Scientists have discovered a compound that restores the capacity to form new memories in aging rats, likely by improving the survival of newborn neurons in the brain’s memory hub. The research, funded in part by the National Institutes of Health, has turned up clues to a neuroprotective mechanism that could lead to a treatment for Alzheimer’s disease.

“This neuroprotective compound, called P7C3, holds special promise because of its medication-friendly properties,” explained Steven McKnight, Ph.D., who co-led the research with Andrew Pieper, M.D., Ph.D., both of University of Texas Southwestern Medical Center, Dallas. “It can be taken orally, crosses the blood-brain barrier with long-lasting effects, and is safely tolerated by mice during many stages of development.”

The researchers report on their findings July 9, 2010 in the journal Cell. Their work was funded, in part, by the NIH’s National Institute of Mental Health (NIMH), a NIH Director’s Pioneer Award funded through the Common Fund and managed by the National Institute of General Medical Sciences, and National Cancer Institute.

“This striking demonstration of a treatment that stems age-related cognitive decline in living animals points the way to potential development of the first cures that will address the core illness process in Alzheimer’s disease,” said NIMH Director Thomas Insel, M.D.

Physical activity, social, or other enriching experiences promote neurogenesis — the birth and maturation of new neurons. This growth takes place in the dentate gyrus, a key area of the brain’s memory hub, the hippocampus. But even in the normal adult brain, most of these newborn neurons die during the month it takes to develop and get wired into brain circuitry. To survive, the cells must run a gauntlet of challenges. Newborn hippocampus neurons fare much worse in aging-related disorders like Alzheimer’s, marked by runaway cell death.

In hopes of finding compounds that might protect such vulnerable neurons during this process, Pieper, McKnight and colleagues tested more than 1000 small molecules in living mice. One of the compounds, designated P7C3, corrected deficits in the brains of adult mice engineered to lack a gene required for the survival of newborn neurons in the hippocampus. Giving P7C3 to the mice reduced programmed death of newborn cells — normalizing stunted growth of branch-like neuronal extensions and thickening an abnormally thin layer of cells by 40 percent. Among clues to the mechanism by which P7C3 works, the researchers discovered that it protects the integrity of machinery for maintaining a cell’s energy level.

To find out if P7C3 could similarly stem aging-associated neuronal death and cognitive decline, the researchers gave the compound to aged rats. Rodents treated with P7C3 for two months significantly outperformed their placebo-treated peers on a water maze task, a standard assay of hippocampus-dependent learning. This was traced to a threefold higher-than-normal level of newborn neurons in the dentate gyrus of the treated animals. Rats were used instead of mice for this phase of the study because the genetically engineered mice could not swim.

The researchers pinpointed a derivative of P7C3, called A20, which is even more protective than the parent compound. They also produced evidence suggesting that two other neuroprotective compounds eyed as possible Alzheimer’s cures may work through the same mechanism as P7C3. The A20 derivative proved 300 times more potent than one of these compounds currently in clinical trials for Alzheimer’s disease. This suggested that even more potent neuroprotective agents could potentially be discovered using the same methods. Following up on these leads, the researchers are now searching for the molecular target of P7C3 – key to discovering the underlying neuroprotective mechanism.

The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

The NIH Common Fund encourages collaboration and supports a series of exceptionally high impact, trans-NIH programs. These new programs are funded through the Common Fund, and managed by the NIH Office of the Director in partnership with the various NIH Institutes, Centers and Offices. Common Fund programs are designed to pursue major opportunities and gaps in biomedical research that no single NIH Institute could tackle alone, but that the agency as a whole can address to make the biggest impact possible on the progress of medical research. Additional information about the NIH Common Fund can be found at http://commonfund.nih.gov.

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The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

Scientists have discovered a mechanism that helps to explain resilience to stress, vulnerability to depression and how antidepressants work. The new findings, in the reward circuit of mouse and human brains, have spurred a high tech dragnet for compounds that boost the action of a key gene regulator there, called deltaFosB.

A molecular main power switch – called a transcription factor – inside neurons, deltaFosB turns multiple genes on and off, triggering the production of proteins that perform a cell’s activities.

“We found that triggering deltaFosB in the reward circuit’s hub is both necessary and sufficient for resilience; it protects mice from developing a depression-like syndrome following chronic social stress,” explained Eric Nestler, M.D., of the Mount Sinai School of Medicine, who led the research team, which was funded by the National Institute of Health’s National Institute of Mental Health (NIMH).

