Saturday, November 12, 2011 - 0 comments

Wonderful Town

By : Steve Mirsky

No wonder it’s “the city that never sleeps.” A study in the May issue of Fertility and Sterility showed that New York City leads the nation in sperm counts. Actually, the study found that the Big Apple outdoes only two other cities. But, more important, the findings contradict previous studies suggesting a global decline in sperm counts.

Unless you are one of those people who thinks Testicles was a hero of the Trojan War, you have probably  read about the possible link between falling sperm counts and chemicals that may behave like estrogens. A 1992 paper by Danish researcher Niels Skakkebaek noted that studies done around the world indicated that  sperm counts had fallen from about 113 million per milliliter in 1938 to 66 million per milliliter in 1990. Combine that with a rise in testicular cancer and genetic reproductive abnormalities in some countries, and experts began to worry that we were on our way to a future of infertility. Accounts of the controversy appeared in this magazine (which is published in New York).

The new study, by Harry Fisch and colleagues at the Columbia-Presbyterian Medical Center (which is in  New York), reports that what Skakkebaek took to be a worldwide decline may have been a  misinterpretation of natural geographic variations. “There are geographic variations in everything—cancer and  heart disease, for example,” Fisch says. “I would be more surprised if sperm counts were the same everywhere.”

Fisch looked at counts for about 1,300 men who had donated at sperm banks in New York, Roseville,  Minn., and Los Angeles between 1970 and 1994. Rather than diminishing, counts rose in New York and Roseville. The differences among cities, however, were striking. Los Angeles came in at 73 million per milliliter, Roseville at 101. Start spreading the news that New York, N.Y., came in at the top of the heap with  a whopping 132.

This New York talent could account for a misperception of an international decline—apparently, it’s not true that if you can make it there, you can make it anywhere. When Fisch examined the 1992 Danish paper, he  found that 94 percent of the men studied before 1970 were from the U.S., 87 percent of them from New   York. But after 1970, only half the subjects came from the U.S.—and only 25 percent of them were New  Yorkers. If geographic variations do exist in sperm production, then what appeared to be a ubiquitous decline may have been merely the result of a shift in study sites.

None of which explains New York’s explosive ability for sperm production. “We don’t know why New York sperm counts are highest,” Fisch admits. In what may or may not be a related story, New York was recently shown to lead the nation in obsessive-compulsive disorder. With so much sperm to count, this was perhaps obvious.
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The Changing Quality of Life

By : Rodger Doyle

These maps show the Physical Quality of Life Index (PQLI), developed by Morris David Morris of Brown University to measure progress among the poorer countries. The PQLI is based on life expectancy at age one and rates of literacy and infant mortality. Values range from a low of 6.3 in the West African nation of the Gambia in 1960 to a high of 94 in Japan in 1990. Because the PQLI is based on end results, it has advantages over other methods. Per capita gross national product in Iran, for example, is less than one third that of Saudi Arabia, yet the 1990 PQLI scores of the two countries are identical, indicating that income and wealth are more evenly distributed in Iran.

The most important conclusion to be drawn from the maps is that despite a huge global increase in population, there was considerable improvement in the quality of life among developing nations, including those in sub-Saharan Africa, the poorest region on the earth. Preliminary data for 1993 show further progress in most areas, a major exception being 13 countries in sub-Saharan Africa that suffered drops in PQLI scores averaging three points, which came as a result of decreased life expectancy and increased infant mortality. Losses are caused, at least in part, by the spread of AIDS, which has affected this area more severely than  any other. But the long-term prospect is not necessarily bleak, for the AIDS epidemic may subside, perhaps  as early as the next decade. Furthermore, the historical record has registered a more or less steady improvement in the PQLI. Other countries that once had scores as low as those in the sub-Saharan region have shown remarkable change: Sri Lanka had a score of only 19 in 1921, but by 1993 it had reached 85. And 100 years ago the U.S. had about the same PQLI score as the sub-Saharan countries do today.

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Headshrinker Convention

By : John Horgan


The first thing one notices on entering New York City’s cavernous Jacob Javits Center, site of the 149th annual meeting of the American Psychiatric Association, is the Eli Lilly exhibit. The golden, shrinelike tower emblazoned with “Prozac” in Day-Glo red stands amid interactive video screens and fiercely cheerful Lilly salespeople touting the wonders of the best-selling antidepressant (sales topped $2 billion last year).

Some 16,000 people—including psychiatrists, psychotherapists, researchers and drug-company representatives—have gathered here in early May for lectures on everything from “Kids Who Kill” and “The Psychobiology of Binge Eating” to emerging markets for psychiatric services. One “area of opportunity,” reveals Melvin Sabshin, medical director of the APA, is forensic psychiatry. “We have more people with psychiatric disorders in jails and prisons than in hospitals,” he explains.


A big buzzword is “parity”—the principle that insurance companies should provide the same coverage for mental disorders as they do for physical ones. A bill calling for mentalhealth parity won approval from the Senate in April after heavy lobbying by the APA but still has to run the gauntlet of the House. “This is about fairness,” declares Marge Roukema—a Republican representative from New Jersey and a fierce advocate of parity—to a cheering audience. Most people who see therapists, argues Roukema (who happens to be married to a psychoanalyst), are not self-absorbed neurotics like the ones depicted in Woody Allen films but people with a real need.

Psychiatrists here voice concern about the encroachment of psychologists and social workers, who usually  charge less than psychiatrists do. On the other hand, psychiatrists are M.D.’s and can prescribe drugs, which are cheaper than protracted talk therapy. And psychiatrists flock to breakfasts and dinners featuring lectures on the latest drugs for insomnia and depression—meals sponsored by Pfizer, SmithKline Beecham and other pharmaceutical firms.

Not every attendee embraces the better-living-through-chemistry philosophy. At a session entitled “The Future of Psychotherapy,” which is attended by only 20 or so people, Gene L. Usdin, a psychiatrist at the Ochsner Clinic in New Orleans, frets that “we are selling our souls” to the drug companies. Another dissenter is a sales rep for Somatics, which has a modest booth in the shadow of the Prozac pavilion. His company, he claims, provides a far more effective treatment for severely depressed patients: electroconvulsive therapy.
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Pot Luck

By : David Schneider

Linear A, an ancient script, is unearthed in Turkey.

MINOAN POTTERY
Recovered from mainland Turkey
Throughout this century, scholars studying the ancient civilizations of the Mediterranean have pondered a vexing puzzle. The mystery unfolded soon after 1900, when the English archaeologist Sir Arthur J. Evans began excavating the buried palace of Minos at Knossos on the island of Crete. Among the many artifacts found were clay tablets bearing two related forms of unintelligible writing that Evans termed Linear A and Linear B script.

Evans, along with many other classicists, struggled for decades to decode the enigmatic symbols. It was an amateur—a young English architect named Michael G. Ventris—who finally deciphered Linear B in 1952, concluding correctly that the language it represented was archaic Greek. The older and more rarely
preserved Linear A code seemed obviously of a different origin, but the identity of that language remained unknown. Now an archaeological discovery in Turkey links the authors of that script—the so-called Minoans—with lands to the east.

There are many thoughts about what language the far-ranging Minoans spoke. Some scholars believe Linear  A inscriptions may be in the language of the Hittites, who some 4,000 years ago dominated what is now Turkey. Others suggest that Linear A transcribes Luwian, a more obscure ancient language of that area. Some have proposed that Linear A symbols spell out Semitic words. It also may be completely possible that the mysterious dialect of the Minoans is not related to any known language at all.

Because there is so little certainty about the origin or extent of Minoan civilization, scholars have been particularly intrigued by the recent findings: Wolf- Dietrich Niemeier of the University of Heidelberg’s Archeological Institute has discovered Minoan artifacts bearing Linear A script on mainland Turkey, marking a strong connection between the ancient inhabitants of Crete and the mainland to the east.

Niemeier’s work began in 1994, at the ruins of Miletus. He had returned to excavations made there by German teams during the 1950s and 1960s. Niemeier installed powerful pumps to lower the water table so that he could explore even deeper levels. Although his initial discovery of Linear A was made during the first season of fieldwork, he did not realize the significance of the find. He thought the curious marks incised on a  shard of pottery were just a graffito, a mere doodle. But in the second year his team uncovered two additional pieces with similar inscriptions. At that point, Niemeier remarks, “I recognized it immediately as Linear A.” He remembered the earlier discovery: “We pulled out the box with the shard, the so-called graffito, and it matched.”

According to Thomas G. Palaima, chairman of the department of classics at the University of Texas at Austin, “There’s absolutely no doubt that this is Linear A.” With only small fragments of pottery bearing three signs found so far, there is not much to read—even if one knew how. Still, this cryptic message helps to paint a picture of the Minoans who lived some 36 centuries ago.

