Jani Schofield diagnosed with schizophrenia

For Jani Schofield, some progress -- and major setbacks
The 6-year-old, who has been diagnosed with schizophrenia, doesn't fare well after a change in her environment, and the stress of caring for her takes a severe toll on her family.
By Shari Roan

4:56 PM PDT, July 8, 2009

On June 29, The Times profiled Jani Schofield, a 6-year-old diagnosed with schizophrenia, and her parents in “Jani’s at the mercy of her mind.” The article examined Jani's bouts of rage, her make-believe world, and Michael and Susan Schofield's efforts to keep their family together while also safely raising Jani and her toddler brother, Bodhi. Here is an update on the Schofield family.

Michael and Susan Schofield's plan to keep two apartments and trade 14-hour shifts caring for their 6-year-old daughter, Jani, worked for awhile.

And Jani returned, with modest success, to her elementary school.

But when school ended two weeks later, so did the Schofields' only real respite care, and their lives began to unravel.

The Schofields clashed with the team of workers from a nonprofit provider of mental health services the family was depending on for support. The social workers tried to help, says Michael, but didn't seem to understand that simple parenting techniques and behavioral therapies were irrelevant when caring for a psychotic child.

The cost of two apartments was crushing, and their money woes mounted. Michael and Susan began to argue more often.

When she was discharged June 1 from UCLA's Resnick Psychiatric Hospital, Jani had fewer hallucinations and was less violent. But within a week at home, she began spending more time in her imaginary world of rats and cats and searing temperatures.

Jani's psychiatrist raised her dose of Thorazine, one of three drugs she takes to control the psychosis, but it had little effect. Moreover, Thorazine causes severe photo-sensitivity so time spent at the park and swimming pool, where Jani is mostly easily entertained, had to be dramatically curtailed. She was soon bored with her tiny apartment.

The detailed daily schedule the Schofields crafted to mimic Jani's schedule at UCLA went by the wayside. The point system the couple planned to use to track Jani's behavior and reward her for progress was forgotten.

Both Michael and Susan battle depression and see a therapist. But Michael grew especially despondent.

After three weeks, the couple's hopes of caring for their daughter at home slipped away. Jani was psychotic most of the time, talking about her imaginary friends, gesturing to them, running to the door to allow them access to the apartment. She threatened her baby brother, Bodhi, sometimes kicking him. The toddler grew more anxious and clingy, and the Schofields began to worry about his psychological health and development.

On June 24, while the family was eating breakfast at Denny's, a drop of orange juice spilled on Jani's slacks, a sensation she cannot stand. She began to remove her pants in the restaurant but had not put on underwear that morning. The couple wrestled with her to keep her dressed while she erupted with fury over her wet clothing.

It took an hour to calm her.

The next day, she screamed at the doctor's office where she was undergoing regular lab tests to check for side effects from the high doses of medications. Later, she carried an imaginary rat in the palm of her hand and cautioned onlookers, "Be careful around him. He squirts."

Susan lost her set of keys and Michael yelled at her. Also that day, the family (other than Jani) was ill with a respiratory virus, and Bodhi was diagnosed with asthma.

On Thursday, June 25, Jani's blood test results came back. Her thyroid levels were abnormal and there was blood in her urine. She complained of constant itching.

Susan stayed home in Bodhi's apartment while Michael turned off the lights in Jani's apartment and drove her to UCLA.

January Schofield was re-admitted to UCLA's Resnick Neuropsychiatric Hospital later that day.

"It was really hard to take her back," Michael says. "It feels like a failure. We really wanted to make it work."

Jani's doctors at UCLA have decided to wean her off her current medications and try Clozaril, a last-ditch anti-psychotic that carries the risk of severe side effects. In the meantime, the Schofields are completing paperwork seeking to have Jani admitted to a study on child schizophrenia at the National Institute of Mental Health in Bethesda, Md.

Michael acknowledges that he and Susan need time to regain their mental and physical health before beginning the next round of Jani's life.

The day Jani was readmitted, says Michael, "I felt such a profound sense of despair. We can't get the services that we need to keep her at home. It breaks my heart that the only way we can get a break is to put her back in the hospital."

The staff at UCLA was kind when they saw their little patient again. She has made some progress, one of the nurses reminded Michael; she is less violent.

Jani remembered the staff well and didn't seem to mind going back to the hospital. But after Michael hugged her and said good-night that Thursday, she began to cry softly -- something she rarely does except in anger.

Michael detected a little sob and paused at the door.

"I called back to her, 'Jani, are you OK?' "

"Yes," she said.

Pedophiles, Hebephiles, and Ephebophiles, Oh My: Erotic Age Orientation Why most "pedophiles" aren't really pedophiles, technically speaking

By Jesse Bering
New Scientist: Mind

Michael Jackson probably wasn’t a pedophile—at least, not in the strict, biological sense of the word. It’s a morally loaded term, pedophile, that has become synonymous with the very basest of evils. (In fact it’s hard to even say it aloud without cringing, isn’t it?) But according to sex researchers, it’s also a grossly misused term.

