Shared goals in spinal cord injury rehabilitation

Siobhan Fitzpatrick and Jim Nuzzo are testing methods that may have the potential to improve existing connections between motor neurons within the spinal cord in people with neurological injury.

People who have experienced spinal cord injury or stroke often lose the ability to activate their muscles, as a result of damage to neural pathways involved in motor control.

Siobhan and Jim are working in A/Prof Janet Taylor’s lab. Their methods are designed to enhance plasticity, or changes in the way neurons communicate, such that the message the neurons send to the muscles will become stronger.

Dr Siobhan Fitzpatrick and Dr Jim Nuzzo

An experimental setup using magnetic stimulation to induce changes in the neural pathways supplying muscles.

Siobhan induces this plasticity by stimulating a person’s brain and motor neurons to the arm with carefully timed pairs of magnetic and electrical current, which are designed to increase the output of the motor neurons.

In contrast, Jim uses physical training to induce plasticity, asking people to bend their arm as fast as possible, with the idea that this vigorous exercise induces just the right nerve-firing pattern to increase motor neuron output.

Both researchers measure changes in biceps muscle response to direct spinal cord stimulation before and after a period of stimulation or exercise.

By exchanging technical expertise and knowledge of the scientific literature, Siobhan and Jim are shedding light on how the activity of spinal motor pathways can be manipulated to improve muscle performance.

‘The World According to Richard’ (Part three)

In the final installment of Richard Schweizer’s blog series, he describes his vision for the future and why speaking out about schizophrenia is so important to him…

For this, the last section of my blog I would like to convey the ups and downs of my life since being successfully medicated. I would also like to talk about my PhD research into schizophrenia. I hope that in telling you this story I may offer some hope for people with mental illness, and perhaps contribute towards a greater understanding of those that suffer, so often, in silence.

It took me many months, perhaps years, to fully accommodate the fact that I had not only a mental illness, but perhaps the most serious of mental illnesses. I had fallen from a great height, and found myself with a new mountain to climb.

The first grasping footholds in this mountain involved getting back into study (luckily my period in the clinic had occurred over the summer, when uni wasn’t sitting). I enrolled part-time to finish my Law degree at Sydney University. I managed to finish without too much difficulty, though I was still suffering bouts of depression and anxiety. Occasionally I would also be in class and things would well-up and get too difficult for me, so I would leave.

In my final year of Law, I applied to do an exchange at a number of US universities. Luckily my old Honours supervisor from my Arts Degree days wrote me a fantastic letter of recommendation, and I was given a spot at New York University. I was off to The Big Apple!

It had always been a dream of mine to live in New York – it’s such an exciting city – and here I was living my dream. The classes were tough, but I decided I would try my darnedest to get good marks. The city was wonderful. So full of life and energy. I had some close family friends there too, so every Tuesday night I would go to their place on the Upper East Side and have schnitzel. They invited me into their home with love, and I am eternally grateful.

There is a story about the health system in New York I would like to relate. The medication I was taking, and still take, is a strong anti-psychotic called Clopine as I mentioned previously. In Australia, I need to have a blood test once a month to receive the drug. In the US the rules are a bit different. I needed the blood test every two weeks. So, in the first two weeks I popped into the hospital with a blood test request, got the results confirmed by a psychiatrist and went into a local pharmacy. I asked for two weeks worth of Clopine.

The lady found the drug and said “five thirty-five”. I replied, “gee, that’s cheap! five dollars and thirty-five cents”. She responded, “No, five hundred and thirty five dollars”. I was blown away. I did not have medical insurance for schizophrenia as it was a pre-existing condition and I had to pay the full price of the drug. In Australia I get the same drug for forty-odd dollars, for a full month. Such was my lesson in the American health-care system. If you have schizophrenia there and need an anti-psychotic, but can’t afford medical insurance, you are simply left to struggle for your sanity. Needless to say, from that point on I sourced my medication from Australia.

I guess the only dark aspect of my time in NY was my occasional bouts of depression. I remember lying in bed for hours; walking around Greenwich Village in the cold trying to perk myself up with exercise; talking to Mum on the phone for stretches at a time. I guess the problem of depression and anxiety is still with me, though as we will see, I have adopted certain strategies to contain these feelings.

