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THE
Issue 1, October 2017
S G NA L
STUDENT MAGAZINE
Neuroscience ● Behaviour ● Psychology ● Mental Health
What’s the point of science outreach? p7 the benefits of sharing your work with the public
Can stress cause dementia? p9 the possible link between high blood pressure and degenerative disorders
FEATURE ARTICLE
FROM WOMB TO TOMB: STRESS ACROSS A LIFETIME understanding how stress can affect our long-term health
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HIGHLIGHTS Letter from the editor
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Feature article: Stress across a lifetime
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Neuro tech: Using light to study the brain
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NeuroBites
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Science outreach—why do it?
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Can stress cause dementia?
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What can our guts tell our brains?
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Crossword competition
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Get involved—opportunities at The Signal
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LETTER FROM THE EDITOR Welcome to the first issue of The Signal student magazine! The Signal was born in Manchester in May 2017 by postgraduate students, with the sole aim to connect members of the student community who are interested in neuroscience, behaviour, psychology, and mental health. We hope that this magazine attracts a wide range of neuroscience enthusiasts, from those deciding what to study at university, to those about to finish their PhD. The theme for this issue is stress—something that affects all of us, can be potentially harmful to our health, but can also be prevented! Here you’ll find articles about the effects of stress on our lifetime health, and some handy tips to reduce stress. We’ve also written some great articles about other exciting neuroscience-related topics which we hope will spark your imagination. We are always on the lookout for new members of the team, so if you’re interested in science communication then please get in touch—contact details can be found at the bottom of page 18. We hope you enjoy the articles in this issue, and look forward to the future of The Signal!
Harry Potter PhD student
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F E AT U R E A R T I C L E From Womb to Tomb: Stress Across a Lifetime Harry Potter
Stress. What does it mean to you? We probably all refer to it after a long or strenuous day at work, during a particularly heated family argument, or when thinking about our finances. But what does the word really mean, and why is it so important in our everyday lives? Can it increase our risk of developing serious health conditions such as obesity, heart disease, and lung cancer? Is it something that can affect our children as they develop in the womb? Is it even something that can affect our children’s children? It may seem surprising, but the answer to all of these questions is yes.
body. Whenever the hypothalamus receives a stress signal, it tells our body to release stress hormones from the pituitary and adrenal glands. This so-called HPA (hypothalamus, pituitary, adrenal) axis releases a surge of stress hormones such as cortisol and adrenaline, which allow us to either extinguish the fire like a firefighter, or run away. You may have heard of this as the fight-or-flight response, which helps us survive dangerous or harmful experiences. So, if we need this response to survive, how can it be harmful to us? Imagine if the fire comes back on Tuesday, and every day next week, and the week after. Ok, a little bit unlikely - but for thousands, if not millions, of people, other types of chronic stress can change their health across their lifetime. When the HPA axis continually pumps out stress hormones, it changes the way we respond to stress, which can result in many different diseases such as depression, cancer, or heart problems.
“We all need a bit of stress in our lives. It’s a survival mechanism” Don’t get me wrong, we all need a bit of stress in our lives. It is after all a survival mechanism. When we experience a stressful situation, our bodies are elegantly prepared to respond in an appropriate way. Imagine walking into work on a Monday morning, and you start to smell smoke. A bit concerning? You walk a little further and you start to see the smoke too. Getting a little stressful in here, right? You reach the end of the corridor, and your office is on fire. You’re pretty stressed right now. As soon as you smell the smoke and see the fire, your nose and eyes send signals to a region of your brain called the amygdala, which is our bodies fear and emotion centre. Much like someone calling 999, the amygdala senses the stressful situation and sends a message to another brain region called the hypothalamus. The hypothalamus acts like a ‘stress call-centre’ for our
The word stress comes from the Old French word ‘estrece’, which means narrowness or oppression. In a way, this definition still applies today – chronic or continued stress can oppress our bodies stress response system and change our biology permanently, in ways that we have never understood better than we do now.