If Jackson did fall outside the norm in his “erotic age orientation”—and we may never know if he did—he was almost certainly what’s called a hebephile, a newly proposed diagnostic classification in which people display a sexual preference for children at the cusp of puberty, between the ages of, roughly, 11 to 14 years of age. Pedophiles, in contrast, show a sexual preference for clearly prepubescent children. There are also ephebophiles (from ephebos, meaning “one arrived at puberty” in Greek), who are mostly attracted to 15- to 16-year-olds; teleiophiles (from teleios, meaning, “full grown” in Greek), who prefer those 17 years of age or older); and even the very rare gerontophile (from gerontos, meaning “old man” in Greek), someone whose sexual preference is for the elderly. So although child sex offenders are often lumped into the single classification of pedophilia, biologically speaking it’s a rather complicated affair. Some have even proposed an additional subcategory of pedophilia, “infantophilia,” to distinguish those individuals most intensely attracted to children below six years of age.

Based on this classification scheme of erotic age orientations, even the world’s best-known fictitious “pedophile,” Humbert Humbert from Nabokov’s masterpiece, Lolita, would more properly be considered a hebephile. (Likewise the protagonist from Thomas Mann’s Death in Venice, a work that I’ve always viewed as something of the “gay Lolita”). Consider Humbert’s telltale description of a “nymphet.” After a brief introduction to those “pale pubescent girls with matted eyelashes,” Humbert explains:

Between the age limits of nine and fourteen there occur maidens who, to certain bewitched travelers, twice or many times older than they, reveal their true nature which is not human, but nymphic (that is, demoniac); and these chosen creatures I propose to designate as “nymphets.”

Although Michael Jackson might have suffered more disgrace from his hebephilic orientation than most, and his name will probably forever be entangled darkly with the sinister phrase “little boys,” he wasn’t the first celebrity or famous figure that could be seen as falling into this hebephilic category. In fact, ironically, Michael Jackson’s first wife, Lisa Marie Presley, is the product of a hebephilic attraction. After all, let’s not forget that Priscilla caught Elvis’s very grownup eye when she was just fourteen, only a year or two older than the boys that Michael Jackson was accused of sexually molesting. Then there’s of course also the scandalous Jerry Lee Lewis incident in which the 23-year-old “Great Balls of Fire” singer married his 13-year-old first cousin.

In the psychiatric community, there’s recently been a hubbub of commotion concerning whether hebephelia should be designated as a medical disorder or, instead, seen simply as a normal variant of sexual orientation and not indicative of brain pathology. There are important policy implications of adding hebephilia to the checklist of mental illnesses, since doing so might allow people who sexually abuse pubescent children to invoke a mental illness defense.

One researcher who is arguing vociferously for the inclusion of hebephilia in the American Psychiatric Association's revised diagnostic manual (the DSM-V) is University of Toronto psychologist Ray Blanchard. In last month’s issue of Archives of Sexual Behavior, Blanchard and his colleagues provide new evidence that many people diagnosed under the traditional label of pedophilia are in fact not as interested in prepubescent children as they are early adolescents.

To tease apart these erotic age orientation differences, Blanchard and his colleagues studied 881 men (straight and gay) in his laboratory using phallometric testing (also known as penile plethysmography) while showing them visual images of differently aged nude models. Because this technique measures penile blood volume changes, it’s seen as being a fairly objective index of sexual arousal to what’s being shown on the screen—which, for those attracted to children and young adolescents, the participant might verbally deny being attracted to. In other words, the penis isn’t a very good liar. So, for example, in Blanchard’s study, the image of a naked 12-year-old girl (nothing prurient, but rather resembling a subject in a medical textbook) was accompanied by the following audiotaped narrative:

“You are watching a late movie on TV with your neighbors’ 12-year-old daughter. You have your arm around her shoulders, and your fingers brush against her chest. You realize that her breasts have begun to develop…”

Blanchard and his coauthors found that the men in their sample fell into somewhat discrete categories of erotic age orientation—some had the strongest penile response to the prepubescent children (the pedophiles), others to the pubescent children (the hebephiles), and the remainder to the adults shown on screen (the teleiophiles). These categories weren’t mutually exclusive. For example, some teleiophiles showed some arousal to pubescent children, some hebephiles showed some attraction to prepubescent children, and so on. But the authors did find that it’s possible to distinguish empirically between a “true pedophile” and a hebephile using this technique, in terms of the age ranges for which men exhibited their strongest arousal. They also conclude that, based on the findings from this study, hebephilia “is relatively common compared with other forms of erotic interest in children.”

In the second half of their article, Blanchard and his colleagues argue that hebephilia should be added to the newly revised DSM-V as a genuine paraphilic mental disorder—differentiating it from pedophilia. But many of his colleagues working in this area are strongly opposed to doing this.

Men who find themselves primarily attracted to young or middle-aged adolescents are clearly disadvantaged in today’s society, but historically (and evolutionarily) this almost certainly wasn’t the case. In fact, hebephiles—or at least ephebephiles—would have had a leg up over their competition. Evolutionary psychologists have found repeatedly that markers of youth correlate highly with perceptions of beauty and attractiveness. For straight men, this makes sense, since a woman’s reproductive value declines steadily after the age of about twenty. Obviously having sex with a prepubescent child would be fruitless—literally. But, whether we like it or not, this isn’t so for a teenage girl who has just come of age, who is reproductively viable and whose brand-new state of fertility can more or less ensure paternity for the male. These evolved motives were portrayed in the film Pretty Baby, in which a young Brooke Shields plays the role of twelve-old-old Violet Neil, a prostitute’s daughter in 1917’s New Orleans whose coveted virginity goes up for auction to the highest bidder.

