Blood expression levels of genes targeted by the stress hormones called glucocorticoids could be a physical measure, or biomarker, of risk for developing Post-Traumatic Stress Disorder (PTSD), according to a study conducted in rats by researchers at the Icahn School of Medicine at Mount Sinai and published August 11 in Proceedings of the National Academy of Sciences (PNAS). That also makes the steroid hormones’ receptor, the glucocorticoid receptor, a potential target for new drugs.
Post-Traumatic Stress Disorder (PTSD) is triggered by a terrifying event, either witnessed or experienced. Symptoms may include flashbacks, nightmares and severe anxiety, as well as uncontrollable thoughts about the event. Not everyone who experiences trauma develops PTSD, which is why the study aimed to identify biomarkers that could better measure each person’s vulnerability to the disorder.
“Our aim was to determine which genes are differentially expressed in relation to PTSD,” said lead investigator Rachel Yehuda, PhD, Professor of Psychiatry and Neuroscience and Director of the Traumatic Stress Studies Division at the Icahn School of Medicine at Mount Sinai. “We found that most of the genes and pathways that are different in PTSD-like animals compared to resilient animals are related to the glucocorticoid receptor, which suggests we might have identified a therapeutic target for treatment of PTSD,” said Dr. Yehuda, who also heads the Mental Health Patient Care Center and PTSD Research Program at the James J. Peters Veterans Affairs Medical Center in the Bronx.
The research team exposed a group of male and female rats to litter soiled by cat urine, a predatory scent that mimics a life-threatening situation. Most PTSD studies until now have used only male rats. Mount Sinai researchers included female rats in this study since women are more vulnerable than men to developing PTSD. The rats were then categorized based on their behavior one week after exposure to the scent. The authors also examined patterns of gene expression in the blood and in stress-responsive brain regions.
After one week of being exposed to soiled cat litter for 10 minutes, vulnerable rats exhibited higher anxiety and hyperarousal, and showed altered glucocorticoid receptor signaling in all tissues compared with resilient rats. Moreover, some rats were treated with a hormone that activates the glucocorticoid receptor called corticosterone one hour after exposure to the cat urine scent. These rats showed lower levels of anxiety and arousal one week later compared with untreated, trauma-exposed rats.
“PTSD is not just a disorder that affects the brain,” said co-investigator Nikolaos Daskalakis, MD, PhD, Associate Research Scientist in the Department of Psychiatry at the Icahn School of Medicine at Mount Sinai. “It involves the entire body, which is why identifying common regulators is key. The glucocorticoid receptor is the one common regulator that consistently stood out.”
A team of researchers from the Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences have developed a new way of using electricity to open the blood-brain-barrier (BBB). The Vascular Enabled Integrated Nanosecond pulse (VEIN pulse) procedure consists of inserting…
Contrary to popular belief, not all meditation techniques produce similar effects of body and mind. Indeed, a recent study by researchers from the National University of Singapore (NUS) has demonstrated for the first time that different types of Buddhist meditation – namely the Vajrayana and Theravada styles of meditation - elicit qualitatively different influences on human physiology and behaviour, producing arousal and relaxation responses respectively.
In particular, the NUS research team found that Vajrayana meditation, which is associated with Tibetan Buddhism, can lead to enhancements in cognitive performance.
The study by Associate Professor Maria Kozhevnikov and Dr Ido Amihai from the Department of Psychology at the NUS Faculty of Arts and Social Sciences was first published in the journal PLOS ONE in July 2014.
Vajrayana and Theravada meditation produce different physiological responses
Previous studies had defined meditation as a relaxation response and had attempted to categorise meditation as either involving focused or distributed attentional systems. Neither of these hypotheses received strong empirical support, and most of the studies focused on Theravada meditative practices.
Assoc Prof Kozhevnikov and Dr Amihai examined four different types of meditative practices: two types of Vajrayana meditations (Tibetan Buddhism) practices (Visualisation of self-generation-as-Deity and Rig-pa) and two types of Theravada practices (Shamatha and Vipassana). They collected electrocardiographic (EKG) and electroencephalographic (EEG) responses and also measured behavioural performance on cognitive tasks using a pool of experienced Theravada practitioners from Thailand and Nepal, as well as Vajrayana practitioners from Nepal.