“Stress comes in many forms and can affect fetal development”
3 Across our lifetime, our bodies go through several important stages of development. Probably the most obvious is before we are born, when we are just a fetus surviving off our mother in the safe confines of the womb. But, like a lot of things, the human body is not perfect, and the womb can’t always protect us to allow us to develop normally. We all know that women should avoid smoking and drinking during pregnancy, but stress can also come in many other forms. The surge of hormones and molecules released during maternal stress are thought to be sensed by the fetus, and can affect development leading to diseases. In 1944, the German-occupied western region of the Netherlands had a severe shortage of food rations. As a result nearly every man, woman, and child was undernourished, having as few as 400 calories per day, and this was later named the Dutch Hunger Winter. Later, in the 1980s, a doctor named David Barker noticed something strange. Women who were a third of the way through pregnancy during the Hunger Winter were much more likely to have children who would grow up with serious health conditions such as obesity. And what about women who were later on in their pregnancy during the Hunger Winter? These women gave birth to children who would be much more likely to grow and develop mental health problems such as depression and schizophrenia. Babies who experience nutritional stress in the womb and who seem healthy at birth can often be afflicted for the rest of their lives with chronic health conditions. But is this an isolated case? What do we know about other forms of stress during pregnancy? The answer is that we’re learning more and more every day, with the help of pioneering scientific research. Pregnancy represents a critical period of brain development for the fetus, and stressful situations experienced by the mother can interrupt these processes. Things like physical and verbal abuse, losing a loved one, experiencing a natural disaster, or even something as simple as catching a cold – these forms of stress are sensed by the developing fetus, and can increase the chance of the child developing mental health problems such as schizophrenia, autism, and depression in later life. Unfortunately it doesn’t stop there. Most of us know that our brain carries on developing until our mid20’s, so it makes sense that we are still vulnerable to the
effects of stress throughout our lives. Like the fire coming back every day, some children experience adverse childhood experiences (known as ACEs), such as verbal, physical, or sexual abuse on a regular basis. This is thought to permanently change the way their brain and body responds to the stress hormones cortisol and adrenaline. The number of ACEs that a child experiences can predict how likely they are to develop conditions like heart disease, illicit drug and alcohol addiction, and mental health problems like depression and schizophrenia.
“Epigenetics … a possible mechanism by which life experiences can alter how our bodies work”
Stress
Increased risk for diseases in the adult offspring So why is this happening? Are stressful experiences ingrained into our DNA? The answer to this is both yes and no. DNA is our bodies ‘blueprint’, and what makes us unique. This blueprint remains the same across our life, and acts like a script so that our bodies know what to produce to keep us alive. Scientists have recently discovered that there is another layer of information on top of our DNA, like a sheet of plastic on top of the blueprint, which can change how our DNA
4 script is read. This discovery, known as epigenetics, is emerging as a possible mechanism by which life experiences can alter how our bodies work. Neuroscientists have shown that when rats don’t care for their pups in the week after birth, the pups grow up to have different epigenetic marks on the DNA in their brains. This changes their behaviour as adults, and can cause them to show symptoms of schizophrenia or depression. The lead scientist from this study, Professor Ian Weaver, says that rats not caring for their pups causes similar diseases to those seen in abused children. There’s plenty of scientific evidence to suggest that these life experiences can be passed onto our children through our epigenetic marks on our DNA, but what about our grandchildren? The recent migrant crisis in Europe has shown the world devastating pictures of families trying to escape war and poverty, leading to children floating in the water for days and people living on the streets and searching for food. A recent study used a scientific method known as a meta-analysis to show that the stress of being an immigrant increases the risk of developing schizophrenia not only for yourself, but more than doubled the risk for both your children and grandchildren. What can we do to stop this happening, for ourselves, and future generations?
“It’s not all doom and gloom – don’t stress about stress!” Scientists are now trying to work out how life experiences affect the epigenetic status of our DNA. They hope that when they understand this, they may be able to prevent or reverse the changes that cause diseases. New technologies can measure different epigenetic marks, such as DNA methylation, which can affect how fast or slow our DNA script is read. Since recognising the lasting effect on our wellbeing, health services have been committed to developing techniques to combat stress. It’s well-known that exercise is good for you and helps us lose weight, but it also helps to prevent schizophrenia and depression, and can even ward off Alzheimer’s and Parkinson’s disease. Mindfulness is a relatively new technique that can be used to help people to relax, reduce stress, and ‘live in
the present moment’. It’s a simple technique, similar to meditating, that encourages us to ignore the busy world around us, and be aware of our body and how we’re feeling. Sound a bit phony to you? Scientific studies have shown that structured mindfulness in children exposed to ACEs can significantly improve long-term health outcomes. Mindfulness is also endorsed by the NHS, and recommended by the National Institute for Health and Care Excellence (NICE) to help fight depression. It’s not all doom and gloom, so don’t stress about stress! Interest in this field of research has boomed in recent years, with many scientists looking to understand how maternal and lifelong stress impact disease development.
