Adolescent brain sensitivity

A few studies indicate that an adolescent's brain may be especially sensitive to new memories, drug use, and social stress.

Adolescence, like infancy, has been said to include distinct sensitive periods during which brain plasticity is heightened; but in a review of the neuroscience literature published on September 23 in Trends in Cognitive Sciences, University College London (UCL) researchers saw little evidence for this claim. However, a small number of studies do support that memory formation, social stress, and drug use are processed differently in the adolescent brain compared to other periods of life.

"Conclusively proving that adolescent sensitive periods exist will require studies comparing children, adolescents, and adults and will need to take into account individual differences in adolescent development," says Delia Fuhrmann, a PhD student in UCL's Institute of Cognitive Neuroscience Developmental Group. "Adolescents are much more likely than children to choose their own environments and choose what they want to experience."

Humans retain some plasticity--changes in brain and behavior in response to environmental demands, experiences, and physiological changes--throughout life. However, during sensitive periods plasticity is heightened and the brain "expects" to be exposed to a particular stimulus. For example, the brains of infants are primed to process visual input and language.

The ability to form memories seems to be augmented during adolescence, one example for how it may be a sensitive period. Memory tests in different cultures show a "reminiscence bump"; at 35 or later, we are more likely to recall autobiographic memories from ages 10 to 30 years than memories prior or subsequent. The recall of music, books, films, and public events from adolescence is also superior compared with that from other periods.

Further, they point out that simple aspects of working memory or ongoing information processing may reach maturity in childhood, while more complex, self-organized working memory abilities continue to improve during early adolescence and recruit frontal brain regions that are still developing. "Working memory can be trained in adolescents, but we don't know how these training effects differ from other age groups," Fuhrmann says. "Such data would be useful for planning curricula because it would tell us what to teach when."

Many mental illnesses have their onset in adolescence and early adulthood, possibly triggered by stress exposure. The UCL team explored studies indicating that both social stress and social exclusion have a disproportionate impact during adolescence. They also argue that adolescence may be a vulnerable period for recovery from these negative experiences.

"Adolescents are slower to forget frightening or negative memories," says Fuhrmann. "This might mean that some treatments for anxiety disorders, which are based on controlled exposure to whatever a patient is afraid of, might be less effective in adolescents and alternative treatments might be needed."

Finally, studies showed that adolescence is also a time of heightened engagement in risky health behaviors, such experimenting with alcohol and other drugs. Young adolescents seem to be particularly susceptible to peer influence on risk perception and risk taking compared with other age groups. Research in rodents also supports that adolescent brains might have an increased sensitivity to marijuana.

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PTSD may be preventable by a drug

Researchers have found a drug that may be able to prevent PTSD.

Scientists at Yerkes National Primate Research Center, Emory University have identified a drug that appears to make memories of fearsome events less durable in mice.

The finding may accelerate the development of treatments for preventing PTSD (post-traumatic stress disorder). The drug, called osanetant, targets a distinct group of brain cells in a region of the brain that controls the formation and consolidation of fear memories.

The results were published in the journal Neuron.

"Potentially, drugs that act on this group of cells could be used to block fear memory consolidation shortly after exposure to a trauma, which would aid in preventing PTSD," says Kerry Ressler, MD, PhD, professor of psychiatry and behavioral sciences at Emory University School of Medicine and Yerkes National Primate Research Center. "PTSD is unique among psychiatric disorders in that we know when it starts -- at the time of the trauma. Finding ways to prevent its development in the first place -- in the emergency department or the battlefield -- is an important and exciting avenue of research in this area."

The first author of the paper is postdoctoral fellow Raül Andero Galí, PhD. Ressler and Andero were sifting through a list of many genes that are activated in the brains of mice after they learn to become afraid of a sound, because the sound is paired with a mild electric shock. The researchers were probing for changes in the central amygdala, a region of the brain known to regulate fear learning.

