A tale of anxiety and reward – the role of stress and pleasure in addiction relapse

At the start of February we heard the horrible news that Philip Seymour Hoffman, a wonderful Academy Award winning actor, had died from a drug overdose. This followed news from last year of the death of Glee star Cory Monteith from a heroin and alcohol overdose. Perhaps the most shocking thing about these deaths was that no-one saw them coming.

Worryingly, the reality is that drug relapses such as these are all too common, but often go unnoticed. Our understanding of the science behind these relapses has come on leaps and bounds in recent years. We have moved from understanding how a drug makes us feel pleasure, to understanding how a drug may cause addiction and subsequent relapse.

Classically, scientists have explained addiction by focusing on how a drug affects the reward systems of the brain. Drugs have the ability to make us feel good due to their actions on this pathway. The reward system of the brain is a circuit that uses the chemical dopamine to stimulate feelings of elation and euphoria. This system has a motivational role and normally encourages survival behaviours such as obtaining food, water and sex. Drugs of addiction can hijack this system to induce euphoric feelings of their own.

Cocaine, for example, is a highly addictive drug that blocks reuptake transporters of dopamine. These transporters normally soak up excess dopamine and ensure that the reward system is not overactive. Cocaine stimulates euphoria by preventing dopamine from being retrieved and increases stimulation of the reward system. Another addictive drug, nicotine directly stimulates the reward system to produce more dopamine.

These classical views work well when considering the motivation to start taking drugs and to continue taking drugs in the initial stages. The drug stimulates feelings of euphoria, ‘rewarding’ the taker. The taker learns to associate taking the drug with these feelings of euphoria and therefore the taker wants to do it more.

This theory can also explain some aspects of withdrawal. Just as activation of the reward system has a physiological role, so does shutting it down. It appears there is such a thing as ‘too much fun’. If we spent all of our time copulating and over-eating we’d be prime targets for predators. Due to this, the body has its own off-switches in our reward pathways that try to limit the amount of pleasure we feel. These normally work by desensitising the brain to dopamine, so that dopamine isn’t able to produce the effects it once could.

Addiction A tale of anxiety and reward – the role of stress and pleasure in addiction relapse

During drug use, when dopamine levels and subsequent pleasurable feelings are sky-high, the brain works to limit the effects of this overload of dopamine. When the drug wears off, dopamine levels fall but the desensitisation to dopamine persists. This causes withdrawal, whereby when there are no drugs to boost dopamine, one fails to gain pleasure from previous pleasurable day-to-day activities. The dopamine released when one has a nice meal for example, is no longer sufficient to cause enough activity in the reward pathways and no satisfaction is felt.

Scientists believed for a while that the reward system could tell us all we need to know about addiction and how it manifests itself throughout the brain. However, tolerance builds and the euphoric responses to these drugs begin to wane. Some users start feeling dysphoria, a horrible sombre feeling, and don’t know why they continue using these drugs as they are no longer experiencing euphoria – the reason why they took the drug in the first place.

On top of that, when doctors and therapists talk to drug addicts who relapse, the addicts often do not talk about wanting to feel pleasure, wanting to feel elation again. They talk of stress building up inside them, the release from this stress they want to feel.

When asked about why they relapsed, previously clean addicts often talk of stressful events leading to their relapse – they lost their job or they broke up with their partner. First-hand accounts suggest this stress seems to be the driver of a relapse, the driver to continued addiction.

This is depicted clearly back in the 19th century by the eccentric American author and poet Edgar Allan Poe:

“I have absolutely no pleasure in the stimulants in which I sometimes so madly indulge. It has not been in the pursuit of pleasure that I have periled life and reputation and reason. It has been the desperate attempt to escape from torturing memories, from a sense of insupportable loneliness and a dread of some strange impending doom.” 

Intrigued by this, scientists have now found many threads of evidence to suggest that stress pathways within the brain play a key role in addiction and relapse. For example, work into this so-called ‘anti-reward system’, has led to proof that stress can instigate drug-seeking behaviours in animal studies.

Our stress pathways are built around a hormone system known as the HPA axis – the hypothalamic-pituitary-adrenal axis. This axis is responsible for regulation of many biological processes but plays a crucial role in stress.

