Category Archives: Annual theme

Stress and the gut – it’s not all in your mind (Part 2)

By Kim E. Barrett, Division of Gastroenterology, Department of Medicine, University of California, San Diego, USA, @Jphysiol_eic.

This article originally appeared in our magazine, Physiology News.

The numerous microbes living inside of us help break down nutrients and “educate” our immune system to fight infection, but how do they help us respond to stress?

The microbiota as a mediator of responses to stress

Gut microbes change when people have intestinal diseases, such as inflammatory bowel diseases and irritable bowel syndrome. Indeed, some of the characteristics of these diseases can be transferred to animals in the lab that lack microbes, using microbes from diseased mice or humans. It is also becoming increasingly clear that gut microbes and their products may have effects well beyond the confines of the intestine itself.

Perhaps the most intriguing aspects of this area of research is that which ties the composition of the gut microbiome to brain function and the brain’s response to stress. Further, the adverse effects of stressful situations on gut function depend on the presence of intestinal microbes. To date, research supports bi-directional communication between the gut and brain (pictured below) that influences the normal function of both bowel and brain alike. This may explain, for example, why some digestive and psychiatric disorders go hand-in-hand (Gareau, 2016).

gut brain

Bi-directional communication between the gut and brain.

Evidence in human patients largely shows correlation not causation so far. Still, it is intriguing to observe that derangements in the microbiome have been associated with many conditions, including depression, autism, schizophrenia and perhaps even Parkinson’s disease (Dinan & Cryan, 2017).

Therapeutic manipulation of the microbiota – from probiotics to transplants

So if both intestinal and neuropsychiatric conditions are potentially caused by changes in the gut microbes (at least in part), and if such alterations also mediate the impact of stress on the relevant organ systems, can we mitigate these outcomes by targeting the microbiota?

Several approaches have been posited to have either positive or negative effects on the make-up of the gut microbiota and its intestinal and extra-intestinal influences.  Perhaps the most obvious of these is the diet. While the gut microbiota was at one time felt to be relatively immutable in adulthood, improved  techniques indicate that its make-up, in fact, is profoundly influenced by the composition of the diet and even by the timing of meals. For example, Western diets, high in meat and fat, decrease the diversity of the microbiota (and may even promote the emergence of pathogenic properties in commensals), whereas diets rich in plant-based fibre increase it.

healthy_diet.jpg

Another approach to targeting the microbiota is the use of antibiotics, although for the reasons discussed in Part 1, these are likely to be mainly deleterious, particularly early in life. The composition of the microbiota can also be altered directly by the administration of probiotics, which are commensal microorganisms (the host benefits, while the microbes are unaffected) selected for their apparent health benefits that can be taken orally.  Studies in animal models demonstrate that probiotics can improve both gut and cognitive function in animals exposed to a variety of stressors, or can negate the cognitive dysfunction accompanying intestinal inflammation or infection.  However, not all probiotics are created equal, and much work remains to be done both to validate animal studies in human clinical trials, and to define characteristics of probiotic strains that predict efficacy in a given clinical setting.

Perhaps the approach to targeting the microbiota that has attracted the most recent public attention is the practice known as faecal microbial transplant (FMT), where faecal material is transferred from a healthy donor (often a relative) to someone suffering from a specific intestinal or extraintestinal disease.  Enthusiasm for FMT derived initially from its dramatic efficacy in some patients suffering from disabling and persistent diarrheal disease as well as other symptoms associated with treatment-resistant infections by C. diff (a harmful bacteria).  More recently, there have been encouraging data suggesting that FMT may be effective in producing remission in inflammatory bowel disease, although the long-term consequences are unknown, and larger, well-controlled studies are needed.  Exploratory reports even suggest beneficial effects of FMT on gastrointestinal and behavioural symptoms of autism, or in obesity and metabolic syndrome (a cluster of conditions that occur together and increase your risk of heart disease, stroke and other conditions), but much further work is needed to validate these preliminary data.  Ideally, FMT procedures should be conducted under carefully-controlled and physician-supervised conditions to screen for the potential presence of pathogens or toxins.  Nevertheless, despite the obvious “yuck” factor, “do-it-yourself” instructions can readily be found online (there are even Facebook groups), and some individuals are sufficiently distressed by their condition to give it a try.

faecal_transplant_pill

Yep, this is exactly what you think it is.