Because Minoan artifacts have been found on several of the Aegean Islands, experts have wondered whether these people presided over a maritime empire that stretched beyond Crete. Did they, for example, rule  overseas colonies, or was it just that they exported their wares? (To make an analogy, one might find Chinese porcelain among items from Victorian England, yet it would be wrong to conclude that China had dominated the British Isles.)

From the type of clay used, it is apparent that the pottery in Miletus was made locally. It is also clear that these Linear A symbols were inscribed before the pot on which they were written was fired. According to  Palaima, these facts (and the observation that one of the signs is rather rare) suggest that Minoan speakers must have been there—probably as members of a Minoan colony.

Greater insight into Minoan society would come from reading Linear A inscriptions, but decoding remains elusive, in part because so few examples have been available to scrutinize. Perhaps archaeologists as determined as Niemeier will eventually recover sufficient text to make decipherment possible. But for the time being, the mystery of Linear A endures.
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Waking Up

By : Tim Beardsley in Washington, D.C.

Finding a purpose for sleep has been as elusive as rest to an insomniac, but researchers are getting much closer.

SLEEP RESEARCHERS
hope to understand the mechanisms of sleep
disorders, which afflict millions of people.
Sleep may well be “a gentle thing, beloved from pole to pole,” as Samuel Taylor Coleridge observed. For physiologists, it remains a biological mystery of the first order. Why should mammals and birds spend such a large part of their lives unresponsive and, worse, vulnerable? Although denying an animal sustenance produces bodily changes that are readily measured, nobody understands what harm is done to an animal—or a person —deprived of sleep. Yet something clearly goes terribly wrong. Researchers have known for more than a decade that a rat prevented from sleeping will lose the ability to maintain body heat and die in about three  weeks, leaving no clues in the form of physiological damage. For humans, sleep deprivation undermines thinking, but science has no explanation.

There are, however, plenty of theories—and thus plenty of enmity in the field. Sleepers lower their metabolic rate, thereby conserving energy. But this does not explain why we lose consciousness. Most researchers believe sleep benefits the brain, perhaps by giving neurons a chance to recuperate. Some, pointing to the fervid neuronal activity during the bouts of REM (rapid-eye movement) sleep that punctuate our nights, suggest we doze to consolidate memories. Others propose that dreams are mental junk being eliminated: we sleep to forget. Although it is too soon to proclaim the conundrum of sleep solved, findings are illuminating processes that seem to control it. At the same time, investigators are refining their ideas about the benefits of slumber for the brain. Understanding its purposes may ultimately help the millions of people who suffer from sleep disorders, which range in severity from the merely irritating to the fatal.

The starting point for many investigations into the control of sleep has been the hypothalamus, a platformlike structure in the brain that has long been known to have an important role. Damage to the back part of the hypothalamus causes somnolence, suggesting that when intact, it maintains alertness. Damage near the front part, in contrast, induces insomnia, indicating that the spur to sleep is there. Investigators have long looked for a controlling circuit for slumber that operates between the two halves of the hypothalamus.

The hypothalamus also plays a part in temperature regulation, and some physiologists have speculated that sleep evolved out of a more primitive thermostat. Last year M. Noor Alam, Dennis McGinty and Ronald Szymusiak of the Department of Veterans Affairs Medical Center in Sepulveda, Calif., found the first evidence of neurons that fill both functions. The team discovered neurons in the front part of the hypothalamus of cats that fire more rapidly when they are warmed by two degrees Celsius—and automatically increase their firing rate while the animal sleeps. The researchers suggest that these neurons are part of the body’s thermostat and that they are responsible for controlling naturally occurring non-REM sleep.

A related discovery was reported earlier this year by Jonathan E. Sherin, Priyattam J. Shiromani, Robert W. McCarley and Clifford B. Saper of Harvard Medical School. These workers uncovered evidence that clusters of neurons in part of the front hypothalamus of rats—a site called the ventrolateral preoptic (VLPO)—seem to be activated when the animal is not awake. The researchers tracked the levels of a gene product that appears to be present whenever a cell is busy: the busy signal in these neurons was greater in animals that had slept more.


Sherin and his colleagues then took another step. They had previously suspected that neurons in the VLPO region send extensions to the rear part of the hypothalamus. By injecting what is called a retrograde tracer into the suspected target region in the rear of the hypothalamus and then following the diffusion of the tracer, they proved that the sleep-active neurons in the VLPO area did indeed project to the back part of the hypothalamus, where they wrap around their target cells. The pathway “probably is playing a major role and may play a critical role in helping sleep,” according to Saper.

Evidence from two quite different avenues of inquiry is consistent with the idea that a crucial piece of the  puzzle resides in that region. One is narcolepsy, which affects 250,000 Americans, causing them suddenly and unpredictably to lose muscle control and fall asleep. Any emotionally laden event—even hearing a joke—can trigger such attacks. Neurologists have supposed that some specific type of brain damage must underlie the condition, but nobody has been able to pinpoint it.

Until now. Jerome M. Siegel of the University of California at Los Angeles studied the brains of narcoleptic Doberman pinschers and found destruction of cells in the amygdala, a region involved in emotional responses. Damage to these areas could explain the symptoms of narcolepsy, Siegel suggests. Moreover, neurons run from the amygdala to the front part of the hypothalamus. It is therefore possible, others observe, that cell death in the amygdala might somehow influence the VLPO, bringing on drowsiness and the loss of muscle control characteristic of REM sleep.

Another VLPO clue comes from studies of circadian rhythms, described roughly as a 24-hour cycle of sleep and waking. Recognized as providing one cue for sleep in animal studies, the circadian clock resides in a part of the hypothalamus called the suprachiasmatic nucleus. And the suprachiasmatic nucleus sends neuronal projections to the VLPO, Saper reports. This pathway could be what directs signals about the time of day from the suprachiasmatic nucleus to the VLPO region.

Details of the neural circuitry that turn on sleep beg the question of what sleep is ultimately for. No damage to the brain prevents sleep indefinitely, notes James M. Krueger of the University of Tennessee. Therefore, Krueger argues, the final explanation must involve a benefit to neural functioning. And he asserts that the benefit is closely linked to the immune system.

Krueger points to experiments conducted by Carol A. Everson, also at Tennessee, showing that rats deprived of sleep have high numbers of bacterial pathogens that are normally suppressed by the immune system. Everson says there is little doubt that the bacteria eventually kill the rats. The exhausted, dying rats fail to develop fever, which would be the normal response to infection. Prolonged sleep deprivation, then, apparently dangerously suppresses the immune system. In humans, even moderate sleep deprivation has a detectable influence on immune system cells.

Further, the effect of sleep on the immune system is not a one-way street: the immune system affects sleep in return. Infections are well known to cause sleepiness, and Krueger has shown that several cytokines, molecules that regulate immune response, can by themselves induce slumber. In addition, cytokines have direct effects on neural development. Krueger and his colleagues have recently demonstrated that in rats, a gene for one cytokine becomes more active in the brain during sleep. He suggests that cytokine activity during sleep reconditions the synapses, the critical junctions between neurons, thereby solidifying memories. The  cytokines also keep the immune system in shape. Neural pathways like the one in the VLPO region, according to Krueger, may simply coordinate a process that arises at the level of small groups of neurons.

Many physiologists still regard Krueger’s ideas as speculative—but later this year Krueger says he will present hard data indicating that cytokines are involved in normal sleep. Genetically engineered mice that lack receptors for two important cytokines, interleukin-1 and tumor necrosis factor, sleep less than usual, Krueger says. So these and related cytokines may well trigger normal sleep in healthy animals, not just the sleepiness of infection and fever.

Whether cytokines, heat-sensitive neurons and the VLPO area indeed hold the key to understanding sleep is a question for the future. But one thing is clear: sleep researchers have never before had so many tantalizing leads or such a full agenda.
Wednesday, November 9, 2011 - 0 comments

Autism : 6. Helping the Handicapped

by : Uta Frith

SELF-ABSORPTION displayed by this
autistic girl is a common feature
of the disorder. In the motion
picture Rain Man, self-absorption
was the key trait of the central
character, an autistic adult
portrayed by actor Dustin Hoffman.
The old image of the child in the glass shell is misleading in more ways than one. It is incorrect to think that  inside the glass shell is a normal individual waiting to emerge, nor is it true that autism is a disorder of  childhood only. The motion picture Rain Man came at the right time to suggest a new image to a receptive public. Here we see Raymond, a middle-aged man who is unworldly, egocentric in the extreme and all too amenable to manipulation by others. He is incapable of understanding his brother’s double-dealing pursuits, transparently obvious though they are to the cinema audience. Through various experiences it becomes possible for the brother to learn from Raymond and to forge an emotional bond with him. This is not a farfetched story. We can learn a great deal about ourselves through the phenomenon of autism.