HPA axis A tale of anxiety and reward – the role of stress and pleasure in addiction relapse

The HPA axis is the stress hormone system of the body.
CRF = corticotrophin releasing factor; ACTH = adrenocorticotropic hormone

Much like other drugs of addiction, drinking alcohol feels good due to its actions on the reward system. In line with addicts of other drugs, alcoholics commonly talk about the release of stress they want to feel. Evidence is building to suggest that alcoholics have increased activity through the HPA axis.

A hormone called cortisol is the final chemical involved in the HPA axis, released from the adrenal glands during times of stress. Compared to occasional drinkers, alcoholics have higher basal levels of cortisol and a higher basal heart rate – two common measures of HPA activity. This pattern has also been seen in other addictions. For example, in previously clean cocaine addicts, higher basal HPA axis activity correlates with an earlier relapse and higher levels of stress hormones (e.g. cortisol) can predict a higher usage of cocaine in the future.

A puzzling scenario surrounding addiction is how most users can enjoy occasional usage but for some, this can spiral uncontrollably into an addiction? The likelihood of different individuals having a higher propensity to addiction could well be explained by differences in how different people respond to stress.

So what begins as a behaviour driven by the reward pathways appears to have now escalated into a behaviour dominated by stress pathways. It seems it is the stress that drives the craving and relapse, not the longing for a ‘reward’.

Armed with this knowledge, work into how we can design medicines to alleviate cravings and prevent relapse has shown early potential. Blocking the first stage of the HPA axis has been able to prevent alcohol addiction in rats. Blocking a suspected link between the stress pathways and the reward pathways has shown to be able to prevent stress-induced cocaine seeking behaviour.

These compounds have yet to be tested in humans but the early promise is there. It is an intriguing theory that the susceptibility to stress of different individuals may explain the varying susceptibility to addiction. This idea provides a basis for further work to try to understand why some individuals can only occasionally use, whilst others become addicted. Relapse is a horribly common situation amongst drug addicts and with the stigma attached giving addicts substantial additional stress, it is well-worth the research to prevent more unnecessary deaths. Unfortunately, this will be too late for those we have already lost, but the future is bright with continued progress in understanding these horrible ordeals.

By Oliver Freeman @ojfreeman

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A smoking revolution – What’s in a cigarette?

Cigarette 300x250 A smoking revolution   Whats in a cigarette?Travel back in time to the forties and fifties. Smoking was seen by some as a fashion statement. This was before we were clued-up on the abundant chemicals and the massive impact it could have on our health.  As research into cigarettes snow-balled, smoking became less fashionable. Even so, there are still many people around the world who smoke.

This week has seen a drastic change in UK laws regarding smoking.

The UK Government has decided to ban smoking in cars when children are passengers. This change has come after shed-loads of research over the last couple of decades has highlighted health risks associated with smoking that far outweigh the benefits.

But is smoking really as harmful as the Government drums into us on a daily basis?

The statistics seem to speak for themselves; almost 80,000 deaths occurred in the UK in 2011 as a direct result of smoking. What’s more, around 11,000 people die from passive smoking each year (according to Cancer Research UK), and around 9,500 children are admitted to hospital with smoking-related problems from passive inhalation.

So what exactly is in cigarettes that make them so addictive and what produces these toxic effects?

Nicotine-  a plant-derived chemical in cigarettes that is responsible for the addictive nature of smoking. The chemical enters the blood stream by inhalation and absorption through the air sacs in the lungs. It is then carried by the blood into our brains, where it binds to cholinergic receptors.  Usual functioning of these receptors helps to maintain some of our normal bodily processes, but  when nicotine is inhaled  it changes the number of these receptors and also alters their sensitivity to nicotine.  This is the mechanism responsible for smoking addiction- nicotine needs to be used regularly to keep the brain ticking over.

Tar- the gunky stuff in cigarettes that is deposited mainly in the gas exchange region of the lung, and carries all the nasty chemicals that are toxic to our bodies. Apparently there are almost 4,000 of these chemicals in each cigarette smoked, many of which can cause cancer.  Not surprisingly, tar can affect the proper functioning of the lungs. It also ‘clogs’ the cilia that trap bacteria and dirt, so that dangerous substances can enter our lungs.

Carbon monoxide- the chemical in cigarettes that significantly reduces the oxygen-carrying ability of our red blood cells, as it is 200 times more attractive to our blood than oxygen. As the lungs are no longer able to supply our bodies with enough oxygen, we start to have issues with our breathing as we try to take in more oxygen, and also put our heart under immense strain as it tries to supply us our organs and muscles with enough oxygen (amongst many other things!).

