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Mental Health News

Following are the latest news and information resources for the various mental health topics that we cover. We hope you will find the news educational and the links in the resources section useful in helping you to get even more in-depth data.

Add Nature, Art And Religion To Life’s Best Anti-Inflammatories

Taking in such spine-tingling wonders as the Grand Canyon, Sistine Chapel ceiling or Schubert’s “Ave Maria” may give a boost to the body’s defense system, according to new research from UC Berkeley.

Researchers have linked positive emotions – especially the awe we feel when touched by the beauty of nature, art and spirituality – with lower levels of pro-inflammatory cytokines, which are proteins that signal the immune system to work harder.

“Our findings demonstrate that positive emotions are associated with the markers of good health,” said Jennifer Stellar, a postdoctoral researcher at the University of Toronto and lead author of the study, which she conducted while at UC Berkeley.

While cytokines are necessary for herding cells to the body’s battlegrounds to fight infection, disease and trauma, sustained high levels of cytokines are associated with poorer health and such disorders as type-2 diabetes, heart disease, arthritis and even Alzheimer’s disease and clinical depression.

It has long been established that a healthy diet and lots of sleep and exercise bolster the body’s defenses against physical and mental illnesses. But the Berkeley study, whose findings were just published in the journal Emotion, is one of the first to look at the role of positive emotions in that arsenal.

“That awe, wonder and beauty promote healthier levels of cytokines suggests that the things we do to experience these emotions – a walk in nature, losing oneself in music, beholding art – has a direct influence upon health and life expectancy,” said UC Berkeley psychologist Dacher Keltner, a co-author of the study.

In two separate experiments, more than 200 young adults reported on a given day the extent to which they had experienced such positive emotions as amusement, awe, compassion, contentment, joy, love and pride. Samples of gum and cheek tissue, known as oral mucosal transudate, taken that same day showed that those who experienced more of these positive emotions, especially awe, wonder and amazement, had the lowest levels of the cytokine, Interleukin 6, a marker of inflammation.

In addition to autoimmune diseases, elevated cytokines have been tied to depression. One recent study found that depressed patients had higher levels of the pro-inflammatory cytokine known as TNF-alpha than their non-depressed counterparts. It is believed that by signaling the brain to produce inflammatory molecules, cytokines can block key hormones and neurotransmitters – such as serotonin and dopamine – that control moods, appetite, sleep and memory.

In answer to why awe would be a potent predictor of reduced pro-inflammatory cytokines, this latest study posits that “awe is associated with curiosity and a desire to explore, suggesting antithetical behavioral responses to those found during inflammation, where individuals typically withdraw from others in their environment,” Stellar said.

As for which came first – the low cytokines or the positive feelings – Stellar said she can’t say for sure: “It is possible that having lower cytokines makes people feel more positive emotions, or that the relationship is bidirectional,” Stellar said.

In addition to Stellar and Keltner, other co-authors and researchers on the study are Neha John-Henderson at the University of Pittsburgh and Craig Anderson, Amie Gordon and Galen McNeil at UC Berkeley.

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Preschool Anxiety Changes The Brain

Anxiety disorders observed in preschoolers — including social phobia, separation anxiety and generalized anxiety disorder — can lead to physiological changes in brain development, a new study from the Yale Child Study Center shows.

The researchers imaged the brains of children with and without preschool anxiety disorders. They found that in those who had an anxiety disorder, the prefrontal cortex and the amygdala, two regions whose “cross-talk” is important in modulating anxiety, effectively talked less to each other in a phenomenon known as weaker functional connectivity. They also found that different anxiety disorders led to different connectivity patterns.

In other words, not only are anxiety disorders strongly based in biology, but they also result in physically different brains.

“Now that [we] know what a mechanistic brain characteristic of anxiety looks like in preschoolers, we have a much more reliable and quantitative [understanding of anxiety rather] than a broad diagnosis,” said Kevin Pelphrey, senior author and the co-director of the center for translational developmental neuroscience.

Helen Egger, senior author and professor of psychiatry and behavioral sciences at Duke University Medical Center, said she believes that preschool anxiety disorders are too often misperceived as transient, insignificant childhood problems. This study, she said, disproves that notion and shows that preschool anxiety disorders can leave “enduring differences in brain function.”