Out of thousands of genes they examined, their "top gene" was Tachykinin 2 or Tac2. The Tac2 gene was turned on more strongly during fear learning in mice that were previously exposed to a model of traumatic stress.

"The Tac2 gene is robustly activated after fear learning and belongs to a pathway that can be specifically blocked with a drug," Ressler says. "It was interesting that Tac2 is highly expressed in one particular part of the amygdala, but with low or no expression in other brain areas related to the formation of fear memories. Also, we found that the cells that express Tac2 are distinct from those other investigators had previously identified as being involved in fear expression."

Tac2 is part of a family of messengers in the nervous system known as tachykinins. Drugs that block a product encoded by Tac2's relative, Tac1, are antiemetics, often prescribed when someone is receiving chemotherapy for cancer.

Osanetant, which blocks the action of Tac2, has been tested in previous clinical studies for schizophrenia and was safe but not effective in addressing that disorder. It has not been tested in humans for PTSD prevention.

"Osanetant is a safe and well-tolerated drug in humans and could be potentially used to prevent PTSD when given shortly after trauma, although more research is needed," Andero says.

Under the influence of osanetant, mice could still learn to become afraid of a sound paired with a shock, but the mice did not freeze as much in response to the sound a day later, even if the drug was given an hour after training.

"Our goal is to specifically impair emotional memories related to a traumatic event instead of all memories associated with it. Thus, the trauma and its circumstances are remembered but the consolidation of fear memories is impaired, which could decrease the likelihood of developing fear-related disorders," Andero says.

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Drug improves common sleep disorder in the blind

A drug that is still being investigated improves a sleep disorder commonly seen in blind people.

An investigational new drug significantly improved a common and debilitating circadian rhythm sleep disorder that frequently affects people who are completely blind, a multicenter study finds.

The results were presented Monday at The Endocrine Society's Annual Meeting in San Francisco.

The new drug, called tasimelteon, selectively targets the master body clock in the brain, which controls the timing of the sleep-wake cycle, alertness patterns and the timing of some hormones, as well as many other aspects of physiology and metabolism. This study found that patients who received tasimelteon had a significantly higher rate of re-synchronization of the body clock as compared to patients who received a placebo. The re-synchronization, in turn, led to an increase in night-time sleep, a reduction in day-time sleep, and greater improvement in overall symptoms as rated by the patients' clinicians. During the course of the study, tasimelteon was safe and well-tolerated.

The timing of wakefulness and sleep is controlled by the circadian, or 24-hour, clock in the brain, which is synchronized, or 'entrained' to the 24-hour day by the light-dark cycle. In addition to promoting wakefulness during daylight hours and sleep during the night-time, the circadian clock helps regulate mood, hormonal rhythms and metabolism.

Among people who are completely blind, however, entrainment of the clock is disrupted due to the total lack of light reaching the brain through the eyes. In the absence of light information, the internal clock reverts to its own non-24-hour rhythm, causing a mismatch between rhythms controlled by the clock, such as the sleep-wake cycle, and the 24-hour social world. On average, the internal clock time is approximately 24.5 hours among totally blind people, and while going to sleep half an hour later each day may not sound significant, it does not take long to become completely misaligned from the 24-hour day. In some cases, this disruption is diagnosed as Non-24 Hour Sleep-Wake Disorder, or N24HSWD. Although changes in sleep are most often recognized and addressed by patients, many aspects of well-being are affected because the circadian clock helps regulate so many systems. In addition to interfering with night-time sleep patterns, misalignment of the circadian clock causes daytime drowsiness, which can make it difficult to function socially and professionally.

