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Authors: D. F. Swaab

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Negative symptoms entail the loss of normal abilities, like taking initiative, organizing one's life, tidying up one's room, and looking after oneself. They also include muted emotions and cognitive deterioration.
Many patients end up as vagrants, sleeping on city streets. They often take addictive substances, which might work early on as a form of self-medication against negative symptoms. In the long run, such substances can exacerbate the positive symptoms and cause damage. Negative symptoms are caused by reduced activity in the prefrontal cortex. A current therapy is to apply transcranial magnetic stimulation to that area. Stimulating the areas of the cerebral cortex that are extra active can also reduce hallucinations.

Schizophrenia is more common in men, who are also more affected by it than women. The initial symptoms of the disease can be difficult to identify. A year or two before their first psychosis, young people often show signs of paranoia, start taking drugs, abandon their studies, and become withdrawn. Isolation can exacerbate the condition. Schizophrenia is largely genetic, so having a relative with schizophrenia heightens your risk of this disorder. The first experience of psychosis peaks around the age of twenty. In women there's a second peak that coincides with menopause. Changing hormone levels during puberty and menopause bring on the disease, though a predisposition for it arises in the womb. Female hormones reduce the negative symptoms of schizophrenia if taken together with standard medication.

As the disease progresses, the brain shrinks and its ventricles (cavities) become larger, creating too much space between the convolutions of the brain, just as in the case of many elderly people. This shrinking certainly isn't caused by treatment, because it was shown to exist back in 1920, long before medication for schizophrenia had been developed. Nor is it specific to schizophrenia. It's also seen in the aging process and in various forms of dementia. In fact, there are no brain changes that are specific to schizophrenia, so diagnosis is entirely dependent on psychiatric investigation. It is, however, important to rule out rare brain diseases whose symptoms can mimic those of schizophrenia. But once the diagnosis has been made, early treatment is very important to prevent further brain damage from psychosis.

SCHIZOPHRENIA, A DEVELOPMENTAL BRAIN DISORDER

Schizophrenia is a developmental brain disorder that is caused by a combination of factors and is present at a very early stage—indeed, the main foundation is laid at conception. Studies of families and twins show that the genetic component of schizophrenia is around 80 percent. The genetic factors are many and varied, differing in each family, but all involve tiny variations in the genes that affect brain development or in the production and breakdown of chemical messengers in the brain. The normal development of the fetal brain can subsequently be further disrupted by a host of nonhereditary factors. Maternal malnourishment during the first three months of pregnancy doubles the risk of schizophrenia. This first emerged in studies of children born in Amsterdam after the famine of 1944–1945 (see
chapter 2
). It was recently confirmed by studies of children born in China during and after the mass starvation in Anhui province in 1959–1961, in the wake of Mao's “Great Leap Forward.” The same risk arises if the fetus is malnourished due to a malfunctioning placenta. Toxic substances in the environment, like lead, can also impair brain development in the womb and increase the likelihood of schizophrenia. In addition, you're more at risk of developing schizophrenia if you were born in the winter or if your mother was exposed to flu during the sixth month of pregnancy. How those two factors interact isn't clear. Toxoplasmosis and the Borna disease virus can also be passed on to the fetus, increasing the risk of schizophrenia. Psychological factors, such as stress during pregnancy, play a role too. Moreover, life events, like the death of a relative and pregnancy during wartime, increase the likelihood that a child will develop schizophrenia in later life.

A strong correlation has been found between problems at birth (e.g., forceps delivery, low birth weight, a period in an incubator, and premature birth) and subsequent schizophrenia. Traditionally, it was assumed that these problems at birth affected a child's brain, increasing the likelihood of their developing schizophrenia. For childbirth
to proceed normally, however, subtle interaction is needed between the brains of both mother and child. So you could see birth as the first functional test of a child's brain. Disruptions to the birth process can therefore be regarded as the first symptoms of malfunctioning brain development, which are later manifested as schizophrenia (see
chapter 1
).