“Antidepressants can reverse this social withdrawal syndrome by boosting deltaFosB. Moreover, deltaFosB is conspicuously depleted in brains of people who suffered from depression. Thus, induction of this protein is a positive adaptation that helps us cope with stress, so we’re hoping to find ways to tweak it pharmacologically,” added Nestler, who also directs the ongoing compound screening project.

Nestler and colleagues report the findings that inspired the hunt online May 16 2010 in the journal Nature Neuroscience.

“This search for small molecules that augment the actions of deltaFosB holds promise for development of a new class of resilience-boosting treatments for depression,” said NIMH director Thomas R. Insel. “The project, funded under the American Recovery and Reinvestment Act of 2009, is a stunning example of how leads from rodent experiments can be quickly followed up and translated into potential clinical applications.”

DeltaFosB is more active in the reward hub, called the nucleus accumbens (see diagram below), than in any other part of the brain. Chronic use of drugs of abuse – or even natural rewards like excess food, sex or exercise – can gradually induce increasing levels of this transcription factor in the reward hub. Nestler and colleagues have shown that this increase in deltaFosB can eventually lead to lasting changes in cells that increase rewarding responses to such stimuli, hijacking an individual’s reward circuitry – addiction.

The new study in mice and human post-mortem brains confirms that the same reward circuitry is similarly corrupted (though to a lesser degree than with drugs of abuse) in depression via effects of stress on deltaFosB.

Depressed patients often lack motivation and the ability to experience reward or pleasure — and depression and addiction often go together. Indeed, mice susceptible to the depression-like syndrome show enhanced responses to drugs of abuse, the researchers have found.

But the similarity ends there. For, while an uptick in deltaFosB promotes addiction, the researchers have determined that it also protects against depression-inducing stress. It turns out that stress triggers the transcription factor in a different mix of nucleus accumbens cell types — working through different receptor types — than do drugs and natural rewards, likely accounting for the opposite effects.

The researchers explored the workings of deltaFosB in a mouse model of depression. Much as depressed patients characteristically withdraw from social contact, mice exposed to aggression by a different dominant mouse daily for 10 days often become socially defeated; they vigorously avoid other mice, even weeks later.

Among key findings in the brain’s reward hub:

• The amount of deltaFosB induced by the stress determined susceptibility or resilience to developing the depression-like behaviors. It counteracted the strong tendency to learn an association, or generalize the aversive experience to all mice.
• Induction of deltaFosB was required for the antidepressant fluoxetine (Prozac) to reverse the stress-induced depression-like syndrome.
• Prolonged isolation from environmental stimuli reduced levels of deltaFosB, increasing vulnerability to depression-like behaviors.
• Among numerous target genes regulated by deltaFosB, a gene that makes a protein called the AMPA receptor is critical for resilience — or protecting mice from the depression-like syndrome. The AMPA receptor is a protein on neurons that boosts the cell’s activity when it binds to the chemical messenger glutamate.
• Increased activity of neurons triggered by heightened sensitivity of AMPA receptors to glutamate increased susceptibility to stress-induced depression-like behavior.
• Induction of deltaFosB calmed the neurons and protected against depression by suppressing AMPA receptors’ sensitivity to glutamate.
• Post-mortem brain tissue of depressed patients contained only about half as much deltaFosB as that of controls, suggesting that poor response to antidepressant treatment may be traceable, in part, to weak induction of the transcription factor.

Reduced deltaFosB in the reward hub likely helps to account for the impaired motivation and reward behavior seen in depression, said Nestler. Boosting it appears to enable an individual to pursue goal-directed behavior despite stress.

The high-tech screening for molecules that boost DeltaFosB, supported by the Recovery Act grant, could lead to development of medications that would help people cope with chronic stress. The molecules could also potentially be used as telltale tracers in brain imaging to chart depressed patients’ treatment progress by reflecting changes in deltaFosB, said Nestler.

LOS ANGELES (EGMN) – Nearly half of preschool children meet age-adjusted criteria for posttraumatic stress disorder after experiencing a significant traumatic event, and some children are symptomatic even after relatively minor medical procedures, according to a researcher from Tulane University in New Orleans.

“Children under 6 years of age are particularly vulnerable to stressful experiences because of the rapid neural development they are undergoing,” said Dr. Stacy S. Drury at the International Conference on Pediatric Psychological Trauma sponsored by the University of Southern California, Los Angeles, and the University of California, Irvine.

In a study of 284 children aged 3-5 years who had been exposed to a traumatic event, 44% met full revised criteria for PTSD with discernable impairing symptoms, said Dr. Drury, who holds faculty positions in the departments of psychiatry, pediatrics, and neurology.