Yet the illness should not be romanticized. We must see autism as a devastating handicap without a cure. The autistic child has a mind that is unlikely to develop self-consciousness. But we can now begin to identify the particular types of social behavior and emotional responsiveness of which autistic individuals are capable. Autistic people can learn to express their needs and to anticipate the behavior of others when it is regulated by external, observable factors rather than by mental states. They can form emotional attachments to others. They often strive to please and earnestly wish to be instructed in the rules of person-toperson contact. There is no doubt that within the stark limitations a degree of satisfying sociability can be achieved.

Autistic aloneness does not have to mean loneliness. The chilling aloofness experienced by many parents is not a permanent feature of their growing autistic child. In fact, it often gives way to a preference for company. Just as it is possible to engineer the environment toward a blind person’s needs or toward people with other special needs, so the environment can be adapted to an autistic person’s needs.

On the other hand, one must be realistic about the degree of adaptation that can be made by the limited person. We can hope for some measure of compensation and a modest ability to cope with adversity. We cannot expect autistic individuals to grow out of the unreflecting mind they did not choose to be born with. Autistic people in turn can look for us to be more sympathetic to their plight as we better understand how their minds are different from ours.

***

UTA FRITH is a senior scientist in the Cognitive Development Unit of the Medical Research Council in London. Born in Germany, she took a degree in psychology in 1964 at the University of the Saarland in Saarbrücken, where she also studied the history of art. Four years later she obtained her Ph.D. in psychology at the University of London. Besides autism, her interests include reading development and dyslexia. She has edited a book in the field of reading development, Cognitive Processes in Spelling, and is the author of  Autism: Explaining the Enigma.

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Autism : 5. Explaining Autism’s Variability

by : Uta Frith

BRAIN SCANS show differences in activity between normal
and autistic people. In normal persons reading a story that requires
inferring the mental state of others, the left medial prefrontal
cortex of the brain was active (left). In persons with Asperger
syndrome performing the same task, an adjacent lower
area was active instead (right). The left medial prefrontal cortex
may be a key component of the theory of mind capability.
The astonishing variability in the signs and symptoms of autism is only beginning to be fully appreciated. Some  autistic individuals never develop speech or nonverbal communication, whereas others become fluent and can  pass for normal in social interactions. A screening test that identifies the lack of shared attention, pretend play and eye contact characteristic of autism—developed by Simon Baron-Cohen of the University of Cambridge and his colleagues at Guys Hospital in London—appears to be remarkably successful in predicting autism in children as young as 18 months.

The most severe cases of autism are associated with mental retardation, but IQ does not consistently correlate with abilities and special talents. Some studies report that up to 10 percent of the autistic population has a savant skill—exceptional ability in one area, such as playing the piano, drawing or mathematics. Significantly, almost all savants are diagnosed as autistic.

One of the most important advances in the field has been the growing recognition of a subgroup of autistic individuals who possess high verbal ability and develop a high degree of social awareness by utilizing an acquired, nonintuitive theory of mind. This variant of autism is called Asperger syndrome, and some individuals who exhibit it have successful academic careers in spite of their interpersonal communication problems, obsessive tendencies and restricted interests. Although autistic individuals with normal or higher IQs can show a high degree of social adaptation, even the most compensated have some difficulty in the give and take of everyday conversation and are unlikely to have intimate friends.

The theory of mind—that autistic individuals lack the ability to understand the role of mental states in others —proved to be a crucial step in explaining how the social and communication deficits of autism could coexist with good general abilities. This hypothesis also predicts that there is a specific substrate or pathway in the brain that gives us the ability to conceive of mental states, and recent brain imaging studies indicate that such an area may be located in the left medial prefrontal cortex. Yet the theory of mind is unable to account for all aspects of autism, such as stereotyped behavior and the desire for sameness or the exceptional talents present in a significant proportion of autistic individuals. Two additional hypotheses have been proposed.


FREEHAND DRAWING by E.C., a male autistic savant,
was made spontaneously and without any corrections.
Although the perspective appears realistic, it
is achieved without the “vanishing points” most artists
would need. Studies by Laurent Mottron and Sylvie
Belleville of the University of Montreal show that
E.C.’s ability to integrate parts of visual patterns is impaired;
he is unable to reproduce anything resembling
a human face but has exceptional ability to remember
and draw individual objects and geometric shapes.

Bruce F. Pennington of the University of Denver and others in the U.S., as well as James Russell and his colleagues at the University of Cambridge in the U.K., have put forward the executive dysfunction hypothesis, which proposes that autistic individuals have a deficit in executive functions such as planning and working memory, impulse control, and initiation and monitoring of action. The processing of executive functions is thought to occur in the prefrontal cortex, and poor performance of these functions is directly related to repetitive thought and stereotyped, rigid behavior in autistic individuals.

Francesca Happé of London University and I have proposed the weak central coherence hypothesis as an explanation for the exceptional talents and restricted interests displayed by some autistic individuals. Weak central coherence refers to a preference by autistic individuals for segmental over holistic information processing. How the brain integrates information is obscure, but long-range connections between the hemispheres may well be involved. There is some evidence that people with autism process information in piecemeal fashion—the total attention of the autistic individual often is captured by fragments or selective features usually of little interest to normal persons. Surprisingly, autistic persons tend to be less susceptible to visual illusions, perhaps because they are less affected by the context in which the figure is embedded.

Because it provides a model for the ability to conceive of mental states, research into autism is stimulating philosophical debate on selfconsciousness. Future studies may lead to the identification of subcomponents or precursors of consciousness in other species, which in turn might lead to a better understanding of the development of conscious experience in humans.

Next : Helping The Handicapped
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Autism : 4. Theory of Mind

by : Uta Frith

Lacking a mechanism for a theory of mind, autistic children develop quite differently from normal ones. Most children acquire more and more sophisticated social and communicative skills as they develop other cognitive abilities. For example, children learn to be aware that there are faked and genuine expressions of feeling. Similarly, they become adept at that essential aspect of human communication—reading between the lines. They learn how to produce and understand humor and irony. In sum, our ability to engage in imaginative ideas, to interpret feelings and to understand intentions beyond the literal content of speech are all accomplishments that depend ultimately on an innate cognitive mechanism. Autistic children find it difficult or impossible to achieve any of these things. We believe this is because the mechanism is faulty.

This cognitive explanation for autism is specific. As a result, it enables us to distinguish the types of situations in which the autistic person will and will not have problems. It does not precludethe existence of special assets and abilities that are independent of the innate mechanism my colleagues and I see as defective. Thus it is that autistic individuals can achieve social skills that do not involve an exchange between two minds. They can learn many useful social routines, even to the extent of sometimes camouflaging their problems. The cognitive deficit we hypothesize is also specific enough not to preclude high achievement by autistic people in such diverse activities as musical performance, artistic drawing, mathematics and memorization of facts.

It remains to be seen how best to explain the coexistence of excellent and abysmal performance by autistic people in abilities that are normally expected to go together. It is still uncertain whether there may be additional damage to emotions that prevents some autistic children from being interested in social stimuli. We have as yet little idea what to make of the single-minded, often obsessive, pursuit of certain activities. With the autistic person, it is as if a powerful integrating force—the effort to seek meaning—were missing.

Next : Explaining Autism’s Variability
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Autism : 3. Defect in Frontal Lobes (2)

by : Uta Frith

In the second year of life, a particularly dramatic manifestation of the critical component can be seen in normal children: the emergence of pretense, or the ability to engage in fantasy and pretend play. Autistic children cannot understand pretense and do not pretend  when they are playing. The difference can be seen in such a typical nursery game as “feeding” a teddy bear or a doll with an empty spoon. The normal child goes through the appropriate motions of feeding and accompanies the action with appropriate slurping noises. The autistic child merely twiddles or flicks the spoon repetitively. It is precisely the absence of early and simple  communicative behaviors, such as shared attention and make-believe play, that often creates the first nagging doubts in the minds of the parents about the development of their child. They rightly feel that they cannot engage the child in the emotional to-and-fro of ordinary life.

UNUSUAL BEHAVIOR is often displayed
by autistic individuals. Autistic
children, for example, tend to fixate
on making toys and other objects spin
and to play repetitively.
My colleague Alan M. Leslie devised a theoretical model of the cognitive mechanisms underlying the key abilities of shared attention and pretense. He postulates an innate mechanism whose function is to form and use what we might call second-order representations. The world around us consists not only of visible bodies and events, captured by first-order representations, but also of invisible minds and mental events, which require second-order representation. Both types of representation have to be kept in mind and kept separate from each other.