Mitigating negative effects of stress

In conclusion, it is clear that our response to stress, whether manifested in our thought patterns or in our gut, is dramatically shaped by the microbiota that resides in the intestines.  Particularly in humans, studies conducted to date have largely been confined to cataloguing the key players in a given setting, but animal data are provocative, and studies focusing on microbes’ roles and functions in humans will doubtless follow.   No matter what, in the coming years, the explosive growth of studies aiming to target the microbiota for health benefits should give us a much better understanding of which approach, if any, is likely to be most beneficial for a given condition and even a given individual, since host factors clearly can also impact our microbial composition.  This work holds the promise of ameliorating negative effects of stress, and perhaps may offer new avenues for the therapy or even prevention of the myriad of stress-related disease states that are increasing in incidence in developed countries.


References

Dinan TG & Cryan JF. (2017). Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration. The Journal of physiology 595, 489-503.

Gareau MG. (2016). Cognitive function and the microbiome. International Review of Neurobiology 131, 227-246.

 

Stress and the gut – it’s not all in your mind (Part 1)

By Kim E. Barrett, Division of Gastroenterology, Department of Medicine, University of California, San Diego, USA, @Jphysiol_eic.

This article originally appeared in our magazine, Physiology News.

We all know that stress has an impact on the function of our digestive system. Whether it is the transient butterflies that accompany an exam or an interview, or the more toxic consequences of chronic stress, our experience of our world and its challenges can profoundly alter our digestion, absorption of nutrients, and excretion.

What has been less fully appreciated, until recently, is that communication between the brain and gut is bi-directional. Gut illnesses may be accompanied by brain disorders, such as anxiety, depression, and memory problems.  The brain and spinal cord are in constant communication with the gut, in part via the “little brain” – the nerves present in the gut that communicate with the brain.

While we humans like to think that we are masters of our own universe, in fact we, along with all other beings, are superorganisms. Our bodies consist not only of our own cells and genome, but also of distinctive populations of ‘friendly microbes’, along with their genes and ability to break down compounds. This so-called “microbiome” is made up mostly of bacteria, the best-studied populations, but also other microbes such as fungi and viruses (which are only now beginning to be examined).  Specialized groups of microbes inhabit various parts of our body, such as the intestines, mouth, skin, lungs, and genitals. The most extensively characterized of these microbiomes is the collection of bacteria in the gut, consisting of thousands of species in a typical healthy human adult. They reside throughout the intestines, but are most heavily concentrated in the colon. There are as many as 1014 of them throughout the gut. That’s ten times the number of human cells in the entire body (Sekirov et al., 2010). Recently, the 10:1 ratio has been disputed, with a claim that the numbers of human cells and gut bacteria are of the same order of magnitude (Sender et al., 2016). Even if this true, the microbes collectively have more genes than our cells do.

We are rapidly learning the ways in which these gut microbes may be important mediators of the cross-talk between the gut and brain. They are, in turn, influenced by environmental conditions, such as stress and diet, in ways that change their impact on both our thinking and digestion.

gut brain

 

Friendly microbes – what do they do for us?

Microbes, in the gut or elsewhere, are not essential for life, as illustrated by the ability to raise animals in a sterile environment in the lab. Nevertheless, the gut microbes in particular offer several advantages to the organism they inhabit. For us, they break down nutrients we can’t, such as dietary fibre, drugs, carcinogens, and compounds that break down into vitamins.  Similarly, the microbiota “educate” the immune system of organs such as our lungs and intestines to fight foreign substances but tolerate the proteins of broken-down food or other harmless microbes.

The organisms of the microbiome also defend against pathogens by crowding them out, producing substances that kill bacteria or keep them from reproducing, or causing the host to create those lethal compounds itself. For this reason, antibiotics that kill beneficial microbes can render patients susceptible to intestinal infections and overgrowth of harmful bacteria, such as Clostridium difficile (C. diff).

gut brain 2

3D cellular model of an intestine by Ben Mellows, PhD Student, University of Reading, UK

Gut microbes and birth

We think that gut microbes exist in the body immediately after birth, although some controversial data suggests the presence of microbes in the fetus before birth. Animals without microbes can be born via Caesarean section (C-section), implying that even if there are microbes in the womb, organisms don’t need them to survive (Perez-Munoz et al., 2017).