No statistically significant differences were seen in rates of PTSD based on the type of trauma children experienced: a single-incident trauma (a motor vehicle accident, burn, or fall) (38%), observed domestic violence (42%), or Hurricane Katrina (48%).

Children were diagnosed using the structured Preschool Age Psychiatric Assessment (PAPA), a validated instrument administered to caregivers.

The study utilized the Preschool PTSD Criteria, which is less reliant on verbalization and abstract thought than DSM-IV PTSD criteria for adults (J. Am. Acad. Child Adolesc. Psychiatry 2003;42:561-70).

Specifically, the criteria developed at Tulane by Dr. Michael S. Scheeringa and associates eliminate developmentally inappropriate items (such as an individual’s sense of a foreshortened future) and instead include such relevant indicators as the loss of previously acquired developmental skills such as language or toilet training.

A new diagnostic cluster appears in preschool criteria for PTSD, requiring at least one of the following behaviors frequently reported in traumatized children: new separation anxiety, new onset of aggression, or new fears without obvious links to the trauma, such as fear of the dark.

A second study assessed PTSD in 69 preschool children seen at a hospital-based primary care clinic more than 12 months after events that ranged from medical encounters that involved no procedures, procedures such as receiving stitches or getting a shot, nonmedical traumas such as motor vehicle accidents, and high-risk events such as abuse or neglect.

Although specific statistics were not released, Dr. Drury showed that even “small things,” like stitches, had a lasting effect on some children.

“Fifteen months after the event, these symptoms were recognizable to parents … and persistent,” she said.

Dr. Drury reviewed burgeoning neurobiological literature demonstrating that early stress results in changes within biocircuitry of the developing brain, altering the central nervous system, cortisol levels, and neurotransmitters.

“Altered neural circuits lead to lasting vulnerability,” she emphasized, adding that much more research needs to be done to pinpoint the timing of trauma and its ramifications on early brain development and behavior.

“Trauma at 1 year is very different than trauma at 3 or at 6 years old, in part because of what areas of the brain are developing most rapidly,” she said.

She and colleagues are developing cognitive behavioral therapies that can be delivered early to parents and children following symptoms of PTSD, or even as a preventive measure for children newly diagnosed with cancer or another serious illness.

Working to reduce “learned helplessness” on the part of the child begins by teaching parents how to reduce overcontrol in the parent-child relationship, leading children to a new sense of efficacy and mastery.

Meanwhile, children learn relaxation techniques, including controlled breathing and muscle contraction and release, an exercise one child enthusiastically dubbed, “old man wiggles.”

Traditional cognitive-behavioral therapy components such as systematic densensitization are adapted for preschoolers, and have been shown to be highly effective in reducing symptoms during 6-12 brief, manualized sessions, she said.

Dr. Drury reported no relevant financial disclosures.

The results are part of the National Health and Nutrition Examination Survey (NHANES), a collaboration between NIMH and the National Center for Health Statistics of the Centers for Disease Control and Prevention. The survey conducted from 2001 to 2004 had 3,042 participants. These most recent results include data from children and adolescents ages 8 to 15, and were published online ahead of print December 14, 2009, in the journal Pediatrics.

“Data on the prevalence of mental disorders among U.S. youth have been varied, making it difficult to truly understand how many children and teens are affected,” said NIMH Director Thomas R. Insel, M.D. “These data from the NHANES survey can serve as an important baseline as we follow trends of mental disorders in children.”

In the study, the young people were interviewed directly. Parents or caregivers also provided information about their children’s mental health. The researchers tracked six mental disorders—generalized anxiety disorder (GAD), panic disorder, eating disorders (anorexia and bulimia), depression, attention deficit hyperactivity disorder (ADHD) and conduct disorder. The participants were also asked about what treatment, if any, they were receiving.

Overall, 13 percent of respondents met criteria for having at least one of the six mental disorders within the last year. About 1.8 percent of the respondents had more than one disorder, usually a combination of ADHD and conduct disorder. Among the specific disorders,

• 8.6 percent had ADHD, with males more likely than females to have the disorder;
• 3.7 percent had depression, with females more likely than males to have the disorder;
• 2.1 percent had conduct disorder;
• 0.7 percent had an anxiety disorder (GAD or panic disorder);
• 0.1 percent had an eating disorder (anorexia or bulimia).

“With the exception of ADHD, the prevalence rates reported here are generally lower than those reported in other published findings of mental disorders in children, but they are comparable to other studies that employed similar methods and criteria,” said lead author Kathleen Merikangas, Ph.D., of NIMH.