This article won first prize for written entry to the Biochemical Society Science Communication competition 2017. The next round opens in January 2017, and the Biochemical Society welcomes written and videos entries from undergraduate and postgraduate students.
Further information on stress and epigenetics. “How childhood trauma affects health across a lifetime”, TED talk by Nadine Burke Harris (2014). Online at: www.youtube.com/watch?v=95ovIJ3dsNk Bourque et al. (2011). A meta-analysis of the risk for psychotic disorders among first- and secondgeneration immigrants. Psychol Med, 41, p897-910. Isles (2015). Neural and behavioral epigenetics; what it is, and what is hype. Genes Brain Behav, 14, p6472. NHS resource on Mindfulness. Online at: www.nhs.uk/conditions/stress-anxiety-depression/ pages/mindfulness.aspx Weaver et al. (2004). Epigenetic programming by maternal behavior. Nat Neurosci, 7, p847-54.
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The story of optogenetics — how neuroscientists are using light to activate, and deactivate, brain regions to investigate their function. PhD student Paul Humphreys reviews recent progress in the field. All physical and emotional activity begins in the brain. Over 80 billion cerebral neurons create intertwined pathways and circuits that communicate through the generation and transmission of electrical impulses. Although we know that certain regions of the brain are responsible for primal functions, specific neuronal communication patterns that give rise to complex behaviours and emotions remain elusive. Crucially, manifestations of psychological disorders, such as anxiety and depression, are thought to have an underlying neurological component that arises due to breakdown in specific neuronal regions. If we can fully reveal the exact neurons responsible for such symptoms, we may be able to develop targeted therapies for their treatment. Attempting to control the brain through external means is nothing new. Scientists have tried to stimulate the brain through electrical and pharmacological means, but neither method has proven to be precise or rapid enough to unpick the complexity of neuronal circuitry. However, in recent years a new solution has come to light. Optogenetics is a novel technology that combines optics and genetics to enable control of cellular activity through light stimulation. The technology works by inserting naturally occurring sensory photoreceptors into the genome of mammalian cells to render them light sensitive. One of the first families of photoreceptors to be adopted for optogenetics were the channel rhodopsins; a family of light-gated ion channels found in algae that control movement in response to blue light. By inserting a channel rhodopsin into the genome of neuronal cells, immediate ion influx and subsequent neuronal firing can be induced simply by flashing a light. Not only can the technology be used to investigate neuronal behaviour in a dish, but it can also be used in live subjects. Mice can be injected with viruses that insert rhodopsin into selectively chosen neurons which are suspected to communicate in the same circuit. Light can
then be flashed using an implanted optical device which causes the entire neuronal circuitry to be activated, inducing behavioural changes. Using this method, neuroscientists have managed to isolate and activate areas of the brain that control behaviours associated with many different psychological conditions, including overeating, addiction and stressinduced anxiety. For example, a study selectively expressed channel rhodopsin in neurons within the locus coeruleus (LC) in mice, an area of the brain associated with anxiety. Neurons within the LC secrete the hormone norepinephrine, which increases in a stress response. Through controlling LC neuronal activation, the neuroscientists could reduce the levels of norepinephrine and consequently relieve the stressassociated symptoms. Although we may be some years away, it’s possible to imagine a future where stresses and anxiety are relieved by the pulsing of a calming blue light.
Suggested reading. McCall et al. (2015) CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress-Induced Anxiety. Neuron 87 (3), 605-620 Sparta et al. (2013) Optogenetic strategies to investigate neural circuitry engaged by stress. Behavioural Brain Research 255, 19-25 Neurons Responsible for Over-eating Revealed. Online at: www.youtube.com/ watch?v=7Mmsah0v9Qc
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Optogenetics is a new tool that lets researchers activate or inhibit neurons in the brain
Scientists from the UK and Switzerland have designed an app to help diagnose diseases such as Alzheimer’s. The game, Sea Hero Quest, anonymously tests user's navigational skills and could be used for earlier identification of dementia symptoms.
