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The weight of the world

Hanging countries, or swapping the countryside for the city, even though it represents the quest for better living conditions, increases the risk of schizophrenia

EDUARDO CESARThe last few years have seen a number of studies coming to maturity, undertaken by physicians in the United Kingdom, Denmark, Germany, the United States and Brazil, relating external causes of a social or environmental order to the emergence of schizophrenia, a mental disturbance up until now associated only with genetics or to anomalies in the brain. Urbanization, migratory movements, racial discrimination, or traumas like sexual abuse in childhood, are seen today as factors that may influence the appearance of this mental disorder, characterized by a progressive distancing from reality. What usually springs up as a continuous irritability, without any apparent reason, slowly burgeons into social isolation, into a lack of interest in appearance, into incoherent thinking, and into muddled talking. In extreme cases, it manifests itself by means of false convictions, like delusions of persecution, or of false perceptions, or hallucinations, when it does not lead to the opposite extreme, muteness and analmost total immobility, known as catatonia.

Even a simple infection may set in motion the biological mechanisms that lead to schizophrenia, a problem that affects some 25 million persons in the world, and about 1 million in Brazil alone. In the 70’s, when he was still studying medicine, Wagner Farid Gattaz was impressed when he read studies that related the increase in cases of schizophrenia in children whose mothers were hit by the influenza virus during an epidemic that took place in Europe in 1957.

Some years afterwards, as an intern in a pediatric hospital in São Paulo, he examined children coming in with vomiting and strong headaches, who were suffering from meningitis, during the epidemic that arose in the state of São Paulo in the 70’s. Usually caused by bacteria, meningitis is an inflammation of the membranes called meninges, which cover the brain and the spinal cord, and which can lead to death in a few hours.

“I spent 30 years wondering what the consequences of meningitis could be for those children who survived, after becoming adults”, says Gattaz. It was a few years ago, as a researcher at the Psychiatry Institute of the University of São Paulo (USP), that he found the answer. With his postgraduate student André Abrahão, Gattaz assessed the state of health of 173 persons (77 men and 96 women) with an average age of 30 years, who had had meningitis between birth and the age of 4. He compared them with their brothers and sisters who had not caught the infection, and found that the occurrence of meningitis in early childhood increases fivefold the risk of schizophrenia appearing at an adult age.

His study, which is being published in the European Archives of Psychiatry and Clinical Neuroscience, strengthens the hypothesis that infectious factors may interact with the organism of each individual, in a different way, and increase the risk of getting the disease. “Our task now is to discover how this interaction occurs”, he comments. “By getting to know the biological and environmental risk factors, we shall be increasing the chances for detecting the disease earlier and thus for starting to treat it sooner.” Schizophrenia is nowadays treated by antipsychotic medicines, associated with strategies for social and professional rehabilitation and reintegration.

The delimitation of environmental risk factors for schizophrenia, debated at an encounter in April 2003 that brought together the world’s principal specialists in this area in Guarujá, on the São Paulo coast, expands the vision of a mental problem that tends to be defined solely on the basis of clinical observations of the patients. “It is worrying to note that urbanization and social fragmentation are stimulating the rapid advance of schizophrenia”, is the comment made by psychiatrist Glynn Harrison, from the University of Bristol, United Kingdom, in a study presented at the congress in Guarujá. “For doctors from all over the world”, says he, “the challenge is to open up the black box of culture and find new ways of dealing with this problem.”

Recent studies confirm the impression that it really is not very healthy to live in a metropolis. The risk of mental problems grows with the levels of urbanization, defined in accordance with the density of domiciles per square kilometer, on a scale with five categories (from less that 500 houses to over 2,500 in the same area), according to a study coordinated by Jim van Os, from Universiteit Maastricht, Holland, with 7,076 persons between the ages of 18 and 64. This same study makes clear the high occurrence of mental illnesses in individuals with traumas, like sexual abuse or the premature loss of parents, particularly the mother, or in immigrants, probably because of the discrimination they suffered in the countries to which they moved.

In a survey carried out with 2.1 million of Swedes born between 1954 and 1983, Elizabeth Cantor-Graee, from Lund University, demonstrated that those who emigrated to Denmark show 2.5 times more probability of developing schizophrenia than the Swedes who remained in the country. According to this study, published in 2003 in the British Journal of Psychiatry, Danes who lived outside their country and returned have almost twice more risk of developing this mental disturbance than their brothers and sisters who stayed in their native land.In another study, published in 2001 in the same magazine, Carsten Böcker Pedersen and Preben Bo Mortensen reported that those who lived in Copenhagen, the capital of Denmark, are subject to a risk two times greater of becoming schizophrenic than their fellow-countrymen who live in the countryside. The preliminary results of a study carried out by the World Health Organization (WHO) in 19 nations show that the rate for serious cases is higher in the countries classified as developed (40%) than inthe developing countries (24%).

For the time being, there are only some rather vague reports on how episodes of life take away people’s mental equilibrium. “Urbanization interacts with each individual’s vulnerabilities and with the family risks for mental illnesses”, says Van Os, from Holland. The environmental factors should have a direct influence on the workings of the neurons (nerve cells) of the brain, altering the connections – or synapses – between them. These modifications in the communication between neurons may weaken the working of the brain, increasing the probability of severe mental instabilities.

The external causes may also act in another way, on a deeper plane, like a trigger that sets off one or more of the 30 or so genes that are in some way related to this problem. Once activated, the genes may act on neurons in the brain, directly or indirectly, by means of metabolic alterations that damage the connections between the nerve cells. But a mere genetic predisposition to schizophrenia does not seem to be sufficient to explain the alteration to the synapses. Decades ago, something important was discovered in studies with identical twins: if one of them becomes schizophrenic, the other has a 50% risk of developing the disease as well. That may be a lot, in the light of the 1% probability of schizophrenia arising in a person with no case of the disease in the family. But, if the cause of schizophrenia were purely genetic, one would expect this risk to be 100%, since identical twins carry the same genes. Even so, between shared genes and shared environments, genes have more weight.

From ten years ago until now, psychiatrists and neurologists have discovered some peculiarities in the brains of schizophrenics that reflect this web of reactions between environment, genes and biochemical processes. There are, for example, alterations in dopamine and glutamate, molecules for communication between neurons, and a lesser circulation of blood in some areas, compared with the brain of mentally health people. In schizophrenics, the cavities in the middle of the brain called ventricles are larger, and the hippocampus, the key to memory and learning, is smaller – and the neurons of the hippocampus get more excited than in other people. Furthermore, adds psychiatrist Stephan Heckers, from the Massachusetts General Hospital, United States, “a kind of nerve cell called an interneuron is missing, which controls the activity of other neurons of the hippocampus”.

The Project
Metabolism of Phospholids in Schizophrenia and Alzheimer’s Disease; Modality Thematic Project; Coordinator Wagner Farid Gattaz – School of Medicine at USP; Investment R$ 1,590,193.43