Those of a lower socioeconomic status were more likely to report any disorder, particularly ADHD, while those of a higher socioeconomic status were more likely to report having an anxiety disorder. Mexican-Americans had significantly higher rates of mood disorders than whites or African-Americans, but overall, few ethnic differences in rates of disorders emerged.

Merikangas and colleagues also found that overall, 55 percent of those with a disorder had consulted with a mental health professional, confirming the trend of an increase in service use for childhood mental disorders, especially ADHD. However, only 32 percent of youth with an anxiety disorder sought treatment, a finding consistent with other studies. Moreover, African-Americans and Mexican-Americans were significantly less likely to seek treatment than whites, reiterating the need to identify and remove barriers to treatment for minority youth, noted the researchers.

“Until now, there has been a dearth of reliable data on the magnitude, course and treatment patterns of mental disorders among U.S. youth,” said Dr. Merikangas. “When combined with data from other nationally representative surveys, the data will provide a valuable basis for making decisions about health care for American youth,” she concluded.

The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

Building on previous investigation of transplants in the nervous system, this critical study confirms that cell transplants can help the brain to heal itself. Ultimately, it may lead to new therapies to help dementia patients. More generally, scientists can now develop and test new ways to help repair an injured nervous system — whether through new drugs, genetically modified cells, transplanted neural (nerve) and non-neural brain cells, or other means.

The discovery was announced in the December issue of Behavioral Neuroscience, published by the American Psychological Association. The findings, according to the authors, confirm the potential of cell grafts to stimulate the release of growth factors for neurons, regenerate or reorganize a part of the brain, and restore cognitive function, in a process called neural plasticity.

This study focused on the hippocampus, considered to be the seat of learning and memory, whose shrinkage in Alzheimer’s disease causes steadily worsening symptoms. The study’s authors targeted a key player in the hippocampal “learning system,” which includes the hippocampus itself, the subiculum (the major output structure connected to the cortex, the self-aware “thinking” part of the brain), and the adjacent entorhinal cortex.

Previously, these scientists had demonstrated that damage to the subiculum in rats led to deterioration of the hippocampus, and problems with learning. The next question was obvious: Could researchers do the opposite, repair the hippocampus and restore the memory functions?

They sought the answer at India’s National Institute for Mental Health and Neuro Sciences and National Centre for Biological Sciences (Tata Institute for Fundamental Research), both in Bangalore. First, the scientists injected a neuron-destroying chemical into the subiculum area of 48 adult rats.

Next, again using precise micro-injections, the scientists transplanted hippocampal cells that had been taken from newborn transgenic mice and cultured in an incubator into the hippocampi of about half the rats. These special cells had a green fluorescent protein used to “label” and track them after transplantation. (Transgenic mice are bred with a little extra DNA that allows their cells to be grown in glass plates in incubators.)

Two months later, the scientists measured how well both the transplant and non-transplant rats learned and remembered, using two well-established maze tests of spatial learning. The rats given cell transplants had recovered completely: On both mazes, they performed as well as those rats which had not had their subiculums damaged. The rats without transplants did not recover: They had many problems learning their way through the mazes.

After studying behavior, the scientists examined what happened in the brain. Under the microscope, it appeared that the transplanted cells had settled mainly in a sub-area of the hippocampus called the dentate gyrus. There, the transplants appeared to promote the secretion of two types of growth factors, namely brain-derived neurotrophic factor and fibroblast growth factor, which boost the growth and survival of the cells that give rise to neurons. In the hippocampi of rats with cell transplants, the expression of brain-derived growth factor went up threefold.

It is significant that transplants can provide more neural growth factors in the hippocampus, because the formation of new neurons there may be critical for cognitive function.

Neural growth factors, also called neurotrophic factors, hold great promise for treating neurological problems. These specialized chemicals “provide an ideal micro-environment for making new neurons,” said co-author Bindu Kutty, PhD. “They also protect existing brain cells, especially following an injury or other neurological insult.”

Further study is needed, especially to understand the underlying repair mechanism and the apparent starring role of growth factor in brain health. Although the current study shows in the lab that brain-cell transplants can restore function, “more studies along these lines using appropriate animal models are required to find definitive answers about the safety and efficacy of such approaches,” said Kutty. “We are still some way from achieving a new therapy based on these findings.”