Understanding adult gay men’s attraction to young males is more of a puzzle. Evolutionary psychologist Frank Muscarella’s “alliance formation theory” is the only one that I’m aware of that attempts to do this. This theory holds that homoerotic behavior between older, high status men and teenage boys serves as a way for the latter to move up in ranks, a sort of power-for-sex bargaining chip. The most obvious example of this type of homosexual dynamic was found in ancient Greece, but male relationships in a handful of New Guinea tribes display these homoerotic patterns as well. There are also, ahem, plenty of present-day examples of this in Congress. Oscar Wilde probably would have signed on to this theoretical perspective. After all, his famous “love that dare not speak its name” wasn’t homosexuality, per se, but rather a “great affection of an elder for a younger man”:

...as there was between David and Jonathan, such as Plato made the very basis of his philosophy, and such as you find in the sonnets of Michelangelo and Shakespeare. It is that deep, spiritual affection that is as pure as it is perfect. It dictates and pervades great works of art like those of Shakespeare and Michelangelo… It is beautiful, it is fine, it is the noblest form of affection. There is nothing unnatural about it. It is intellectual, and it repeatedly exists between an elder and a younger man, when the elder man has intellect, and the younger man has all the joy, hope and glamour of life before him. That it should be so, the world does not understand. The world mocks at it and sometimes puts one in the pillory for it.

But, generally speaking, Muscarella’s theory doesn’t seem to pull a lot of weight. Not many teenage boys in any culture seem terribly interested in taking this particular route to success. Rather—and I may be wrong about this—but I think most teenage boys would prefer to scrub toilets for the rest of their lives or sell soft bagels at the mall than become the sexual plaything of an “older gentlemen.”

In any event, given the biological (even adaptive) verities of being attracted to adolescents, most experts in this area find it completely illogical for Blanchard to recommend adding hebephilia to the revised DSM-V. (Especially since other more clearly maladaptive paraphilias—such as gerontophilia, in which men are attracted primarily to elderly, post-menopausal women—are not presently included in the diagnostic manual.) The push to pathologize hebephilia, argues forensic psychologist Karen Franklin, appears to be motivated more by “a booming cottage industry” in forensic psychology, not coincidentally linked with a “punitive era of moral panic." Because “civil incapacitation” (basically, the government’s ability to strip a person of his or her civil rights in the interests of public safety) requires that the person be suffering from a diagnosable mental disorder or abnormality, Franklin calls Blanchard’s proposal “a textbook example of subjective values masquerading as science.” Another critic, forensic psychologist Gregory DeClue, suggests that such medical classifications are being based on arbitrary distinctions dictated by cultural standards:

Pedophilia is a mental disorder. Homosexuality is not. Should hebephilia of ephebophilia or gerontophilia be considered mental disorders? How about sexual preference for people with different (or with the same) ethnic characteristics as oneself?

And Marquette University psychologist Thomas Zander, points out that since chronological age doesn’t always perfectly match physical age, including these subtle shades of erotic age preferences would be problematic from a diagnostic perspective:

Imagine how much more impractical it would be to require forensic evaluators to determine the existence of pedophilia based on the stage of adolescence of the examinee’s victim. Such determinations could literally devolve into a splitting of pubic hairs.

One unexplored question, and one inseparable from the case of Michael Jackson, is whether we tend to be more forgiving of a person’s sexual peccadilloes when that individual has some invaluable or culturally irreplaceable abilities. For example, consider the following true story:

There once was a man who fancied young boys. Being that laws were more lax in other nations, this man decided to travel to a foreign country, leaving his wife and young daughter behind, where he met up with another Westerner who shared in his predilections for pederasty, and there the two of them spent their happy vacation scouring the seedy underground of this country searching for pimps and renting out boys for sex.

Now if you’re like most people, you’re probably experiencing a shiver of disgust and a spark of rage. You likely feel these men should have their testicles drawn and quartered by wild mares, be thrown to a burly group of rapists, castrated with garden sheers or, if you’re the pragmatic sort, treated as any other sick animal in the herd would be treated, with a humane bullet to the temple or perhaps a swift and sure current of potassium chloride injected into the arm.

But notice the subtle change in your perceptions when I tell you that these events are from the autobiography of André Gide, who in 1947—long after he’d publicized these very details—won the Nobel prize in literature. Gide is in fact bowdlerizing his time in Algiers with none other than Oscar Wilde.

Wilde took a key out of his pocket and showed me into a tiny apartment of two rooms… The youths followed him, each of them wrapped in a burnous that hid his face. Then the guide left us and Wilde sent me into the further room with little Mohammed and shut himself up in the other with the [other boy]. Every time since then that I have sought after pleasure, it is the memory of that night I have pursued.

It’s not that we think it’s perfectly fine for Gide and Wilde to have sex with minors or even that they shouldn’t have been punished for such behaviors. (In fact Wilde was sentenced in London to two years hard labor for related offenses not long after this Maghreb excursion with Gide and died in penniless ignominy.) But somehow, as with our commingled feelings for Michael Jackson, “the greatest entertainer of all time,” the fact that these men were national treasures somehow dilutes our moralistic anger, as though we’re more willing to suffer their vices given the remarkable literary gifts they bestowed.

Would you really have wanted Oscar Wilde euthanized as though he were a sick animal? Should André Gide, whom the New York Times hailed in their obituary as a man “judged the greatest French writer of this century by the literary cognoscenti,” have been deprived of his pen, torn to pieces by illiterate thugs? It’s complicated. And although in principle we know that all men are equal in the eyes of the law, just as we did for Michael Jackson during his child molestation trials, I have a hunch that many people tend to feel (and uncomfortably so) a little sympathy for the Devil under such circumstances.

