Drug could get into the autistic mind

New Scientist Magazine
01 June 2010 by Celeste Biever

CAN people with autism take a pill to improve their social skills? For the first time, drugs are being tested that could address the social difficulties associated with autism and other learning disorders by tackling some of the brain chemistry thought to underlie them.

The only drugs currently prescribed to people with autism seek to dampen aggression and anxiety. The new drugs, now in the very early stages of clinical testing, address some of the classic symptoms of autism.

"People may learn more, learn to speak better, learn social skills and to be more communicative," says Randall Carpenter of Seaside Therapeutics in Cambridge, Massachusetts, which is testing one of the drugs.

Geraldine Dawson, chief science officer at the charity Autism Speaks and a psychiatrist at the University of North Carolina at Chapel Hill, is equally enthusiastic about the prospect of a new class of drugs. "For the first time we are seeing drugs that could tackle core autism symptoms," she says.

For the first time we are seeing drugs that could tackle the core symptoms of autism
The Seaside trial is aimed at a learning disorder called fragile X, which is associated with autism. People with fragile X carry a mutation in a gene involved in strengthening brain connections associated with salient experiences. Stronger brain connections allow people to distinguish these events from background noise, making this a key process in learning.

Carpenter and his colleagues are testing a drug called arbaclofen, which seems to reverse the effect of the mutation. At the International Meeting for Autism Research in Philadelphia, Pennsylvania, on 23 May, they presented initial results suggesting that the drug may improve the social skills of people with fragile X and autism, including improved communication and general sociability, and fewer outbursts.

Seaside's trial is not the only attempt to alter the brain chemistry of people with autism. The hormone oxytocin, also known as the cuddle chemical, helps us connect social contact with feelings of pleasure, and some people with autism produce less of it. Several teams are looking into boosting oxytocin to relieve symptoms of autism.

At the Philadelphia meeting, a team led by Evdokia Anagnostou, a child neurologist at Bloorview Research Institute in Toronto, Canada, reported that people given the hormone twice daily for six weeks were more likely to be better at recognising emotions and at social functioning, and had a better quality of life than others given a placebo.

Trying to alter the brain chemistry thought to underlie autistic behaviour has never been done before in this way, says Uta Frith of University College London. "If they succeed it would be marvellous." But she cautions that the drugs have not yet been shown to work better than behavioural interventions and that most causes of autism are still deeply mysterious.

Carpenter points out that behavioural interventions don't work for everyone, and both approaches could be useful. "If we come up with an effective treatment, parents are going to embrace that."

Non-expert treatment shown to be more effective than primary care in soothing widespread anxiety

By Katherine Harmon

NEW YORK—One-size-fits-all treatments are particularly rare in the mental health world, where each patient's ailments can seem unique.

But a team of researchers seems to have found a therapeutic model to treat anxiety disorders as wide-ranging as post-traumatic stress disorder (PTSD), social phobia and panic disorder. Lead study author Dr. Peter Roy-Byrne, of the Department of Psychiatry and Behavioral Sciences at the University of Washington School of Medicine, presented the findings May 18 at a press briefing in New York convened by JAMA, Journal of the American Medical Association.

When taken together, anxiety disorders affect about 18 percent of the population (which is more than twice the rate of depression). Some three fourths of people with mental disorders are managed in primary care (which Roy-Byrne called "the de facto mental health system"), but getting those patients—especially those with anxiety disorders—to see mental health specialists is much harder than getting them to see a radiologist, Roy-Byrne noted.

He and his team devised a flexible, collaborative care system that lightened loads for both doctors and psychiatrists (or psychologists) while making it easier for patients to get the help they needed. By enlisting the skills of nurses or masters-level clinicians with some training in anxiety management and an online patient progress tracking system, the treatment plan could adapt to patients without sending them to an expensive psychiatrist or psychologist, which has been shown to be especially difficult in anxiety patients (and could also allow specialists more time to address patients who most need their care). And a controlled trial, published May 19 in JAMA, showed promising results.

The researchers randomized 1,004 patients with at least one anxiety disorder (with and without major depression) to either their treatment model (which offered a choice of drug-based therapy as prescribed by overseeing doctors, computer-assisted cognitive behavioral therapy or a combination of both) or standard care (any treatment by their primary physician, recommended counselor or medication).

