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.

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.


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.

Pot Luck

By : David Schneider

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

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.

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.

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.

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