Cigarette 2 300x203 A smoking revolution   Whats in a cigarette?

Arsenic- a carcinogen that affects how the body repairs DNA.

Benzene- a solvent and carcinogen used in petrol

Formaldehyde- a chemical and carcinogen most commonly used to preserve dead bodies.

Polonium – a radioactive substance

Hydrogen cyanide- poisonous gas that damages the heart and blood vessels

Yet despite these major health risks, large numbers of us are still regularly lighting up.

In 2012 approximately 20% of the UK population smoked cigarettes on a regular basis. Astonishing statistics also showed that 10% of school pupils aged 15 were regular smokers. Not only this, but the average number of cigarettes smoked per day was 12.  Despite these figures, many smokers say that they wanted to give up smoking.

Based on all the frankly quite frightening research that hasn’t been brought to our attention, reducing smoking and passive inhalation is something that the Government is beginning to take seriously. Some of the changes that have already been introduced are;

  • Government bans smoking in public buildings and enclosed places in 2007. Having just been old enough to go to clubs and pubs before the smoking ban came into place, I really reaped the benefits when smoking was banned in public places. I was able to enjoy a night out with my friends, without coming home smelling of an ash tray. I wouldn’t have minded so much if I actually smoked myself!
  • Stopping promotion of tobacco products- Advertising of cigarettes is banned (2003), and supermarkets are permitted to hide tobacco displays (2012).
  • Tobacco tax- Tax rates on cigarettes are high, apparently with the aim to put people off smoking, and nothing to do with the revenue it makes them!
  • Anti-smoking campaigns- These campaigns aim to get people to quit smoking by making them aware of the health risks, dissuading young people from taking up smoking and trying to educate people on the risks of passive smoking.
  • E-cigarettes- These electronic imitation of cigarettes are currently a massive craze in the UK. In theory these are a great alternate to smoking; they retain all the ‘good parts’ of smoking, without all the added health risks. As these are relatively new they are not well regulated, so more research is needed to evaluate their health impact.

We know for certain that smoking is damaging to the body and has serious health implications. I have provided a (somewhat biased) summary of the health-related impact that smoking can have, from a non-smokers perspective. Another thing is also clear; the Government are taking smoking seriously. They are tackling this issue in a number of vital ways from trying to stop the ‘glamorisation’ of smoking by banning advertisements, reducing the impact on non-smokers, research and regulation into ‘better’ alternatives and in my opinion the best way possible; educating the public on the harmful effects of smoking. Next time you reach for a cigarette just cast a thought to some of the chemicals and toxins that you are putting into your body, and be aware of how this may be affecting yours, or someone else’s health.

 

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What is a headache?

We all know the feeling after a long stressful day, when the tensions of the past few 415px Tension headache 150x150 What is a headache?hours begin to amass in your temples, perhaps starting as a dull throb before advancing in waves to a deep pounding ache. The headache is a common malady, but what mechanisms lay behind these debilitating pains and which aspects of your life may be triggering them?

The question of why and how we experience headaches is significantly harder to answer than you might imagine. Particularly since the term ‘headache’ is in itself non-specific, being a broad term used to describe a range of common head pains, each of which may stem from a different underlying cause. Interestingly, however, one thing we do know is that the pain you experience during a headache does not originate from the brain itself. Indeed, the brain lacks pain receptors (nociceptors), therefore does not have the capacity to feel pain.

543px Gray507 150x150 What is a headache?But then where does the pain of a headache come from? The pain we experience during an everyday headache originates in pain-sensitive structures surrounding the skull. These include; the extracranial arteries, veins, cranial and spinal nerves, neck and pericranial muscles – all of which express pain receptors and are therefore susceptible to these sensations.

It is possible to pin down a number of simple lifestyle factors which commonly contribute to the development of headaches. These include; emotional disturbances, stress and mental tension, certain types of food, alcohol, cigarette smoke, exercise and even the way you wear your hair – hair-dos (including the tight ponytail, braids, headbands and even tight hats) can strain the connective tissue that lies across the scalp and cause headaches. So simply letting your hair down can relieve this pressure and thus the pain of the headache.