Second-order representations serve to make sense of otherwise contradictory or incongruous information. Suppose a normal child, Beth, sees her mother holding a banana in such a way as to be pretending that it is a telephone. Beth has in mind facts about bananas and facts about telephones—first-order representations.  evertheless, Beth is not the least bit confused and will not start eating telephones or talking to bananas. Confusion is avoided because Beth computes from the concept of pretending (a second-order representation) that her mother is engaging simultaneously in an imaginary activity and a real one.

As Leslie describes the mental process, pretending should be understood as computing a three-term relation between an actual situation, an imaginary situation and an agent who does the pretending. The imaginary situation is then not treated as the real situation. Believing can be understood in the same way as pretending. This insight enabled us to predict that autistic children would not be able to understand that someone can have a mistaken belief about the world.

Together with our colleague Simon Baron-Cohen, we tested this prediction by adapting an experiment  originally devised by two Austrian developmental psychologists, Heinz Wimmer and Josef Perner. The test has become known as the Sally-Anne task. Sally and Anne are playing together. Sally has a marble that she puts in a basket before leaving the room. While she is out, Anne moves the marble to a box. When Sally returns, wanting to retrieve the marble, she of course looks in the basket. If this scenario is presented as, say, a puppet show to normal children who are four years of age or more, they understand that Sally will look in the basket even though they know the marble is not there. In other words, they can represent Sally’s erroneous belief as well as the true state of things. Yet in our test, 16 of 20 autistic children with a mean mental age of nine failed the task—answering that Sally would look in the box—in spite of being able to answer correctly a variety of other questions relating to the facts of the episode. They could not conceptualize the possibility that Sally believed something that was not true.

Many comparable experiments have been carried out in other laboratories, largely confirming our prediction:  utistic children are specifically impaired in their understanding of mental states. They appear to lack the innate component underlying this ability. This component, when it works normally, has the most far-reaching consequences for higher-order conscious processes. It underpins the special feature of the human mind: the ability to reflect on itself. Thus, the triad of impairments in autism—in communication, imagination and socialization—is explained by the failure of a single cognitive mechanism. In everyday life, even very able autistic individuals find it hard to keep in mind simultaneously a reality and the fact that someone else may hold a misconception of that reality.

The automatic ability of normal people to judge mental states enables us to be, in a sense, mind readers. With sufficient experience we can form and use a theory of mind that allows us to speculate about psychological motives for our behavior and to manipulate other people’s opinions, beliefs and attitudes. Autistic individuals lack the automatic ability to represent beliefs, and therefore they also lack a theory of mind. They cannot understand how behavior is caused by mental states or how beliefs and attitudes can be manipulated. Hence, they find it difficult to understand deception. The psychological undercurrents of real life as well as literature—in short, all that gives spice to social relations—for them remain a closed book. “People talk to each other with their eyes,” said one observant autistic youth. “What is it that they are saying?”

Next : Theory of Mind
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Autism : 3. Defect in Frontal Lobes (1)

by : Uta Frith

Structural abnormalities in the brains of autistic individuals have turned up in anatomic studies and brain-imaging procedures. Both epidemiological and neuropsychological studies have demonstrated that autism is strongly correlated with mental retardation, which is itself clearly linked to physiological abnormality. This fact fits well with the idea that autism results from a distinct brain abnormality that is often part of more extensive damage. If the abnormality is pervasive, the mental retardation will be more severe, and the likelihood of damage to the critical brain system will increase. Conversely, it is possible for the critical system alone to be damaged. In such cases, autism is not accompanied by mental retardation.

CLOSE LINK between autism and mental
retardation is reflected in this chart.
The percentage of children showing the
social impairments typical of autism is
highest at low levels of intelligence as
measured by tests in which an intelligence
quotient (IQ) below 70 is subnormal. For
example, 86 percent of 44 children in the
lowest IQ range showed the social impairments
of autism. The data are drawn
from a population of about 35,000 children
aged under 15 years.
Neuropsychological testing has also contributed evidence for the existence of a fairly circumscribed brain  abnormality. Autistic individuals who are otherwise able show specific and extensive deficits on certain tests that involve planning, initiative and spontaneous generation of new ideas. The same deficits appear in patients who have frontal lobe lesions. Therefore, it seems plausible that whatever the defective brain structure or system is, the frontal lobes are implicated.

Population studies carried out by Lorna Wing and her colleagues at the Medical Research Council’s Social Psychiatry Unit in London reveal that the different symptoms of autism do not occur together simply by coincidence. Three core features in particular—impairments in communication, imagination and socialization—form a distinct triad. The impairment in communication includes such diverse phenomena as muteness and delay in learning to talk, as well as problems in comprehending or using nonverbal body  language. Other autistic individuals speak fluently but are overliteral in their understanding of language. The impairment in imagination appears in young autistic children as repetitive play with objects and in some autistic adults as an obsessive interest in facts. The impairment in socialization includes ineptness and inappropriate behavior in a wide range of reciprocal interactions, such as the ability to make and keep friends. Nevertheless, many autistic individuals prefer to have company and are eager to please.

The question is why these  pairments, and only these, occur together. The challenge to psychological theorists
was clear: to search for a single cognitive component that would explain the deficits yet still allow for the abilities that autistic people display in certain aspects of interpersonal interactions. My colleagues at the Medical Research Council’s Cognitive Development Unit in London and I think we have identified just such a component. It is a cognitive mechanism of a highly complex and abstract nature that could be described in  computational terms. As a shorthand, one can refer to this component by one of its main functions, namely, the ability to think about thoughts or to imagine another individual’s state of mind. We propose that this  component is damaged in autism. Furthermore, we suggest that this mental component is innate and has a unique brain substrate. If it were possible to pinpoint that substrate—whether it is in fact an anatomical structure, a physiological system or a chemical pathway—one might be able to identify the biological origin of autism.

The power of this component in normal development becomes obvious very early. From the end of the first year onward, infants begin to participate in what has been called shared attention. For example, a normal child will point to something for no reason other than to share his interest in it with someone else. Autistic children  do not show shared attention. Indeed, the absence of this behavior may well be one of the earliest signs of  autism. When an autistic child points at an object, it is only because he wants it.

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Autism (part 2)

by : Uta Frith

Autism is rare. According to the strict criteria applied by Kanner, it appears in four of every 10,000 births. With the somewhat wider criteria used in current diagnostic practice, the incidence is much higher: one or two in 1,000 births, about the same as Down’s syndrome. Two to four times as many boys as girls are affected.


For many years, autism was thought to be a purely psychological disorder without an organic basis. At first, no obvious neurological problems were found. The autistic children did not necessarily have low intellectual ability, and they often looked physically normal. For these reasons, psychogenic theories were proposed and  taken seriously for many years. They focused on the idea that a child could become autistic because of some  existentially threatening experience. A lack of maternal bonding or a disastrous experience of rejection, so the theory went, might drive an infant to withdraw into an inner world of fantasy that the outside world never penetrates.


These theories are unsupported by any empirical evidence. They are unlikely to be supported because there are many instances of extreme rejection and deprivation in childhood, none of which have resulted in autism. Unfortunately, therapies vaguely based on such notions are still putting pressure on parents to accept a burden of guilt for the supposedly avoidable and reversible breakdown of interpersonal interactions. In contrast, well-structured behavior modification programs have often helped families in the management of autistic children, especially children with severe behavior problems. Such programs do not claim to reinstate normal development in the children.

The insupportability of the psychogenic explanation of autism led a number of workers to search for a biological cause. Their efforts implicate a defective structure in the brain, but that structure has not yet been identified. The defect is believed to affect the thinking of autistic people, making them unable to evaluate their  own thoughts or to perceive clearly what might be going on in someone else’s mind.

Autism appears to be closely associated with several other clinical and medical conditions. They include maternal rubella and chromosomal abnormality, as well as early injury to the brain and infantile seizures. Most impressive, perhaps, are studies showing that autism can have a genetic basis. Both identical twins are much more likely to be autistic than are both fraternal twins. Moreover, the likelihood that autism will occur twice in the same family is 50 to 100 times greater than would be expected by chance alone.

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Autism (part 1)

by : Uta Frith


Autistic people suffer from a biological defect. Although they cannot be cured, much can be done to improve their lives.

The image often invoked to describe autism is that of a beautiful child imprisoned in a glass shell. For decades, many parents have clung to this view, hoping that one day a means might be found to break the invisible barrier. Cures have been proclaimed, but not one of them has been backed by evidence. The shell remains intact. Perhaps the time has come for the whole image to be shattered. Then at last we might be able to catch a glimpse of what the minds of autistic individuals are truly like.