Back Home

3Richard family copy

Richard Schweizer with his brother Marcus and parents Sonja and Norbert at home.

I returned to Australia in 2005 and decided to do a Masters, in either Fine Arts or Journalism. My parents thought the latter was a good idea, so I went with it and enrolled part-time at the University of Technology, Sydney. I enjoyed the degree, although I earned a Pass mark in one course – the only time it has ever happened to me.

It was around this time that I decided to become a patient ambassador for the Schizophrenia Research Institute; a voice for people with schizophrenia. I had always had good public speaking skills, and I felt that the issue needed to be discussed; that my strong recovery and participation in life may give hope to some who were struggling. There was also a deeply personal reason for “coming out” as a person with schizophrenia.

I wanted to turn what was the worst thing in my life into one of the better, if not the best thing in my life. I also felt, in my moments of despairing depression, that holding on to a sense of purpose, of something bigger, helped me deal with dark feelings. Maybe, like my behavior as a child, I wanted to be Superman again – though this time the Superman of a broken mind.

I knew I would face difficulties. I knew I would have to open very personal parts of myself up to public scrutiny. I knew there would be stigma.

But it has turned out to be one of the best decisions of my life. I feel energized when given the chance to tell my story. I appreciate the fact that people come up to me after hearing me speak and tell me of their own struggles with mental illness, or the struggles of a friend or relative. I feel like I am on a mission – a mission to help de-stigmatise schizophrenia. Hence the message I wrote at the beginning of this blog: schizophrenia is normal.

My PhD

I had finished my Masters in Journalism and felt at a loose end. I asked my father one day: “Do you think I am capable of doing a PhD?”. He replied, emphatically, “Yes!”. I needed his approval, and got it.

I enrolled to do a PhD in Sociology part-time at Sydney University. I knew I would need to write on a topic that I felt was important to me, and important to others. It seemed natural to write about schizophrenia. Again, I was turning one of the worst things in my life into one of the best.

That was five years ago. I have come so far since then.

I have interviewed a dozen people around the state about their struggles with schizophrenia. I have read countless books, some personal, some scholarly, on the nature of schizophrenia. I have written – oh how I have written! At the time of publishing this blog I have completed a methods chapter, three theory chapters, three results chapters and a discussion. I am also sitting on the fourth draft of my Introduction. I hope, in a month or so’s time, to have a complete first draft of my thesis. I have an excellent supervisory team who understand my special concerns, who respect the work I do, and who give honest feedback. I have enjoyed the process greatly.

Where do I stand now? 

Well, there’s always further to go. I would like to find a partner, to marry, maybe have kids. I still have to move out of home (yes, I know – thirty-three years old and still at home!), I have lovely parents.

I am proud to have made contact with dozens of people with mental illnesses of their own. I have been on an Australian Story episode with my learned friend, schizophrenia researcher Professor Cyndi Shannon Weickert from NeuRA. My father and I appeared in a Two of Us article for the SMH and I was recently interviewed for an episode of All in the Mind on Radio National as part of Mental Heath week. I have talked at conferences and seminars. I am hoping to have the opportunity to talk at my old school. I present a community radio show on Eastside Radio, 89.7 fm (have a listen!). I play bass in a band called Crash Through. Once I finish my PhD I would like to work in the field of mental health policy.

Not bad for a man who once contemplated the darkest of thoughts in the midst of psychiatric torment.

The band
(L to R) Members of Crash Through. Alicia Nagle, Richard Schweizer, Tim McAlpin and Phil Morgan at the Metro Theatre in Sydney.

Coda

What would I like you to take away from my story? A couple of things: One, schizophrenia does not have to be a death knell. Many people with schizophrenia can go on to live productive and happy lives. Two, schizophrenia does not automatically make you crazed and violent. Indeed, people with schizophrenia are more likely to be the victims of violence than its author. Three, people with schizophrenia still need love, support and understanding. If you have a friend or family member who appears to be doing it tough, it’s ok to ask, “Are you ok?”

And finally, perhaps the most important thought. Mental illness is normal as I suggested in Part 1. Schizophrenia is normal. We can no longer treat people with schizophrenia as outcasts; as lepers of the mind. Perhaps we may alleviate some of the suffering people with schizophrenia have and will face in trying to live their lives if we view the disease this way. People with schizophrenia must be welcomed back into the fold of society. They need understanding and acceptance.