Article: “Transplantation of Hippocampal Cell Lines Improves Spatial Learning in Rats with Ventral Subicular Lesions,” J. Rekha, PhD, National Institute of Mental Health and Neuro Sciences (NIMHANS), Deemed University, India; Sridhara Chakravarthy, PhD, National Centre for Biological Sciences, Tata Institute for Fundamental Research (NCBS, TIFR), India; L. R. Veena, master’s student in biotechnology, NIMHANS; People’s Education Society Institute of Technology, India; Vani P. Kalai, master’s student in biotechnology, NIMHANS; Rupam Choudhury, Junior Research Fellow, NCBS, TIFR; Harsha N. Halahalli, PhD student, Phalguni Anand Alladi, PhD, Anandh Dhanushkodi, PhD, and M. Nirmala, PhD student, NIMHANS; Geetha M. Swamilingiah; PhD, NCBS, TIFR; Maulishree Agrahari, PhD, People’s Education Society Institute of Technology, India; T. R. Raju, PhD, NIMHANS; M. M. Panicker, PhD, NCBS, TIFR; Bindu M. Kitty, PhD, NIMHANS; Behavioral Neuroscience, Vol. 123, No. 6.

(Full text of the article is available from the APA Public Affairs Office)

Bindu Kutty can be reached by e-mail or at the following numbers: 091-80-2656 5075 or 091-80-2656 0431 (residence), 091-94-4978 9375 (mobile), or 091-80-2699 5170 (office).

The American Psychological Association, in Washington, D.C., is the largest scientific and professional organization representing psychology in the United States and is the world’s largest association of psychologists. APA’s membership includes more than 150,000 researchers, educators, clinicians, consultants and students. Through its divisions in 54 subfields of psychology and affiliations with 60 state, territorial and Canadian provincial associations, APA works to advance psychology as a science, as a profession and as a means of promoting health, education and human welfare.

Scientists have for the first time selectively blocked a conditioned fear memory in humans with a behavioral manipulation. Participants remained free of the fear memory for at least a year. The research builds on emerging evidence from animal studies that reactivating an emotional memory opens a 6-hour window of opportunity in which a training procedure can alter it.

“Our results suggest a non-pharmacological, naturalistic approach to more effectively manage emotional memories,” said Elizabeth Phelps, Ph.D., of New York University, a grantee of the National Institutes of Health’s National Institute of Mental Health (NIMH).

Phelps and NIMH grantee and NYU colleague Joseph LeDoux, Ph.D., led the research team that reports on their discovery online Dec. 9, 2009 in the journal Nature.

“Inspired by basic science studies in rodents, these new findings in humans hold promise for being translated into improved therapies for the treatment of anxiety disorders, such as post-traumatic stress disorder (PTSD),” said NIMH Director Thomas R. Insel, M.D.

The results add support to the hypothesis that emotional memories are reconsolidated – rendered vulnerable to being modified – each time they are retrieved. That is, reactivating a memory opens what researchers call “reconsolidation window,” a time-limited period when it can be changed.

“This adaptive update mechanism appears to have evolved to allow new information available at the time of retrieval to be incorporated into the brain’s original representation of the memory,” explained Phelps.

Earlier this year, LeDoux and colleagues exploited this potentially clinically important insight to erase a fear memory in rats. They first conditioned rats to fear a tone by pairing it with intermittent shocks. A day later, the rats were re-exposed to the tone, reactivating the fear memory. They then underwent a process to rewrite the fear, called extinction training, in which the tone was repeatedly presented without shocks.

However, the timing of this extinction training proved critical. Fear of the stimulus was erased only in rats trained within a 6-hour reconsolidation window after re-exposure to the feared tone. Fear responses returned in animals trained after the window closed, when the memory had apparently already solidified.

Normally, extinction training suppresses but does not erase the original fear memory. By first reactivating it – sounding the tone – just prior to extinction training, LeDoux and colleagues permanently erased the fear memory. In the new study, Phelps and colleagues similarly conditioned human participants to fear colored squares by intermittently pairing them with mild wrist shocks.

As with the rats, a day later, the memory was first reactivated by re-exposing participants to the feared squares. A measure of nervous system arousal confirmed that they experienced a fear response. Extinction training – repeated trials of exposure to the colored squares without shocks – followed.

Again as in the rats, a day later, the fear response was banished only in human participants who underwent the extinction training soon after the fear reactivation. Those trained after the 6-hour consolidation window remained afraid of the squares – as did a control group that received extinction training without first experiencing reactivation of the fear memory.

In a follow-up experiment to gauge long-term effects a year later, 19 of the original participants received a potent regimen to re-instate the fear: four shocks followed by presentations of the colored squares.

Remarkably, those who had undergone extinction training within the reconsolidation window were largely spared significant effects. By contrast, those whose training had been delayed 6 hours or who hadn’t experienced fear memory reactivation prior to extinction training experienced significant reinstatement of the fear response.