Psychological and physiological research has shown that autistic people are not living in rich inner worlds but instead are victims of a biological defect that makes their minds very different from those of normal individuals. Happily, however, autistic people are not beyond the reach of emotional contact and attachment to others.

Thus, we can make the world more hospitable for autistic individuals just as we can, say, for the blind. To do  so, we need to understand what autism is like—a most challenging task. We can imagine being blind, but  autism seems unfathomable. For centuries, we have known that blindness is often a peripheral defect at the sensory-motor level of the nervous system, but only recently has autism been appreciated as a central defect at the highest level of cognitive processing.  Autism, like blindness, persists throughout life, and it responds to special efforts in compensatory education. It can give rise to triumphant feats of coping but can also lead to disastrous secondary consequences— anxiety, panic and depression. Much can be done to prevent problems. Understanding the nature of the handicap must be the first step in any such effort.

Autism existed long before it was described and named by Leo Kanner of the Johns Hopkins Children’s Psychiatric Clinic. Kanner published his landmark paper in 1943 after he had observed 11 children who seemed to him to form a recognizable group. All had in common four traits: a preference for aloneness, an insistence on sameness, a liking for elaborate routines and some abilities that seemed remarkable compared with the deficits.

Concurrently, though quite independently, Hans Asperger of the University Pediatric Clinic in Vienna prepared his doctoral thesis on the same type of child. He also used the term “autism” to refer to the core features of the disorder. Both men borrowed the label from adult psychiatry, where it had been used to refer to the progressive loss of contact with the outside world experienced by schizophrenics. Autistic children seemed to suffer such a lack of contact with the world around them from a very early age.

Kanner’s first case, Donald, has long served as a prototype for diagnosis. It had been evident early in life that the boy was different from other children. At two years of age, he could hum and sing tunes accurately from memory. Soon he learned to count to 100 and to recite both the alphabet and the 25 questions and answers of the Presbyterian catechism. Yet he had a mania for making toys and other objects spin. Instead of playing like other toddlers, he arranged beads and other things in groups of different colors or threw them on the floor, delighting in the sounds they made. Words for him had a literal, inflexible meaning.

Donald was first seen by Kanner at age five. Kanner observed that the boy paid no attention to people around him. When someone interfered with his solitary activities, he was never angry with the interfering person but impatiently removed the hand that was in his way. His mother was the only person with whom he had any significant contact, and that seemed attributable mainly to the great effort she made to share activities with him. By the time Donald was about eight years old, his conversation consisted largely of repetitive questions. His relation to people remained limited to his immediate wants and needs, and his attempts at contact stopped as soon as he was told or given what he had asked for.

Some of the other children Kanner described were mute, and he found that even those who spoke did not really communicate but used language in a very odd way. For example, Paul, who was five, would parrot speech verbatim. He would say “You want candy” when he meant “I want candy.” He was in the habit of  repeating, almost every day, “Don’t throw the dog off the balcony,” an utterance his mother traced to an earlier incident with a toy dog.

Twenty years after he had first seen them, Kanner reassessed the members of his original group of children. Some of them seemed to have adapted socially much better than others, although their failure to communicate and to form relationships remained, as did their pedantry and single-mindedness. Two prerequisites for better adjustment, though no guarantees of it, were the presence of speech before age five and relatively high intellectual ability. The brightest autistic individuals had, in their teens, become uneasily aware of their peculiarities and had made conscious efforts to conform. Nevertheless, even the best adapted were rarely able to be self-reliant or to form friendships. The one circumstance that seemed to be helpful in all the cases was an extremely structured environment.

As soon as the work of the pioneers became known, every major clinic began to identify autistic children. It was found that such children, in addition to their social impairments, have substantial intellectual handicaps. Although many of them perform relatively well on certain tests, such as copying mosaic patterns with blocks, even the most able tend to do badly on test questions that can be answered only by the application of  common sense.

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(Part 6-End) Evidence for a Biological Influence in Male Homosexuality

by : Simon LeVay and Dean H. Hamer

At each marker, a pair of gay brothers was scored as concordant if they inherited identical markers from their mother or as discordant if they inherited different ones. Fifty percent of the markers were expected to be identical by chance. Corrections were also made for the possibility of the mother's having two copies of the same marker.


GENE SHARING in the Xq28 region is significantly greater in gay brothers
than in the general population. Of 40 pairs of gay brothers studied, 33 pairs
shared the Xq28 region. In a control group of 314 randomly selected pairs
of brothers, Xq28 markers were found to be almost equally distributed.

The results of this study were striking. Over most of the X chromosome the markers were randomly distributed between the gay brothers. But at the tip of the long arm of the X chromosome, in a region known as Xq28, there was a considerable excess of concordant brothers: 33 pairs shared the same marker, whereas only seven pairs did not. Although the sample size was not large, the result was statistically significant: the probability of such a skewed ratio occurring by chance alone is less than one in 200. In a control group of 314 randomly selected pairs of brothers, most of whom can be presumed to be heterosexual, Xq28 markers were randomly distributed.

The most straightforward interpretation of the finding is that chromosomal region Xq28 contains a gene that influences male sexual orientation. The study provides the strongest evidence to date that human sexuality is influenced by heredity because it directly examines the genetic information, the DNA. But as with all initial studies, there are some caveats.

First, the result needs to be replicated: several other claims of finding genes related to personality traits have proved controversial. Second, the gene itself has not yet been isolated. The study locates it within a region of  the X chromosome that is about four million base pairs in length. This region represents less than 0.2 percent  of the total human genome, but it is still large enough to contain several hundred genes. Finding the needle in this haystack will require either large numbers of families or more complete information about the DNA sequence to identify all possible coding regions. As it happens, Xq28 is extraordinarily rich in genetic loci and will probably be one of the first regions of the human genome to be sequenced in its entirety.

A third caveat is that researchers do not know quantitatively how important a role Xq28 plays in male sexual orientation. Within the population of gay brothers studied, seven of 40 brothers did not share markers. Assuming that 20  siblings should inherit identical markers by chance alone, 36 percent of the gay brothers show no link between homosexuality and Xq28. Perhaps these men inherited diÝerent genes or were influenced by nongenetic physiological factors or by the environment. Among all gay men -most of whom do not have gay brothers- the influence of Xq28 is even less clear. Also unknown is the role of Xq28, and other genetic loci, in female sexual orientation.

How might a genetic locus at Xq28 affect sexuality? One idea is that the hypothetical gene affects hormone synthesis or metabolism. A candidate for such a gene was the androgen receptor locus, which encodes a protein essential for masculinization of the human brain and is, moreover, located on the X chromosome. To test this idea, Jeremy Nathans, Jennifer P. Macke, Van L. King and Terry R. Brown of Johns Hopkins
University teamed up with Bailey of Northwestern and Hamer, Hu and Hu of the NIH. They compared the molecular structure of the androgen receptor gene in 197 homosexual men and 213 predominantly heterosexual men. But no signiÞcant variations in the protein coding sequences were found. Also, linkage studies showed no correlation between homosexuality in brothers and inheritance of the androgen receptor locus. Most significant of all, the locus turned out to be at Xq11, far from the Xq28 region. This study  excludes the androgen receptor from playing a significant role in male sexual orientation.

A second idea is that the hypothetical gene acts indirectly, through personality or temperament, rather than directly on sexual-object choice. For example, people who are genetically selfreliant might be more likely to acknowledge and act on same-sex feelings than are people who are dependent on the approval of others.

Finally, the intriguing possibility arises that the Xq28 gene product bears directly on the development of sexually dimorphic brain regions such as INAH3. At the simplest level, such an agent could act autonomously, perhaps in the womb, by stimulating the survival of specific neurons in preheterosexual males or by promoting their death in females and prehomosexual men. In a more complex model, the gene product could change the sensitivity of a neuronal circuit in the hypothalamus to stimulation by environmental cues, perhaps in the first few years of life. Here the genes serve to predispose rather than to predetermine. Whether this fanciful notion  contains a grain of truth remains to be seen. It is in fact experimentally testable, using current tools of molecular genetics and neurobiology.

Our research has attracted an extraordinary degree of public attention, not so much because of any conceptual breakthrough -the idea that genes and the brain are involved in human behavior is hardly new- but  because it touches on a deep conflict in contemporary American society. We believe scientific research can help dispel some of the myths about homosexuality that in the past have clouded the image of lesbians and gay men. We also recognize, however, that increasing knowledge of biology may eventually bring with it the power to infringe on the natural rights of individuals and to impoverish the world of its human diversity. It is important that our society expand discussions of how new scientific information should be used to benefit the human race in its entirety.