"Tasimelteon addresses the root cause of this disorder by resetting the circadian clock in the brain," said the study's lead author Steven W. Lockley, Ph.D., a neuroscientist at Brigham and Women's Hospital and associate professor at Harvard Medical School in Boston, MA. "The medication is able to replace the time cue usually provided by light and synchronize the circadian clock in totally blind people. None of the traditional medications used to treat sleep disorders or sleepiness have this ability and therefore tasimelteon has the potential to be the first circadian regulator approved by the Food and Drug Administration for the treatment of Non-24 Hour Sleep-Wake Disorder in the blind."

Study participants included 84 patients from 34 medical centers in the United States and Germany. They were between the ages of 18 and 75 years, and 40 percent were female. All participants exhibited disordered sleeping patterns related to total blindness.

Investigators randomly assigned participants to receive either the study drug or a placebo at the same time each day, one hour before their normal bedtime, for the duration of the 26-week study. The study was double-masked, which means that neither investigators nor participants knew which group was receiving tasimelteon.

The effect of the drug on the timing of body clock was assessed from the rhythms of melatonin and cortisol measured in urine samples, in addition to obtaining information about sleep patterns and feelings of well-being.

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Drug targets both autism and fetal alcohol disorder

A new drug targets autism and fetal alcohol disorder showing the disorders may be treated by similar mechanisms.

In a surprising new finding, a Northwestern Medicine® study has found a common molecular vulnerability in autism and fetal alcohol spectrum disorder. Both disorders have symptoms of social impairment and originate during brain development in utero.

This the first research to explore a common mechanism for these disorders and link their molecular vulnerabilities.

The study found male offspring of rat mothers who were given alcohol during pregnancy have social impairment and altered levels of autism-related genes found in humans. Female offspring were not affected.

Alcohol Damage is Reversible

But the alcohol damage can be reversed. A low dose of the thyroid hormone thyroxin given to alcohol consuming rat mothers at critical times during their pregnancy alleviated social impairments and reversed the expression of autism-related genes in their male offspring, the study reports.

Could Novel Drug Treat Both Disorders?

"The beneficial effects of thyroxin in this animal model raises an exciting question -- whether novel drug targets and treatments could be developed for both these disorders," said Eva Redei, the senior author of the study and professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine.

The study will be published June 13, 2013 in the journal Alcoholism: Clinical & Experimental Research.
Redei stressed caution in interpreting these results for their relevance to treatments in human fetal alcohol spectrum disorder and autism spectrum disorder.

"Human studies are needed to establish that the parallel we saw in the animal model exists in these diseases," Redei said. The study does not mean alcohol consumed by the mother is the cause of autism, she emphasized.

"The novel finding here is that these two disorders share molecular vulnerabilities and if we understand those we are closer to finding treatments," said Redei, also the David Lawrence Stein Professor of Psychiatric Diseases Affecting Children and Adolescents.

Redei decided to investigate a possible link between the two disorders when she observed similarities between the two. Both are neurodevelopmental, have symptoms of social impairment and affect males more or differently than females. Autism affects males versus females in a nine to one ratio; social impairment in this model of alcohol spectrum disorder is male specific.

In a previous study, Redei and colleagues administered a much larger dose of thyroid hormone to alcohol consuming rat mothers during their pregnancy and found that the male offsprings' learning and memory deficit was reversed by this treatment.

In the current study, Redei wanted to find the smallest dose of thyroid hormone that effectively reverses the behavioral consequences of fetal alcohol spectrum disorder.

"We wanted to find the smallest dose to correct the behavioral abnormalities that wouldn't create an overly high level of thyroid hormones during development, which can be detrimental," Redei said.

Thyroid Hormone Prevents Deficit in Genes and Social Behavior

In the study, Northwestern scientists administered alcohol to pregnant female rats. Then they examined the levels of ten genes known to be vulnerability genes in human autism in the brains of the male offspring. They found the levels of those same genes were affected.

To test the offspring's behavior, the rats were put in a cage with a small, non-threatening rat pup. A normal social interaction is for the rat to spend a lot of time sniffing and engaging the pup. These rats, however, hardly sniffed the pups compared to the control rats, indicating their impaired social behavior.