...investing in plastic surgery could improve parenting ability and success. A recent study has revealed that children positively associate attractiveness and trustworthiness. What's more, the more trustworthy you are, the more likely they are to listen experiencing the traumatic event itself through flashbacks or nightmares, the numbing of emotions as well as being very anxious; this can lead to other mental health problems such as depression.
Post-traumatic stress disorder (PTDSD) is a debilitating anxiety disorder that often manifests as a result of abusive or traumatic experiences e.g. military veterans or victims of sexual abuse. The symptoms include re-
Current treatment options include psychotherapy and medication such as antidepressants, although these aren’t effective for many sufferers. The U.S. Food and Drug Administration has recently
NEURO BITES when you tell them that they ‘have to go to bed now or they’ll be eaten by goblins’. Consider it an investment in your parenting and quality of life.
approved MDMA, more commonly known as the Class A drug ecstasy, for phase III clinical trials to treat PTSD, in combination with sessions of psychotherapy. This holds promise for a more effective PTSD treatment, as well as highlighting the potentially therapeutic role of mind-altering drugs in treating disease. Whilst offering hope for PTSD sufferers, recreational use, possession, or supply of MDMA remains illegal in the UK.
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Life as a scientist isn’t all about sitting in a lab wearing a coat and goggles. PhD student Jack Barton writes about the benefits of science outreach.
When I mention that I’ve gone out and spoken to people about my research, my supervisors seem excited and comment on how good it will be for my academic CV. Well, besides getting concerned I am doing too much extra stuff. As a person who has spent plenty of time ‘bugging’ people about science, I didn’t realise that I had already been doing something akin to outreach for years. To me, it was simply getting people to see how accessible and interesting science can be. For anyone who is interested in science, there is hopefully also an interest in starting a dialogue (also known as talking) with others about it. To me, this is all that science outreach is. It is about engaging nonscientists (and scientists from other fields) in our work. This should be done in a way that does not alienate people with jargon or unnecessary complication, and it can involve practical demonstrations of complex concepts through engaging displays, writing and the use of metaphors (and even dance). These skills are important
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Excuse me sir, do you have some time for me to chat to you about our Lord and Saviour, empirical evidence? *Oh no, it’s a scientist, just keep walking and pretend we didn’t hear him…* Sir… Sir, can’t I convince you to let science into your life? It has truly blessed mine. Read 7 months ago
for any future scientist. I won’t harp on about ‘post-truth worlds’ and ‘echo-chambers’, but I think now more than ever it is vital that scientists involve the public in the research process and encourage critical analysis of the evidence that’s out there. If we don’t, then scientists will continue to be treated as the owners of arcane knowledge that everyone else has to simply accept without scrutiny. This has clear implications for us all. So, why else should you take part in science outreach as a student? Well, a perfectly good and simple reason is because it’s fun! There is something very satisfying about getting people interested in what you do, or at least provoking interesting questions about research in general. It’s not uncommon for people to put up their “I’m not going to be able to understand science” shields, but it is a sheer pleasure to see people lower these and get involved. We may have spent years studying a specific research area, or even a small question, but that shouldn’t mean we are the only ones with interesting questions to ask. Second, it enables you to engage with a wide range of different audiences. So far, as part of science outreach I have worked with: primary school children, GCSE students, A-Level students, young media apprentices, adults of all ages, other PhD students, other academics in similar and different fields, artists, museums and ice dragons. Okay, I may have made the last one up, but these are only a few of the potential audiences that you could engage with. There are infinitely more that you could end up working with to ensure that your event, talk, art-piece or writing project is successful. For example, there is currently a fantastic initiative in Manchester to get local poets and scientists to produce thought-provoking art, and scientists can also inform fiction with real research. The third reason is a bit more mercenary but still important: career development. Funding organisations like to see where their money is going, and one easy way to
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assess impact is through public engagement. If you are able to illustrate that you’re comfortable engaging people in fun and exciting ways about your research, you also show that you are able to disseminate it effectively to the public who ultimately pay for it. This highlights your passion for an area and also shows your mastery through being able to explain even the most complex notion in a globally understandable manner.