A number of the factors which lead to headaches (including certain foods, cigarette smoke and alcohol) involve the blood vessels which lie around the brain. For example, inhaling nicotine from cigarette smoke causes narrowing of blood vessels around the skull. Narrowing of these vessels can often induce extremely painful headaches. Changes in blood pressure also explain hangover and exercise headaches and why, for some people, certain foods can act as headache triggers.

6708719835 b2f15fc2e3 150x150 What is a headache?The episodic tension headache (the type you may get after a long day at work) is the most commonly occurring type of headache. However despite the extensive research into the cause of migraines, this common type of headache remains one of the least investigated. As relief can normally be sought through over-the counter painkillers, most sufferers will not consult a doctor. The mechanisms underlying what specifically causes these headaches remains elusive, however, a number of theories regarding their pathophysiology have been proposed:

It appears that the occurrence of headaches are commonly linked to general problems of the musculoskeletal system. Skeletal muscle constitutes the largest muscle mass of the body, controlling movement, breathing, facial expressions and numerous other normal physiological functions. Each individual skeletal muscle is composed of hundreds of cells, arranged in muscle fibres. Each muscle fibre is connected to the nervous system via interactions with a single branch (an axon) of a nerve cell.

Each fibre of a muscle can relax or contract in response to signals sent from the brain via these nerves. These muscle fibres also contain sensory receptors which can feedback the health of the muscle to the brain. This helps tell you when the muscle is tired or overstretched for example. Abnormal activity in these nerves, perhaps as a consequence of injury, stress or poor posture, can therefore result in the relay of pain signals to the brain. For example, bad posture places abnormal pressure on the muscles of the neck which can result in heightened tension and the subsequent development of ‘tension headaches’.

Interestingly, tension headaches can also be induced by activation of so-called ‘trigger points’. A trigger point is defined as ‘a hypersensitive area of the body, associated with taut bands within a skeletal muscle’. Pressure or compression on these localized trigger points can cause the referral of pain along linked nerves to a nearby area. So, the presence of active trigger points in your head, neck and shoulder muscles can refer pain that will be subsequently experienced as a headache.

A number of studies have confirmed this, identifying an increased number of trigger points in the muscles of the head in patients prone to headaches, compared with patients who do not regularly experience headaches. What causes these trigger points to develop in the first place still remains unclear, however, some have speculated that they may be associated with past muscular injuries, fatigue, diet and even as a result of chronic repetitive strain, such as persistent typing.

5621720708 3e3b9c45c1 150x150 What is a headache?Infrequent headaches, while menacing, are nothing compared to their chronic cousins. Infrequent headaches can become chronic as a result of changes that originate in the brain and spinal cord. This involves so called ‘second-order’ nerve cells which act as connectors between peripheral organs (e.g. the skin and muscles) and nerve cells in the spinal cord and brain.

A number of studies have proposed that chronic tension headaches may be triggered by changes in the sensitivity of these second order nerves, particularly those in the spinal cord and an area of the brain known as the trigeminal nucleus. This process is known as ‘central sensitization’ and can alter pain thresholds and trigger nerve cell activity. It is hypothesized that, in the presence of persistent stress or pain signals from peripheral muscles (such as that brought about through regular bad posture), nerve cells can grow forming new connections and effective contacts to low-threshold nerves that do not normally signal for pain. Furthermore, increased sensitivity can be caused by the enhanced release of chemicals that facilitate nerve cell communication. This increase in the number of pain signalling nerves and their sensitivity to strain and tension results in enhanced pain sensitivity, lower pain thresholds and the development of chronic pain states.

Chronic pain states, may be a result of prolonged stress and musculoskeletal tension, alongside central changes in the brain and spinal cord. So, if regular headaches are wearing you down you might benefit from trying to reducing your stress levels, being aware of dietary triggers, improving your posture and trying exercises to relax your muscles.

Post by: Isabelle Abbey-Vital

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Michael Schumacher’s traumatic brain injury explained

Schumi di GP Kanada 2011 cropped Michael Schumachers traumatic brain injury explained

Photo by Mark McArdle

Seven times Formula 1 World Champion and holder of a huge number of driving records, Michael Schumacher is thought of as the greatest F1 driver of all time, a champion among champions. On 29th December last year on a ski slope in the French Alps, Schumacher fell and hit his head on a jagged rock. Witness reports claim that he lost consciousness for about a minute, but that ten minutes later, when the emergency helicopter arrived, he was conscious and alert. Over the next two hours, however, Schumacher’s condition deteriorated and since that day, he has had two head operations and has remained in intensive care under a medically-induced coma.