In this column presented by Scientific American Mind magazine, research psychologist Jesse Bering of Queen's University Belfast ponders some of the more obscure aspects of everyday human behavior. Ever wonder why yawning is contagious, why we point with our index fingers instead of our thumbs or whether being breastfed as an infant influences your sexual preferences as an adult? Get a closer look at the latest data as “Bering in Mind” tackles these and other quirky questions about human nature.

Mind over Matter!

Disorderly genius: How chaos drives the brain

HAVE you ever experienced that eerie feeling of a thought popping into your head as if from nowhere, with no clue as to why you had that particular idea at that particular time? You may think that such fleeting thoughts, however random they seem, must be the product of predictable and rational processes. After all, the brain cannot be random, can it? Surely it processes information using ordered, logical operations, like a powerful computer?

Actually, no. In reality, your brain operates on the edge of chaos. Though much of the time it runs in an orderly and stable way, every now and again it suddenly and unpredictably lurches into a blizzard of noise.



Neuroscientists have long suspected as much. Only recently, however, have they come up with proof that brains work this way. Now they are trying to work out why. Some believe that near-chaotic states may be crucial to memory, and could explain why some people are smarter than others.

In technical terms, systems on the edge of chaos are said to be in a state of "self-organised criticality". These systems are right on the boundary between stable, orderly behaviour - such as a swinging pendulum - and the unpredictable world of chaos, as exemplified by turbulence.

The quintessential example of self-organised criticality is a growing sand pile. As grains build up, the pile grows in a predictable way until, suddenly and without warning, it hits a critical point and collapses. These "sand avalanches" occur spontaneously and are almost impossible to predict, so the system is said to be both critical and self-organising. Earthquakes, avalanches and wildfires are also thought to behave like this, with periods of stability followed by catastrophic periods of instability that rearrange the system into a new, temporarily stable state.

Self-organised criticality has another defining feature: even though individual sand avalanches are impossible to predict, their overall distribution is regular. The avalanches are "scale invariant", which means that avalanches of all possible sizes occur. They also follow a "power law" distribution, which means bigger avalanches happen less often than smaller avalanches, according to a strict mathematical ratio. Earthquakes offer the best real-world example. Quakes of magnitude 5.0 on the Richter scale happen 10 times as often as quakes of magnitude 6.0, and 100 times as often as quakes of magnitude 7.0.

These are purely physical systems, but the brain has much in common with them. Networks of brain cells alternate between periods of calm and periods of instability - "avalanches" of electrical activity that cascade through the neurons. Like real avalanches, exactly how these cascades occur and the resulting state of the brain are unpredictable.

It might seem precarious to have a brain that plunges randomly into periods of instability, but the disorder is actually essential to the brain's ability to transmit information and solve problems. "Lying at the critical point allows the brain to rapidly adapt to new circumstances," says Andreas Meyer-Lindenberg from the Central Institute of Mental Health in Mannheim, Germany.
Disorder is essential to the brain's ability to transmit information and solve problems

The idea that the brain might be fundamentally disordered in some way first emerged in the late 1980s, when physicists working on chaos theory - then a relatively new branch of science - suggested it might help explain how the brain works.

The focus at that time was something called deterministic chaos, in which a small perturbation can lead to a huge change in the system - the famous "butterfly effect". That would make the brain unpredictable but not actually random, because the butterfly effect is a phenomenon of physical laws that do not depend on chance. Researchers built elaborate computational models to test the idea, but unfortunately they did not behave like real brains. "Although the results were beautiful and elegant, models based on deterministic chaos just didn't seem applicable when looking at the human brain," says Karl Friston, a neuroscientist at University College London.

In the 1990s, it emerged that the brain generates random noise, and hence cannot be described by deterministic chaos. When neuroscientists incorporated this randomness into their models, they found that it created systems on the border between order and disorder - self-organised criticality.

More recently, experiments have confirmed that these models accurately describe what real brain tissue does. They build on the observation that when a single neuron fires, it can trigger its neighbours to fire too, causing a cascade or avalanche of activity that can propagate across small networks of brain cells. This results in alternating periods of quiescence and activity - remarkably like the build-up and collapse of a sand pile.
Neural avalanches

In 2003, John Beggs of Indiana University in Bloomington began investigating spontaneous electrical activity in thin slices of rat brain tissue. He found that these neural avalanches are scale invariant and that their size obeys a power law. Importantly, the ratio of large to small avalanches fit the predictions of the computational models that had first suggested that the brain might be in a state of self-organised criticality (The Journal of Neuroscience, vol 23, p 11167).

To investigate further, Beggs's team measured how many other neurons a single cell in a slice of rat brain activates, on average, when it fires. They followed this line of enquiry because another property of self-organised criticality is that each event, on average, triggers only one other. In forest fires, for example, each burning tree sets alight one other tree on average - that's why fires keep going, but also why whole forests don't catch fire all at once.

Sure enough, the team found that each neuron triggered on average only one other. A value much greater than one would lead to a chaotic system, because any small perturbations in the electrical activity would soon be amplified, as in the butterfly effect. "It would be the equivalent of an epileptic seizure," says Beggs. If the value was much lower than one, on the other hand, the avalanche would soon die out.