The fourth reason is that science outreach provides you with new skills, as well as a chance to work on existing ones. The different types of outreach you can engage in are numerous, and there are few skills you would be cut off from developing by engaging in outreach. The obvious ones include writing, public speaking, time management, creativity and event organisation. For example, I used to be terrified of public speaking, but throwing myself into it as part of outreach has (almost) completely flipped that on its head. The final reason is one which might seem strange at first but bear with me. Science outreach can remind you of why you even started to research a topic in the first place. As a PhD student, I have faced the dreaded imposter syndrome and questioned whether research is
really for me on more than one occasion. Honestly, I can say that being dragged away from my computer or the lab and chatting to people about what I do dissolves those negative feelings pretty quickly. When you are not bogged down in the specifics of power calculations or what task to use, you can take a step back from your work and see it from the outside in. Mental health is something which many young academics struggle with and it is dealt with poorly, despite it being a well‑known issue. Although I can’t provide a citation for this (yet), science outreach can help you to still feel productive (because we seem to need that in life as scientists) and rediscover why you started your research project in the first place. If that can also make a few people go ‘wow’ in the process, then it can hardly be a bad thing. So, hopefully it should be evident by now that you should consider engaging in science outreach. There are lots of different opportunities for this and you should take advantage of as many of them as you can. If there is nothing that attracts your interest, then devise your own event! I’m still eager to see full length plays based on research and more collaboration with the arts. If nothing else, you could always consider writing for new and exciting publications that are keen to take on new writers (hint, hint). Manchester Science festival. Online at: www.manchestersciencefestival.com/event/ experimental-words-2 Mental health in academia. Online at: www.theguardian.com/higher-educationnetwork/2017/mar/03/mental-health-academia-offsick
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Regenerative medicine PhD student Geoffrey Potjewyd reports on the link between increased stress and hypertension in younger life and heightened risk of dementia in later life. Dementias are neurodegenerative diseases which cause progressive cognitive decline and shrinking of brain mass. Alzheimer’s disease and vascular dementia are the two most common forms of dementia, with vascular dysfunction forming part of pathology for both disease forms. Aging is the major risk factor for onset of dementia, which coupled with our increasingly aging population has resulted in startling predictions for a future increase in dementia cases over the coming years. In addition to our aging population, stressful and increasingly poor dietary lifestyles have resulted in higher blood pressure throughout the population, potentially worsening the rate of onset and progression of dementia through vascular dysfunction.
Vasculature is crucial to effective brain function. Although the brain only comprises 2% of the overall bodyweight, 20% of cardiac output (overall blood flow from the heart) is delivered to this organ. Therefore, cerebral blood flow is critical to delivering the oxygen and nutrients that the brain needs for cognition and regular function. Extended periods of time with high blood pressure – often brought on by stressful situations – can be detrimental to cerebral blood flow, and can damage blood vessels, leading to reduced clearance of toxic proteins associated with Alzheimer’s disease and other dementias.
Although there is a clear link between stress, hypertension and onset of dementia, it is also clear the role played is not directly causal, with a co-operative role in induction of late-onset disease being much more likely. Despite the non-direct causal link, the steady reduction in stress levels and blood pressure at an earlier stage in life could potentially reduce the burden of dementia cases drastically; with studies showing high blood pressure and stress levels from a young age or in middle ages can increase the risk of dementia.
“High blood pressure can damage blood vessels, leading to reduced clearance of toxic proteins” At present, there are drug trials which look at reducing the vascular impact and its contribution to dementia cases through reducing blood pressure. The increase in high salt diets which heighten blood pressure combined with stress levels that come with modern day lifestyle pressures also contribute to the onset of cardiovascular diseases, one of the other major diseases to affect western populations. This makes it extremely important to take care of ourselves and reduce the risk of dementia, and other associated stress related diseases.
Further reading on stress and dementia. “Is there a link between stress and dementia risk?”, blog by the Alzheimer’s Society (2017). Online at: blog.alzheimers.org.uk/research/stress-and-dementia Edmin, C.A. et al. (2016). Blood Pressure and Risk of Vascular Dementia. Stroke 47, p1429-35. Tadic, M. et al. (2016). Hypertension and cognitive dysfunction in elderly: blood pressure management for this global burden. BMC Cardiovascular Disorders, 16, p208.