Epidurales Haematom Michael Schumachers traumatic brain injury explained

An epidural haemotoma caused by a fracture in the skull (indicated by the arrow). Image by Hellerhoff.

Traumatic brain injury, or TBI, is quite a vague medical term and simply describes any injury to the brain sustained by a trauma – that is, a serious whack to the head. TBI is the most common brain disorder in young people: while older people are at higher risk from degenerative diseases, young people are more likely to find themselves in car crashes, fights or…ski accidents.

The specific type of TBI that Schumacher is believed to have suffered is an epidural haemotoma (click here for a seriously gory video of a haemotoma clot removal – you have been warned). Between the brain and the skull are a number of protective layers; these are membranes which encapsulate the brain and spinal cord, all of which swim around in cerebrospinal fluid. An epidural haemotoma is a bleed between the tough outermost membrane, called the dura mater, and the skull. Technically this sort of bleed isn’t in the brain itself, but this injury seriously affects the brain due to one important factor: pressure.

Brain herniation types 2 Michael Schumachers traumatic brain injury explained

Six ways a brain squeezed by a bleed can go. Coning (indicated by number 6) is a last resort but compresses respiratory centres and can be fatal. Image by Rupert Millard.

Since the skull is an almost totally enclosed space, a bleed that grows too big in size could end up pushing, not just on the inside of the skull, but on the brain itself – squeezing it into an ever-decreasing volume. When put under pressure the only way the brain can physically go is down towards the spinal cord, but if this happens, the brainstem at the base of the brain may become compressed. This horrible scenario, known as ‘coning’, has a really high fatality rate, as the brainstem is needed to keep our heart pumping and lungs breathing. So keeping intracranial (in-skull) pressure low after TBI is key.

Doctors have reported that, as well as a haemotoma, Schumacher suffered contusion and oedema. Cerebral contusion is essentially bruising, as you might expect in other parts of the body: tiny blood vessels bleed when they have suffered a serious hit – in this case either from the rock itself, or from the other side of Schumacher’s skull in a ‘rebound’ type impact. Oedema, or swelling, may come as a result of the contusion – like when a bruised knee swells – and again would need to be curbed in order to prevent the pressure inside the skull from rising dangerously.

 Michael Schumachers traumatic brain injury explained

Illustration by Max Andrews.

So what have the doctors done to treat Michael Schumacher’s condition? Well, firstly, the surgeon Prof. Stephan Chabardes has reportedly performed two operations to remove blood clots from the haemotoma, as well as a craniectomy – removal of part of the skull – in order to relieve the intracranial pressure and prevent coning. Craniectomy has been used for some time to treat both TBI and stroke, but remains somewhat controversial, mainly because of the risks of further bleeds, infections, or herniation of brain tissue through the surgically-made hole in the skull.

The second main strategy in treating Michael Schumacher has been to keep him under an artificial or medically-induced coma. This involves sedating him with strong anaesthetic agents. Propofol, which quietens brain activity by boosting inhibitory GABAA (‘off’) receptor activity and by blocking sodium (‘on’) ion channels in neurons, or barbiturates, which also enhance GABAA receptors, but block excitatory glutamate (‘on’) channels could be used to keep him sedated and to ‘slow’ his brain down. Slowing is achieved through a net reduction in excitatory activity within the brain. Thus, the medically-induced coma not only stops the patient being conscious, through what no doubt would be a painful experience, but also limits the amount of activity-related blood flow, curbs swelling and prevents what’s known as excitotoxicity.

Pts bar graph by severity Michael Schumachers traumatic brain injury explained

Risk of post-trauma seizures after TBI by the severity of the initial injury. Graph by Delldot (wiki).

Excitotoxicity can occur after TBI, stroke or in patients with epilepsy. It is a term used to describe what happens when brain cells run out of energy or become overloaded with excitatory inputs. In this state cells become overexcited and die, either immediately, or after a delay. Seizures, which can cause excitotoxic cell death, are fairly common after severe TBI and are thought to drive brain damage after the original injury. Seizures after TBI can be worsened by swelling and higher temperatures, so it is likely that Schumacher has been kept a few degrees cooler than his normal body temperature to limit this risk.