They observed that physiological responses during the Theravada meditation differ significantly from those during the Vajrayana meditation. Theravada meditation produced enhanced parasympathetic activation (relaxation). In contrast, Vajrayana meditation did not show any evidence of parasympathetic activity but showed an activation of the sympathetic system (arousal).
The researchers had also observed an immediate dramatic increase in performance on cognitive tasks following only Vajrayana styles of meditation. They noted that such dramatic boost in attentional capacity is impossible during a state of relaxation. Their results show that Vajrayana and Theravada styles of meditation are based on different neurophysiological mechanisms, which give rise to either an arousal or relaxation response.
Applications of the research findings
The findings from the study showed that Vajrayana meditation can lead to dramatic enhancement in cognitive performance, suggesting that Vajrayana meditation could be especially useful in situations where it is important to perform at one’s best, such as during competition or states of urgency. On the other hand, Theravada styles of meditation are an excellent way to decrease stress, release tension, and promote deep relaxation.
After seeing that even a single session of Vajrayana meditation can lead to radical enhancements in brain performance, Assoc Prof Kozhevnikov and Dr Amihai will be investigating whether permanent changes could occur after long-term practice. The researchers are also looking at how non-practitioners can benefit from such meditative practices.
Assoc Prof Kozhevnikov said, “Vajrayana meditation typically requires years of practice, so we are also looking into whether it is also possible to acquire the beneficial effects of brain performance by practicing certain essential elements of the meditation. This would provide an effective and practical method for non-practitioners to quickly increase brain performance in times of need.”
Children with high everyday levels of a protein released into the blood in response to infection are at greater risk of developing depression and psychosis in adulthood, according to new research which suggests a role for the immune system in mental illness.
The study, published today in JAMA Psychiatry, indicates that mental illness and chronic physical illness such as coronary heart disease and type 2 diabetes may share common biological mechanisms.
When we are exposed to an infection, for example influenza or a stomach bug, our immune system fights back to control and remove the infection. During this process, immune cells flood the blood stream with proteins such as interleukin-6 (IL-6), a tell-tale marker of infection. However, even when we are healthy, our bodies carry trace levels of these proteins – known as ‘inflammatory markers’ – which rise exponentially in response to infection.
Now, researchers have carried out the first ever longitudinal study – a study that follows the same cohort of people over a long period of time – to examine the link between these markers in childhood and subsequent mental illness.
A team of scientists led by the University of Cambridge studied a sample of 4,500 individuals from the Avon Longitudinal Study of Parents and Children – also known as Children of the 90s – taking blood samples at age 9 and following up at age 18 to see if they had experienced episodes of depression or psychosis. The team divided the individuals into three groups, depending on whether their everyday levels of IL-6 were low, medium or high. They found that those children in the ‘high’ group were nearly two times more likely to have experienced depression or psychosis than those in the ‘low’ group.
Dr Golam Khandaker from the Department of Psychiatry at the University of Cambridge, who led the study, says: “Our immune system acts like a thermostat, turned down low most of the time, but cranked up when we have an infection. In some people, the thermostat is always set slightly higher, behaving as if they have a persistent low level infection – these people appear to be at a higher risk of developing depression and psychosis. It’s too early to say whether this association is causal, and we are carrying out additional studies to examine this association further.”
The research indicates that chronic physical illness such as coronary heart disease and type 2 diabetes may share a common mechanism with mental illness. People with depression and schizophrenia are known to have a much higher risk of developing heart disease and diabetes, and elevated levels of IL-6 have previously been shown to increase the risk of heart disease and type 2 diabetes.
Professor Peter Jones, Head of the Department of Psychiatry and senior author of the study, says: “Inflammation may be a common mechanism that influences both our physical and mental health. It is possible that early life adversity and stress lead to persistent increase in levels of IL-6 and other inflammatory markers in our body, which, in turn, increase the risk of a number of chronic physical and mental illness.”
Indeed, low birth weight, a marker of impaired foetal development, is associated with increased everyday levels of inflammatory markers as well as greater risks of heart disease, diabetes, depression and schizophrenia in adults.
This potential common mechanism could help explain why physical exercise and diet, classic ways of reducing risk of heart disease, for example, are also thought to improve mood and help depression. The group is now planning additional studies to confirm whether inflammation is a common link between chronic physical and mental illness.