In a second experiment, low doses of thyroxin were administered to alcohol consuming pregnant rats. When their male offspring subsequently were put in a cage with a rat pup, the offspring exhibited normal sniffing behavior and their brains showed normal levels of the autism-related genes.

"The thyroxin reversed the deficit both in the level of their genes and their social behavior," Redei said.
Elif Tunc-Ozcan, the lead study author and a graduate student in Redei's lab, is researching how prenatal thyroid hormone supplementation reverses the behavioral deficits in the fetal alcohol spectrum disorder model.

"If our study proves to be relevant to human fetal alcohol spectrum disorder and, perhaps, even for autism spectrum disorder, it could help those suffering from these disorders," Tunc-Ozcan said.

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The harm of using ADHD medication to study

This article discusses the negative effects of students using ADHD medication for the purpose of studying.

Adderall and other ADHD medications are among the most prescribed drugs in America.

Quite a few of those pills don't end up being used to treat ADHD, though. They're used as "smart drugs" or "study drugs" by students who find the pills give them a mental edge.

The American Academy of Neurology now says: Stop that.

The brain docs are directing that advice first and foremost to their fellow physicians, the ones who have been writing all those scrips for people who don't have ADHD, or who perhaps don't think about all the pills their patients sell on the student black market.

"We don't believe that doctors are supposed to be drug dispensers for healthy people," says William Graf, a professor of pediatrics and neurology at the Yale School of Medicine. "This is an ethics issue."

But the message is also being sent to teenagers and their parents, some of whom who might think that giving their child a little leg up for a big test isn't such a bad thing. The buzz term for that? "Pediatric neuroenhancement."

Prescribing ADHD drugs to children who don't have the disorder is "not justifiable," according to the American Academy of Neurology's new position paper. That's because children's brains are still developing, the paper says, and they don't have the ability to weigh the risks and benefits of medication.

Prescribing study drugs is "inadvisable" in teenagers, the Academy said, a word chosen to reflect both teenagers' growing autonomy, and the fact that the Academy can't tell doctors what drugs they can and can't prescribe.

The number of children diagnosed with ADHD rose 24 percent from 2001 to 2011, according to a study published earlier this year. Over the same time, the number of prescriptions for Adderall and other ADHD drugs has soared exponentially.

More pills in circulation means more pills that can be bought, borrowed, or snitched. Various surveys report that 8 to 35 percent of college students say they have used stimulant pills to improve school performance.

The neurologists are not saying that stimulant drugs shouldn't be used to treat ADHD, which is characterized by problems with attention and hyperactivity. "We're not touching that here," Graf told Shots.

What they are saying is that doctors have a moral obligation to protect the best interests of the child — who doesn't yet have legal control over health care decisions — and to prevent the misuse of medication.

Amphetamines like Adderall and Vyvanse can be addictive, which is why they're classified as Schedule II controlled substances, along with Oxycontin and morphine. Side effects can be as simple as insomnia, or as serious as sudden high blood pressure, irregular heartbeat, and seizures.

Other popular ADHD drugs like Concerta and Ritalin are methlphenidates, and are considered less risky. But they can cause a wide range of side effects including insomnia, aggression, mood and behavior changes, twitching, and shaking.

About 15 percent of 12^th graders say they misuse prescription drugs, according to the 2012 Monitoring the Future survey, and about 6 percent say they've misused Ritalin or Adderall. Adderall is the only drug class that showed increased use in 2012, the federal survey reported.

"As a society we have a pill for everything," Graf says. "It's one thing if you're taking something from the Vitamin Shoppe. It's another thing if you're talking about amphetamines."

Doctors should talk with patients and parents about why they feel the need for academic performance enhancing drugs, Graf says. Then they should point out that there are other ways to deal with competition and anxiety.

"We have to get back to the basics," Graf says. "Sleep, exercise, and social interaction."

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