 Michael Schumachers traumatic brain injury explained

Data as interpreted from Laureys S, Owen AM, Schiff ND (2004). “Brain function in coma, vegetative state, and related disorders”. The Lancet Neurology 3 (9): 537–546. Graph by Shin Andy Chung.

If he is still in a medically-induced coma, or is gradually being weaned off the anaesthetic agents, Schumacher may be undergoing physical therapy to move his limbs and joints to prevent muscle wastage, or contracture, which is irreversible muscle shortening. If his condition improves and he is able to move, his limbs will need re-strengthening.

Some conflicting reports suggest that doctors treating Michael Schumacher may have started removing him from his coma. If they are doing this, the full extent of their patient’s rehabilitation needs won’t become clear for some time. While I obviously hope the driving legend makes a full and speedy recovery, it is hugely unlikely that his brain will completely recover all its previous functions. The brain is such a delicate organ and Schumacher’s tragic case only highlights its fragility.

 Michael Schumachers traumatic brain injury explained

Hugo Lloris in 2012. Photo by Stanislav Vedmid.

Schumacher’s injuries also raise the debate on the guidelines of treating head injuries in sports. Last November, Tottenham’s Hugo Lloris lost consciousness after a hit to his head during a football match, but after waking up was allowed to return to the pitch to finish the game. Lucid intervals, such as the one reported shortly after Schumacher’s fall, can be deceptive and players of contact sports should always be given immediate medical attention after losing consciousness. It’s no news that the cumulative effects on the brain of losing consciousness multiple times – as many boxers do on a regular basis – are to be avoided at all costs.

Every year in the USA, 1.7 million TBIs – more than double the number of heart attacks – contribute to almost a third of all accidental deaths as well as varying levels of lasting disability. While we hold our fingers crossed for Michael Schumacher’s successful rehabilitation, we must also think of the other thousands of people, and their families dealing with the long-term aftermath of serious brain injuries around the world.

 Post by Natasha Bray

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Playing at a better future: Could video games improve your life?

954632422 bdaace0ea6 m Playing at a better future: Could video games improve your life?Your brain is plastic. No, not like the picture to the right but in the sense that everything which makes us who we are (our thoughts, beliefs and understanding of the world around us) can be subject to change. This change may come from our interactions with the world, as we learn to adapt and live in a changing environment, or the change may come from within, as we make conscious decisions to view the world differently. This natural plasticity helped our ancestors adapt when their environments changed and undoubtedly played an important role in their continued survival. However, a recent media storm has grown around the way brains, especially teenage brains, may be altered in response to societies’ increasing use of technology. This interest has raised concerns surrounding the impact technology, such as social media and video games, could have on the growing brain.

5292485408 47104b91b6 199x300 Playing at a better future: Could video games improve your life?Video games in particular may be thought to bring together a ‘perfect storm’ of attributes primed to alter your brain. Specifically, they provide us with challenges that stretch our abilities but that are also matched to the our current gaming level; thus, are always achievable. This type of challenge makes us feel particularly good, since we feel as though we have earned our own rewards (such as in-game experience points or unlocking a new level of game play) through what we perceive to be hard work. Thus, we feel a sense of accomplishment and our brains are thought to undergo changes which reinforce certain game-related behaviours.

A number of scientific studies have explored the negative effects gaming can have on the developing brain. And, there have been a range of reactive articles exploring the notion of a dystopian future where a generation of emotionally blunted sociopathic adults cruise around heartlessly re-enacting crimes from games such as Grand Theft Auto. However, it is important to understand that many diverse activities lead to changes in brain structure and function and that these changes are not always negative. Indeed, some studies are now beginning to highlight the positive effects games have on development and how games may be designed to improve mental function.

2305701220 0fc3d01183 m Playing at a better future: Could video games improve your life?Interestingly, game developers and scientists are now coming together in the hope of tackling depression, a major cause of disability, especially amongst young adults (up to a quarter of young people will have experienced a depressive disorder by the age of 19). Sadly, shortages in trained councillors and the reluctance of some young people to seek traditional help means that fewer than a fifth of young people with depressive disorders will actually receive treatment.