The research also hints at interesting ways of potentially treating illnesses such as depression: anti-inflammatory drugs. Treatment with anti-inflammatory agents leads to levels of inflammatory markers falling to normal. Previous research has suggested that anti-inflammatory drugs such as aspirin used in conjunction with antipsychotic treatments may be more effective than just the antipsychotics themselves. A multicentre trial is currently underway, into whether the antibiotic minocycline, used for the treatment of acne, can be used to treat lack of enjoyment, social withdrawal, apathy and other so called negative symptoms in schizophrenia. Minocycline is able to penetrate the ‘blood-brain barrier’, a highly selective permeability barrier which protects the central nervous system from potentially harmful substances circulating in our blood.
The ‘blood-brain barrier’ is also at the centre of a potential puzzle raised by research such as today’s research: how can the immune system have an effect in the brain when many inflammatory markers and antibodies cannot penetrate this barrier? Studies in mice suggest that the answer may lie in the vagus nerve, which connects the brain to the abdomen. When activated by inflammatory markers in the gut, it sends a signal to the brain, where immune cells produce proteins such as IL-6, leading to increased metabolism (and hence decreased levels) of the ‘happiness hormone’ serotonin in the brain. Similarly, the signals trigger an increase in toxic chemicals such as nitric oxide, quinolonic acid, and kynurenic acid, which are bad for the functioning of nerve cells.
Researchers at the Gladstone Institutes have shown that reducing brain levels of the protein tau effectively blocks the development of disease in a mouse model of Dravet syndrome, a severe intractable form of childhood epilepsy. This therapeutic strategy not only suppressed seizure activity and…
Passengers who survived terrifying Air Transat flight in 2001, help psychologists uncover new clues about post-traumatic stress vulnerability
An extraordinary opportunity to study memory and post-traumatic stress disorder (PTSD) in a group of Air Transat passengers who experienced 30 minutes of unimaginable terror over the Atlantic Ocean in 2001 has resulted in the discovery of a potential risk factor that may help predict who is most…
Jumping from failure to failure with undiminished enthusiasm is the big secret of success.
Pioneering physicist Savas Dimopoulos in Particle Fever, the excellent documentary about the Large Hadron Collider and the search for the Higgs boson – a tenacity that characterized some of the greatest achievers and innovators in history.
Pair with Pixar’s cofounder on the importance of fostering a fail-forward culture.(via explore-blog)
Inspired by bird nests or vanishing building techniques, architecture based on natural materials is an expanding focus in both sculpture garden and urban landscape. The 2007 Natural Architecture book compiled some of the practitioners of bamboo building and structural weaving, and this month Natural Architecture Now: New Projects from Outside the Boundaries of Design by Francesca Tatarella continues the dialogue.
“When a tiger starts to move towards you, you need to know whether it is something you are actually seeing or whether it’s just something that you remember or have imagined,” says Prof. Julio Martinez-Trujillo of McGill’s Department of Physiology. The researcher and his team have discovered that there is a clear frontier in the brain between the area that encodes information about what is immediately before the eyes and the area that encodes the abstract representations that are the product of our short-term memory or imagination. It is an important advance in brain mapping and opens the doors to further research in the area of short-term memory.
These finding, which are described in an article just published in Nature Neuroscience, resolve a question that has occupied neuroscientists for years. Namely that of how and where exactly in the brain the visual information coming from our eyes is first transformed into short-term memories. “We found that while one area in the brain processes information about what we are currently seeing, an area right beside it stores the information in short-term memory,” says McGill PhD student Diego Mendoza-Halliday, first author of the article. “What is so exciting about this finding is that until now, no one knew the place where visual information first gets transformed into short-term memory.”
The researchers arrived at this conclusion by measuring the neuronal activity in these two areas in the brains of macaques as they first looked at, and then after a short time (1.2 - 2 seconds) remembered, a random sequence of dots moving across a computer screen like rainfall. What surprised Martinez-Trujillo and his team was how clearly demarcated the divide was between the activities and functions of the two brain areas, and this despite the fact that they lie side-by-side.
“It is rare to find this kind of sharp boundary in biological systems of any kind,” says Martinez-Trujillo. “Most of the time, when you look at the function of different brain areas, there is more of a transitional zone, more grey and not such a clear border between black and white. I think the evolutionary reason for this clear frontier is that it helped us to survive in dangerous situations.”