Patients receiving medication in the experimental group were advised about type and dosage as well as given additional guidance about healthy lifestyle habits, such as sleep hygiene and behavioral tips. Those getting cognitive behavioral therapy met with a nurse or masters-level clinician to work through a computer-guided program, which provided questions, examples and videos to guide the sessions as well as tailor and reinforce concepts. Primary care physicians and psychiatrists or psychologists oversaw the progress of patients and administrators via an online tracking system that charted attendance, performance and wellbeing so that they could follow-up or intervene if necessary.

The trial itself was open to patients' changing needs, so if patients entered the trial on ineffective levels of medication but didn't want to switch, the docs allowed them to stay on their preferred regimen. And if an experimental-group patient was not improving on a current path (of cognitive behavior therapy or pharmacological treatment), doctors could immediately see that and recommend alternative courses of action.

After a series of blinded follow-ups with patients (at six, 12 and 18 months after the start of the trial), the researchers found that with just six to eight sessions, patients in the treatment group were "averaging really negligible symptoms," he said. Fifty-one percent of people in the flexible, monitored treatment group were in remission at 18 months, compared to 36 percent of the usual care group.

The results "showed how we could use technology" to treat a broad range of anxiety disorders, Roy-Byrne noted on Tuesday. And because the treatment model was effective for a broad range of disorders, it could help the many people who have more than one ailment, "which is the rule rather than the exception," he added.

By using clinician-administered, evidence-based strategy, he said, "you can get a lot of people better fast." And the social implications of the model were not lost on Roy-Byrne. He noted that the days of the well-to-do and well-insured seeking in-depth psychiatric help for every minor mental health issue might be numbered. "How can you more responsibly distribute the expertise?" he asked. With an evidence-based treatment protocol, he concluded, the psychiatric and psychological big guns could be reserved for those who really needed them.

We are the Evil In Man

A lecture by Carl G. Jung...

Mothers' Depression Can Go Well Beyond Child's Infancy

Mothers' Depression Can Go Well Beyond Child's Infancy
Many mothers continue to have depressive symptoms well into their child's youth, which can have lasting impacts on their children's development, but new research shows short therapy sessions can improve outlook.

By Katherine Harmon

Vast amounts of research on postpartum depression have focused on difficulties facing new mothers, and studies of adult depression have focused on individual struggles. Depression in mothers with children over the age of six months, however, is less discussed but exceedingly common. At least 12 percent of women in any given year—many of whom are mothers—and 20 percent of disadvantaged mothers have depressive symptoms.

New findings, presented May 1 at the Pediatric Academic Societies meeting in Vancouver, Canada, provide hope, showing that proper screening and brief cognitive behavior therapy can be a big help to both the mothers and their children.

"Anyone can be depressed," says Carol Weitzman, an associate professor of developmental-behavior pediatrics at Yale University School of Medicine and lead researcher on the study. But when an adult is caring for children, depression can have large and lasting effects on the kids, making maternal depression "a big public health problem for children," she notes. "The effects of depression on children are very profound. We can't look at children's health and function without looking at parents' functioning."

Depressed moms, weak bonds
Maternal depression is not an isolated event but part of "a continuum that actually starts prenatally," explains Janice Cooper, interim director of the National Center for Children in Poverty at Columbia University's Mailman School of Public Health. Regardless of a child's age, "moms with depression are less able to bond well with their children," she says.

Many mothers with depression are less likely to engage positively with their children, such as playing, reading or singing. They may even have trouble managing basic child well-being tasks, such as arranging doctor's checkups, childproofing a home or buckling children up in cars. Additionally, Cooper points out, depressed parents tend to be less consistent in their parenting. As symptoms wax and wane, discipline and engagement can fluctuate, leaving children in less-stable environments. All of these behaviors can influence cognitive, social and physical development, she says.

In many instances, maternal depression can initiate what Cooper calls a "vicious cycle." When depressed mothers do not respond well to their children, the children tend not to respond well to the mother, adding to the mother's concern, anxiety and general malaise. And these feelings are more likely to increase as the child gets older, a finding that surprised even Weitzman. These growing anxieties might stem from increased concern about difficulties children might face as they get older, she hypothesizes.