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of the future? Could music therapy be used to treat depression and other diseases? Margarida Trigo investigates. Chronic stress results in an array of physiological problems. Stress may cause the shrinking of higher brain networks resulting in the death of brain cells, depressive moods and impairment of the immune system, all of which may contribute to premature ageing. Over the past decade, music has been tested as a novel therapy to reverse these effects by using specific frequencies and rhythms. We are all drawn to music - the “chills� some people experience when listening to a really good song are a result of activation of the dopamine reward system in the brain (the same system activated when eating and during sex). Experiencing, processing and responding to music requires complex integration of sensory and motor information, as well as attentional and emotional inputs. In order for this to happen, a large network of bilateral brain areas are involved when we listen to and process musical stimuli. Over the past decade music has been tested as a novel therapy to reverse these effects by using specific
frequencies and rhythms. Vibroacoustic therapy attempts to recreate the neuronal stimulation of music by using low frequency sounds to produce vibrations, which are then directly applied to the body of a patient though speakers in their chair or bed. Vibroacoustic therapy has been shown to decrease symptoms in Parkinson’s disease, fibromyalgia and depression. A distinct meta-analysis of 400 studies has shown that music not only improves the function of the immune system, but may also reduce stress. It showed that music was more effective than prescribed drugs in reducing anxiety through reduction in the production of the stress hormone cortisol, and simultaneously increasing production of an antibody called immunoglobulin. This has been replicated by other groups who also show that group singing reduces stress and improves mental wellbeing. All I have to say is: prepare for the future, where you will be prescribed music!
Interesting information on music therapy. O'Kelly "Music therapy and neuroscience: Opportunities and challenges." Voices: A World Forum for Music Therapy. Vol. 16. No. 2. 2016. American Psychological Association article on music as medicine. Online at: www.apa.org/ monitor/2013/11/music.aspx
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CAREERS SP TLIGHT Breaking the cycle of academia Sometimes life as a research student can seem relentless and inescapable. Psychology PhD student Natalie Busby writes about lessons that can be learned from a scientific career outside academia. Everyone assumes that doing academic research is a hugely stressful, all-consuming venture. And two years into my PhD, hundreds of cups of coffee and several failed experiments later, I’m realising, to some extent, that is exactly what it is. Flexible working hours often result in never-ending work days and an inability to leave work at work, and working independently on your own project often moulds you into your own harshest critic. Halfway through my own PhD I took a break to intern at a medical imaging company. Companies such as this conduct cutting-edge research in diverse teams of psychologists, physicists, biologists, and neuroscientists to name a few. Instead of researching for academic journal papers, the research here is for companies who are developing new research equipment or drugs which, if successful, can be used clinically to treat or diagnose illnesses. It was a research career I had never even considered, but one that immediately felt much less flexible but much more obviously meaningful. This research wasn’t necessarily discovering new theories or explanations but, if successful, could be changing the course of diagnosis or treatment for a clinical population. And that felt exciting! This internship opened my eyes not only to a whole new potential career route, but also to a whole new
working environment. At noon on my first day when everyone started leaving the office I thought it was a fire drill but they were actually just going for lunch. Lunchtime in my PhD office is a few hurried bites of a sandwich between clicking through analyses or while reading a research paper. I followed them and sat outside in the sunshine feeling like a naughty schoolchild skipping a lesson.
“Academic research doesn’t have to be such an allconsuming stressful career choice” I could feel the stress melting away as I had the chance to talk to these people, find out their backgrounds and what they were working on, and when 4pm rolled around my usual mid-afternoon slump was yet to hit and I was still feeling productive. At 5pm everyone said their goodbyes and left for the day. I walked slowly to my car, thinking about all the things I could do with my free time this evening. And that’s not to say that no work was done, it was the opposite in fact. The month I spent on my internship was probably one of my most productive. And it led me to realise that academic research doesn’t have to be such an allconsuming stressful career choice. Maybe once you realise that it is just a job, and that a lunch-break or a day off might actually boost productivity, academic research might become a much less stressful endeavour.