Preschoolers between the ages of two and five were tested using the Preschool Age Psychiatric Assessment, developed by Egger. The assessment comprises interviews with children’s parents about their children’s behavior and feelings. When those children reached the ages of five to nine, the researchers then administered fMRI scans to observe any changes in the brain.

The changes varied depending on the type of anxiety disorder, giving biological credence to Egger’s hypothesis that the different anxiety disorders are fundamentally distinct.

“It’s very interesting,” said Gabriela Rosenblau, a postdoctoral associate at the Child Study Center, noting that these anxiety disorders are typically differentiated by associated symptoms and behaviors. These findings, though, show that the disorders are also differentiated by biology, and there may be potential neural markers to distinguish them.

Whether these physical brain changes can be fixed is not known yet. Neuroscientists are still grappling with the magnitude of neuroplasticity, or to what extent grown brains can change. But Pelphrey believes there is a good chance.

“Five years ago, you would have had scientists saying, ‘[Changing brain connectivity is] not possible in adults … You’re not going to change their underlying brain biology,’” Pelphrey said. “But I think neuroscientists are more and more surprised as to just how plastic the brain is all the way through adulthood.”

According to Michael Crowley, co-director of the Center for Translational Developmental Neuroscience, the study was the first to administer fMRIs to children at such an early age. He said he thinks that looking at the biological underpinnings of anxiety can help us refine treatments and understand how to make them more “potent.”

Egger added that early treatment will be key in reducing suffering caused by preschool anxiety disorders. She also noted that treatment has to be disorder-specific — not all anxiety disorders can be clumped together.

The researchers said their next step is to test the effectiveness of various interventions by administering fMRIs to participants and observing changes in brain connectivity.

Approximately 5 to 6 percent of preschoolers suffer from an anxiety disorder. Anxiety disorders are caused by the “interplay” of genetics, biology and environmental factors.

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Common Allergy, Depression Meds May Increase Odds Of Dementia

Long-term and/or high-dose use of a class of medications used for hay fever, depression and other ills has been linked in a new study to a higher risk of dementia.

The drugs -- called anticholinergics -- include nonprescription diphenhydramine (Benadryl) and tricyclic antidepressants like doxepin (Sinequan). This class of medications also includes older antihistamines like chlorpheniramine (Chlor-Trimeton) and "antimuscarinic" drugs for bladder control, such as oxybutynin (Ditropan).

However, the study could only point to an association between long-term or high-dose use of these drugs and a higher risk of dementia, it could not prove cause-and-effect.

Also, the relationship "did not occur at the lowest dosage range but did occur at higher dosages used long-term," said one expert, Dr. Alan Manevitz, a clinical psychiatrist at Lenox Hill Hospital in New York City. He was not involved in the new study.

Manevitz also stressed that consumers "should not abruptly stop any current medication treatment but rather should first consult with their physician."

The new study was led by Shelly Gray of the Group Health Research Institute-University of Washington. Her team explained that the anticholinergic class of medications work by blocking a neurochemical called acetylcholine, in both the brain and body.

Manevitz noted that people "suffering from Alzheimer's disease typically show a marked shortage of acetylcholine."

The new study tracked outcomes for more than 3,500 seniors who were followed for more than seven years. Gray's group found that people who took at least 10 milligrams per day of Sinequan, 4 mg per day of Benadryl, or 5 mg per day of Ditropan for more than three years were at greater risk for developing dementia.

Manevitz noted that occasional use of these medications did not seem to be tied to a rise in dementia risk. "The risk of dementia was due to a cumulative total of exposure, not to an acute short course of treatment," he said.

And, Gray said in an institute news release, "Older adults should be aware that many medications -- including some available without a prescription, such as over-the-counter sleep aids -- have strong anticholinergic effects. And they should tell their health care providers about all their over-the-counter [drug] use," she added.

However, "no one should stop taking any therapy without consulting their health care provider," said Gray, director of the geriatric pharmacy program at the University of Washington's School of Pharmacy.