Exploring options
Given the high rates of maternal depression and its impact on the mother-child bond, Weitzman and her colleagues are seeking to understand how it can be better diagnosed and treated. "I think that we should be sitting up and really taking notice when we see numbers like that," Weitzman says. "For certain kinds of disorders, we would be all over that, but we still carry a lot of stigma for mental health."

The issue of maternal depression is outsized in disadvantaged families, and depressed mothers are less likely to be employed, probably increasing stress. A combination of other factors, such as less educated parents, also put children at higher risk for poor developmental outcomes even without a depressed parent.

In the new randomized study of 71 underserved mothers with depressive symptoms, Weitzman and her team examined how several short, on-site cognitive behavior therapy sessions compared with traditional referrals for improving both maternal symptoms and how mothers rated their children's behavior.

Conventionally, observant doctors might suggest specialists for women who seem to be depressed. For the study, Weitzman and her group gave women who were randomized into this control group substantial case management, in which they spoke with a social worker and were helped with referrals. In the cognitive behavior therapy group, the social workers "tried to help people make the link from their moods and behavior to how it affected their children." The six two-hour therapy sessions covered the relationship between thought, mood, behavior and physical feelings. It got the mothers to identify stigmas, practice relaxation techniques, reduce negative thinking, and explore the link between maternal mood and behavior and child mood and behavior.

Both groups showed improvement, but the cognitive behavioral therapy group "significantly reduced their ratings of problem behavior in their young children," Weitzman and her colleagues conclude in their abstract.

"These are great findings," says Cooper, who was not involved in the study. "We know that depression is highly treatable," she notes, adding that these data give credence to other work showing the importance of diagnosing and treating disadvantaged mothers with depression.

The follow-up period for Weitzman's study did not provide long-term assessments of mother and child behavior, and as Cooper notes, not all mothers can be helped by cognitive behavior therapy. In some cases, she says, the best solution is including some joint parent-child therapy: "For some families, they really do need help developing that parent-child relationship, rebonding, reconnecting with their children."

Incorporating treatment
But finding a way to integrate both screening and treatment into an already tenuous health care environment can be challenging. "We should be bringing this stuff right into pediatrics," Weitzman says. They have found that a simple screening, whether it is via a paper survey or simple questions from a pediatrician, is feasible to incorporate into a standard well-child visit. It will help, she notes, if pediatricians are aware of some of the red flags, such as infrequent (or overly frequent) doctor visits, negative description of young children or other behavioral signals. But once doctors recognize signs of depression, there are often few resources—especially for disadvantaged families—to recommend and even fewer on-site cognitive behavior therapy programs like the one in the study. And even in their study, Weitzman notes, there were high dropout rates, which emphasize the need for treatments that are easy for families.

Beyond the challenge of providing sessions and making sure those who need treatment get it, the cost of these programs can be prohibitive. Finding a way to establish screening and treatment protocols so they are not only convenient for families and practitioners but also integrated into the reimbursement structure is likely to be difficult. Because many programs address postpartum depression through six months, it can be hard to find reimbursable programs that will address maternal and parent-child bonding in treatment, Cooper notes.

As with other diseases, however, treating it is likely to pay off in the long run. Depressed adults often miss work or have trouble retaining consistent employment, resulting in lost productivity. "We know that depression is a huge cost to our society," Cooper says. And beyond the individual, improving parental state of mind pays long-term dividends for improved child development, she notes, adding that any booster to "foster those bonds and make sure those children have the most quality early childhood experience" is a solid investment. Citing a frequently used figure for cost-benefit analysis, Cooper notes that, "for every $1 invested in early childhood, we save $8.… If you think of it in terms of prevention, this is a huge benefit to society."

First, however, the concept surrounding maternal depression needs to change, Weitzman notes. "Depression is a chronic disorder—it waxes and it wanes," she says. "We just need to expand and broaden our thinking [from the idea] that there's this short time after the birth of a baby that someone can be depressed."

Understanding Dreams

Dreams about taking exam, being naked -- what they mean
By Elizabeth Landau, CNN

(CNN) -- You're in a classroom and the teacher puts an exam face down on your desk. You pick it up and can't really make out what's on it; it's blurry, or it's in another language, or it's in a subject you didn't study.