A research group, lead by professor Sally Merry at the University of Auckland, have developed a role playing game (SPARX), based around the principles of cognitive behavioural therapy (CBT), which aims to help young people cope with depressive disorders. SPARX is an interactive first person role playing game which allows the user to design a playable character, who is then charged with restoring ‘balance’ to a fantasy world dominated by GNATs (Gloomy Negative Automatic Thoughts). The game leads the screen shot 2012 05 07 at 19.53.51.0 cinema 640.0 300x300 Playing at a better future: Could video games improve your life?player through a range of interactive levels where they learn different CBT techniques aimed at interrupting and readdressing negative thought patterns. At the beginning and end of each level the user interacts with a ‘guide’ who explains the purpose of the in-game activities, provides education, gauges the players mood and sets them real-life challenges (equivalent to homework). Players’ progress is monitored throughout and young people who are not seen to improve are prompted to seek further help from their referring clinicians (a trailer of SPARX is available at www.sparx.org.nz).

Studies suggest that SPARX significantly reduces depression, hopelessness and anxiety in young gamers and that the game is at least as good as traditional CBT. Game designers have also worked hard to make sure the game is engaging for young people; and this seems to have worked: 60% of players completed the whole game while 86% completed at least 4 levels and the majority of young people stated that they would recommend the game to their friends. This is a pretty impressive statistic, since teenage gamers are notoriously hard to please and a self help fantasy RPG certainly sounds like the kind of thing teens would dismiss as being ‘lame’. The success of this intervention suggests that such games could be a great way to treat patients who do not have access to therapy or who may be reluctant to engage with conventional therapeutic methods.

Ultimately the world of gaming is huge and only getting larger. It is currently estimated that by the age of 21 the average young gamer will have spent around 10,000 hours gaming; this is almost equivalent to the time they will have spent in school! With young adults investing so much of their free time in the gaming world, it’s about time we set about understanding the influence games have on development and perhaps, as SPARX has done, start putting these games to work for us. Just think, if we could harness the pleasure gamers feel when working towards gaming-related goals, we could use this medium not only to educate but perhaps also to encourage people to ‘play’ at the biggest puzzle game around – scientific research. The future seems full of amazing possibilities, so put your game face on and join the fun!

Post by: Sarah Fox

 

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First patients enrolled on study aimed to improve outcome following brain injury.

Formed from around 80-90 billion neurons and with a consistency so soft you could cut

trauma 150x150 First patients enrolled on study aimed to improve outcome following brain injury.

A head CT image taken years after a traumatic brain injury, showing an empty space marked by the arrow were the damage occurred.

it with a table knife, the brain is a delicate vulnerable organ. Unfortunately, despite its hard outer shell (the skull), the brain is still susceptible to many forms of damage, both external and internal. Two common forms of brain damage are subarachnoid haemorrhage (SAH – a type of stroke caused by bleeding in and around the brain) and traumatic brain injury (TBI – occurring when an external force causes injury to the brain, i.e. hitting your head). It is not always possible to prevent this type of injury, however, scientists from Edge Therapeutics, Inc are currently working hard to develop life-saving hospital products capable of improving the outcome of patients following SAH and TBI.

Edge Therapeutics are currently enrolling patients on Phase I/II clinical trials for their pipeline drug EG-1962. Despite its inaccessible name, EG-1962 is designed to perform a unique and possibly life-saving function. The drug is designed to treat a state known as delayed cerebral ischemia (DCI). DCI is a complication and major cause of death and disability which occurs in patients within the first two weeks following brain injury. As the name suggests, DCI causes cellular damage through ischaemia (restriction of blood flow to the tissue). This ischaemia can result from a number of mechanisms stemming from the site of brain injury, including cerebral vasospasm (a narrowing of vessels carrying blood), cortical spreading ischaemia (decreased blood flow caused by mass activation of large populations of brain cells) and microthrombembolism (a blockage of blood flow around small, trauma-induced blood clots).

blood 150x150 First patients enrolled on study aimed to improve outcome following brain injury.

Cerebral angiogram showing the blood vessels in a brain.

EG-1962, also referred to as nimodipine microparticles, is a novel preparation of the FDA-approved drug nimodipine. This preparation encapsulates nimodipine in a biodegradable coating which can be injected directly at the site of injury, releasing nimodipine steadily over a period of 21 days. This new system is thought to be an improvement on the current method of oral delivery, which is more likely to cause nasty side effects (such as low blood pressure and lung complications) and less likely to supply sufficient drug to areas where it is needed.

E. Francois Aldrich, M.D. (an Associate Professor of Neurosurgery at the University of Maryland and the Chief of Cerebrovascular Surgery) stated that he hopes the study will help select on optimal dose of EG-1962, which could potentially prevent DCI, therefore improving the lives of a number of patients suffering from various forms of brain injury.

