‘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.

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.

Targetting the impact of HAND

HIV-associated neurocognitive disorder (HAND) is a major neurological complication in HIV-positive persons. It impairs cognitive activity, including memory, learning, attention, problem solving and decision making. Symptoms can vary from confusion to forgetfulness, behavioural changes, nerve pain and sometimes apathy.

Dr Lucette Cysique

Dr Lucette Cysique

The widespread use of combined antiretroviral treatment has reduced the incidence of the most severe form of the disorder, HIV-associated dementia, from 8% to 2%. However, the prevalence of mild to moderate degrees of neurocognitive deficits persists in up to 50% of sufferers, with phases of relapse and remission. Symptoms are not severe enough to be referred to as dementia, yet they impact on quality of life and independence.

Research questions being asked at NeuRA include: to what extent does HAND regress with antiretroviral treatment or cognitive training? Can early treatment reduce HAND incidence? Are HIV-positive persons more likely to have HAND as they age, and could this accelerate common neurodegenerative diseases? Do alcohol and substance use disorders exacerbate HAND? How can we improve the early detection of HAND using improved neuropsychological and/or neuroimaging methods?

To answer these questions, Dr. Lucette Cysique leads and co-leads several studies in Australia working with partners including the UNSW, St Vincent’s Hospital, The Alfred Hospital in Melbourne, and HIV clinics in NSW. Internationally, the University of California San Diego and McGill University in Canada are also part of the research program. NeuRA’s research is pivotal to this exchange network.

A pilot study to assess if computerised cognitive training will improve symptoms of HAND is currently recruiting participants.

Visible neuroscience

Imaging techniques enable neuroscientists to learn about the structure and function of cells in the nervous system. Here, Dr Zoltán Rusznák shares some captivating images of the brain and how they were made.

Neurons are the building block cells of the brain and spinal cord, communicating with each other through synapses to regulate nervous system function. Relating the shape, size, and location of neurons to their function is important in understanding mechanisms in brain health and disease. However, because neurons are small, three-dimensional, and embedded among many other cells in the nervous system, special techniques are required to be able to see them. The following pictures show neurons in the cochlear nucleus, which is the part of the brain that decodes sound information from the ear.

Stacking up to localise sound

Globular bushy cells illuminated by a fluorescent stain

Globular bushy cells illuminated by a fluorescent stain

What’s in this picture? Globular bushy cells are neurons in the cochlear nucleus that act as sophisticated timing devices. They measure tiny delays in how quickly a sound reaches both ears, which is the basis of how we localise the source of a sound.

How was it made? The picture on the left was taken with a camera attached to a microscope. It shows a round bushy cell body in the middle of a single, very thin slice of brain tissue – a slice only 0.06% of the thickness of a grain of salt! The right-hand picture is a stack of 40 images taken from successive slices of the same piece of brain tissue – imagine a stack of salami coming out of a deli slicer. The image stack results in a view of much greater depth, so that a second bushy cell body becomes visible, as well as a detailed view of the synaptic nerve terminals, indicated by the several bright green structures on the cell bodies.

Putting the puzzle together

Giant neurons illuminated by a fluorescent stain

Giant neurons illuminated by a fluorescent stain

What’s in this picture? ‘Giant neurons’ of the cochlear nucleus receive sound information from the ear and help to localise the source of sound from a single ear.

How was it made? These pictures are also made from stacks of single images, like in the previous picture. However, since the giant neurons are so, well, giant, many adjacent image stacks have to be assembled like a puzzle in order to capture the many branching nerve endings. Each square in the pictures corresponds to a single field of view of the microscope.

Merging muscarinic receptors

Granule cells and muscarinic receptors illuminated by fluorescent stains

Granule cells and muscarinic receptors illuminated by fluorescent stains

What’s in this picture? These small round neurons in the cochlear nucleus are called granule cells. Neurons have proteins on their surface called receptors that respond to chemical messengers and transmit signals throughout the neuron. Sometimes we want to know the specific type and location of receptors that a messenger binds to in order to transmit its signal.

How was the picture made? Different fluorescent dyes are used to distinguish the receptor from the rest of the neuron. The left-most image shows green, bead-like dots that indicate the presence of a particular type of receptor called a muscarinic M3 receptor in a slice of brain tissue. The middle picture is taken from the very same piece of brain tissue, but the tissue is instead stained blue to define the nucleus of the granule cells. When the green and blue images are merged (right-hand picture), the green dots are showed to be surrounding the blue cell nuclei. This tells us that the receptors are located on the surface of the granule cells, and suggests that these receptors mediate the effects of certain neurochemical messengers in the cochlear nucleus. This information is helpful to determine how hearing works and what might go wrong in auditory disorders.

Dementia: when do I know I have a problem, and what is happening in my brain?