You feel like you're going to fail, even though it's been years since you've actually been in school.

People commonly relive this scenario in their dreams, even decades after their last graduation. While many high school, college and graduate school students are cramming for real exams this week, you may dream about it if you have anxiety about being judged, or if you're in a situation you don't know how to handle, experts say.

Dreams are "an extremely rich source of practical advice, and other alternatives about what we're doing in our lives," said Deirdre Barrett, Harvard psychologist and author of "The Committee of Sleep" and "Trauma and Dreams." "They're just coming from such a different part of ourselves that they're a very good supplement to our waking, rational thinking."

The dreaming brain

Scientists know about as much about the dreaming brain as they do the waking brain -- in other words, there's still a lot to learn about how the brain creates the dreaming consciousness and wakeful consciousness, said William Dement, leading sleep researcher at Stanford University.

Dreaming happens during the REM (rapid eye movement) stage of sleep. In a typical sleep cycle, there are 68 minutes of non-REM sleep and 22 minutes of REM sleep. An eight-hour night of sleep will include about six REM periods, during which multiple dreams can occur.

The body is temporarily paralyzed during REM sleep. But in a rare condition called REM behavior disorder, people act out what they are doing in their dreams, be it talking or running into a wall.

You are conscious in your dreams in basically the same way you are conscious in real life, but you don't remember dreams as well because memory processing is down, Dement said. The continuity of real life experiences helps you distinguish waking life from the dream world. For example, you don't magically reappear in a different setting in the real world, whereas it might appear that way in a single night of dreaming.

"In some ways, it's very good we don't remember our dreams very well," he said. "You'd constantly be saying, 'Did that happen, or was it a dream?' "

Inside your dreams

The symbols and events in dreams can mean many different things to different people, Barrett said. A dog might signal unconditional love to someone who has positive feelings toward canines; someone else with a fear of dogs might dream about them as a reflection of trauma.

But themes such as the "test you're not prepared for" do tend to have common meanings for people. A similar dream occurs for people who had experience in acting as a child: They dream that they forgot there was an audition that day, or that they get to an audition and it's in a garbled language, or they studied the wrong script -- they're being judged, or don't know what to do in this situation. People also commonly have dreams in which they are naked in public, associated with feeling exposed or ashamed. This could signal that the dreamer feels socially inadequate in some way, Barrett said

These are "psychological dreams" that are telling you that you should figure out where in life you are having a block, or how you should handle your difficult problem, said Dr. Judith Orloff, author of "Second Sight" and assistant clinical professor of psychiatry at the University of California, Los Angeles.

Nightmares can shed light into the dark areas of people's lives, Orloff said. They confront people with what they are most afraid of, and can be used to work through underlying problems.

Orloff had one patient who repeatedly dreamed she was being chased on a cliff by an "evil pursuer" who was going to hurt her. The patient and psychologist figured out that the pursuer represented the woman's abusive father. After working through it, the nightmare did not repeat.

Letting your dreams help you

If you want further insight into a difficult decision, consider asking a question before you go to bed, and then seeing what happens in your dream, Orloff said. Get a dream journal and write down the question at night; in the morning, without getting out of bed, write down everything you remember.

One patient of Orloff's had to make a difficult decision about whether to take a new job, and dreamed that she was in the new position but had a negative experience. This helped her realize that she did not get along with the boss, and she decided against the job, Orloff said.

Dement said he is somewhat skeptical about putting a lot of weight in dream interpretation. Dreams are often hard to remember, the associations in them can mean multiple things, and you shouldn't stress if you can't recall details, he said. It can be quite difficult to summon a memorable dream to answer a question in the way that Orloff recommends, he said.

But Dement agreed that dreams can help with major life events. He himself once had a life-changing dream: He had been trying to quit smoking, but simply could not, and dreamed that he had coughed up pink sputum indicative of cancer.

"I felt just utter complete despair -- I would never see my children grow up, I did it to myself because I didn't quit, I hadn't put enough aside to take care of my family," he said. "Then I woke up. I never smoked another cigarette."