Beggs's work provides good evidence that self-organised criticality is important on the level of small networks of neurons. But what about on a larger scale? More recently, it has become clear that brain activity also shows signs of self-organised criticality on a larger scale.

As it processes information, the brain often synchronises large groups of neurons to fire at the same frequency, a process called "phase-locking". Like broadcasting different radio stations at different frequencies, this allows different "task forces" of neurons to communicate among themselves without interference from others.

The brain also constantly reorganises its task forces, so the stable periods of phase-locking are interspersed with unstable periods in which the neurons fire out of sync in a blizzard of activity. This, again, is reminiscent of a sand pile. Could it be another example of self-organised criticality in the brain?

In 2006, Meyer-Lindenberg and his team made the first stab at answering that question. They used brain scans to map the connections between regions of the human brain and discovered that they form a "small-world network" - exactly the right architecture to support self-organised criticality.

Small-world networks lie somewhere between regular networks, where each node is connected to its nearest neighbours, and random networks, which have no regular structure but many long-distance connections between nodes at opposite sides of the network (see diagram). Small-world networks take the most useful aspects of both systems. In places, the nodes have many connections with their neighbours, but the network also contains random and often long links between nodes that are very far away from one another.

For the brain, it's the perfect compromise. One of the characteristics of small-world networks is that you can communicate to any other part of the network through just a few nodes - the "six degrees of separation" reputed to link any two people in the world. In the brain, the number is 13.

Meyer-Lindenberg created a computer simulation of a small-world network with 13 degrees of separation. Each node was represented by an electrical oscillator that approximated a neuron's activity. The results confirmed that the brain has just the right architecture for its activity to sit on the tipping point between order and disorder, although the team didn't measure neural activity itself (Proceedings of the National Academy of Sciences, vol 103, p 19518).

That clinching evidence arrived earlier this year, when Ed Bullmore of the University of Cambridge and his team used brain scanners to record neural activity in 19 human volunteers. They looked at the entire range of brainwave frequencies, from 0.05 hertz all the way up to 125 hertz, across 200 different regions of the brain.
Power laws again

The team found that the duration both of phase-locking and unstable resynchronisation periods followed a power-law distribution. Crucially, this was true at all frequencies, which means the phenomenon is scale invariant - the other key criterion for self-organised criticality.

What's more, when the team tried to reproduce the activity they saw in the volunteers' brains in computer models, they found that they could only do so if the models were in a state of self-organised criticality (PLoS Computational Biology, vol 5, p e1000314). "The models only showed similar patterns of synchronisation to the brain when they were in the critical state," says Bullmore.

The work of Bullmore's team is compelling evidence that self-organised criticality is an essential property of brain activity, says neuroscientist David Liley at Swinburne University of Technology in Melbourne, Australia, who has worked on computational models of chaos in the brain.

But why should that be? Perhaps because self-organised criticality is the perfect starting point for many of the brain's functions.

The neuronal avalanches that Beggs investigated, for example, are perfect for transmitting information across the brain. If the brain was in a more stable state, these avalanches would die out before the message had been transmitted. If it was chaotic, each avalanche could swamp the brain.

At the critical point, however, you get maximum transmission with minimum risk of descending into chaos. "One of the advantages of self-organised criticality is that the avalanches can propagate over many links," says Beggs. "You can have very long chains that won't blow up on you."

Self-organised criticality also appears to allow the brain to adapt to new situations, by quickly rearranging which neurons are synchronised to a particular frequency. "The closer we get to the boundary of instability, the more quickly a particular stimulus will send the brain into a new state," says Liley.

It may also play a role in memory. Beggs's team noticed that certain chains of neurons would fire repeatedly in avalanches, sometimes over several hours (The Journal of Neuroscience, vol 24, p 5216). Because an entire chain can be triggered by the firing of one neuron, these chains could be the stuff of memory, argues Beggs: memories may come to mind unexpectedly because a neuron fires randomly or could be triggered unpredictably by a neuronal avalanche.

The balance between phase-locking and instability within the brain has also been linked to intelligence - at least, to IQ. Last year, Robert Thatcher from the University of South Florida in Tampa made EEG measurements of 17 children, aged between 5 and 17 years, who also performed an IQ test.
The balance between stability and instability in the brain has been linked with intelligence, at least as measured by scores on an IQ test

He found that the length of time the children's brains spent in both the stable phase-locked states and the unstable phase-shifting states correlated with their IQ scores. For example, phase shifts typically last 55 milliseconds, but an additional 1 millisecond seemed to add as many as 20 points to the child's IQ. A shorter time in the stable phase-locked state also corresponded with greater intelligence - with a difference of 1 millisecond adding 4.6 IQ points to a child's score (NeuroImage, vol 42, p 1639).

Thatcher says this is because a longer phase shift allows the brain to recruit many more neurons for the problem at hand. "It's like casting a net and capturing as many neurons as possible at any one time," he says. The result is a greater overall processing power that contributes to higher intelligence.

Hovering on the edge of chaos provides brains with their amazing capacity to process information and rapidly adapt to our ever-changing environment, but what happens if we stray either side of the boundary? The most obvious assumption would be that all of us are a short step away from mental illness. Meyer-Lindenberg suggests that schizophrenia may be caused by parts of the brain straying away from the critical point. However, for now that is purely speculative.