The current study, dubbed NEWTON (Nimodipine microparticles to Enhance recovery While reducing TOxicity after subarachNoid hemorrhage), will enrol up to 96 patients in approximately 20 centres internationally. This study aims to ensure EG-1962 is safe; to discover the most safely effective dose; and to assess whether EG-1962 offers a significant improvement over oral nimodipine. Results are expected in the first half of this year and Dr. R. Loch Macdonald, Chief Scientific Officer at Edge Therapeutics, hopes that these findings will lead to further advances in the clinical development of the drug.

Although a significant number of drugs undergoing Phase I/II trials will fail to progress any further, it is hoped that this treatment or similar preparations may soon be available to reduce the damage caused by DCI.

Post by: Sarah Fox

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Science in 2014: What will the future hold?

The new year is usually reserved for looking back and reflecting over what has just gone. But it’s also a good time to look forward into the upcoming year and think about what it may bring.

Science is no exception to this. 2013 has been a remarkable year; we had our first taste of lab-grown meat, the Curiosity Rover found water on Mars and Richard III turned up in a car park. But what will 2014 bring to the world of science?

The Rosetta Spacecraft will hopefully tell us more about comets and the origins of the universe

comet Science in 2014: What will the future hold?

The Rosetta Spacecraft was launched in 2004 and has been on a 10 year journey towards the comet 67P/Churyumov-Gerasimenko. The spacecraft, which has been in a state of hibernation since July 2011, will wake up on January 20th 2014. It is hoped that Rosetta will begin mapping the comet in August and eventually land a probe on its surface in November, then Rosetta will travel with the comet towards the Sun until December 2015. It is hoped that the information gathered from Rosetta will help to better understand the role comets play in the origins of the universe.

Better diagnostic techniques for cancer

syringe 150x150 Science in 2014: What will the future hold?

Last year, laboratory supply giants Qiagen teamed up with the company Exosome Diagnostics to develop a less invasive test for cancer and other diseases, which may one day replace standard tissue biopsies. This technology makes use of tiny spheres of fat called exosomes. Exosomes are formed inside cells, before being released into the body where they travel in fluids such as spinal fluid, urine and blood. The inside of these exosomes can contain many bits of information about the cells they were released from, including genetic material such as RNA and DNA. It is hoped that 2014 will see the implementation of technologies which harvest exosomes from body fluid and use the information they contain for early diagnosis and development of new treatment strategies.

Increased research into three-parent embryos

embryo 300x214 Science in 2014: What will the future hold?

Last year, I reported that the Human Fertilisation and Embryology Authority (HFEA) ethics committee were debating whether to allow research into three parent embryos in the UK. The committee found that there was widespread support for the technique and so approved the proposal. This means that the UK is the first country to approve the use of an IVF technique using the DNA from a mother, father and mitochondrial donor. Parliament are now producing draft regulations and the legislation should hopefully be put into place by the end of this year. This means that 2014 could be the start of a journey which may ultimately lead to the eradication of certain inherited diseases from family lines.

Laboratory-grown organs becoming closer to reality

petri dishes 214x300 Science in 2014: What will the future hold?

The last few years have seen a big increase in the number of organs successfully grown in the lab and this technology is now providing real benefits for patients as lab-grown organs, including windpipes and bladders, are being used as transplants.

The ability to grow complex organs, such as a liver or pancreas, would be a huge leap forward which could revolutionise transplantation techniques and help cure diseases such as diabetes. In 2013 it was reported that scientists were able to produce tiny livers and mini brains outside of the body. This amazing technology may one day provide the answer to our shortage of transplant donors, while lab-grown organs derived from a patient’s own stem cells may also eliminate the problem of transplant rejection. Although, it is unlikely the coming year will see the development of fully functioning complex lab-grown organs, these techniques have come forward in leaps and bounds and, hopefully, 2014 will bring us another step closer to growing complex organs outside the body.

Of course, this is just the tip of the iceberg. One of the most exciting things about science is that it isn’t always clear what the future holds. We have very little idea really what will be discovered in 2014; I’m looking forward to watching the stories unfold and the discoveries roll in.

Post by: Louise Walker

What do you think 2014 will hold for scientific discovery? Please let us know in the comments below

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