Dr James Burrell is a Senior Research Officer and clinical neurologist whose research interests lie in linking clinical symptoms and pathology in dementia syndromes.

Dr James Burrell

Dr James Burrell

In my work as a clinical neurologist, I often encounter people who are concerned that they might be developing the dreaded d-word: dementia. They report being more forgetful than previously, forgetting the names of people, places or things, or perhaps just not feeling as ‘sharp’ as they once did. In my experience, these sorts of concerns are common. Importantly, however, only a proportion of people with such symptoms actually go on to develop dementia.

Working out who will develop dementia, and more specifically which type of dementia will be developed, is one of the major challenges cognitive researchers and clinicians face. We are presented with two separate, but related problems: first, how can we tell when minor forgetfulness heralds the onset of something more serious? Secondly, if someone has an obvious dementia, how can we make an early and accurate molecular diagnosis?

We know from many well-designed studies that neurodegenerative disorders begin years before any symptoms develop, and that to be effective a treatment will most likely need to start at the very earliest stages, before any significant and permanent damage develops. On the other hand, not everyone with mild cognitive symptoms actually progresses to develop dementia. Being able to accurately identify patients at risk of developing dementia at a very early stage is one of the major goals of research in neurodegenerative diseases.

In the Frontier clinic based here at NeuRA, we are often faced with the opposite problem: we assess patients with early dementia who present with memory, language, or behavioural disturbances, but it can be difficult to work out the specific underlying brain disease. In many ways, our research aims to bridge this gap between the problems related to ageing that people face in their everyday lives and the physical changes in the brain that are ultimately responsible. We use a combination of methods, including detailed clinical assessment, neuropsychological or cognitive testing, sophisticated brain imaging, neurophysiological techniques, gene testing, and even blood and tissue biomarkers, to try and better link cognitive symptoms and specific brain diseases. With collaborators in the UK we have even developed a new app, for cognitive testing in clinical practice (ACEmobile™ for iPad, available from the Apple App Store). Only after we can make an early and accurate diagnosis of a neurodegenerative brain disorder will the hunt for a meaningful treatment really forge ahead.

Contracture: understanding mechanisms and testing treatments

As part of a new National Health and Medical Research Council Program Grant on motor impairment, Prof Rob Herbert aims to advance the transfer of new understanding of physiology and pathophysiology in motor impairment toward the clinical outcome of improved motor function.

Prof Rob Herbert

Prof Rob Herbert

Motor impairment is a common consequence of a number of illnesses and injuries. One type of motor impairment that is an important cause of physical disability is muscle contracture. A contracture is a stiffening of the muscles that limits normal joint movement, and severe contractures cause deformities that are the most visible manifestation of brain damage. Contractures arise when brain lesions, including those that arise from stroke or traumatic brain injury, cause paralysis or spasticity. Paralysis and spasticity change the mechanical environment of muscles – that is, they cause muscles to experience different patterns of activity, different changes in length and different forces than would normally be experienced. The muscles adapt in response to their altered mechanical environment by becoming stiffer, causing joints to become less mobile.

Contracture is a common problem. In a recent study, my colleagues and I monitored 200 consecutive people admitted to a Sydney hospital with the diagnosis of stroke. Six months after admission, half of all those people had developed at least one contracture. Contractures are also common in people with many other sorts of brain lesions. For example, contractures are prevalent in people who have had a traumatic brain injury, or who have multiple sclerosis or cerebral palsy.

Contractures prevent joint movement, so they cause physical disability. For example, many people who have had a stroke or traumatic brain injury develop contractures of the calf muscles. Calf muscle contractures impede ankle motion, making it difficult to stand up from a chair or walk normally. In the same way, contractures of shoulder muscles can impair the ability to reach and contractures of wrist and finger muscles can impair grasp. Severe muscle contractures can cause the limb to adopt a fixed position. For many people, contractures become a much greater impediment to normal movement than the paralysis or spasticity that initially caused the contracture to develop.

There has been surprisingly little research into the mechanisms of contracture. As a result, the mechanisms are poorly understood. Studies on animals have shown that it is possible to make muscles become short or stiff with a number of experimental procedures. For example, leg muscles can be made short by immobilising the leg in a plaster cast, and diaphragm muscles can be made short by inducing emphysema (a lung disease). These studies show that the stiffening of muscles can occur either because of changes in the muscle tissue (the muscle “fibres” or “fascicles”), or because of changes in the tendons that join muscle fascicles to bones. But studies on animal muscles can’t tell us about the mechanisms of contractures seen in human populations. Surprisingly, it is still not clear whether contractures in people who have had a stroke or traumatic brain injury are due to changes in the muscle fascicles or tendons.