In a similar experiment, the researchers also confirmed that the fear memory was blocked only for the specific colored square for which fear memory was reactivated prior to extinction training. The effect did not generalize to a differently colored square associated with the shocks. This indicated that memory re-writing during reconsolidation is highly specific and that prior reactivation with the specific stimuli is critical.

“Timing may have a more important role in the control of fear than previously appreciated,” Phelps suggested. “Our memory reflects our last retrieval of it rather than an exact account of the original event.”

Evidence suggests that the behavioral manipulation may work through the same molecular mechanisms as experimental medications under study for quelling traumatic emotional memories.

“Using a more natural intervention that captures the adaptive purpose of reconsolidation allows a safe and easily implemented way to prevent the return of fear,” suggest the investigators.

References

Preventing the return of fear in humans using reconsolidation update mechanisms. Schiller D, Monfils MH, Raio CM, Johnson DC, LeDoux JE, Phelps EA. Nature. 2009 December 9.

Extinction-reconsolidation boundaries: key to persistent attenuation of fear memories. Monfils MH, Cowansage KK, Klann E, LeDoux JE. Science. 2009 May 15;324(5929):951-5. Epub 2009 Apr 2.PMID: 19342552

“We have known that behavioral training can enhance brain function.” said NIMH Director Thomas R. Insel, M.D. “The exciting breakthrough here is detecting changes in brain connectivity with behavioral treatment. This finding with reading deficits suggests an exciting new approach to be tested in the treatment of mental disorders, which increasingly appear to be due to problems in specific brain circuits.”

For the study, Timothy Keller, Ph.D., and Marcel Just, Ph.D., both of Carnegie Mellon University, randomly assigned 35 poor readers ages 8-12, to an intensive, remedial reading program, and 12 to a control group that received normal classroom instruction. For comparison, the researchers also included 25 children of similar age who were rated as average or above-average readers by their teachers. The average readers also received only normal classroom instruction.

Four remedial reading programs were offered, but few differences in reading improvements were seen among them. As such, results for participants in these programs were evaluated as a group. All of the programs were given over a six month schooling period, for five days a week in 50-minute sessions (100 hours total), with three students per teacher. The focus of these programs was improving readers’ ability to decode unfamiliar words.

Using a technology called diffusion tensor imaging (DTI), the researchers were able to measure structural properties of the children’s white matter, the insulation-clad fibers that provide efficient communication in the central nervous system. Specifically, DTI shows the movement of water molecules through white matter, reflecting the quality of white matter connections. The better the connection, the more the water molecules move in the same direction, providing a higher “bandwidth” for information transfer between brain regions.

At the outset of the study, poor readers showed lower quality white matter than average readers in a brain region called the anterior left centrum semiovale. Six months later, at the completion of the intensive training, the poor readers showed significant increases in the quality of this region. Children who did not receive the training did not show this increase, suggesting that the changes seen in the remedial training group were not due to natural maturation of the brain.

In an effort to further pinpoint the mechanism underlying this change, the researchers deduced that a process called myelination may be key. Myelin is akin to electrical insulation, allowing for more rapid and efficient communication between nerve cells in the brain. However, the directional association between brain changes and reading improvements remains unclear—whether intensive training brings about increased myelination that results in improved word decoding skills, or whether improved word decoding skills leads to changes in reading habits that result in greater myelination.

“Our findings support not only the positive effects of remediation and rehabilitation for reading disabilities, but may also lead to improved treatments for a range of developmental conditions related to brain connectivity, such as autism,” noted Just.

Source: Timothy Keller, Ph.D.; Marcel Just, Ph.D.

Left brain image shows the area of lower quality white matter (blue area) among poor readers relative to good readers at the beginning of the study.

Center brain image shows the area where the white matter quality increased (red/yellow area) among poor readers who received the remedial reading instruction.

Right brain image shows that following the instruction, there were no differences between the poor and average readers with respect to the quality of their white matter.

Reference

Keller TA, Just MA. Altering cortical connectivity: Remediation-induced changes in the white matter of poor readers. Neuron.

Approximately seven in ten Americans report that money is a significant source of stress (71 percent), according to APA’s 2009 Stress in America survey, with similarly high percentages reporting stress resulting from work (69 percent) and the economy (63 percent). More than half of adults (55 percent) also cited family responsibilities as a significant source of stress in their lives.

“According to our survey three quarters of adults in this country already report moderate to high levels of stress,” says psychologist Katherine Nordal, PhD, APA’s executive director for professional practice. “The holiday season can bring with it additional emotional and financial stressors that can negatively impact both physical and mental health.”