Instead, "health care providers should regularly review their older patients' drug regimens -- including over-the-counter medications -- to look for chances to use fewer anticholinergic medications at lower doses," she advised.

The study, published Jan. 26 in JAMA Internal Medicine, is the first to link higher use of anticholinergic medications to increased risk of dementia, the researchers said. It is also the first to suggest that the dementia risk associated with these drugs may not be reversible even years after people stop taking them.

Manevitz called the new study "well designed," and said the reversibility issue is a troubling one.

"The general view has been that mild cognitive impairment is reversible in discontinuation of anticholinergic medication therapy," he said, but this study seems to find otherwise.

According to Manevitz, "we need to educate patients and their families about over-the-counter medicines and alternative therapies. Also, elderly people in nursing homes tend to have a long list of medicines that need to be reviewed periodically for need to continue, interactions and redundancy."

He believes doctors should think about substitutes for anticholinergics when possible, prescribe the lowest dose possible, and stop the medication as soon as is medically advisable.

Gray offered similar advice. "If providers need to prescribe a medication with anticholinergic effects because it is the best therapy for their patient, they should use the lowest effective dose, monitor the therapy regularly to ensure it's working, and stop the therapy if it's ineffective," she suggested.

She said that substitutes are available for some anticholinergic drugs, including a selective serotonin re-uptake inhibitor (SSRI) antidepressant like citalopram (Celexa) or fluoxitene (Prozac) for depression, or a second-generation antihistamine such as loratadine (Claritin) for allergy relief.

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Regular Walking Can Help Ease Depression

Moderate-intensity exercise, or even just walking, can improve quality of life for depressed middle-aged women, a large Australian study suggests.

Women who averaged 150 minutes of moderate exercise (golf, tennis, aerobics classes, swimming, or line-dancing) or 200 minutes of walking every week had more energy, socialized more, felt better emotionally, and weren't as limited by their depression when researchers followed up after three years.

They also had less pain and did better physically, although the psychological benefit was greater.

With depression so prevalent, "there is an urgent need" to identify treatments, including non-medical options that people can do themselves, said Kristiann Heesch, who led the study.

Heesch, senior lecturer at Queensland University of Technology, and her colleagues point out in a January 13 online article in the American Journal of Preventive Medicine that depression is expected to be the second-leading cause of global disease by 2030 and the leading cause in high-income countries.

One in 10 U.S. adults suffers from depression, according to the Centers for Disease Control and Prevention. Women are 70% more likely to be depressed at some point in their lives than men, according to the National Institute of Mental Health.

In previous research, Heesch found that exercise and walking could boost physical and emotional health in women who are not depressed.

In fact, Heesch said in an email, physical activity may have an even greater effect on psychological health-related quality of life in women in their 50s and 60s who are depressed.

Her team analyzed data on 1,904 women born in 1946-1951 who answered questions about their exercise habits, physical health, and mental health in 2001, 2004, 2007, and 2010. In 2001, all of them had reported at least 10 depressive symptoms, indicating mild to moderate depression.

But over time, their physical health, mental health, pain, physical functioning, vitality, and social functioning all improved when they did 150 minutes of moderate-intensity physical activity or 200 minutes of walking in an average week.

More exercise was linked to greater improvements, but even low amounts of exercise had benefits.

"The good news is that while the most benefits require 150 minutes per week of moderate-intensity physical activity or 200 minutes of walking, even smaller amounts . . . can improve well-being," Heesch said.

Dr. Madhukar Trivedi, who holds the Betty Jo Hay Distinguished Chair in Mental Health at the University of Texas Southwestern Medical Center in Dallas, said the study had some major strengths, including its large number of women, their physical and psychological improvements over time, and the estimate of how much exercise was needed to improve quality of life.

Trivedi, who was not involved in the study, also noted that it focused on women at "the very age where risks (for depression) are high."

"It does improve quality of life. That is not a new finding, but there remains skepticism in the culture that walking really does anything for depression or vitality - and this shows that it does," said Trivedi.

He noted that the benefits in the study were much stronger in the immediate future than in the long run, and that being consistently and vigorously active proved most beneficial.

