the stress axis. We respond to stress by activating nerve cells in the hypothalamus, which send a substance called corticotropin-releasing hormone (CRH) to the pituitary gland and the brain. The pituitary gland in turn stimulates the adrenal gland to produce the stress hormone cortisol. CRH and cortisol equip our brains and bodies to cope with stressful situations. But if the stress axis becomes overactive, a stressful event can lead to the overproduction of both CRH and cortisol, and these substances can affect the brain so strongly that depression results.
Genetic factors can cause the stress axis to be put into a higher gear during development. This is why certain tight-knit groups, like the Amish in the United States, have a higher than average rate of depression. Depression has been seen to run in certain famous families, like that of Virginia Woolf. Studies of families with this condition helped to locate the first variations in genes (polymorphisms) that increase the risk of depression. Many tiny variations in genes for chemical messengers in the brain also predispose individuals to this condition. People whose mothers were pregnant during the Hunger Winter of 1944â1945 (
fig. 9
), when famine struck Dutch cities, have a higher incidence of depression. Food shortages are a thing of the past now, but the stress axis can also be permanently activated by a malfunctioning placenta, causing a child to be malnourished and underweight at birth. Exposure to nicotine or certain medicines (like DES) in the womb also increases the risk of depression. After birth, the stress axis of a child who is seriously neglected or abused can be
permanently set on red alert. Lasting changes of this type caused by external factors affecting gene expressionâin this case of the stress axis genesâare known as epigenetic programming.
We have also found that female hormones (estrogens) stimulate the stress axis, while the male hormone (testosterone) inhibits the stress axis, which would explain why women are twice as likely as men to suffer from depression.
So depression is basically a developmental disorder of the hypothalamus. If a person's genetic background and development cause their stress axis to be switched to a high setting, it overreacts to stressful life events, which can lead to depression. In adulthood, depression can also be caused by other factors, for instance certain types of medication. Prednisone, a much-prescribed synthetic corticosteroid drug, frequently causes mood disorders when taken in high doses. Brain infarcts or damage from MS lesions, particularly on the left half of the brain, also increase the risk of depression, due to the stress axis becoming hyperactive when it's no longer controlled by the cerebral cortex.
Different Types of Depression
We all have a greater sense of well-being in summer than in winter. Some people suffer from extreme seasonal mood swings, though. In summer they can develop hypomania (a state approaching mania) or even become truly manic, while suffering severe depression in winter. This is known as seasonal affective disorder, appropriately shortened to SAD. The former West German chancellor Willy Brandt would tend to become depressed as autumn progressed and the days grew shorter. During these bleak periods, he couldn't bear to see anyone, not even his wife. Seasonal depression is triggered by a lack of sunlight in winter; exposure to sunlight alleviates the symptoms. In the United States there are even insurance companies that send SAD patients from the north of the country to a southern state in order to speed up their recovery. Information on the amount of light
in our surroundings is relayed directly to the biological clock, which isn't just a day-night clock but also a seasonal clock, which plays an important role in SAD. Tiny variations in the genes that make the biological clock function pose a risk factor for depressions of this type.
A bipolar disorder with periods of mania and depression can also occur without any clear seasonal link. When Mrs. De Vries came back from walking the dog in the nearby dunes, she found her husband, who had just retired, slumped over the breakfast table, apparently lifeless. She immediately called the emergency services, and the medics tried to revive him, but without success. In the days that followed, her husband's body lay on a bier in the living room. His widow was full of energy, quite tireless in fact, and after the cremation this became even more pronounced. She developed hypomania and then became truly manic a few days later. She went around to all her acquaintances with mementos of her husband, laughing excitedly. In the middle of the night she would call the police, only to menace them with a hockey stick when they arrived at her house. When she threatened her adult daughter with a knife because she didn't want to be incarcerated in a psychiatric institution and be given electroshock treatment, as had happened to her father, the situation became untenable. At length she was persuaded to enter a clinic. There her mania became even worse, despite the medication. She told everyone excitedly that she'd always wanted to stay in this fabulous hotel, and after each hospital meal she would leave a one-guilder tip for the excellent waiters. She would skip through the clinic, singing, arm in arm with a friend who visited her every day, time and again introducing her to a “former classmate,” an unfortunate man who had never seen her before and was being driven mad by her constantly harking back to their mythical school days. Her condition improved briefly, and then she fell prey to a terrible depression. The story ended happily, however: She made a full recovery and is enjoying life to the fullest with her eight grandchildren.
The Dutch cabinet minister Ger Klein also suffered from a bipolar
disorder (see
chapter 15
). Hypomanic periods can be very productive. The composer Robert Schumann composed over twenty works in his hypomanic phases, in 1840 and in 1849, while he was unable to compose at all during his periods of depression, in 1844 and 1854. In the winter of 1854 he tried to commit suicide by jumping into the icy Rhine river. He was rescued and spent the last two years of his life in a mental institution. Johannes Brahms, deeply shocked by the illness and death of his friend, started work on
Ein Deutsches Requiem
, which he dedicated to Robert Schumann, his mother, and humanity.
The Russian leader Nikita Khrushchev suffered from alternating depressive and hypomanic phases. After he was deposed in 1964, he fell into a deep depression. In the case of government leaders, especially, there's a strong tendency to deny the existence of a bipolar disorder, because of doubts about the ability of individuals with this condition to make well-informed decisions. Winston Churchill suffered from terrible bouts of depression, which he called his “black dog.” According to his private secretary, he could also become madly excited and experienced extreme mood swings with bursts of energy. The terms
hypomania
and
mania
weren't used at the time, but it seems from eyewitness accounts that he must have been bipolar. Lyndon Johnson, who became president after John F. Kennedy was assassinated in 1963, was afflicted by such severe depression after surgery to have his gallbladder and a kidney stone removed that he considered resignation. He, too, had a bipolar disorder, characterized by episodes of profanity and temper. Whether he received medication for it isn't known.
When depression doesn't involve hypomanic or manic interludes, it's classified as unipolar depression or “major depression,” of which melancholic depression is a subtype, involving severe disruption of the day-night rhythm and loss of appetite. The type of depression induced by prednisone or similar substances, called atypical depression, is marked by an increased appetite and need for sleep.
The Various Brain Systems and Areas Involved in Depression
Various cell groups become hyperactive in the hypothalamus of depressive patients. In many cases, the stress axis (the hypothalamus-pituitary-adrenal axis) is strongly activated. In postmortem brain material from donors with lifelong periods of serious depression we found a considerable increase in the number of cells in the hypothalamus producing CRH, even if the patient hadn't died during a depressive episode. This ties in with the theory that the stress axis has been set in a higher gear during the development of such individuals. We know that the activation of CRH neurons contributes to the symptoms of depression, because if CRH is injected in the brains of laboratory animals they develop the same symptoms: diminished appetite, changes to the motor system, sleep disorders, fearfulness, and loss of sexual interest. An increase is also found in other stress hormones, like the hormones vasopressin (produced in the hypothalamus) and cortisol (produced in the adrenal gland), which contribute to such symptoms.