***

SIMON LEVAY and DEAN H. HAMER investigate the biological roots of homosexuality. LeVay earned a doctorate in neuroanatomy at the University of Gšttingen in Germany. In 1971 he went to Harvard University to work with David Hubel and Torsten Wiesel on the brain's visual system. He moved to the Salk Institute for Biological Studies in San Diego in 1984 to head the vision laboratory. In 1992 he left Salk to found the Institute of Gay and Lesbian Education. Hamer received his Ph.D. in biological chemistry from Harvard in 1977. For the past 17 years, he has been at the National Institutes of Health, where he is now chief of the section on gene structure and regulation at the National Cancer Institute. He studies the role of genes both in  sexual orientation and in complex medical conditions, including progression of HIV and Kaposi's sarcoma.
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(Part 5) Evidence for a Biological Influence in Male Homosexuality

by : Simon LeVay and Dean H. Hamer

PINPOINTING GENES shared by gay
brothers (darker brown) first involved
taking DNA from subjects. Several billion
copies of speciÞc regions of the X
chromosome were then made using the
polymerase chain reaction, and the different
fragments were separated by gel
electrophoresis. Gay brothers shared
a marker, in this hypothetical example
CA11, in the Xq28 region at rates far
greater than predicted by chance.
Why are most gay male relatives of gay men on the mother's side of the family? One possibility -that the subjects somehow knew more about their maternal relatives- seems unlikely because opposite-sex
gay relatives of gay males and lesbians were equally distributed between both sides of the family. Another explanation is that homosexuality, while being transmitted by both parents, is expressed only in one sex in this case, males. When expressed, the trait reduces the reproductive rate and must therefore be disproportionately passed on by the mother. Such an effect may partially account for the concentration of gay men's gay relatives on the maternal side of the family. But proof of this hypothesis will require Þnding an appropriate gene on an autosomal chromosome, which is inherited from either parent.

A third possibility is X chromosome linkage. A man has two sex chromosomes: a Y, inherited from his father, and an X, cut and pasted from the two X chromosomes carried by his mother. Therefore, any trait that is influenced by a gene on the X chromosome will tend to be inherited through the mother's side and will be preferentially observed in brothers, maternal uncles and maternal cousins, which is exactly the observed pattern.

To test this hypothesis, Hamer and his colleagues embarked on a linkage study of the X chromosome in gay men. Linkage analysis is based on two principles of genetics. If a trait is genetically influenced, then relatives who share the trait will share the gene more often than is expected by chance, this is true even if the gene plays only a small part.  Also, genes that are close together on a chromosome are almost always inherited together. Therefore, if there is a gene that influences sexual orientation, it should be 'linked' to a nearby DNA marker that tends to travel along with it in families. For traits affected by only one gene, linkage can precisely locate the gene on a chromosome. But for complex traits such as sexual orientation, linkage also helps to determine whether a genetic component really exists.

To initiate a linkage analysis of male sexual orientation, the first requirement was to find informative markers, segments of DNA that flag locations on a chromosome. Fortunately, the Human Genome Project has already generated a large catalogue of markers spanning all of the X chromosomes. The most useful ones are short, repeated DNA sequences that have slightly different lengths in different persons. To detect the markers, the researchers used the polymerase chain reaction to make several billion copies of specific regions of the chromosome and then separated the different fragments by the method of gel electrophoresis.

The second step in the linkage analysis was to locate suitable families. When scientists study simple traits such as color blindness or sickle cell anemia -which involve a single gene- they tend  to analyze large, multigenerational families in which each member clearly either has or does not have the trait. Such an approach was unsuited for studying sexual orientation. First, identifying someone as not homosexual is tricky; the person may be concealing his or her true orientation or may not be aware of it. Because homosexuality was even more stigmatized in the past, multigenerational families are especially problematic in this regard. Moreover, genetic modeling shows that for traits that involve several different genes expressed at varying levels, studying large families can actually decrease the chances of finding a linked gene: too many exceptions are included.

For these reasons, Hamer and his coworkers decided to focus on nuclear families with two gay sons. One advantage of this approach is that individuals who say they are homosexual are unlikely to be mistaken.  Furthermore, the approach can detect a single linked gene even if other genes or noninherited factors are required for its expression. For instance, suppose that being gay requires an X chromosome gene together with another gene on an autosome, plus some set of environmental circumstances. Studying gay brothers would give a clear-cut result because both would have the X chromosome gene. In contrast, heterosexual brothers of gay men would sometimes share the X chromosome gene and sometimes not, leading to confusing results.

Genetic analysts now believe that studying siblings is the key to traits that are aÝected by many elements. Because Hamer and his colleagues were most interested in Þnding a gene that expresses itself only in men but is transmitted through women, they restricted their search to families with gay men but no gay father-gay son  pairs.

Forty such families were recruited. DNA samples were prepared from the gay brothers and, where possible, from their mothers or sisters. The samples were typed for 22 markers that span the X chromosome from the tip of the short arm to the end of the long arm.

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(Part 4) Evidence for a Biological Influence in Male Homosexuality

by : Simon LeVay and Dean H. Hamer




Twin and family tree studies are based on the principle that genetically influenced traits run in families. The first modern study on the patterns of homosexuality within families was published in 1985 by Richard C. Pillard and James D. Weinrich of Boston University. Since then, Þve other systematic studies on the twins and siblings of gay men and lesbians have been reported.

The pooled data for men show that about 57 percent of identical twins, 24 percent of fraternal twins and 13 percent of brothers of gay men are also gay. For women, approximately 50 percent of identical twins, 16 percent of fraternal twins and 13 percent of sisters of lesbians are also lesbian. When these data are compared with baseline rates of homosexuality, a good amount of family clustering of sexual orientation becomes evident for both sexes. In fact, J. Michael Bailey of Northwestern University and his co-workers estimate that the overall heritability of sexual orientation -that proportion of the variance in a trait that comes from genes- is about 53 percent for men and 52 percent for women. (The family clustering is most obvious for relatives of the same sex, less so for male-female pairs.)

To evaluate the genetic component of sexual orientation and to clarify its mode of inheritance, we need a systematic survey of the extended families of gay men and lesbians. One of us (Hamer), Stella Hu, Victoria L. Magnuson, Nan Hu and Angela M. L. Pattatucci of the National Institutes of Health have initiated such a study. It is part of a larger one by the National Cancer Institute to investigate risk factors for certain cancers that are more frequent in some segments of the gay population.

Hamer and his colleagues initial survey of males confirmed the sibling results of Pillard and Weinrich. A brother of a gay man had a 14 percent  likelihood of being gay as compared with 2 percent for the men without gay brothers. (The study used an unusually stringent deÞnition of homosexuality, leading to the low average rate.) Among more distant relatives, an unexpected pattern showed up: maternal uncles had a 7 percent chance of being gay, whereas sons of maternal aunts had an 8 percent chance. Fathers, paternal uncles and the three other types of cousins showed no correlation at all.

Although this study pointed to a genetic component, homosexuality occurred much less frequently than a single gene inherited in simple Mendelian fashion would suggest. One interpretation, that genes are more important in some families than in others, is borne out by looking at families having two gay brothers. Compared with randomly chosen families, rates of homosexuality in maternal uncles increased from 7 to 10 percent and in maternal cousins from 8 to 13 percent. This familial clustering, even in relatives outside the nuclear family, presents an additional argument for a genetic root to sexual orientation.

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(Part 3) Evidence for a Biological Influence in Male Homosexuality

by : Simon LeVay and Dean H. Hamer

What might lie behind these apparent correlations between sexual orientation and brain structure? Logically, three possibilities exist. One is that the structural differences were present early in life -perhaps even before birth- and helped to establish the men's sexual orientation. The second is that the differences arose in adult life as a result of the men's sexual feelings or behavior. The third possibility is that there is no causal connection, but both sexual orientation and the brain structures in question are linked to some third variable, such as a developmental event during uterine or early postnatal life.


Family trees of male sexual orientation show the rates of homosexuality
(darker brown) in maternally related males. Rates in paternal relatives were
not significantly above the average population rate of 2 percent. This finding
raised the possibility of involvement of the X chromosome (shown below).
Males have two sex chromosomes—a Y inherited from the father and an X from
the mother. Thus, a trait inherited through the mother’s side might logically be
influenced by a gene on one of her X chromosomes (indicated here in red ). In
fact, further experiments showed that one small area at the tip of the X chromosome—
Xq28—was shared by a large percentage of gay brothers.