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The city of blinding lights The 2017 Nobel Prize in Physiology or Medicine has been awarded to three neurobiologists for “their discoveries of molecular mechanisms controlling the circadian rhythm". PhD student Sarika Paul explains what it all means. Humans, alongside every other organism on this planet evolved alongside a robust and predictable 24 hour light dark cycle. This has resulted in almost all body systems oscillating, predictably, over 24 hours, our circadian rhythms. The most obvious of these rhythms is the sleep wake cycle, however these cycles are also found in your heart rate, immune function, muscle strength and cognitive function. These oscillations have been occurring for millennia. The advent of electric lighting however, has enabled us to overcome the natural light dark cycle. Light provides a timing signal to the body by supressing the production of a hormone called melatonin, this hormone plays an important role in triggering sleep, but it has other roles, including in regulating the concentrations of other hormones (oestrogen and progesterone).
implicated as risk factors for mood disorders such as bipolar, and most recently in mouse models of epilepsy. Light itself can also induce a release of cortisol, the stress hormone, which has profound effects throughout the body, on blood pressure, blood sugar and heart rate. Extended exposure to light at night has also been linked to increased rates of mood disruptions.
“Circadian rhythms have become an incredibly popular area of science� In modern societies, incidence of both cancers and mental health disorders are increasing, and while some of this can be attributed to increased diagnosis, our lifestyle is also being examined, and chronic light exposure might be to blame. Circadian rhythms have become an incredibly popular area of science, and indeed just won the Nobel prize for the molecular mechanisms that underpin these oscillations. And it is not all doom and gloom, as increasing our understanding of the mechanisms behind these negative effects has led to new treatments. A relatively new medication known as Agomelatin acts on the melatonin receptor, and works as an effective anti-depressant.
Due to electric lighting, our exposure to daytime levels of light exposure have been extended by 4-7 hours, this is a huge proportion of time in which we are artificially supressing melatonin release. Night time light exposure has been linked to increased incidences of breast cancer, and it is thought that melatonin signalling might mediate this, via its interaction with other oestrogen and progesterone. This effect is so serious that the WHO has listed shift work as a probable carcinogen. The molecular components of the circadian system have also been
Light itself can be used as a treatment, logically, for the treatment of seasonal affective disorder, but also, more recently, for the treatment of bipolar disorder. The mechanisms are unclear, and the timing of light delivery appears to be crucial, but these results open up the circadian systems as therapeutic targets. Nobel Prize press release 2017 www.nobelprize.org/ nobel_prizes/medicine/ laureates/2017/ press.html
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Emerging evidence suggests that our guts play a larger role in the way we think and feel than we previously thought. Postdoctoral researcher Dr Leah Kivivali explains how.
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What is Seasonal Affective Disorder (SAD) and why are our moods affected by the time of year? Behavioural Neuroscience PhD student Harry Potter reviews recent progress in understanding the disorder. We all know about the mental health crisis that the world is facing today. The Mental Health Foundation estimate that 1 in 6 people have experienced a mental health issue in the last week alone. We hear about the most common disorders all the time, like depression, schizophrenia, and bipolar disorder. But scientists have started to recognise all sorts of other disorders in recent years. Seasonal Affective disorder, or SAD for short, is a mental health disorder which affects about 1.2% of the global population, and has symptoms very similar to depression. These include persistent low mood, feelings of despair and guilt, and inability to derive pleasure from daily activities. The unique feature of SAD is that episodes appear to be linked, as the name suggests, to the seasons of the year. The symptoms often get better during the summer months, and return during winter. A common misconception in the study of affective disorders (that is, disorders which have an effect on our affect – otherwise known as our mood) is that patients are just in an acute low mood. Large population studies have shown that certain genetic mutations dramatically increase our risk of developing affective disorders, as well as environmental factors like early life trauma, or chronic stress. So what causes SAD?
A study in 1998 showed that people with SAD had a mutation in the receptor for serotonin, a neurotransmitter that controls feeling of well-being and happiness. When patients with SAD had a diet low in the amino acid tryptophan, which is metabolised to produce serotonin in the brain, their depressive symptoms got worse.