Thatcher, meanwhile, has found that certain regions in the brains of people with autism spend less time than average in the unstable, phase-shifting states. These abnormalities reduce the capacity to process information and, suggestively, are found only in the regions associated with social behaviour. "These regions have shifted from chaos to more stable activity," he says. The work might also help us understand epilepsy better: in an epileptic fit, the brain has a tendency to suddenly fire synchronously, and deviation from the critical point could explain this.

"They say it's a fine line between genius and madness," says Liley. "Maybe we're finally beginning to understand the wisdom of this statement."

David Robson is a junior editor at New Scientist

Much Touted “Depression Risk Gene” May Not Add to Risk After All

June 16, 2009

New Look at Data Confirms Strong Association between Depression and Stressful Life Events
computer generated image of DNA

Stressful life events are strongly associated with a person's risk for major depression, but a certain gene variation long thought to increase risk in conjunction with stressful life events actually may have no effect, according to researchers funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health. The study, published in the June 17, 2009, issue of the Journal of the American Medical Association, challenges a widely accepted approach to studying risk factors for depression.

"Rigorous re-evaluations of published studies provide the checks and balances necessary for scientific progress," said Thomas R. Insel, M.D., director of NIMH. "We are still in the early days of understanding how genes and environment interact to increase the risk for depression."

Most mental disorders are thought to be caused by a combination of many genetic risk factors interacting with environmental triggers. However, finding the exact combinations continues to present significant challenges to research.

Advances in scientific understanding and technologies during the past decade have led to powerful tools for studying how genetic and environmental factors can affect a person's risk for disease. Such advances allowed mental health researchers in 2003 to show that a gene involved in serotonin activity increased the risk of major depression in people who had a number of stressful life events over a five-year period (see "More About the Science" below for more information about this gene and serotonin). Coming at a time of heightened research interest in these gene-environment interactions and the relative lack of progress in the field for mental disorders, this study received wide acclaim and had a far-reaching influence. Not only have considerable resources been invested in subsequent studies that built on this finding, but also some researchers have proposed marketing the gene test to the public, claiming to be able to predict a person's risk for depression.

However, efforts to replicate the 2003 study's findings—a key step in scientific progress that helps show whether a particular finding was a chance event—have had inconsistent results.

To examine whether the 2003 study's finding had been confirmed, a group of scientists from NIMH and six universities with expertise in epidemiology, biostatistics, genetics, and psychiatry reviewed the status of relevant replication studies. Led by Kathleen Merikangas, Ph.D., of the NIMH Intramural Research Program, the workgroup did a meta-analysis, re-analyzing data on 14,250 participants in 14 studies published from 2003 through March 2009. Of these, the researchers also re-analyzed original data, including unpublished information, on 10,943 participants from 10 studies published before 2008. The workgroup analyzed these original data to see whether there were gender differences in the associations between the serotonin genotype, stressful life events, and depression.

By applying the same definitions of study variables and data analysis methods used in the 2003 study, the workgroup found a strong association between the number of stressful life events and risk of depression across the studies. However, the presumed high-risk version of the serotonin transporter gene did not show a relationship to increased risk for major depression, alone or in interaction with stressful life events, in the analysis of the 14 studies. Their findings were the same in men and women alone in the analysis of original data from 10 studies.

The workgroup noted that their analysis had some limitations. Individual level data were available for only 10 of the 14 studies published before 2008. However, these limitations would have had little effect on the overall findings because the number of participants in the studies not included was only a small proportion of the total sample.

These findings may account for the difficulty many researchers have faced in attempting to replicate the 2003 study. This analysis confirms some earlier reviews that had also questioned the validity of the gene's effect on depression risk. However, the workgroup emphasized that the intent of its analysis was not to deter research on gene-environment interactions for mental disorders.

"Identifying gene-environment interactions is most successful when studies can focus on a single gene with a major effect, or when the environmental exposure has a strong effect," said lead author Neil Risch, Ph.D., University of California, San Francisco and Kaiser Permanente Northern California. "In the case of modest gene effects or environmental impacts, the statistical power to detect an interaction will be low, and thus weak positive results should be interpreted carefully."

The authors concluded that incorporating environmental exposures in candidate gene studies (those that study a particular gene) may be as likely to yield false positive findings as the candidate gene studies themselves. Therefore, the results of other studies using the same approach as the 2003 study also deserve thorough review and meta-analysis.

"Even though our re-analysis did not confirm an association between the serotonin gene and depression, the finding that the environmental factor was strongly associated with depression in several studies reminds us that environmental factors are also involved in the complex pathways leading to mental disorders," noted Merikangas. "Future progress will require thoughtful integration of the tools of genetics, epidemiology, and clinical and behavioral sciences."

The authors on the paper include Neil Risch, Ph.D., University of California at San Francisco and Kaiser Permanente Northern California; Richard Herrell, Ph.D., NIMH; Thomas Lehner, Ph.D., NIMH; Kung-Yee Liang, Ph.D., Johns Hopkins University; Lindon Eaves, Ph.D., Virginia Commonwealth University; Josephine Hoh, Ph.D., Yale University; Andrea Griem, NIMH; Maria Kovacs, Ph.D., University of Pittsburgh; Jurg Ott, Ph.D., Rockefeller University; Kathleen Ries Merikangas, Ph.D., NIMH.
More About the Science

Serotonin is one of several chemical messengers in the brain, or neurotransmitters, which help brain cells communicate with one another. Among many other functions, serotonin is involved in regulating mood. Problems with making or using the right amount of serotonin have been linked to many mental disorders, including depression, bipolar disorder, anxiety disorder, autism, and schizophrenia.