After birth, an environment full of stimuli increases the risk of schizophrenia. You're more likely to develop the disease if you live in a city than in the country. Migrants are also at increased risk, probably because of the difficult social circumstances in which they often live. Quite a few adolescents go to their doctor with the first symptoms of schizophrenia after smoking joints. Whether cannabis induces the disease or simply brings forward the moment at which symptoms occur is still a subject of fierce debate.

It is clear from the brains of schizophrenia patients that the disorder arises very early in life. In schizophrenics, a high percentage of cells in the hippocampus are in disarray—something that can only have happened during the first half of pregnancy. Abnormal patterns of brain convolution are also found, as well as groups of cells that have failed to migrate to the right place in the cerebral cortex. This too can only happen during early development.

So although most people with schizophrenia are admitted to clinics as young adults, the foundation for the disease is laid in the womb. It's terrible to think that as late as the 1970s, psychotherapists were spreading the pernicious message that schizophrenia was caused by a mother's coldness and mixed messages (the double bind theory). Family therapists were given the task of reeducating mothers or even of “rescuing” children from the clutches of their pathological environment, a situation that caused extra pain for parents struggling to do their best for their children. The Dutch psychiatrist Carla Rus was so alienated by this approach that she stopped training as a family therapist. My mother, on the other hand, had her own views on what caused schizophrenia. She had a button printed with the words, “Madness is inherited, you get it from your children.”

HALLUCINATIONS DUE TO A LACK OF STIMULI

I doubt if a single individual could be found among the whole of mankind free from some form of insanity. The only difference is one of degree. A man who sees a gourd and takes it for his wife is called insane because this happens to very few people.

Desiderius Erasmus (1469–1536)

If brain structures stop receiving information in a normal way, they start making up information. This applies both to sensory information—from ears, eyes, and limbs—and memory information. A fifty-seven-year-old man who had been suffering from a disease of the inner ear for twenty years found that in the space of twelve months his hearing had greatly deteriorated despite his two hearing aids. During that year he was plagued by nonstop music in his head. Day and night he heard the national anthem, Christmas carols, psalms, and sometimes children's songs. Though distorted, he could always recognize the tune and sometimes sang along. These musical hallucinations are a form of tinnitus better known to patient associations than to the average doctor.

When your brain manufactures information on the spot where it's normally processed, it's interpreted as if it had entered from outside, via the normal route. If the auditory cortex (
fig. 22
), for example, stops receiving the information it normally gets from the ears, it starts to work overtime, producing something that that part of the brain normally processes: music. You would therefore expect the maddening tunes to disappear if you stimulated the auditory cortex. However, it wasn't easy for the man I met to find a doctor prepared to try that. In the end, he was treated by Dirk de Ridder of Antwerp. A short test involving electromagnetic stimulation of the auditory cortex caused his tinnitus to vanish, only to return gradually after a few days. He then splurged on a pair of €4,000 Varibel “hearing glasses” developed by Delft University of Technology, which greatly
improved his hearing and reduced his tinnitus. This shows that the brain stops producing old information once it receives fresh input again, and it makes no difference whether the input is meaningful (the hearing glasses) or has no information content (the electromagnetic stimulation).

Charles Bonnet syndrome is another phenomenon wherein the brain manufactures information to compensate for a lack of input. The condition provokes colorful visual hallucinations in individuals with impaired sight, typically older people with cataracts, glaucoma, or retinal bleeding. The hallucinations—often complex, vivid images of people—tend to occur in dim light and quiet surroundings. Sufferers of Charles Bonnet syndrome are aware that their hallucinations aren't real and find that they usually disappear if they shut their eyes. An eighty-three-year-old woman who had played an active role in the Dutch resistance during the Second World War and who had become practically blind due to glaucoma confided anxiously to her daughter that whenever she blinked her eyes she saw swastikas.

In the case of Charles Bonnet syndrome, the visual cortex (
fig. 22
) receives insufficient information from the eyes and starts to produce its own pictures. A similar phenomenon occurs in the case of memory loss. People who suffer from Korsakoff's syndrome, a dementia that results from alcohol abuse, produce fake memories of events that never took place, known as confabulations. Phantom sensations following amputation appear to be based on the same principle. Lacking customary input from a limb, the brain “makes up” the presence of a missing arm or leg. Hallucinations can also be a sign of neurodegenerative diseases like Lewy body dementia, which often involves impaired visual perception, and Alzheimer's disease and Parkinson's disease.