These days, "more and more of these larger prospective studies are beginning to show that people with depression benefit from this," he said.

But, Trivedi noted, more research should be done on how much exercise is needed to lift depression. He said research could become more objective by using new technology, such as iPhones, to monitor physical activity instead of relying on self-reports.

"My speculation is that those women who did not see the benefit probably stopped or reduced their activity . . . it may be those are the women who need a more vigorous exercise to benefit," Trivedi said.

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A Simple Intervention Can Make Your Brain More Receptive To Health Advice

A new discovery shows how a simple intervention—self-affirmation – can open our brains to accept advice that is hard to hear.  

“Self-affirmation involves reflecting on core values,” explained Emily Falk, the study’s lead author and director of the Communication Neuroscience Laboratory at University of Pennsylvania’s Annenberg School for Communication. Has your doctor ever told you to get more exercise?  Has your spouse ever suggested you eat healthier? Even though the advice comes from good intentions, most people feel defensive when confronted with suggestions that point out their weaknesses. Reflecting on values that bring us meaning can help people see otherwise threatening messages as valuable and self-relevant. “Our work shows that when people are affirmed, their brains process subsequent messages differently.”

Along with colleagues at Annenberg, The University of Michigan and The University of California Los Angeles, Falk and her team used functional magnetic resonance imaging (fMRI) to examine a part of the brain involved in processing self-relevance called ventromedial prefrontal cortex (VMPFC).  The team examined activity in this region as sedentary adults were given the type of advice they might get from a doctor (e.g. – “People who sit less are at lower risk for certain diseases.”).  Participants who were guided through a self-affirmation exercise before getting the health advice showed higher levels of activity in this key brain region during the health advice, and then went on to show a steeper decline in couch-potato-type sedentary behaviors in the month following the intervention.  Those who were instructed to think about values that weren’t as important to them showed lower levels of activity in the key brain region during exposure to the health advice and maintained their original levels of sedentary behavior.  The results are reported in the Early Edition of the Proceedings of the National Academy of Science the week of February 2.   

Past studies have shown that brain activity in VMPFC during health messages can predict behavior change better than individuals’ own intentions, and this study sheds new light on why.  VMPFC is the brain region most commonly activated when participants think about themselves and when they ascribe value to ideas. The new results show that opening the brain in this way is a key pathway to behavior change.  “Understanding the brain opens the door to new health interventions that target this same pathway,” Falk noted.

“We were particularly interested in using self-affirmation to help people become more active because sedentary behavior is one of the biggest health threats faced by both Americans and people around the world,” said Falk.  Overly sedentary lifestyles are becoming a big problem; in some regions nearly 85 percent of an adult population leads an inactive lifestyle. This can cause multiple health problems, including poor heart health, diabetes, and cancer, just to name three. Increasing activity even small amount can have an important impact on both mental and physical health. 

The team studied 67 sedentary adults from a range of backgrounds.  Participants wore devices on their wrists to objectively measure their activity levels for a week before and a month after the intervention.  Participants were also sent text messages reinforcing the main messages delivered in the fMRI scanner.  Volunteers were shown health messages like “According to the American Heart Association, people at your level of physical inactivity are at much higher risk for developing heart disease,” or “After an hour of sitting, try standing for five minutes. Stand up while you read, watch TV, talk on the phone, fold laundry, or write an email.”  For some participants, these health messages were packaged with a self-affirmation message like “think of a time when you will help a friend or family member reach an accomplishment.”   When health messages were paired with self-affirmation, volunteers demonstrated more activity in VMPFC activity during the health message and also went on to follow the advice more.

Psychologists have used self-affirmation as a technique to improve outcomes ranging from health behaviors in high risk patients to increasing academic performance in at risk youth, suggesting that the findings may be applicable across a wide range of interventions.  “Our findings highlight that something as simple as reflecting on core values can fundamentally change the way our brains respond to the kinds of messages we encounter every day,” Falk noted.  “Over time, that makes the potential impact huge.”

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Common Pesticide May Increase Risk Of ADHD

A commonly used pesticide may alter the development of the brain’s dopamine system -- responsible for emotional expression and cognitive function – and increase the risk of attention deficit hyperactivity disorder in children, according to a new Rutgers study.