There are many genes that code for serotonin. Some of these genes guide serotonin production and other are involved in its activity. The serotonin transporter gene makes a protein that directs serotonin from the space between brain cells-where most neurotransmitters are relayed from one cell to another-back into cells, where it can be reused. Since the most widely prescribed class of medications for treating major depression acts by blocking this transporter protein, the gene has been a prime suspect in mood and anxiety disorders.

The serotonin transporter gene has many versions. Since everyone inherits a copy of this gene from each parent, a person may have two copies of the same version or one copy each of two different versions. One version of the serotonin transporter gene makes less protein, resulting in decreased transport of serotonin back into cells. This version has also long been the focus of depression research due to its suggested effect on risk.

Read more about NIMH research on depression and genetic risk factors
Reference

Risch N, Herrell R, Lehner T, Liang KY, Eaves L, Hoh J, Griem A, Kovacs M, Ott J, Merikangas KR. Interaction between the Serotonin Transporter Gene, Stressful Life Events and Risk of Depression: A Meta-Analysis. JAMA. 2009 Jun 17;301(23):2462-71.

Car Exhaust Associated With Premature Births in Southern California

Mothers living near freeways and congested roads are more likely to give birth to premature babies and suffer from preeclampsia

By Marla Cone and Environmental Health News

Women exposed to air pollution from freeways and congested roads are much more likely to give birth to premature babies and suffer from preeclampsia, according to a study by University of California scientists published Wednesday.

The findings, based on pregnant women in the Long Beach/Orange County region of Southern California, add to the growing evidence that car and truck exhaust can jeopardize the health of babies while they are in the womb.

Reviewing the birth records of more than 81,000 infants, researchers found that the risk of having a baby born before 30 weeks of gestation increased 128 percent for women who live near the worst traffic-generated air pollution.

In addition, preeclampsia increased 42 percent for women who lived in those areas, according to the study, published online in the scientific journal Environmental Health Perspectives. Preclampsia, a serious illness that involves high blood pressure, can endanger the baby and the mother.

The team of scientists from UCLA and University of California, Irvine studied babies born in Long Beach, near the Ports of Los Angeles and Long Beach, and in adjacent Orange County. Those areas are traversed by several major freeways used by commuters as well as heavy-duty trucks delivering goods to and from the ports.

The infants’ birth records were matched with their addresses and then compared with traffic patterns and estimates of two pollutants—particulates and nitrogen oxides—from vehicles near the mothers’ homes.

The study was unique in that the researchers constructed a database estimating what the pregnant women breathed in their own neighborhoods--within three kilometers, or less than two miles, of their homes. Previous studies have used general air pollution measurements, which is a less accurate estimate of what people are exposed to.

Only traffic-generated emissions were included in the study, not pollutants from factories and other sources.

Fetuses “are in a very sensitive stage of development” that could be vulnerable to the toxic substances inhaled by their mothers, said Jun Wu, an assistant professor of epidemiology at UC Irvine and the study’s lead author.

Other recent studies have linked air pollutants to preterm births and low birth weights. But until now, “no study has associated air pollution with preeclampsia. This is the first one,” Wu said.

Tracey Woodruff, director of University of California, San Francisco’s Program on Reproductive Health and the Environment, said the research offers a relatively “new twist on air pollution,” since most scientists have focused on respiratory and cardiovascular diseases.

“This is just one more piece of the scientific evidence that air pollution can have effects on adverse pregnancy outcomes,” said Woodruff, who was not involved in the research.

The babies in the study were born between 1997 and 2006 at four hospitals: Long Beach Memorial and three in Orange County--Anaheim Memorial, Orange Coast Memorial in Fountain Valley and Saddleback Memorial in Laguna Hills.

Maria Gugerty, a Long Beach resident, said she always has wondered what might have caused her son, Will, to be born premature, at 31 weeks. Her son was likely one of the preemies reviewed in the study since he was born at Long Beach Memorial in 1997.

“My pregnancy was completely fine, but all of a sudden my water broke. It seemed completely random and the doctors were never able to determine any physical reason for it,” she said. “I was so careful during my pregnancy. No alcohol, no smoking and a good diet. So I’ve always wondered if it was something in the environment, not necessarily air pollution but the environment in general.”

Another Long Beach mother, Susan Taylor, said her doctor thought a gum infection most likely was the cause of her daughter, Maddy, being born early, also at 31 weeks. But, she said, “we did live near a very busy, noisy intersection.”

Like most women, Gugerty and Taylor didn't know there was a connection between air pollution and pregnancies. But Gugerty said that she “absolutely” worries about the potential health effects of the pollution around her home in Long Beach. Her son, now 12, has asthma.

About half of the babies included in the study were born in Long Beach. Air pollution experts have said that people living in that area faced a variety of increased health risks, including cancer and reduced lung function, due to heavy traffic and other sources of air pollution related to the ports and freeways.

Every year, more than half a million infants are born prematurely in the United States. In the study, 8 percent of the 81,186 babies were preterm, including 1 percent that were “very preterm,” or under 30 weeks of gestation.

The link to air pollution was strongest for the “very preterm” babies, who often weigh less than three pounds and have the greatest risk of serious health problems. The researchers compared women who lived in areas with the most traffic-related pollution with women who lived in areas with the least traffic pollution. Those in the polluted areas were 128 percent more likely to deliver “very preterm” babies.