In schizophrenia, input to areas of the cerebral cortex is also reduced, so the hallucinations it provokes could be caused by the same mechanism. Depending on the area of the cortex that is overactive, schizophrenia patients see or hear things that aren't there. A group headed by René Kahn in Utrecht has indeed shown, in a series of
pioneering experiments, that electromagnetic stimulation of the brain reduces hallucinations in schizophrenia patients. Conversely, isolation cells, in which these patients tend to be confined during acute stages of the disease, diminish brain input even further and can thus make their symptoms much worse.

Mountaineers, especially when alone, sometimes have very vivid hallucinations (hearing voices, seeing people, or having out-of-body experiences) or are overcome by fear. So it's interesting that the revelations received by the leaders of the world's three main religions were preceded by a period of isolation in the mountains. On two occasions, Moses received the Ten Commandments from the Lord on Mount Sinai. On the second occasion he spent “forty days and forty nights” there alone “without eating bread or drinking water.” When Jesus took the disciples Peter, John, and James up a mountain to pray, they had a vision of Moses and Elijah. The Prophet Muhammad saw the Archangel Gabriel during his lonely vigil on Mount Hira. These experiences involved seeing bright lights, hearing voices, and experiencing fear, just as in the case of mountaineers. When the brain is very isolated it starts to use stored experiences and thoughts to manufacture things—sometimes even new religions.

OTHER HALLUCINATIONS

When we remember we are all mad, the mysteries disappear and life stands explained.

Mark Twain (1835–1910)

Delirium

Hallucinations are by no means confined to schizophrenia. They are most common in cases of delirium. In the Netherlands, around one hundred thousand patients a year experience delirium. Most of them are elderly people who have been operated on under general anesthesia
(because of a broken hip, for instance). For an old brain, an anesthetic is like a dose of near-lethal poison. In intensive care, up to 80 percent of patients experience delirium. Delirium can also result if the brain's functioning is impaired by pneumonia, dehydration, medication, drugs, or malnourishment. In older people it can even be caused by a simple urinary infection. Then there's the famous delirium tremens, which isn't solely caused by alcohol poisoning—it can result from alcohol deprivation. Brain damage due to lack of oxygen, low blood sugar, or an infarct can also induce delirium.

Delirious patients are extremely confused. They are often restless, have memory problems, and are aggressive, noisy, and sometimes hyperactive to the point of falling out of bed and breaking something, ending up in even worse shape than they were before. But there's also a peaceful type or phase of delirium in which patients simply lie in bed apathetically, staring blankly. Their consciousness is impaired. They don't know where they are or sometimes even who they are. They can't think straight or concentrate. The condition sometimes resembles dementia, but delirium strikes all of a sudden, while the onset of dementia is gradual. Delirious patients will hallucinate, often seeing creepy crawlies everywhere. Some have been known to refuse food or drink because it appeared to be covered with ants. One patient saw beetles coming out of the ceiling. Feverish children can have visions of cartoon characters (one little girl reported seeing Donald Duck riding her father's bicycle along her bedroom wall). The hallucinations and delusions are often frightening. One patient, a Holocaust survivor, thought that he was being sent back to a concentration camp and was terrified of his doctors and nurses, believing that they had come to get him. In his desperate attempts to escape, he tore his drip out of his arm and then the tube through which he was being fed—a dangerous thing to do, because if the food had gotten into his lungs he could have developed pneumonia. A female patient thought that she had been tied up and raped in the hospital. An old friend of mine, refusing to believe that his
operation was over, asked the doctor why on earth he had visited him in the middle of the night. He went on to reprimand the doctor for not having the decency, during this nighttime visit, to answer his queries about the results of his blood test. My friend believed that he had then gone to the laboratory himself to get the test results. Both the doctor's visit and his nocturnal trip to the laboratory had in fact been a hallucination. An old lady who fought tooth and nail with the nursing staff explained later that she thought her bed was her grave. She made desperate attempts to climb out, but the nurses kept pushing her back in.

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