The research published Wednesday in the Journal of the Federation of American Societies for Experimental Biology (FASEB), by Rutgers scientists and colleagues from Emory University, the University of Rochester Medical Center, and Wake Forest University discovered that mice exposed to the pyrethroid pesticide deltamethrin in utero and during breastfeeding exhibited several features of ADHD, including dysfunctional dopamine signaling in the brain, hyperactivity, working memory, attention deficits and impulsive-like behavior.

These findings provide strong evidence, using data from animal models and humans, that exposure to pyrethroid pesticides, including deltamethrin, may be a risk factor for ADHD, says lead author Jason Richardson, associate professor in the Department and Environmental and Occupational Medicine at Rutgers Robert Wood Johnson Medical School and a member of the Environmental and Occupational Health Sciences Institute (EOHSI).

“Although we can’t change genetic susceptibility to ADHD, there may be modifiable environmental factors, including exposures to pesticides that we should be examining in more detail,” says Richardson.

Attention deficit hyperactivity disorder most often affects children, with an estimated 11 percent of children between the ages of 4-17– about 6.4 million – diagnosed as of 2011. Boys are three to four times more likely to be diagnosed than girls. While early symptoms, including an inability to sit still, pay attention and follow directions, begin between the ages of 3 to 6, diagnosis is usually made after the child starts attending school full time.

Importantly, in this study, the male mice were affected more than the female mice, similar to what is observed in children with ADHD. The ADHD-like behaviors persisted in the mice through adulthood, even though the pesticide, considered to be less toxic and used on golf courses, in the home, and on gardens, lawns and vegetable crops, was no longer detected in their system.

There is strong scientific evidence that genetics plays a role in susceptibility to the disorder, but no specific gene has been found that causes ADHD and scientists believe that environmental factors may also contribute to the development of the behavioral condition.

Using data from the Centers for Disease Control, National Health and Nutrition Examination Survey (NHANES) the study analyzed health care questionnaires and urine samples of 2,123 children and adolescents.

Researchers asked parents whether a physician had ever diagnosed their child with ADHD and cross-referenced each child’s prescription drug history to determine if any of the most common ADHD medications had been prescribed. Children with higher pyrethroid pesticide metabolite levels in their urine were more than twice as likely to be diagnosed with ADHD.

Young children and pregnant women may be more susceptible to pesticide exposure because their bodies do not metabolize the chemicals as quickly. This is why, Richardson says, human studies need to be conducted to determine how exposure affects the developing fetus and young children.

 “We need to make sure these pesticides are being used correctly and not unduly expose those who may be at a higher risk,” Richardson says.

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Feelings Of Loneliness And Depression Linked To Binge-Watching Television

It seems harmless: getting settled in for a night of marathon session for a favorite TV show, like House of Cards. But why do we binge-watch TV, and can it really be harmless? A recent study by researchers at the University of Texas at Austin found that the more lonely and depressed you are, the more likely you are to binge-watch.

Yoon Hi Sung, Eun Yeon Kang and Wei-Na Lee from the University of Texas at Austin will present their findings at the 65th Annual Conference of the International Communication Association in San Juan, Puerto Rico. The researchers conducted a survey on 316 18- to 29-year-olds on how often they watched TV; how often they had feelings of loneliness, depression and self-regulation deficiency; and finally on how often they binge-watched TV. They found that the more lonely and depressed the study participants were, the more likely they were to binge-watch TV, using this activity to move away from negative feelings.

The findings also showed that those who lacked the ability to control themselves were more likely to binge-watch. These viewers were unable to stop clicking "Next" even when they were aware that they had other tasks to complete.

Little empirical research has been done on binge-watching since it is such a new behavior. Psychological factors such as loneliness, depression, and self-regulation deficiency have been known as important indicators of binge behavior in general. For example, people engage in addictive behaviors to temporarily forget the reality that involves loneliness and depression. Also, an individual's lack of self-regulation is likely to influence the level of his or her addictive behavior. Therefore, this study tried to understand binge-watching behavior from this set of known factors.