There is just as much uncertainty about how to prevent and treat contracture. For the last half-century, physiotherapists and nurses have applied stretches to muscles, or passively moved limbs, or applied splints or casts to stretch the limb, with the aim of preventing or treating contractures. But recent research suggests these interventions have little effect. For example, in one study, 63 volunteers who had experienced a stroke were randomly allocated to receive either a wrist splint or no splint. Two months later there was no discernable difference in the stiffness of the wrist of people who had or had not been splinted. There have now been over 35 studies like these, and they quite consistently show little or no effect of stretch or movement-based interventions. For now at least, there are no treatments that have been clearly shown to prevent or reverse contracture.

Eventually, scientific research will provide answers, both about the mechanisms of contracture, and about how to prevent and treat contracture. The first steps have been made in identifying the abnormalities of gene expression that are ultimately expressed as contracture. New ideas for treatments are being generated by basic research, for subsequent testing in clinical trials. Our motor impairment program will study human volunteers and patients to learn more about normal motor function and the mechanisms of motor impairment, and to test the clinical efficacy and mechanisms of novel treatment interventions. The development of new techniques for imaging and measuring the internal architecture of muscles using MRI provides one promising advance. One study will look at how muscle tendons and fascicles are recruited during movement, which will inform subsequent clinical studies in people in whom contracture is common, such as people with stroke, spinal cord injury and multiple sclerosis.

Hopefully, the next decade will see major advances in both our understanding of the mechanisms of contracture and how to treat them.

An example of one of the unique muscle images generated by Prof Herbert's team. In the centre is a human leg muscle. The blue lines show the course of muscle cells in six locations in the muscle. The insets provide information about how the cells terminate on the tendinous sheets that cover the upper and lower surfaces of the muscle.

An example of one of the unique muscle images generated by Prof Herbert’s team. In the centre is a human leg muscle. The blue lines show the course of muscle cells in six locations in the muscle. The insets provide information about how the cells terminate on the tendinous sheets that cover the upper and lower surfaces of the muscle.

An international approach to tackling Parkinson’s disease

Dr Nic Dzamko and Prof Glenda Halliday have put together an international team dedicated to researching the causes of Parkinson’s disease. They will be the first in the world to use valuable early clinical samples to identify the genetic and molecular underpinnings of this brain illness.

Parkinson’s disease is a debilitating neurodegenerative disorder with no current cure. 1 in every 30 Australians is diagnosed with Parkinson’s disease, and these numbers are predicted to rise. Over the last 10-15 years, it has emerged that genes play an important role in the risk of developing Parkinson’s disease. Approximately 16 genes have now been identified that increase the risk of developing Parkinson’s disease. Understanding what these genes do in the healthy brain, and how their functionality might go wrong, has become a major focus in the search for clues about the cause of this disease.

Dzamko2

Dr Nic Dzamko in the laboratory

One of these genes, called LRRK2, has received considerable attention. The LRRK2 gene encodes a protein that belongs to a class of enzymes called kinases, which is interesting to researchers because many anti-cancer drugs developed by the pharmaceutical industry also act by blocking kinases. In the past few years, more than 20 drugs that can block the kinase LRRK2 have been patented. While it is hoped that these drugs may be beneficial for the treatment of Parkinson’s disease, more work needs to be done to understand exactly what LRRK2 does, and therefore whether drugs that block its action will be safe and therapeutically useful. To better understand the function of LRRK2, our team at NeuRA has initiated two new projects in collaboration with scientists from around the world.

The first project involves us leading a group of scientists from London, Tokyo, California and the Netherlands. Using 400 samples that have been sent to us from these locations, and that cover a range of brain regions at different disease stages, we will determine if, when and where the expression of the LRRK2 enzyme goes wrong in the Parkinson’s brain.

The second project aims to investigate the idea that inflammation is linked with Parkinson’s disease, in collaboration with researchers in the US and Europe. This project is particularly exciting, as it may identify much-needed markers of early disease. By working with the worldwide LRRK2 Cohort Consortium, established by the Michael J Fox Foundation for Parkinson’s Research, we have access to more and better samples to ultimately obtain more meaningful data. We will measure a range of biological markers associated with inflammation in serum and cerebrospinal fluid. By comparing the extent and type of inflammation in people who do and do not have certain genetic mutations, and between people with Parkinson’s disease and healthy controls, we will identify whether inflammation is an early sign of Parkinson’s disease. This world-first access to blood samples from people with a large genetic risk of getting Parkinson’s, but who do not yet have the disease symptoms, is a chance to try and identify potential treatments for the early stages of this illness.

These projects have taken about a year and over 300 emails to come together. Although meetings are often scheduled in the very early hours of the morning to accommodate time zones, working together as an international team to leverage skills and resources is an important step toward solving the problem of Parkinson’s disease. Of course, our work would not be possible without the funding we have received for these projects from the Michael J Fox Foundation and the Shake it Up Australia Foundation.