The risk of less severe preterm babies—those born between 30 and 37 weeks--was about 30 percent higher for women living in the areas with a lot of traffic emissions.

About 3 percent of the study’s pregnant women had preeclampsia, which can result in premature babies. Its causes are unknown, although doctors think it is related to abnormal growth of the placenta.

The new study focused on “an important area of research, since there are a lot of reasons to believe that there is something happening with environmental chemicals and preeclampsia,” Woodruff said. “Women with preeclampsia have high blood pressure, and some air pollutants can increase blood pressure. This is a serious condition, and these women are at risk of adverse pregnancy outcomes.”

Scientists are uncertain how air pollutants might trigger premature babies. The chemicals may interfere with placental development, which would impair the nutrients and oxygen delivered to the fetus. Or they could trigger oxidative stress—when cells are overwhelmed and DNA is damaged by reactive compounds in the environment called free radicals.

Wu said it is likely that other pollutants are to blame, not the fine particles and nitrogen oxides. Instead, those two pollutants could be an indicator of other toxic compounds in vehicle exhaust, such as polycyclic aromatic compounds. A recent study of babies in New York City linked those compounds, called PAHs, to preterm and low-weight babies.

Wu said doctors should warn pregnant women about air pollution because “they should be aware of these issues.” While most can’t move to avoid traffic emissions, Wu said they might be able to take precautions, such as reducing their commutes or closing their windows in cars and homes.

But avoiding air pollution is virtually impossible, Woodruff said, so “pregnant women should be aware of the risks and advocate for the kinds of [government] actions that reduce overall exposure to air pollution.”

The authors said a major limitation of their research is that it only looked at where the women lived when their babies were born, not where they lived or worked during their pregnancies, or whether they had long commutes in heavily polluted areas. Still, they said by using neighborhood data, they were probably more accurate in estimating the women’s exposures than past researchers have been.

Beate Ritz, an epidemiology professor at UCLA’s School of Public Health, was the study’s senior author. Her research has focused on using geographic information to map people’s exposure to pollutants and chemicals and search for links to chronic diseases such as Parkinson's and cancer.

Woodruff said many researchers are starting to use such data, which only has been available in recent years, because it can provide “reasonable estimates of what people are exposed to.”

Plug and Play

Plug and Play: Researchers Expand Clinical Study of Neural Interface Brain Implant
BrainGate moves to phase II testing as scientists search for a way to return life to paralyzed limbs

By Larry Greenemeier

Having proved in 2004 that plugging a sensor into the human brain's motor cortex could turn the thoughts of paralysis victims into action, a team of Brown University scientists now has the green light from the U.S. Food and Drug Administration (FDA) and the Massachusetts General Hospital (MGH) institutional review board to expand its efforts developing technology that reconnects the brain to lifeless limbs.

Brown's BrainGate Neural Interface System—conceived in 2000 with the help of a $4.25-million U.S. Defense Department grant—includes a baby aspirin–size brain sensor containing 100 electrodes, each thinner than a human hair, that connects to the surface of the motor cortex (the part of the brain that enables voluntary movement), registers electrical signals from nearby neurons, and transmits them through gold wires to a set of computers, processors and monitors. (ScientificAmerican.com in 2006 wrote about one patient's experience using BrainGate during its first phase of trials.)

The researchers designed BrainGate to assist those suffering from spinal cord injuries, muscular dystrophy, brain stem stroke, amyotrophic lateral sclerosis (ALS, or Lou Gehrig's Disease), and other motor neuron diseases. During the initial testing five years ago, patients suffering from paralysis demonstrated their ability to use brain signals sent from their motor cortex to control external devices such as computer screen cursors and robotic arms just by thinking about them. "The signals may have been disconnected from the (participant's) limb, but they were still there," says Leigh Hochberg, a Brown associate professor of engineering and a vascular and critical care neurologist at MGH who is helping lead the research.

Due to the high risk of plugging a device directly into the brain, the FDA in 2004 granted the BrainGate system an investigational device exemption so that researchers could begin testing the unit in patients and collect data about its safety and effectiveness. Thanks to the success of those early tests, the researchers last week kicked off a pilot clinical trial, dubbed BrainGate2. Although the technology is similar to what was used in the original testing, the researchers are looking to enlist up to 15 patients this time and gather more information that will help them better understand brain signals as well as "the method by which we decode them," Hochberg says. Since the initial four-person clinical trial launched five years ago, "we have a better appreciation for things that we need to learn."

A successful BrainGate2 trial could open up a number of new possibilities, including the use of a second sensor to stimulate both sides of the motor cortex, says John Donoghue, a Brown neuroscience professor and director of the Brown Institute for Brain Science. Researchers thus far have implanted the sensor in the side of the brain that controls a patient's dominant side—the left cortex for righties and the right cortex for lefties.

BrainGate2 is part of a larger mission to help paralysis victims regain control of their bodies. "We want to reconnect the brain back to the muscles and eventually back to the entire limb," Donoghue says. "We are attempting to recreate parts of the nervous system that have been disconnected from the brain."

Hochberg expects this second phase to last for several years, "depending on what we learn and how quickly we learn it." The research project has received about $8 million in funding over the past three years from a number of organizations, including the National Institutes of Health (NIH) and the U.S. Department of Veterans Affairs.