For babies delivered vaginally, their gut microbes are initially very similar to the mother’s vaginal microbiota, whereas they differ substantially for babies delivered by C-section. An intriguing recent study partially restored “normal” microbes in the gut, mouth, and skin by exposing babies delivered via C-section to the mother’s vaginal fluids. The authors thought that this might reverse the known association between C-section deliveries and an increased risk for immune and metabolic disorders (Dominguez-Bello et al., 2016).

For the first year or two of life, the baby’s microbes are relatively simple and variable, but they gradually take on the characteristics of a mature, adult-like microbiome. These early years are also a critical period for maturation of the immune system, so it makes sense that disrupting the maturation of the infant’s microbes also predisposes them to autoimmune and allergic diseases. For example, the increasing tendency to protect babies from germs or an excessive early-life use of antibiotics may set them up for an increased later risk of asthma, metabolic disease or obesity. This is called the “hygiene hypothesis” (Schulfer & Blaser, 2015).

Stay tuned for the part 2 of the series next week to learn about how gut microbes respond to stress, and the efficacy of therapeutics, from probiotics to transplants.


References

Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, Cox LM, Amir A, Gonzalez A, Bokulich NA, Song SJ, Hoashi M, Rivera-Vinas JI, Mendez K, Knight R & Clemente JC. (2016). Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat Med 22, 250-253.

Perez-Munoz ME, Arrieta MC, Ramer-Tait AE & Walter J. (2017). A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome 5, 48.

Schulfer A & Blaser MJ. (2015). Risks of antibiotic exposures early in life on the developing microbiome. PLoS Pathog 11, e1004903.

Sekirov I, Russell SL, Antunes LC & Finlay BB. (2010). Gut microbiota in health and disease. Physiological reviews 90, 859-904.

Stressing out the immune system

Excerpt from a Physiology News feature by Natalie Riddell, School of Biosciences and Medicine, University of Surrey, UK, @N_Riddell_Immun

Natalie Riddell LatitudeStress can get under our skin. It can influence each and every physiological system, and all of the major contemporary diseases in the UK, including cardiovascular disease, inflammatory disorders, metabolic syndrome, infectious diseases and cancer, have been associated with stress. Stress affects everyone, and levels of anxiety and mental health disorders are increasing with work-related stress now being the second most commonly reported illness in the UK workforce. Over the last four decades, research in the area of Psychoneuroimmunology (PNI) has identified stress induced immune alterations as a potential mediator between chronic stress and ill-health.

In the 1970s, Holmes and Rahe developed a scale to subjectively grade stress, [which inspired our recent survey of stress in modern Britain]. They ranked over 40 different types of life stressors, such as the death of someone close to you, changes in relationship status, work-related stress, even Christmas, and they assigned each stressor a score. The total tally of stress scores that a person had experienced in the last year could accurately predict the likeliness of future illness. This demonstrated that stress and illness were closely related. In the 1990’s, Cohen et al., eloquently demonstrated that psychological stress increased the rates of respiratory infections and clinical symptoms in participants inoculated with the common cold (Cohen, Tyrrell et al. 1993). Subsequent studies revealed that every organ, tissue and cell of the immune system could be altered by psychological stress. The involvement of immune alterations in stress induced diseases was recognised and the field of PNI was born.

Defining stress

Stress is highly subjective. Something that I may class as stressful (watching Arsenal this season), may not be stressful to other people (Tottenham supporters). So how can we define stress? In the 1960s, the psychologist Richard Lazarus introduced the concept that stress is a process consisting of three distinct steps. First, a stimulus (i.e., the stressor) has to be present and perceived. Second, the stimulus initiates a conscious or sub-conscious process whereby the stressor is evaluated in relation to available coping options. If the demands of the situation exceed the ability to cope, then the situation is perceived as stressful. Thirdly, this results in a stress response involving emotional (e.g., anxiety, embarrassment) and biological (e.g., autonomic-endocrine) adaptations. Put simply; stress is a situation or event that exceeds, or is perceived to exceed, the individual’s ability to cope, that then triggers an emotional and biological response.

circadian4

Image: Darryl Leja, NHGRI

The stress adaptation response and immunity

The biological adaptation to stress is activation of the sympathetic nervous system. The same biological response is induced whether the stressor is psychological, such as anxiety or embarrassment, or physical, for example, exercise, trauma or fever. In the case of psychological stress, the individual perceives an inability to cope and this results in the amygdala, a part of the brain that contributes to emotion processing, sending a distress signal to the nearby hypothalamus. The hypothalamus can communicate with the rest of the body via either of two arms of the involuntary nervous system: “rest and digest” (parasympathetic) or “fight or flight” (sympathetic). During stress, this “fight or flight” system is triggered and various physiological changes occur, including an increase in heart rate, respiration and energy production. This promotes survival of the individual by maximising physical capacity to cope with the stressor.