Just like you.

Just like me.

Art and architecture at NeuRA

Bettina Bartos is the architect who designed NeuRA’s Margarete Ainsworth building. She shares how the building’s design was developed, and how the innovative vision of Artbank and its collection of Australian art put the finishing touches on this much-welcomed facility.

There is nothing new about the synergy between art and science. Indeed, Leonardo Da Vinci is probably best known for his artworks that were informed by scientific investigation. So it seemed only appropriate that the new building for NeuRA provide an opportunity to highlight the natural overlap between art and science.

Having seen various artworks that existing NeuRA building occupants had used to personalise their workspaces, and gifts of artworks from patients, it seemed as though staff and visitors alike would appreciate having larger pieces located throughout the building.

Isobel Johnston series

The external facetted glass form of the building was designed to facilitate a memorable image for NeuRA, and speak of the cutting-edge research occurring within. The internal arrangement was no less important, with the driving forces being to encourage and facilitate interaction and collaboration between staff, and to maximise natural light and the feeling of space to both laboratory and office areas.

This, in turn, led to the design of a series of spaces, such as the large triple-height atrium with its connecting bridge links and the generous lift cores on every level, which also provided a perfect opportunity for the incorporation and display of art.

Artworks needed to be generous and bold in order to do the space justice; however, the purchase of a large number of substantial artworks was not economically feasible. This led to the idea of “borrowing” significant pieces for long-term display.

I had heard about an organisation called Artbank, an Australian Government support program that acquires the work of living, Australian contemporary artists who make their collection available to the general public through a leasing program.

The Artbank collection has been building for over 30 years, and with around 10,000 artworks, it is one of the largest collections of Australian art in the world, holding “some of the greatest examples of Indigenous and non-Indigenous artwork produced during the past four decades”. 100% of the revenue generated from leasing is directed towards supporting living artists, so I was excited to be able to initiate a great opportunity to expose NeuRA building occupants and visitors to some great examples of Australian contemporary art, whilst at the same time supporting Australian art and culture.

The brief to Artbank was simple: to select pieces that responded to both the NeuRA vision and the architectural significance of the building. Artwork needed to be placed in prominent locations to maximise the experience for everyone, and needed to complement the strong internal colour scheme of the building. Being able to find artwork that had a ‘scientific theme’ would be an added bonus. Given that many of the artworks would also be able to be viewed from both near and far, it was important that individual pieces were able to respond to a changing perspective.

Working closely with one of Artbank’s art consultants, a site visit was arranged to gain an understanding of NeuRA and its research programs, and the architectural quality of the space itself. From this, Artbank began with a preliminary selection of artworks that they felt met our brief.

However, with so many artworks in Artbank’s collection, choosing the final pieces was not a simple task. As the selection of art is such a personal experience, it was important to choose pieces that were not too polarising, but at the same time had enough interest to generate discussion and create stimulating spaces. After many hours spent in Artbank’s warehouse sorting through rack after rack of art, and then checking against availability and budget, we had our collection!

Frank Hodgkinson - "Sun"

Frank Hodgkinson – “Sun”

Now, if you wander through the Margarete Ainsworth building you will see a selection of incredible artworks from some of Australia’s leading contemporary artists, including Frank Hodgkinson, Matthew Johnson, Wendy Kelly, David Sequeira, Philip Watkins, Isobel Johnston, and William Breen.

What can our genes tell us about mental illness?

Bipolar disorder affects 350,000 Australians, and has been ranked in the top 20 most disabling disorders globally, making it even more disabling than depression. Dr Jan Fullerton‘s research aims to better understand how genes contribute to bipolar disorder.

Dr Jan Fullerton in the lab

Dr Jan Fullerton in the lab

Bipolar disorder is characterised by oscillating periods of mania and depression. These changes in mood are sometimes accompanied by psychotic episodes and escalating impulsive and risk-taking behaviour, potentially leading to financial and social ruin. While people usually revert to normal mood and behaviour between these episodes, bipolar disorder has a severe impact on its sufferers, increasing suicide risk fifteen-fold.

