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Studies Point to Physical Causes for Brain Differences

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<i> Konner, a non</i> -<i> practicing physician, teaches medical anthropology at Emory University. His column appears every other week</i>

A recent study of the brains of schizophrenics got me thinking about how all of us--normal (whatever that means) and abnormal--get to be the way we are.

The study, published in the New England Journal of Medicine on March 22, took the unusual and powerful approach of looking at identical twins in which only one of the pair had schizophrenia. This condition, probably the worst of mental illnesses, includes such symptoms as extreme social withdrawal, severe paranoia and obsessive delusional thinking. It usually begins in the late teen-age years or early 20s, and continues throughout life. Drug treatments help somewhat, as does a controlled family setting or other social milieu, but the illness is basically incurable. It affects up to 1% of the adult population.

Usually, when scientists study schizophrenic twins, they want to find that identical twins are matched--either both ill, or both well. This, combined with divergence in nonidentical twins, points to a genetic cause of the illness: same genes, same mental condition. Such studies have often pointed to a genetic cause for schizophrenia. But the fact is that a substantial number of identical twins diverge for the condition; one has it, the other does not. This fact does two things.

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First, it proves that environmental causes count. If two individuals with the same genes can differ so drastically, one suffering from a devastating mental impairment while the other functions well in life, then some element in their environments must have hurt the one or protected the other. Second, it gives us a marvelous opportunity for research. We have long accepted that schizophrenia is partly genetic, partly environmental. What better way to puzzle out the environmental causes than to study genetically identical twins who differ in their mental states.

Psychologists have thought about environmental causes of schizophrenia for generations. Sigmund Freud advanced some psychoanalytic theories based on one or two cases. More rigorous research psychologists have put forward hypotheses ranging from the so-called “schizophrenogenic mother”--very cold but very controlling in early childhood--to stressful adolescent experiences just before the onset of the illness. It has been difficult to prove any of these hypotheses, but most people have assumed that the environmental component of schizophrenia must be in the psychological environment.

Now we must all think differently. The new study, conducted by Richard Suddath, Daniel Weinberger and others at the National Institute of Mental Health, found striking differences in the brains of the divergent twins. As measured by magnetic resonance imaging, which produces a beautiful picture of brain anatomy without causing harm, the fluid spaces in the brains of the schizophrenic twin were consistently larger, and the surrounding brain structures consistently smaller, than for the normally functioning, genetically identical twin brother or sister. In 12 of the 15 divergent pairs, the differences could be seen with the naked eye.

This discovery creates a real problem for those who seek a partial cause of schizophrenia in the psychological environment--mothering, sibling rivalry, adolescent stress and the like. Although it is true that such experiences may be able to influence the brain itself, no one has seriously suggested that changes in brain anatomy as big as the ones observed here could be produced by such experiential factors. Rather, such differences are likely to arise from environmental factors that are not psychological: head injury, viral or bacterial infection, and chemical toxins are good candidates. These may act at any stage of life before the onset of the illness, including in early childhood, or even in the womb, when the brain is still developing.

So what does this tell me about my more-or-less non-schizophrenic brain, or yours? Within psychology, arguments have raged about how much of human behavior can be attributed to the genes, as opposed to the environment. As often as it is said that the key question is not “how much?” but “how?”--how do the various causes interact to produce the mind?--still we hunger for numbers that will tell us how much is genetic, because we assume that the rest is more easily changeable.

In the April 13 issue of Science, Robert Plomin, a leading authority on these matters, reviews evidence that 30% to 50% of both intellectual and personality variation is genetic. We have been in this ballpark for many years, but it is good to have better evidence to confirm the estimates. They show that most of the variation in the mind comes from the environment.

The trouble is, psychologists, educators, and even most parents in our society reflexively assume that environment is equivalent to learning, culture and other aspects of psychological experience. The schizophrenic twin study reminds us that people can have different brains without having different genes. If schizophrenics have different brains, from physical, chemical and biological causes in the environment rather than psychological ones, then the door is open for speculation--and research--on the non-psychological causes of individual differences in general.

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I don’t deny, of course, that learning and culture are powerful. Watch me with my own children, and you will see a man who believes in the power of psychological experience. Yet I also recognize that people have different brains.

Some of the differences come from genes; some from learning. Yet there is a third contribution, operating from the time of conception, when the genes join together, until the end of life; brain changes that come from physical, chemical and biological causes in the environment.

A few, such as alcohol and cocaine, affect the developing brain in increasingly known ways. But most are mysterious, and until we realize that environment does not necessarily mean learning, we are not likely to find out about how they work, or how to make them work for us, instead of against us.

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