During each 24-hour cycle of the day, our eyes transmit light signals to a region of the brain called the suprachiasmatic nucleus (or SCN for short). The SCN acts as a master clock, and using these light signals, sends signals to every other cell in our body to tell them whether it’s day or night. This process, known as circadian rhythms, is essential for letting our cells know what metabolic processes they need to be doing. People with SAD seem to deviate from this 24-hour cycle, which may push this precisely timed rhythm off cue. Some
16 scientists think that the shorter days in the winter may contribute to this, and leave people with SAD more susceptible to circadian rhythm abnormalities.
Light box therapy is based on a similar concept, and involves sitting next to a special lamp for up to an hour each day to try and reset the body clock.
“Patients with SAD have asymmetrical metabolic activity in their brains”
Scientific studies have expanded our understanding of SAD, and are leading to new ways to treat the disorder. The NHS and Mind websites have more resources and information on SAD, available in the links below.
But does this have any implications for the normal functioning of the brain? When patients with SAD had their brains imaged in scanners, researchers found that they had asymmetrical metabolic activity in the left and right sides of their brains. Specifically, they showed that there was a much higher rate of metabolic activity in the left medial prefrontal cortex.
More infor mation on diagnosing and treating SAD.
A recent study in 2017 has shown that compared to healthy controls, people with SAD experience specific cognitive deficits during winter months. For example, they had impairments in working memory, and cognitive processing speed. These deficits were also related to the severity of depressive symptoms that patients reported – in other words, the more severe the depression symptoms, the more severe the cognitive impairments. Now that we’re understanding more about SAD, scientists are trying to develop therapies and lifestyle changes that could help to treat it. The Royal College of Psychiatrists recommend getting as much exposure to natural light as possible, to try and properly entrain our 24-hour body clocks. As well as this, light box therapy has shown to be effective in treating some cases of SAD, although some scientists and doctors aren’t convinced of the benefits.
NHS resource on SAD. Online at: www.nhs.uk/Conditions/seasonal -affectivedisorder/Pages/Introduction.aspx Information on SAD from the charity Mind. Online at: www.mind.org.uk/information-support/ types-of-mental-health-problems/seasonal-affectivedisorder-sad/#.WeC9v1tSyUk Rosenthal et al. (1998). Role of serotonin transporter promoter repeat length polymorphism (5 -HTTLPR) in seasonality and seasonal affective disorder. Mol Psychiatry, 3, p175-177. Hjordt et al. (2017). Season-independent cognitive deficits in seasonal affective disorder and their relation to depressive symptoms. Psychiatry Res. Online at: www.ncbi.nlm.nih.gov/ pubmed/28780278
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CROSSWORD COMPETITION Fill in the answers to find the letters on the green tiles—an anagram of these will give you a word found in an article in this magazine. Tweet us @ T he S i gna l U o M with your answer to be in with a chance of winning a prize!
Down
Across
1. Unit of sound intensity (7)
2. US state (10)
2. Major division of the vertebrate brain which coordinates muscular activity (10)
7. The second studio album of American rock band R.E.M., Shiny Happy ______ (6)
3. Plastic construction toy (4)
8. Dorset town with a large natural harbour (5)
4. Enemy (3)
10. Referring to the processes which alter DNA transcription, e.g. methylation (11)
5. Unit prefix denoting 10-9 (4) 6. Endocrine gland responsible for cortisol secretion (7) 8. 1980’s Japanese arcade game (3-3) 9. Vulnerable species of mammal (5,5) 11. Official language of Myanmar (7) 12. British athlete, Sir Mo _____ (5) 14. Metropolitan borough of Greater Manchester; to completely cover (4)
11. American TV series drama starring Dominic Purcell and Wentworth Miller, Prison _____ (5) 13. (Informal) a mixed drink not containing alcohol (8) 14. A person with dark brown hair (8) 15. Relating to stars (7)
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Acknowledgements The Signal is an entirely voluntary venture, made up of students, scientists, and keen science communicators across several universities. Below is a list of contributors, both writers and editors, without whom producing this magazine would not be possible, and their current home institutions: Jack Barton (The University of Manchester) Natalie Busby (The University of Manchester) Chris Hoyle (The University of Manchester) Paul Humphreys (The University of Manchester) Leah Kivivali (The University of Melbourne) Sarika Paul (The University of Manchester) Geoffrey Potjewyd (The University of Manchester) Harry Potter (The University of Manchester) Jules Schneider (The University of Manchester & Cardiff University) Margarida Trigo (The University of Manchester)
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