Important discoveries have also emerged as a consequence of dreams. Otto Loewi, a German pharmacologist, is said to have dreamed about an experiment to show that the transmission of nerve impulses is chemical, not electrical. The experiment worked in real life, and Loewi went on to the Nobel Prize in medicine in 1936.

Some artists and musicians use their dreams for inspiration. The writer Robert Louis Stevenson drew on his dreams for "The Strange Case of Dr. Jekyll and Mr. Hyde."

The bottom line: Trust your waking, logical thinking, but don't ignore what your intuitive, feeling-based, visual side might have to say about difficult decisions through dreams, Barrett said.

"It can be very important to look to our dreams on anything that we're kind of stuck on in our waking lives, because the dream thoughts are likely to be so different, and they may really think outside the box and come up with an answer that we haven't awake," Barrett said.

DMT is in your head, but it may be too weird for the psychedelic renaissance

By John Horgan

You know that psychedelics are making a comeback when the New York Times says so on page 1. In “Hallucinogens Have Doctors Tuning In,” John Tierney reports on how doctors at schools like Harvard, Johns Hopkins, UCLA and NYU are testing the potential of psilocybin and other hallucinogens for treating depression, obsessive-compulsive disorder, post-traumatic stress disorder, alcoholism—and for inducing spiritual experiences.

Tierney’s brisk overview neglects to mention the most mind-bending of all psychedelics: dimethyltryptamine, or DMT. It was first synthesized by a British chemist in the 1930s, and its psychotropic properties were discovered some 20 years later by the Hungarian-born chemist Stephen Szara, who later became a researcher for the National Institute on Drug Abuse.

Why is DMT so fascinating? For starters, DMT is the only psychedelic known to occur naturally in the human body. In 1972, the Nobel laureate Julius Axelrod of the National Institutes of Health discovered DMT in human brain tissue, leading to speculation that the compound plays a role in psychosis. Research into that possibility—and into psychedelics in general--was abandoned because of the growing backlash against these compounds.

In 1990, however, Rick Strassman, a psychiatrist at the University of New Mexico, obtained permission from federal authorities to inject DMT into human volunteers. Strassman, a Buddhist, suspected that endogenous DMT might contribute to mystical experiences. From 1990 to 1995, he supervised more than 400 DMT sessions involving 60 subjects at the University of New Mexico. Many subjects reported that they dissolved blissfully into a radiant light or sensed the presence of a powerful, god-like being.

On the other hand, 25 subjects underwent what Strassman called “adverse effects,” including terrifying hallucinations of “aliens” that took the shape of robots, insects, or reptiles. Some subjects remained convinced that these aliens were real in spite of Strassman’s efforts to convince them otherwise. In part out of concern about these adverse effects, Strassman discontinued his research, which he describes in his 2000 book DMT: The Spirit Molecule.

DMT is also the primary active ingredient of ayahuasca, a tea that Amazonian tribes brew from two plants and drink as a sacred medicine. After hearing about ayahuasca from the legendary Harvard botanist Richard Shultes, the beat writer William Burroughs traveled to South America and swilled the stuff in 1953. In a letter to the poet Allen Ginsberg, Burroughs said that during his first ayahuasca trip he thought he had been poisoned, and he felt himself turning into half-man-half-woman. Burroughs nonetheless drank the tea again and praised its ability to facilitate “space time travel.”

By the mid-20th century ayahuasca had also been adopted as a sacrament by several urban sects in Brazil. The largest of these is the Uniao Do Vegetal, which combines elements of Christianity with indigenous Indian beliefs. Researchers led by the UCLA psychiatrist Charles Grob (who is mentioned in Tierney’s story) have reported that Brazilian UDV members are on average healthier physiologically and psychologically than a control group. UDV members also claimed that ayahuasca had helped them overcome alcoholism, drug addiction and other self-destructive behaviors. A decade ago, a branch of the UDV based in New Mexico sued for the right to consume ayahuasca legally in the U.S. In 2006 the U.S. Supreme Court ruled in favor of the group.

In Antipodes of the Mind, the Israeli psychologist Benny Shanon, who has consumed ayahuasca more than 100 times, provides a gripping account of his own and others’ visions. Shanon says the tea transformed him from a “devout atheist” into a spiritual believer awestruck by the mysteries of nature and the human mind. Yet Shanon, like Strassman, acknowledges that these hallucinogenic experiences pose risks. Quoting one ayahuasca shaman, Shanon warns that ayahuasca can also be “the worst of liars,” leaving some users gripped by delusions.