Bipolar disorder is partly heritable, but we have a limited understanding of the specific genetic causes. By comparing the genetic sequences of many people who have the illness with those of many people who do not, a small number of genetic differences have been identified that individually account for a very small fraction (<1%) of disease risk, but which as a group contribute a larger fraction. However, a large proportion of the genes that contribute to bipolar disorder remain unknown, and it is also not well understood how genetic variation changes the way the brain functions to bring about the illness.

At NeuRA, we are embarking on an exciting new project to identify genes that contribute to the risk of bipolar disorder. Studying a large breadth of the population has been effective in identifying common disease-related variations in genes. However, by studying unique families that have a high density of illness (i.e. more than 4 individuals affected in a family tree), rare gene variants that contribute to disease are more readily identified. We will analyse genetic material from extended families to see whether the disease in those families is due to the collective impact of several rare gene variants.

Pedigree diagram of two families affected by bipolar disorder. Circles represent females and squares represent males.

Pedigree diagram of two families affected by bipolar disorder. Circles represent females and squares represent males.

Using a technology called massively-parallel sequencing we will compare the sequences of the expressed part of the genome (referred to as the ‘exome’: this part of the DNA only constitutes about 1% of the total genome, but is the portion of the genome which directly encodes proteins, which are essential to maintain normal functions of the body). This ‘next-generation’ sequencing technology dramatically increases the extent and accuracy of genetic data over previous methods. We will look for changes in genetic code, even down to a single nucleotide building block (i.e. the A, G, C, or T base), and determine whether there are an abnormal number of copies of a gene in an individual, since sometimes genes (or parts thereof) can be deleted or duplicated. Once these aberrations are identified, we will match them with linkage analysis data to determine whether they are likely to cause the disorder in a specific family. The molecular pathways affected by these genetic factors will be explored, relating novel genes to other genes previously implicated in disease risk.

Our data will be combined with data generated by other members of the international Bipolar Sequencing Consortium and Psychiatric Genomics Consortium to shed light on genes and molecular pathways that are commonly affected in people with bipolar disorder. Once the variants that lead to the loss of gene function in rare, highly penetrant forms of bipolar disorder are identified, the way in which disease risk is inherited will become clearer. This will lead to significant insights into what is actually wrong in the brains of people with this severe illness, and hopefully to new treatment strategies.

Beyond DNA code: epigenetics

Why is it that if you keep an active mental life by playing complicated board games or learning a language, or if you keep physically fit, you are less likely to succumb to dementia? A/Prof John Kwok is addressing this question by looking at how lifestyle can alter the function of genes related to dementia.

A/Prof John Kwok

A/Prof John Kwok

To do this, he is engaging with the burgeoning field of epigenetics. Genes have to be expressed (i.e. switched on or off) in a tightly regulated manner for our bodies to function correctly. For example, genes get switched on and off when we are born, or when we hit puberty, in response to hormones or tissue growth. While there are parts of our DNA that control how genes are switched on, there are also epigenetic factors, outside our DNA, that can do this. These factors act like a dimmer switch that changes the brightness of a light.

Diet, exercise, and mental activity can ‘dim the brightness’ of genes that might lead to illness, or enhance genes that promote brain health. Not only do these lifestyle factors change gene expression, but their effect might be inherited by the next generation, even if the relevant gene’s DNA sequence itself is not inherited. Understanding the mechanisms of how this happens is a focus of many areas of NeuRA’s work. The study of epigenetics is important in exploring new possibilities for health care.

Binge drinking and brain development

The effect underage drinking has on a developing brain is a question Prof Caroline Rae is seeking to answer. An alarming 19-23% of adolescents have binge-drunk in the last week, and this proportion is increasing in young females. 13% of all deaths in young Australians are a direct result of alcohol use, with alcohol use patterns in the young becoming more extreme.

Drunk teens with vodka bottle

At this age, the frontal lobes of teenagers are still developing. This development progresses into the early 30s, but most occurs in the teenage years. Alcohol is very likely to be affecting the development of the brain and its connections. The recent trend to mix high-caffeine drinks with alcohol could be exacerbating the problem.

Currently, there is very little scientific evidence on the effects of early binge drinking. Prof Rae and her collaborator, Prof Maree Teesson at the National Drug and Alcohol Research Center (NDARC), aim to uncover what happens in a teenager’s brain when binge drinking occurs. They will then identify the neurocognitive consequences of binge drinking, such as whether it affects memory, the ability to recognise emotions on other people’s faces, or the ability to inhibit impulses. The structural and functional effects of binge drinking on the brain are also under examination.