Psychologists urge parents to pay particular attention to the stress their children may experience during the holidays. APA’s Stress in America survey found that children are nearly two times more likely to worry about financial concerns than their parents realize. Specifically, 30 percent of youth say they worry about their family having enough money, while only 18 percent of parents report that this is a source of stress for their child.

“While the holidays are stressful for many people, there are some things we can all do to manage that stress and enjoy the season,” says Dr. Nordal. “Given the concerns our young people are reporting about stress and money, parents need to be good models for managing stress in healthy ways.”

APA suggests the following strategies to manage holiday stress and enjoy the season:

1. Take time for yourself. Taking care of yourself helps you to take better care of others in your life. Go for a long walk or take time out to read or listen to your favorite music. By slowing down you will actually have more energy to accomplish your goals.
2. Volunteer. Many charitable organizations face new challenges as a result of the ongoing economic downturn. Find a local charity, such as a soup kitchen or a shelter, where you and your family can volunteer together. Helping others who are less fortunate can put hardships in perspective and can build stronger family relationships.
3. Set realistic expectations. No holiday celebration is perfect; view inevitable missteps as opportunities to demonstrate flexibility and resilience. Create a realistic budget and remind your children that the holidays aren’t about expensive gifts.
4. Remember what’s important. Commercialism can overshadow the true sentiment of the holiday season. When your holiday expense list is running longer than your monthly budget, scale back. Remind yourself that family, friends and the relationships in our lives are what matter most.
5. Seek support. Talk about stress related to the holidays with your friends and family. Getting things out in the open can help you navigate your feelings and work toward a solution. If you continue to feel overwhelmed, consider talking with a professional such as a psychologist to help you develop coping strategies and better manage your stress. A psychologist has the skills and professional training to help people learn to manage stress and cope more effectively with life problems, using techniques based on best available research and their clinical skills and experience, and taking into account an individual’s unique values, goals and circumstances. Psychologists have doctoral degrees and are licensed by the state in which they practice. They receive one of the highest levels of education of all health care professionals, spending an average of seven years in education and training after they receive their undergraduate degrees.

Stress in America is part of APA’s Mind/Body Health public education campaign. For additional information on stress and lifestyle and behavior, visit www.apahelpcenter.org, read the campaign blog www.yourmindyourbody.org, and follow @apahelpcenter on Twitter.

Psychologists are available immediately for interviews related to holiday stress prevention and management. To request an interview, contact Angel Brownawell or Luana Bossolo at Luana Bossolo.

Methodology

The 2009 Stress in America Survey was conducted online within the United States by Harris Interactive on behalf of the American Psychological Association, between July 21, 2009 and August 4, 2009 among 1,568 adults aged 18+ who reside in the U.S. This report also includes the results of a YouthQuery survey conducted between August 19 and 27, 2009 among 1,206 young people aged 8-17 years old. Results were weighted as needed for age, sex, race/ethnicity, education, region, and household income. Propensity score weighting was also used to adjust for respondents’ propensity to be online. No estimates of theoretical sampling error can be calculated; a full methodology is available.

The American Psychological Association, in Washington, D.C., is the largest scientific and professional organization representing psychology in the United States and is the world’s largest association of psychologists. APA’s membership includes more than 150,000 researchers, educators, clinicians, consultants, and students. Through its divisions in 54 subfields of psychology and affiliations with 60 state, territorial and Canadian provincial associations, APA works to advance psychology as a science, as a profession, and as a means of promoting health, education, and human welfare.

Harris Interactive is a global leader in custom market research. With a long and rich history in multimodal research that is powered by our science and technology, Harris Interactive assists clients in achieving business results. Harris Interactive serves clients globally through its North American, European, and Asian offices and a network of independent market research firms. For more information, please visit www.harrisinteractive.com.

The finding strengthens evidence that early brain dysfunction increases the risk for criminal offending, since learning to associate a cue with a frightening outcome, known as fear conditioning, relies on the amygdala and prefrontal cortex.

Nearly 1,800 children were studied over 20 years by Yu Gao, Ph.D., and colleagues in the United States and the United Kingdom. When subjects were 3 years of age, fear conditioning was assessed by measuring electrical activity of the skin after presentation of two types of long auditory tones. One tone was usually followed by a short, loud, unpleasant sound, conditioning the child’s reaction to this tone due to anticipation of the unpleasant noise. The other tone served as a control tone, which was deeper in pitch and had no unpleasant association. Skin conductance measures the nervous system’s control over sweat secretion that is part of the body’s fear response.

Normal fear conditioning would result in greater skin responses to the conditioned tone than to the control tone. According to the authors, poor fear conditioning is hypothesized to predispose to crime because “individuals who lack fear are less likely to avoid situations, contexts, and events that are associated with future punishment—resulting in a lack of conscience.”