During stress, signalling from the “fight or flight” sympathetic nervous system causes the adrenal gland to secrete the two main stress hormones; adrenaline and cortisol. These hormones can spread and act throughout the body via the circulation. The sympathetic nervous system innervates all of the organs of the immune system, and individual immune cells can directly respond to changes in circulating levels of adrenaline and cortisol. Stress is therefore able to alter every process of immunity, from the initial development of stem cells into early immune cells in the bone marrow, through to the triggering of immune responses to specific antigens in the lymph nodes. Even when in the peripheral tissues, such as the skin or gut, where mature immune cells are most likely to encounter infections, the cells can be regulated by stress hormones. It is therefore unsurprising that the immune system is a modifiable target of stress.

Read Natalie’s full article in our magazine Physiology News to find out how acute stress changes the composition of the blood, and why our Stone Age brain can’t cope with the constant stress of modern life. Her feature takes a more detailed dive into the effects of stress on the immune system’s day-night (circadian) rhythm, and points to stress management as an easy and affordable way to make us healthier.

Reference

Cohen, S., D. A. Tyrrell and A. P. Smith (1993). Negative life events, perceived stress, negative affect, and susceptibility to the common cold. J Pers Soc Psychol 64(1): 131-140.

 

 

Getting stressed out at the Lancashire Science Festival

By Rachel Boardman, University of Nottingham, UK, @boardventures

Two weeks ago, I formed part of The Physiological Society’s team of enthusiastic volunteers in the Biology Big Top area of Lancashire Science Festival. Dressed to impress in our ‘I love physiology’ t-shirts, we were all set to engage our audience about the effects of stress on the body.

img_2483-e1500305671413.jpg

After measuring a participant’s blood pressure and heart rate we would then expose them to either a mental or physical stress. The mental stress consisted of playing whack-a-mole – a version of the popular arcade game where you hit the mole when it lights up – while being asked maths questions. Evil, right?

I had a go, to errm test it out, and one of my fellow volunteers challenged me to count backwards from 100. Not so bad, I thought. She then added, “In 7s.”

“Oh errm.. 100, 93… errr…86. Yeah I’m out.”

A few of our participants were amazingly good at this (unlike me) while some heard the word maths and immediately opted for the physical stressor, the cold pressor test.IMG_2518

This involved sticking your hand in an ice-cold bucket of water for 1 minute (we toned it down to 30 seconds for the younger children because we’re not harsh). The shock on each participant’s face as they realised how cold the water actually was followed by the realisation that a whole 60 seconds doing this was far longer than they had realised. Most showed clear signs of discomfort, squirming and fidgeting in their seat, increasing their breathing rate and even providing a running commentary on just how they were feeling, but there were others that sat quite still with a wry smile on their face that said ‘this isn’t that cold’.

Once we had suitably stressed our victims participants out, we measured their blood pressure and heart rate again. What would you expect to happen?DEcsbysXUAAdU07.jpg

Well, if you know anything about science, then you will know that it doesn’t always go to plan. That is precisely what happened to us. The majority of people’s blood pressure and heart rate did increase. However, we also had participants who seemingly reacted to these stressors by relaxing, or for whom only blood pressure or heart rate changed. That’s science, guys!

Read Rachel’s full article on her blog, The Boardventures.

Running away from stress…literally

By Molly Campbell, University of Leeds, @mollyrcampbell

Exercise – for some, it’s a hobby, for others, a burden. We all know exercise is good for us. Yet, ironically, many people feel too busy or stressed to exercise regularly. Particularly during exam time, who wants to swap an hour of revision for an hour of tiring yourself out?

Research actually suggests that committing to exercise when you are experiencing stress can lower your stress response both now, and in the future. Regular exercise can be particularly helpful in boosting your mood, and thus your motivation to do work. Scientific research suggests that exercise elevates molecules in the body associated with the feeling of joy, whilst decreasing those that cause stress.