What about resilience and wellbeing? The flipside of mental illness

Dr Justine Gatt is an NHMRC Research Fellow who has recently joined the NeuRA team. Her research focuses on understanding the flipside of mental illness: why some people are more resilient to stress than others. It is hoped that these characteristics can be promoted in people who may be less resilient.

Dr Justine Gatt

Dr Justine Gatt

In Australia, nearly half of the population experience a mental disorder at some point in their lifetime, with the most common disorders being anxiety or depression. These disorders can occur in anyone, at any age, but adolescents and young adults are particularly vulnerable as their brain is still undergoing the final stages of development. Exposure to trauma or adversity during childhood or adulthood can often trigger symptoms of these disorders. On the other hand, the presence of certain protective factors may make an individual more resilient to the effects of stress and adversity. Notably, the absence of mental illness does not necessarily imply the presence of optimal mental health, and only a small proportion of people who have no mental illness symptoms are actually functioning optimally and are resilient.

Most psychiatric research has focused on understanding mechanisms of risk for different mental disorders and ways to diagnose and treat them. In comparison, there are very few studies that try to understand the mechanisms of resilience. Our research program aims to understand mental health using a new framework. This includes defining the neural underpinnings of resilience using techniques such as magnetic resonance imaging (MRI) and electroencephalography (EEG) measures of brain function. We also examine the genetics of resilience using saliva samples for DNA analysis.

I am currently analysing data from over 1,600 healthy adult twins who participated in the TWIN-E Study of Emotional Wellbeing. Our team has developed a new questionnaire called COMPAS-W to measure wellbeing. It measures qualities, such as composure, positivity, self-worth and mastery over one’s environment, that are self-reported by study subjects. The questionnaire has been validated against objective psychological tests for symptoms of depression and anxiety. Using measures from this broad source base is helpful when linking biological variables like genetics and brain function, and allows us to explore how innate and environmental factors may moderate our wellbeing, with twin heritability estimates at 48%. The good news is that this means that wellbeing is malleable and can be promoted with intervention.

Comparing between twins allows us to determine the relative contribution of genetics and environment to changes in the volume of grey matter in different parts of the brain. Changes are highlighted in colour. (Gatt et al 2012, Twin Research and Human Genetics)

Comparing identical and non-identical twins allows us to determine the relative contribution of genetics and environment to differences in the volume of grey matter in different parts of the brain. Differences are highlighted in colour. (Gatt et al 2012, Twin Research and Human Genetics)

Another aspect of our research tests how interventions work to promote resilience. We are working with industry partners to test different e-health tools. One of these tools, called MyBrainSolutions, provides targeted, personalised emotional and cognitive solutions over the Internet. To measure resilience, we are testing games that promote positivity (e.g., gratitude training and positive affirmations) and stress management (e.g., the negative thought challenger and MyCalmBeat), as well as executive control games that aim to boost working memory, attention, and goal setting.

Understanding the biology of resilience is the first step towards personalised health solutions. It provides the foundation of features that could be nurtured in low-resilient individuals in order to prevent psychiatric illness. This ‘resilience bio-signature’ could be used as a diagnostic tool for predicting risk for developing mental illness following trauma. At-risk children or adults could then be provided with simple tools to train them to better adapt to life stressors and make them more resilient for the future.

Justine was recently awarded a competitive National Health and Medical Research Council (NHMRC) Career Development Fellowship to conduct this research program. As evidence of innovation and research excellence, Justine was lucky enough to receive the Commonwealth Health Minister’s Award for Excellence in Health and Medical Research in June 2014. The TWIN-E study was a collaborative study with Prof Leanne Williams (Stanford University, previously University of Sydney) as Chief Investigator and co-investigators Prof Peter Schofield (NeuRA), A/Prof Anthony Harris (University of Sydney), Prof Richard Clark (Flinders University), and Dr Justine Gatt (previously as ARC APDI postdoctoral research fellow, University of Sydney) and supported by an Australian Research Council Linkage (LP 0883621) grant with Brain Resource as industry partner.