"Even though some people argue that binge-watching is a harmless addiction, findings from our study suggest that binge-watching should no longer be viewed this way," Sung said. "Physical fatigue and problems such as obesity and other health problems are related to binge-watching and they are a cause for concern. When binge-watching becomes rampant, viewers may start to neglect their work and their relationships with others. Even though people know they should not, they have difficulty resisting the desire to watch episodes continuously. Our research is a step toward exploring binge-watching as an important media and social phenomenon."

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Diet And Nutrition Essential For Mental Health

Evidence is rapidly growing showing vital relationships between both diet quality and potential nutritional deficiencies and mental health, a new international collaboration led by the University of Melbourne and Deakin University has revealed.

Published in The Lancet Psychiatry today, leading academics state that as with a range of medical conditions, psychiatry and public health should now recognise and embrace diet and nutrition as key determinants of mental health.

Lead author, Dr Jerome Sarris from the University of Melbourne and a member of the International Society for Nutritional Psychiatry Research (ISNPR), said psychiatry is at a critical stage, with the current medically-focused model having achieved only modest benefits in addressing the global burden of poor mental health.

“While the determinants of mental health are complex, the emerging and compelling evidence for nutrition as a key factor in the high prevalence and incidence of mental disorders suggests that nutrition is as important to psychiatry as it is to cardiology, endocrinology and gastroenterology,” Dr Sarris said.

“In the last few years, significant links have been established between nutritional quality and mental health. Scientifically rigorous studies have made important contributions to our understanding of the role of nutrition in mental health,” he said.

Findings of the review revealed that in addition to dietary improvement, evidence now supports the contention that nutrient-based prescription has the potential to assist in the management of mental disorders at the individual and population level.

Studies show that many of these nutrients have a clear link to brain health, including omega-3s, B vitamins (particularly folate and B12), choline, iron, zinc, magnesium, S-adenosyl methionine (SAMe), vitamin D, and amino acids.

“While we advocate for these to be consumed in the diet where possible, additional select prescription of these as nutraceuticals (nutrient supplements) may also be justified,” Dr Sarris said.

Associate Professor Felice Jacka, a Principal Research Fellow from Deakin University and president of the ISNPR noted that many studies have shown associations between healthy dietary patterns and a reduced prevalence of and risk for depression and suicide across cultures and age groups.

“Maternal and early-life nutrition is also emerging as a factor in mental health outcomes in children, while severe deficiencies in some essential nutrients during critical developmental periods have long been implicated in the development of both depressive and psychotic disorders,” she said.

A systematic review published in late 2014 has also confirmed a relationship between ‘unhealthy’ dietary patterns and poorer mental health in children and adolescents. Given the early age of onset for depression and anxiety, these data point to dietary improvement as a way of preventing the initial incidence of common mental disorders.

Dr Sarris, an executive member of the ISNPR, believes that it is time to advocate for a more integrative approach to psychiatry, with diet and nutrition as key elements.

“It is time for clinicians to consider diet and additional nutrients as part of the treating package to manage the enormous burden of mental ill health,” he said.

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Alzheimer’s: Treating Anxiety Slows Decline

Alzheimer ’s disease (AD) has a long preclinical phase in which pathology develops years or decades before clinical symptoms. In study in JAMA Psychiatry, Robert Pietrzak, PhD, MPH and colleagues report that depression, anxiety and cognitive decline are associated with presence of Amyloidβ but that patients will benefit if their depression and anxiety are treated.

“Given that there is currently no standard anti-amyloid therapy and that anxiety symptoms are amenable to treatment, these findings may help inform risk stratification and management of the preclinical phase of AD,” the team wrote.

In the multicenter study a cohort of 333 healthy adult patients were recruited and 25% were assessed with brain scans to detect Amyloidβ. The subjects were age 60 and up. About half had memory complaints. They also got neuropsychological evaluations. One goal was to see if the presence of Amyloidβ was related to the onset and intensity of depression and anxiety. The hope was that if that turned out to be the case, ameliorating those mental health conditions with lessen cognitive decline.