Post-exercise feelings of bliss

The term ‘runner’s high’ was coined in the 1970’s following an apparent worldwide increase in the number of people running long distance. This feeling of elation was attributed to the increased levels of endorphins in runners’ blood after exercise. Since then, many studies have been conducted that expand on this work to clarify exactly how exercise produces this ‘feel good’ effect.

Exercise also increases the release of endocannabinoids in the body. These are a type of cannabinoid that are endogenous, meaning they are made within our body. Endocannabinoids serve as a message between cells. Cells receive the message when the endocannabinoid attaches to another molecule, called a receptor, on the outside of a receiver cell. The receiver cells for endocannabinoids are in the central nervous system (brain and spinal cord) as well as other parts of the body. This elicits a wide range of beneficial effects.

The chemical anandamide, one type of endocannabinoid, gets its name from the Sanskrit word ‘ananda’ meaning joy. It is created in areas of the brain involved in motivation, memory, and higher cognitive function. Whilst its exact function has not been clarified, increased levels of anandamide are associated with states of heightened happiness. Anandamide can enter the brain through the so-called blood-brain barrier. This means that an increase of anandamide in the blood is followed by an increase of the chemical in the brain.

An experiment by Elsa Heyman and her colleagues demonstrated that, following a period of intense exercise, cyclists have increased levels of anandamide in their blood (1). This increase in anandamide was correlated with the increase of a molecule that is extremely important for the growth and maintenance of neurons in the brain, called brain-derived neurotrophic factor (BDNF).

Johannes Fuss and his colleagues used mouse models to demonstrate that exercising on a running wheel produced a significant increase in anandamide levels, which was correlated with a substantial reduction in anxious behaviours (2). When the researchers gave the mice a drug to block the cannabinoid receptors, to which anandamide binds, this reduction in anxiety was reversed.

Together, these findings therefore suggest an emerging role for the endocannabinoid system in producing the feeling of well-being and stress relief people experience after exercise. However, anandamide is broken down in the body very rapidly, possibly explaining why exercise is most beneficial when done regularly.

Sweat away your stress

Susanne Droste and her colleagues investigated the short-term effects of exercise on stress hormones in mice (3). Adult male mice were provided access to a running wheel for four weeks before undergoing a series of behavioural tests. Exercising mice were found to exhibit a significant decrease in corticosterone (the equivalent of the stress hormone, cortisol, in rodents) responses to a novel environment compared to control animals that had not exercised. These animals were also found to be less anxious in behavioural tests.

Researchers have also found long-term changes in the stress response after repeated exercise. Mindfulness experts suggest exercise, such as running or yoga, can indeed be a meditation practice carried out ‘on the go’. By placing focus on the repetitive movement of our joints and the increase in our heart rate, and the general effects exercise exerts on our body, we are distracted from the thoughts circling through our mind. Repeatedly applying this focus, particularly when high levels of stress cause us to be entangled in our thoughts, can produce long-term changes in the bodily tools we rely on to calm down. Ann Kennedy and her colleagues found that several studies show that this improves breathing rate and depth, lowers heart rate, and increases our ‘rest and digest’ response, or the so-called parasympathetic nervous system (4).

Although it may seem a chore to take time out of the day to get your body in motion, research about our physiology suggests that your brain (and therefore your grades) will benefit from doing so!

References:

  1. Heyman, E. Gamelin, F.X., Goekint, M., Piscitelli, F., Roelands, B., Leclair, E., Di Marzo, V. and Meeusen, R. 2012. Intense exercise increases circulating endocannabinoid and BDNF levels in humans—possible implications for reward and depression. 37(6), pp. 844-851.
  2. Fuss, J. Steinle, J., Bindila, L., Auer, M., Kirchherr, H., Lutz, B. and Gass, P. Runners high depends on cannabinoid receptors in mice. PNAS. 112(42).
  3. Droste, S.K., Gesing, A., Ulbricht, S., Muller, M.B., Linthorst, A.C and Reul, J.M. 2003. Effects of long-term voluntary exercise on the mouse hypothalamic-pituitary-adrenocortical axis. Endocrinology. 144(7), pp. 3012-3023.
  4. Kennedy, A. and Resnick, P. 2015. Mindfulness and Physical Activity. American Journal of Lifestyle Medicine. 9(13), pp. 221-223.