I drank ayahuasca a decade ago while researching my book Rational Mysticism . It tastes like stale beer dregs flavored with cigarette butts. After I threw up, I had a cosmic panic attack, in which I was menaced by malevolent, dayglo-hued polyhedra. I have no desire to repeat this experience.

I applaud the psychedelic renaissance, with this caveat: Spiritual texts often emphasize the dangers of mystical experiences, whether generated by drugs, fasting, meditation or other means. That is the theme of an old Talmudic tale in which four rabbis are brought into the presence of God. One becomes a heretic, one goes crazy, one drops dead and one returns home with his faith affirmed.

Communication Breakdown in Brain Caused by a Gene Defect May Contribute to Schizophrenia

15 years after a gene defect was found to increase the risk of schizophrenia 30-fold, scientists have figured out how it might cause the brain disorder's debilitating symptoms

By Katie Moisse

More than 15 years after a genetic variant was shown to predispose its carriers to schizophrenia, scientists have finally uncovered how the chromosomal abnormality might cause symptoms of the brain disorder. By studying mice with a similar gene defect, the research team from Columbia University Medical Center linked abnormalities in behavior to a faulty connection between the hippocampus and the prefrontal cortex—two brain areas important for learning and memory.

"We know that this genetic deficit predisposes us to schizophrenia, and now we have identified a clear pathophysiological mechanism of how [it] confers this risk…," Maria Karayiorgou, co-author on the study published April 1 in Nature and lead author on the 1994 publication identifying the genetic variant in Brain Research, said in a prepared statement. (Scientific American is part of Nature Publishing Group.)

Thirty percent of people carrying the variant—a small deletion of genetic material on chromosome 22—will go on to develop the schizophrenia, making it "one of largest genetic risk factors" for the disease, according to senior author Joshua Gordon. The odds of someone in the general U.S. population developing the disorder are one in 100, but those odds jump to one in 10 for people with an affected first-degree relative, and one in three for people with a schizophrenic identical twin, highlighting the role of genes in the development of the disease.

People with schizophrenia suffer from a loss of contact with reality, confused thinking, delusions and hallucinations—usually hearing internal voices. Scientists think that no single gene defect causes the disease. Rather, they theorize that several genetic variations passed on haphazardly from one generation to the next are to blame, along with certain environmental factors—making it harder to understand how various neurological processes might be going wrong. But by spotting interrelated behavioral and physiological differences in their mouse model, the Columbia team has implicated communication between brain areas as one such process.

The researchers measured the neural activity between the hippocampus and the prefrontal cortex while normal mice and those with the genetic deletion performed a task—learning and remembering the whereabouts of a food reward on a T-shaped maze. "We found that successful completion of the task in our healthy mice required the two regions of the brain—the hippocampus and the prefrontal cortex—to work together," Gordon said in a prepared statement. "And in our mouse model, the information transfer was less efficient or was unable to take place at all." The experiment even revealed a dose effect—the mice who had the least communication between the hippocampus and the prefrontal cortex turned in the worst performances negotiating the maze.

The researchers are excited to have discovered a possible mechanism linking the genetic variant to the behavioral deficits in schizophrenia. "We now know that one of the consequences of that deletion is to disrupt functional communication between these two brain regions, and we have evidence from the study that the disruption actually has an impact on a cognitive behavior that is disrupted in patients," said Joseph Gogos, the study's other senior author, in a prepared statement. "It is possible that similar abnormalities in functional connectivity may also account for other symptoms of the disease and can be used to better assess treatment response, and, most importantly, to develop new medications."

In addition to its role in the heightened risk for schizophrenia, "the gene deletion also increases the risk for other cognitive and psychiatric disorders," said Dolores Malaspina, a psychiatrist at New York University Langone Medical Center who was not involved in the study. The study is "an important step in illuminating how the deletion may be related to a brain dysfunction that is present in some people with mental illness," she added. "This is important information whether or not any of [the genes involved] turn out to be common causes of schizophrenia in the population."