By age 23, 137 subjects had convictions for serious crimes. These individuals showed a lack of fear conditioning at age 3 whereas noncriminal subjects with similar characteristics, including social adversity, exhibited normal fear conditioning.

The report will appear online on November 16 at AJP in Advance, the online advance edition of The American Journal of Psychiatry (AJP), the official journal of the American Psychiatric Association. Data collection was supported by the Medical Research Council (U.K.), Wellcome Trust (U.K.), and National Institute of Mental Health.

The American Journal of Psychiatry is the oldest continuously published medical specialty journal in the United States and was recently named one of the “Most Influential Journals in Biology & Medicine of the Last 100 Years.” Statements in this press release or the articles in the Journal are not official policy statements of the American Psychiatric Association.

The American Psychiatric Association is a national medical specialty society whose more than 38,000 physician members specialize in diagnosis, treatment, prevention and research of mental illnesses including substance use disorders. Visit the APA at www.psych.org and www.HealthyMinds.org.

Stress, Compassion Fatigue in VA and U.S. Army Hospitals

Contacts: Steve Vetzner, (703) 797-2588 or svetzner@mentalhealthamerica.net

Jared Klose, (302) 434-8707 or jklose@stargroup1.com

ALEXANDRIA, Va. (November 10, 2009)-Mental Health America today announced it is partnering with Prescription Audio, a Philadelphia-area based firm (Voorhees, N.J.), to make the company’s scientifically based sound therapy available without charge as a download to veterans, active duty servicemen and women, their family members and health care providers.

“We applaud Prescription Audio for making this therapy available for free and are proud to partner with them,” said David Shern, Ph.D., president and CEO of Mental Health America. “It is a valuable stress management and anxiety reduction tool that can immediately help our active duty troops, veterans, their families and caregivers.”

Similar Prescription Audio sound therapy is currently being prescribed within the Department of Veterans Affairs and US Army hospitals to aid in the treatment of Post-Traumatic Stress Disorder (PTSD), insomnia, high stress and compassion fatigue.

In honor of Veterans Day, and in light of recent events including the Fort Hood shootings, 250,000 copies of the download are being made available at no charge to any veteran, active duty servicemen and women, their families, as well as compassion fatigued healthcare providers suffering from mental health symptoms related to the treatment of PTSD and other related conditions. The value of the products and services being donated is approximately 5 million dollars.

“In these trying times, we felt like we had to do something to support our warriors, veterans, their families and the mental health professionals that serve them,” said Jill Slane, CEO of Prescription Audio. Individuals can learn more about sound therapy, discover how it can start helping them and access the download by going to Mental Health America’s Operation Healthy Reunion’s site at http://www.mentalhealthamerica.net/reunions/resources.cfm or by clicking here.

Prescription Audio was developed by Jill and Rod Slane, a husband-wife team, in 2005. Rod Slane has used his more than 40 years experience as a composer and innovative sound engineer to create the Life Program, followed by Natural Wellness Therapy in 2006.

One of the company’s early aims was to help ease the anguish of veterans suffering from PTSD.  By using proprietary sound technology, Prescription Audio’s array of MP3 and CD programs provide natural mental and general health solutions that diminish anxiety and its many detrimental manifestations, while enabling anyone to quickly and easily achieve a meditative state of mind.

Prescription Audio provides products and services through its Life Program^TM to the U.S. military’s Institute of Surgical Research Stress Management Program for Healthcare Providers, a strong testament to the power and effectiveness of their approach. In this application, vibrational sound therapy is utilized to help reduce the high rate of turnover in trauma healthcare workers within military hospitals by teaching stress management tactics, leading to improved mental health and increased resiliency.

About Mental Health America

Mental Health America is the country’s leading nonprofit dedicated to helping all people live mentally healthier lives. With our century of service to America and our more than 300 affiliates nationwide, we represent a national movement that promotes mental wellness for the health and well-being of the nation – everyday and in times of crisis.

About Prescription Audio

Prescription Audio is the developer of Sound Solutions for a Healthier Life. By using proprietary sound technology, Prescription Audio provides natural mental and physical health solutions that diminish stress and its many detrimental manifestations, while enabling anyone to quickly and easily achieve a meditative state of mind.  The company offers a wide variety of portable MP3 and CD programs that promote healthy living through natural wellness.  Prescription Audio’s natural wellness solutions utilize audio vibrations embedded within a proprietary multi-layered sound technology to assist with positive metamorphosis in total mind-body well-being.  Please visit www.PrescriptionAudio.com to learn more.