The discovery comes after five years spent by Martinez-Trujillo and his team doing research in the area. Despite this fact, he acknowledges that there was a certain amount of serendipity, and a lot of technological help involved in being able to capture a signal that travels for 3 milliseconds and fires synapses in neurons that lie right beside one another.
Martinez-Trujillo and his team continue to work on mapping the receptors and connectivity between these two areas of the brain. But what is most important for him is to try and relate this discovery to schizophrenia and other diseases that involve hallucinations, and in order to do so he is working with a psychiatrist at Montreal’s Douglas Hospital.
Two years ago, the parents of Chloe Olivarez watched painfully as their daughter experienced epileptic seizures hundreds of times a day. The seizures, caused by a rare metabolic disease that depleted her brain of needed glucose, left Chloe nearly unresponsive, and slow to develop.
Within hours, treatment with an edible oil dramatically reduced the number of seizures for then-4-year-old Chloe, one of 14 participants in a small UT Southwestern Medical Center clinical trial.
“Immediately we noticed fewer seizures. From the Chloe we knew two years ago to today, this is a completely different child. She has done amazingly well,” said Brandi Olivarez, Chloe’s mother.
For Chloe and the other trial participants who suffer from the disease called Glut1 deficiency (G1D), seizure frequency declined significantly. Most showed a rapid increase in brain metabolism and improved neuropsychological performance, findings that suggested the oil derived from castor beans called triheptanoin, ameliorated the brain glucose-depletion associated with this genetic disorder, which is often undiagnosed.
“This study paves the way for a medical food designation for triheptanoin, thus significantly expanding therapeutic options for many patients,” said Dr. Juan Pascual, Associate Professor of Neurology and Neurotherapeutics, Physiology, and Pediatrics at UT Southwestern and lead author of a study on the findings, published in JAMA Neurology.
For the estimated 38,000 Americans suffering from this disease, the only proven treatment has been a high-fat ketogenic diet, which only works for about two-thirds of patients. In addition, this diet carries long-term risks, such as development of kidney stones and metabolic abnormalities.
Based on the results of this trial, triheptanoin appears to work as efficiently as the ketogenic diet; however, more research needs to be done before the oil is made available as a medical food therapy, researchers said.
“Triheptanoin byproducts produced in the liver and also in the brain refill brain chemicals that we found are preferentially diminished in the disorder, and this effect is precisely what defines a medical food rather than a drug,” said Dr. Pascual, who heads UT Southwestern’s Rare Brain Disorders Program, maintains an appointment in the Eugene McDermott Center for Human Growth and Development, and holds The Once Upon a Time Foundation Professorship in Pediatric Neurologic Diseases.
The oil, approved for use in research only, is an ingredient in some cosmetic products and is added to butter in some European countries. It is not commercially available in the U.S. for clinical use.
Triheptanoin’s success as an experimental treatment for other metabolic diseases, along with preclinical success in G1D mice, led Dr. Pascual and his trial collaborator, Dr. Charles Roe, Clinical Professor of Neurology and Neurotherapeutics, to first conceive the idea and then launch this trial for G1D patients. The 14 pediatric and adult patients in the study consumed varying amounts of the oil, based on their body weight, four times a day. Given the trial’s success, Dr. Pascual plans further research to refine the optimal dosage toward the goal of facilitating medical food designation of triheptanoin as a new G1D treatment.
While some trial participants reported mild stomach upset as a side effect, for Chloe the oil has been a miracle medicine without negative effects. Her parents, Brandi and Josh Olivarez of Waco, Texas, continue to be amazed by her progress.
“Before, she was having so many seizures a day that she couldn’t even talk. Now she sings all the time, she can eat whatever she wants, and her speech is greatly improved. She still has some learning delays, but has come a long way,” said Mrs. Olivarez.
Many Glut1 patients suffer from movement disorders that limit their physical capabilities, but that does not appear to be the case with Chloe. As for the seizures, she still has minor ones occasionally, but they are not debilitating.
“She is now able to run a solid mile without stopping. This would not have been possible without the oil,” Mrs. Olivarez said. “Before, she had almost no muscle tone, was lethargic and had a very wide gait due to trying to balance herself while walking, which was very tiring for her.”
To better understand this disease, UT Southwestern established a patient-completed registry to track G1D incidence and what treatments work or do not work for those registered.