In tracking the patients, the team found that even when patients had Amyloidβ those with low anxiety developed less cognitive decline than did a group with Amyloidβ and high anxiety.

“Elevated anxiety symptoms may exacerbate Amyloidβ related cognitive impairment by increasing endogenous levels of glucocorticoids, which consequently damages brain regions such as the hippocampus, and result in more pronounced decline in memory and related cognitive functions over time,” they wrote. They also cited animal studies on Amyloidβ toxicity that linked the protein to changes in the hypothalamic-pituitary-adrenal axis regulation and to increases in glucocorticoids.

Anxiety can negatively affect encoding and retention of verbal information, as well as other cognitive processes like executive function, they wrote.

Even subthreshold anxiety may exacerbate Amyloidβ-related cognitive decline, they said.

Among the study’s limitations, they noted, is the possibility that other biological factors such as neuronal loss, gliosis, and hyperphosphory-related tau protein aggregates are to blame for cognitive decline in preclinical AD.

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First-Ever View Of Protein Structure May Lead To Better Anxiety Drugs

When new medicines are invented, the drug may hit the intended target and nullify the symptoms, but nailing a bull's eye - one that produces zero side effects - can be quite elusive.

New research conducted at Michigan State University and published in the current issue of Science has, for the first time, revealed the crystal structure of a key protein, TSPO, which is associated with several forms of anxiety disorders. By identifying the structure at the atomic level, scientists can now pinpoint where drugs may interact with the protein.

“Many other scientists have studied this protein, but what exactly it is doing has been very difficult to determine,” said Shelagh Ferguson-Miller, University Distinguished Professor of biochemistry and molecular biology. “Drugs and other compounds bind to TSPO, but without knowing the structure, their effects are hard to interpret. Now that we’ve obtained the structure, it could provide important clues regarding anxiety disorders and the basis for a new generation of anti-anxiety drugs.”

These next-generation treatments could be years away, she added. This is partly due to TSPO being shunned from the spotlight. Even though it was discovered in 1977 during studies of the anxiety-controlling characteristics of Valium, it was deemed as a peripheral binding site, one not pursued by pharmaceutical companies as a key target for new drugs.

Interestingly enough, TSPO is found at high levels in regions of tissue damage. This finding was used to aid in imaging areas of inflammation in the brain. In these PET scans, doctors can view damaged regions because TSPO is concentrated and highlighted there.

Using X-ray technology rather than PET scans, Ferguson-Miller and her team were able to solve the crystal structure of the protein ­– creating an image of TSPO at a molecular level. This gave the researchers an increased understanding on how TSPO interacts with cholesterol and how this relationship affects the creation of steroid hormones.

Cholesterol plays a key role in the creation of steroid hormones. Without cholesterol, steroids hormones couldn’t be made. It appears that TSPO plays a key role in shuttling cholesterol into mitochondria, the cells’ powerhouse where the cholesterol is converted to hormones that are essential for our bodily functions.

The team also identified a TSPO mutant, which provided an important breakthrough. People suffering from conditions such as bipolar disease are found to have a higher probability of having this TSPO mutation, which is fairly prevalent. Cholesterol seemed to bind less strongly, perhaps related to the fact that the mutant structure is more ridged, limiting cholesterol interaction.

“When we compared the two forms of TSPO, normal and mutated, we were able to see substantial differences in structure,” Ferguson-Miller said. “This could be a clue as to why the human mutant form has an association with anxiety disorders.”

This insight into a previously unseen structure, one that could lead to new understanding of human disease, provides a strong argument for conducting basic science research.

The TSPO proteins used in this work came from bacteria rather than human cells, but they are closely related. Getting enough of the pure human protein to carry out these types of investigations is difficult, though a future objective of these scientists.

“One reason that TSPO’s function has been so hard to pin down is that many studies have been done in the complex and diverse environments of whole cells and tissues, where a clear-cut interpretation of the results is difficult,” said Fei Li, MSU postdoctoral researcher and co-author. “We were able to obtain a pure protein that was still functional, but isolated from these complications.”

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Did You Know?

About one in 21 people (4.7 per cent) of people will have major depression at any point in time.

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