We cannot decide among these possibilities with any certainty. On the basis of animal research, however, we and the second scenario, that the structural differences came about in adulthood, unlikely. In rats, for example, the sexually dimorphic cell group in the medial preoptic area appears plastic in its response to androgens during early brain development but later is largely resistant to change. We favor the Þrst possibility, that the structural differences arose during the period of brain development and consequently contributed to sexual behavior. Because the medial preoptic region of the hypothalamus is implicated in sexual behavior in monkeys, the size of INAH3 in men may indeed influence sexual orientation. But such a causal connection is speculative at this point.

Assuming that some of the structural differences related to sexual orientation were present at birth in certain individuals, how did they arise? One candidate is the interaction between gonadal steroids and the developing brain; this interaction is responsible for differences in the structure of male and female brains. A number of  scientists have speculated that atypical levels of circulating androgens in some fetuses cause them to grow into homosexual adults. Specifically, they suggest that androgen levels are unusually low in male fetuses that become gay and unusually high in female fetuses that become lesbian.

A more likely possibility is that there are intrinsic differences in the way individual brains respond to androgens during development, even when the hormone levels are themselves no different. This response requires a complex molecular machinery, starting with the androgen receptors but presumably including a variety of  proteins and genes whose identity and roles are still unknown.

At first glance, the very notion of gay genes might seem absurd. How could genes that draw men or women to members of the same sex survive the Darwinian screening for reproductive fitness? Surely the parents of most gay men and lesbians are heterosexual? In view of such apparent incongruities, research focuses on genes that sway rather than determine sexual orientation. The two main approaches to seeking such genes are twin and family studies and DNA linkage analysis.

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(Part 2) Evidence for a Biological Influence in Male Homosexuality

by : Simon LeVay and Dean H. Hamer

Researchers have long sought within the human brain some manifestation of the most obvious classes into which we are divided male and female. Such sex differentiation of the brain's structure, called sexual dimorphism, proved hard to establish. On average, a man's brain has a slightly larger size that goes along with his larger body; other than that, casual inspection does not reveal any obvious dissimilarity between the sexes. Even under a microscope, the architecture of men's and women's brains is very similar. Not surprisingly, the first significant observations of sexual dimorphism were made in laboratory animals.

Of particular importance is a study of rats conducted by Roger A. Gorski of the University of California at Los Angeles. In 1978 Gorski was inspecting the rat's hypothalamus, a region at the base of its brain that is involved in instinctive behaviors and the regulation of metabolism. He found that one group of cells near the front of the hypothalamus is several times larger in male than in female rats. Although this cell group is very  small, less than a millimeter across even in males, the difference between the sexes is quite visible in appropriately stained slices of tissue, even without the aid of a microscope.

Gorski's finding was especially interesting because the general region of the hypothalamus in which this cell group occurs, known as the medial preoptic area, has been implicated in the generation of sexual behavior in particular, behaviors typically displayed by males. For example, male monkeys with damaged medial preoptic areas are apparently indifferent to sex with female monkeys, and electrical stimulation of this region can make an inactive male monkey approach and mount a female. It should be said, however, that we have yet to find in monkeys a cell group analogous to the sexually dimorphic one occurring in rats.

Nor is the exact function of the rat's sexually dimorphic cell group known. What is known, from a study by Gorski and his co-workers, is that androgens typical male hormones play a key role in bringing about the dimorphism during development. Neurons within the cell group are rich in receptors for sex hormones, both for androgens testosterone is the main representative and for female hormones known as estrogens. Although male and female rats initially have about the same numbers of neurons in the medial preoptic area, a surge of testosterone secreted by the testes of male fetuses around the time of birth acts to stabilize their neuronal population. In females the lack of such a surge allows many neurons in this cell group to die, leading to the typically smaller structure. Interestingly, it is only for a few days before and after birth that the medial preoptic neurons are sensitive to androgen; removing andoes not cause the neurons to die.

Gorski and his colleagues at U.C.L.A., especially his student Laura S. Allen, have also found dimorphic structures in the human brain. A cell group named INAH3 (derived from 'third interstitial nucleus of the anterior hypothalamus') in the medial preoptic region of the hypothalamus is about three times larger in men than in women. (Notably, however, size varies considerably even within one sex.)

In 1990 one of us (LeVay) decided to check whether INAH3 or some other cell group in the medial preoptic area varies in size with sexual orientation as well as with sex. This hypothesis was something of a long shot, given the prevailing notion that sexual orientation is a 'high-level' aspect of personality molded by environment and culture. Information from such elevated sources is thought to be processed primarily by the cerebral cortex and not by 'lower' centers such as the hypothalamus.

LeVay examined the hypothalamus in autopsy specimens from 19 homosexual men, all of whom had died of complications of AIDS, and 16 heterosexual men, six of whom had also died of AIDS. (The sexual orientation of those who had died of non-AIDS causes was not determined. But assuming a distribution similar to that of the general populace, no more than one or two of them were likely to have been gay.) LeVay also included specimens from six women whose sexual orientation was unknown.

HYPOTHALAMUS of the human brain was examined for differences related to
sexual orientation. The hypothalamus of each of the 41 subjects was stained
to mark neuronal cell groups. The cell group termed INAH3 in the medial preoptic
area was more than twice as large in the men as it was in the women.
INAH3 also turned out to be two to three times larger in straight men than
it was in gay men (micrographs at far right ). This finding suggests a difference
related to male sexual orientation about as great as that related to sex.
After encoding the specimens to eliminate subjective bias, LeVay cut each hypothalamus into serial slices, stained these to mark the neuronal cell groups and measured their cross-sectional areas under a microscope. Armed with information about the areas, plus the thickness of the slices, he could readily calculate the volumes of each cell group. In addition to Allen and Gorski's sexually dimorphic nucleus INAH3, LeVay examined three other nearby groups: INAH1, INAH2 and INAH4.

Like Allen and Gorski, LeVay observed that INAH3 was more than twice as large in the men as in the women. But INAH3 was also between two and three times larger in the straight men than in the gay men. In some gay men, as in the example shown at the top of the opposite page, the cell group was altogether absent. Statistical analysis indicated that the probability of this result's being attributed to chance was about one in 1,000. In fact, there was no significant difference between volumes of INAH3 in the gay men and in the women. So the investigation suggested a dimorphism related to male sexual orientation about as great as that related to sex.

A primary concern in such a study is whether the observed structural differences are caused by some variable other than the one of interest. A major suspect here was AIDS. The AIDS virus itself, as well as other infectious agents that take advantage of a weakened immune system, can cause serious damage to brain cells. Was this the reason for the small size of INAH3 in the gay men, all of whom had died of AIDS?

Several lines of evidence indicate otherwise. First, the heterosexual men who died of AIDS had INAH3 volumes no different from those who died of other causes. Second, the AIDS victims with small INAH3s did not have case histories distinct from those with large INAH3s; for instance, they had not been ill longer before they died. Third, the other three cell groups in the medial preoptic areaÑINAH1, INAH2 and INAH4, turned out to be no smaller in the AIDS victims. If the disease were having a nonspeciÞc destructive effect, one would have suspected otherwise. Finally, after completing the main study, LeVay obtained the hypothalamus of one gay man who had died of non-AIDS causes. This specimen, processed 'blind' along with several specimens from heterosexual men of similar age, confirmed the main study: the volume of INAH3 in the gay man was less than half that of INAH3 in the heterosexual men.

One other feature in brains that is related to sexual orientation has been reported by Allen and Gorski. They found that the anterior commissure, a bundle of Þbers running across the midline of the brain, is smallest in heterosexual men, larger in women and largest in gay men. After correcting for overall brain size, the anterior commissure in women and in gay men were comparable in size.

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(Part 1) Evidence for a Biological Influence in Male Homosexuality

by : Simon LeVay and Dean H. Hamer

Two pieces of evidence, a structure within the human brain and a genetic link, point to a biological component for male homosexuality.

Most men are sexually attracted to women, most women to men. To many people, this seems only the natural order of things, the appropriate manifestation of biological instinct, reinforced by education, religion and the law. Yet a significant minority of men and women estimates range from 1 to 5 percent are attracted exclusively to members of their own sex. Many others are drawn, in varying degrees, to both men and women.

How are we to understand such diversity in sexual orientation? Does it derive from variations in our genes or  our physiology, from the intricacies of our personal history or from some confluence of these? Is it for that matter a choice rather than a compulsion? Probably no one factor alone can elucidate so complex and variable a trait as sexual orientation. But recent laboratory studies, including our own, indicate that genes and brain development play a signifcant role. How, we do not yet know. It may be that genes influence the sexual differentiation of the brain and its interaction with the outside world, thus diversifying its already vast range of responses to sexual stimuli.