 

The Glastonbury of Neuroscience

By Anjanette Harris, University of Edinburgh, @anjiefitch

I have been to many music festivals in my time, but last month I went to my first Neuroscience Festival. Every two years, the British Neuroscience Association holds the Festival of Neuroscience, which boasts a jam-packed program of research talks from experts across many disciplines within neuroscience, as well as workshops and discussion forums. It is quite simply the national celebration of neuroscience.

Last month, nestled amongst the canals of Birmingham, the International Conference Center provided the perfect backdrop for over 1500 scientists from around the world to get together, share their latest data, and enthuse one another. This year, The Physiological Society hosted a strand running through the festival called The Neurobiology of Stress as part of their annual theme Making Sense of Stress. One of the symposia, organised by Professor Megan Holmes, brought together researchers from around the world, including myself, to present our work on imaging the emotional brain.

What puts us at risk of depression?

18622695_10208627150588993_458180351_n

Dr Stella Chan, a lecturer in clinical psychology from the University of Edinburgh, kicked off with the staggering statistic that half of all cases of depression first occur in adolescence. Stella reminded us that adolescence is a tricky time in which teenagers struggle with intense emotions on the road to self-discovery. But why do some youngsters develop depression while others don’t?

To answer this question, Stella studies how young people perceive themselves and the world around them. One startling finding is that those at risk of depression find it harder to see joy in other people’s faces. Because Stella uses teenagers at risk of, but not yet suffering from, depression she is able to see if there are changes in perception that may flag up that a youngster is likely to develop depression. If Stella can untangle whether a negative self-opinion is the cause or consequence of depression, she may be able to develop mind-training techniques to prevent depression in those at risk.

Untangling cause and effect using mice

18578637_10208627150508991_1109602824_n

Dr Marloes Henckens, a post-doctoral researcher from the Donders Institute at Radboud University, presented her work on the effects of stress on brain function. She uses both human and mouse subjects to help her distinguish between cause and effect. Marloes began by setting her work in context; she highlighted that the brain is a collection of networks and that brain disorders are probably caused by disorders of the connections between different networks.

With that in mind, Marloes showed that stressing humans or giving them stress hormones caused the connections that make up the fear network to become stronger. While this is useful for priming a person to tackle danger, it may lead to an anxiety disorder, such as post traumatic stress disorder (PTSD) in which suffers are haunted by intense unpleasant memories. Marloes takes pictures of the brains of mice with PTSD-like symptoms and has shown that reduced activity at the front of the brain (important for reducing unpleasant memories) is a consequence and not the cause of PTSD. It remains to be seen how connections between different networks are affected in mice with PTSD.

Hormonal influences on brain activity in rats
awake

The following speaker, Professor Craig Ferris of Northeastern University, is the pioneer of imaging rats’ brains while they are awake. Craig began with a whistle-stop tour of the groundbreaking technology that he and his team have developed. His special scanning technology allows researchers to monitor brain activity while the rats are responding to things. For example, Craig showed changes in brain activity in mother rats as their pups start to suckle. It comes as no surprise that the brain areas involved in reward and motivation are active with breast-feeding. In fact, in these rats, breast-feeding is more rewarding than cocaine!

Craig then presented images of brain activity involved in aggression. To observe this, he first took pictures of the brain of a male rat that was happily lying in the scanner with its girlfriend, and then introduced an unfamiliar male rat and observed the changes in the first rat’s brain. The abrupt change in brain activity that was seen in the male rat’s brain might be described as blind rage, as it is similar to that observed with the onset of a seizure. Craig’s ambition knows no bounds: he finished his talk with musing on whether he could fit a killer whale into his brain scanner!

The impact of stress on emotional memory in rats

anjie.png

The final speaker was me, Dr Anjanette Harris. I’m a post-doctoral researcher from the laboratory of Megan Holmes at the University of Edinburgh. I want to understand how stress affects brain function. This is particularly tricky to study in humans, especially if we want to look at the effects of early life stress on the brain, so we use rats (read more on the importance of using rodents in psychiatric research in my previous blog post). The work that I presented uses the technology of Craig Ferris coupled with memory exercises for rats that we specialize in designing. We have shown that rats that experience stress in early life form stronger memories of unpleasant experiences. These rats also have stronger activity in brain areas involved in fear when recalling unpleasant experiences in adulthood. This mirrors what is found in humans and means that we may be able to test potential therapies for human memory disorders on rats, ensuring that the treatments target appropriate areas in the brain.

Just Take A Breath

By Molly Campbell, University of Leeds, @mollyrcampbell

Take deep breaths. Try to relax. Stay calm. In stressful situations, this is the advice we often receive. More often than not, this tends to work.

What you might not be aware of is that this advice is thousands of years old, and is also supported by extensive scientific research. You’ve heard of the Buddha, right? At the core of the Buddhist teachings of mindfulness, meaning focusing on the present moment, is placing attention and focus on the breath. This has beneficial effects on our nervous system and subsequently our health.

yogi

Picture this. You are revising a particularly hard topic, perhaps a subject that you desperately need to ace to secure your college or university place. A train of thoughts frantically rushes through your brain and you panic. I’m not going to get the grade I want! I’m not going to get my college place and this will ruin everything for me! Sound familiar?

In these situations, our ‘fight or flight response’ (the sympathetic nervous system) can go into overdrive. Our heart rate increases, as does our blood pressure. This stress response actually limits the function of some of our vital organs – most notably the digestive system. It also limits our cognitive abilities, making it difficult to focus on the task at hand. So where does breathing come into the equation?

fightorflight.PNG

The breath is interesting because we can control it despite it being a function of the autonomic (or subconscious) nervous system. Pranayama, or ‘yogic breathing’ involves manipulating and deepening the breath; by doing so we cultivate awareness and consciousness that actually allows us to take the reins and stimulate our ‘rest and digest’ response (the parasympathetic nervous system), inducing relaxation.

How does this work? The vagus nerve, coined the ‘mind-body’ connection, is the longest nerve in the body. To avoid delving too deep into its anatomical route, let’s just say it innervates many organs and regulates many important functions. In the early 1900s, the German physiologist Otto Loewi found that simulating the vagus nerve reduces heart rate by releasing a substance that he called ‘Vagusstoff’. We now know that ‘Vagusstoff’ is actually the chemical acetylcholine that affects brain activity.

When we breathe deeply using our diaphragm, we create pressure in our abdomen that stimulates the vagus nerve to secrete acetylcholine. Acetylcholine slows down the heart and increases the activity of the digestive system.

Stimulating our ‘rest and digest’ response also inhibits our ‘fight or flight response’. One effect of this is decreasing the release of adrenaline from the adrenal medulla. This then reduces the action of adrenaline in the brain. This is another mechanism behind the physiological workings of breathing for relaxation.

In March of this year, scientists in Italy measured the physiological and psychological responses of students who performed deep breathing (Perciavalle et al., 2017). Considering that the 38 volunteers were university students, the findings are particularly relevant to exam stress. Half of the 38 volunteers did deep breathing exercises once a week for 10 weeks.

The exercises included paying attention to how one breath differs from another, and contracting and releasing the muscles. After 10 weeks, students had lower levels of the stress hormone cortisol, and lower heart rates.

In focusing on deepening the breath, we calm the nervous system and prevent our body going into ‘fight or flight’ overdrive. This sense of calm and clarity can help bring our attention to the present moment. Our anxiety about exams is regarding the future (What will happen if I fail?) or based on a mistake we made in the past. Using the breath to be present and aware allows us to focus on the now, on the task at hand. So, in times of stress – just take a breath!

References:

Nezlek, J., Holas, P., Rusanowska, M., Krejtz, I. 2016. Being present in the moment: Event-level relationships between mindfulness and stress, positivity, and importance. Personality and individual differences. 93(2016), pp. 1-5.

Bordoni, B and Zanier, E. 2013. Anatomic connections of the diaphragm: influence of respiration on the body system. Journal of Multidisciplinary Healthcare. 6(281-289)

McCoy, A. and Tan, Y. 2014. Otto Loewi  (1873-1961): Dreamer and Nobel Laureate. Singapore Medicine Journal. 55(1), pp. 3-4.

Perciavalle, V., Blandini, M., Fecarotta, P., Buscemi, A., Di Corrado, D., Bertolo, L., Fichera, F. and Coco, M. 2017. The role of deep breathing on stress. Neurological Sciences. 38(3), pp.451-458.