The search for biological roots of sexual orientation has run along two broad lines. The first draws on observations made in yet another hunt that for physical differences between men's and women's brains. As we shall see, 'gay' and 'straight' brains may be differentiated in curiously analogous fashion. The second approach is to scout out genes by studying the patterns in which homosexuality occurs in families and by directly examining the hereditary material, DNA.


Next :  Part 2
Sunday, November 6, 2011 - 0 comments

Voices in Your Head : 5. Limited Talk Time

By : Bettina Thraenhardt

Fortunately, it is not always necessary to eliminate the voices completely to decrease the discomfort they cause. Most people who experience acoustic hallucinations attribute a purpose to their voices. How they view their voices—wellmeaning or out to destroy them—is almost always a function of what they hear. In 2003 Mark van der Gaag, now at the Free University Amsterdam in the Netherlands, found that only two of 43 patients evaluated their hallucinations differently from what researchers expected. Some patients are convinced that critical voices are actually well-meaning. “As therapists, we need to pay more attention to how a person explains the phenomenon,” Bock concludes. Therapists who immediately talk in terms of severe mental illness often only make the problem worse, risking that the patient will withdraw. The sooner a patient begins to talk about the voices, the less power those voices tend to have.
Quiet! Some voices
torment sufferers
with constant
insults. People
who hear voices
often live extremely
withdrawn
lives—and
the hallucinations,
in turn, fuel
social rejection

Frequently, it is enough to reframe the voices. Even if they are overwhelmingly negative, other intentions or characteristics may be attributed to them through therapy. According to guidelines developed by Netzwerk Stimmenhoeren, a German organization dedicated to founding self-help groups and supporting the affected, their families and the psychiatric community, the main goal is to make sufferers “masters in their own house” again. Patients can sometimes regain this control not only by listening to the voices but by answering them, concentrating on positive messages and agreeing to specifi c, limited talking times.

Another mainstay of treatment involves changing a patient’s social interactions. Often a person’s relationship with his or her voices mirrors those with real people, as Mark Hayward, now at the University of Surrey in England, demonstrated in 2003. If, for example, a person usually subordinates herself to someone else, she will tend to hear dominant voices. The net effect is that the hallucinations become increasingly real. Networks of fellow sufferers may help people reduce the isolation they feel and make strides in recovery. “I got to the point where I couldn’t take it anymore,” Laurie says, explaining why she dared to “come out.” Laurie agreed to make time for her voices in the morning, and, in exchange, they agreed to leave her alone the rest of the day. The approach may seem odd, but it worked. Now, she says, “My voices simply don’t scare me anymore.

***


BETTINA THRAENHARDT is a psychologist and science journalist in Bonn, Germany.
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Voices in Your Head : 4. Hushed Voices

By : Bettina Thraenhardt

For those who do suffer from their inner voices, researchers are trying to fi nd ways of hushing them. Antipsychotic medications work for some but not all patients. As an alternative, Ralph E. Hoffman and his co-workers at the Yale University School of Medicine have investigated the potential of transcranial magnetic stimulation (TMS), a technique by which they can decrease brain activity in certain regions using magnetic fields. They have applied TMS to the regions involved in speech processing. In 2000 they suppressed acoustic hallucinations in 12 schizophrenic patients by decreasing the arousability of the temporoparietal cortex. In a follow-up study in 2005 they treated 50 patients for nine days with low-frequency impulses and found that verbal hallucinations decreased markedly in more than half the patients—an effect that lasted for at least three months.

The occurrence of hallucinations varies with age and race, according to a survey of the public in England and Wales. Louise C. Johns of the Institute of Psychiatry at King’s College London and her colleagues reviewed data from 2,867 whites and 5,196 members of minority ethnic groups.
Hallucinations were most common among teens in the white sample but among those in their 20s and 50s in the Caribbean group. In the South Asian sample, prevalence varied only very little by age. Overall, 4 percent of whites reported hearing or seeing things. In comparison, rates were 2.5 times higher among Caribbeans and half as much among South Asians.

Cultural Differencies

SOURCE :
“OCCURRENCE OF HALLUCINATORY EXPERIENCES IN A COMMUNIT Y SAMPLE AND ETHNIC VARIATIONS,”
BY L . C. JOHNS, J . Y. NAZROO, P. BEBBINGTON AND E . KUIPERS IN BRITISH JOURNAL OF PSYCHIATRY,
VOL. 180; 2002  

Next : Limited Talk Time
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Voices in Your Head : 3. Too Much and Too Little

By : Bettina Thraenhardt

How do these perceptions come about in the absence of external stimuli? As Bock explains, acoustic hallucinations may arise from “too much inside” or “too little outside.” On one side of this theoretical coin, Bock suggests that, psychologically, some affected people may hold too much on the inside. Sufferers have  often experienced some kind of trauma as a child or adult, such as neglect, abuse, rape or a severe accident.  Many then suffer from unresolved confl icts or find themselves in situations that overwhelm them. In these cases, verbal hallucinations may serve as signals that they need to pay attention to their own inner voice.

From a neurobiological perspective, the notion of “too much inside” makes sense in that some sufferers appear to interpret their own thoughts as alien. Some researchers therefore suspect that the hallucinations involve a failure in a specifi c feedback circuit in the brain, which normally tells us that “I” am now thinking or speaking, not someone else. This hypothesis— that self-generated speech gets misattributed— seems to apply especially well to hallucinating schizophrenics, about whom researchers have the most information.

Philip K. McGuire and his colleague Louise C. Johns of the Institute of Psychiatry at King’s College London  tested the model by having several schizophrenic patients, as well as people with no psychiatric history, speak into a microphone.  At the same time, the test subjects listened to their voices, distorted by the researchers, through headphones. The participants were asked to press a button if they thought they were listening to themselves. In general, the schizophrenics had greater diffi culties identifying their own voices. Those who had active hallucinations most often attributed their speech to an external source, particularly when what they said into the microphone was disparaging or contemptuous.

Studies using brain-imaging techniques have also elucidated the physiological mechanisms that underlie verbal hallucinations. In 1993 McGuire and his colleagues scanned the brains of 12 schizophrenics while they were hearing voices and while they were not. They found that during the hallucinations the greatest increase in brain activity took place in Broca’s area, a region involved not in hearing speech but in producing it. Other speech- processing areas of the brain, including the superior temporal gyrus in the left temporal lobe, are under close scrutiny. This gyrus, or bump, is responsible for speech perception and plays a crucial role in the integration of acoustic and speech information. Various researchers, among them Thomas Dierks of the University of Bern in Switzerland, have demonstrated that it also plays a key role in verbal hallucinations.

In 1999 Dierks, who was then at the University of Frankfurt, and his co-workers used functional magnetic resonance imaging (fMRI) to observe the brains of three schizophrenic patients while they were hearing voices. In addition to the superior temporal gyrus, they found activity in the primary auditory cortex, which normally processes sounds from the outside world. No wonder these patients believed their hallucinations were real: their brains responded to them much as they did to actual speech. Several other studies have produced intriguing fi ndings, among them that the left superior temporal gyrus seems consistently smaller in patients with severe acoustic hallucinations. Exactly what this size difference signifi es is still the subject of speculation.

On the fl ip side of Bock’s theoretical coin, hearing voices is not always a consequence of neurobiological change. Sometimes the brain simply receives too few stimuli from the outside world. People who hear voices often live extremely withdrawn lives—and the hallucinations, in turn, fuel social rejection. Some sailors and hikers, for example, who have endured stimulus-poor conditions for prolonged periods have reported auditory hallucinations. Indeed, Rilke’s angel spoke only after he had lived for two months in isolation at Duino Castle. Deafness, too, can present a kind of isolation. In 1992 Detlef Koempf, a neurologist at the University Medical Center of Schleswig-Holstein, Germany, discovered that musical hallucinations are not uncommon in older peoplewho have lost some hearing. He hypothesizes that the brain stores auditory information that it has captured over an extended period. If the external output is cut off, the deposited signals may take on a life of their own.

Whether hearing voices presents a medical problem depends largely on how much a person suffers. A Dutch team headed by Marius Romme, then at the University of Maastricht in the Netherlands, found signifi can't differences in the types of auditory hallucinations experienced by schizophrenics and people who were psychiatrically normal.Both groups reported dialogues, running commentary or the vocalization of their own thoughts. The mentally ill, however, far more frequently described negative voices: “You stupid idiot!” or “As usual, you revealed our family secrets!” The other study participants usually heard benign voices that  encouraged them: “Come on, you can do it!” or “It really wasn’t your fault.” In addition, they were more likely to feel that they were in control of the voices.

Next : Hushed Voices