Category Archives: Schizophrenia

Star-shaped cells: a clue to differences in schizophrenia pathology?

Dr Vibeke Sørensen Catts is a schizophrenia researcher. Her interests lie in exploring the biological factors that help brain cells grow and die, and how these pathways might be altered in schizophrenia. Here she describes her discovery that certain types of brain cells are inflamed in some people with schizophrenia. This recent finding opens new understanding of what goes wrong in this disorder and how it might be treated.

Dr Vibeke Catts

Dr Vibeke Catts

One of the problems with trying to understand a serious mental illness like schizophrenia is that it doesn’t manifest in the same way in all people. In fact, there is a wide range of symptoms and brain abnormalities across its sufferers, who number 1 out of every 100 people.

My colleagues and I were able to turn this variability to some advantage in our research, by deliberately grouping the people we studied according to the molecular features associated with their illness.

A previous study in the Schizophrenia Research Laboratory had found that one third of people with schizophrenia had high levels of biological markers of inflammation in their brain. The identification of this ‘high inflammatory’ group contributed to an increased understanding among researchers that inflammation contributes to schizophrenia pathophysiology, but the ‘how’ of this process was still not well understood.

Inflammation is a protective bodily response to injury or illness, and in the short term is important for normal processes like muscle growth, but is detrimental over a chronic time course. During inflammatory processes, certain specialised cells are activated, releasing chemicals that regulate symptoms such as swelling and pain. In the brain, this process is known as gliosis, and involves extra growth of the ‘support cells’ of the brain, such as microglia and astrocytes. Earlier studies have shown that microgliosis is present in the brains of people with schizophrenia, but it has not been determined how this links to the increased inflammation in the brain that we had observed in some schizophrenia patients.

To see whether the activation of astrocytes (named for their star-shaped appearance) might be the missing link between a general marker of inflammation such as microgliosis and the other inflammatory markers observed in the brain of this group of schizophrenia patients, we measured a protein called GFAP in the prefrontal cortex of people with schizophrenia. GFAP stands for glial fibrillary acidic protein, and it is a marker for astrogliosis.

Taking a closer look at the brain

We did not find an overall difference in GFAP between people with schizophrenia and healthy controls. This didn’t surprise us, since there is so much variability between schizophrenia patients, and because we had previously observed inflammation in the brain of only a subset, rather than all of the schizophrenia patients. However, when we measured GFAP in that ‘high inflammatory’ subset, this group had increased evidence for astrogliosis than the ‘low inflammatory’ group of schizophrenia patients. Furthermore, the shape of the astrocytes in the ‘high inflammatory’ group was different to the ‘low inflammatory’ group.

Questions, answers, and . . . more questions

Our findings are interesting, but highlight the need for further research. Is the response of astrocytes lower in some people with schizophrenia than in other brain illnesses such as Alzheimer’s disease where inflammation and astrogliosis is abundant? Or perhaps the response starts out normally, but is halted over time due to other factors at play in the illness? For example, antipsychotic medications used to treat schizophrenia symptoms may inhibit the process of gliosis, and so an individual’s exposure to these medications needs to be considered in trying to sort out the contribution of these cellular processes to disease.

Regardless, a continuing discussion of whether gliosis plays a major role in schizophrenia is important. Schizophrenia is considered a disorder of aberrant brain development rather than of brain degeneration. However, our data suggest that it is premature to rule out the idea that some individuals experience a different course of illness such that neurodegeneration associated with inflammation is an integral part of what goes wrong. This would in turn inform tailored treatment development for these people.

‘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

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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.

‘The World According to Richard’ (Part Two)

In Part Two of Richard Schweizer’s blog, entitled ‘The Road to Wellness’, he takes us into the Sydney Clinic where he was admitted not long after his schizophrenia diagnosis.

I spent about 3 months in the Sydney Clinic; a private mental health facility in Sydney’s Eastern Suburbs. My time there was not that bad. I have good things to say about the staff. I remember one nurse talking to me about my life, my mind, my illness. She made the observation that people suffering schizophrenia, particularly during the on-set of psychosis, need ‘not too little, but not too much’ stimulation. I still find this to be fairly accurate today.

My time at the clinic is, like the early period of my illness, somewhat hazy. This may be because I think I was put on sedatives initially. I have memories of lying in bed, while my parents sat beside me. To this day I thank the fates that my parents were so close by, so supportive. It’s one of the main reasons I’m still around today.

The Sydney Clinic began with me seeing a psychiatrist and getting a diagnosis. I talked at length about what I had been experiencing, what I had done, how I felt. The doctor was particularly interested in my pot smoking; I guess he wanted to ensure that what I had was onset-schizophrenia, and not drug-induced psychosis (typically drug-induced psychosis is very intense for its sufferers, but tends to pass when the sufferer stops taking the drug causing the psychosis). He was very measured, very calm and analytical. I can’t even remember if he pronounced the diagnosis, or if it was my GP who had said that. Either way, I knew I was sick. I knew I had a mental illness.

As I write, another memory of the period occurs to me. Before talking to my mum and seeing my GP, I made several efforts to clear my mind and put myself on an even keel. As I have said, I went to a free counselling service several times. I tried cleaning and organizing my room and I saw an eye specialist for my ocular problems. I also went to see my family homeopath, a wonderfully kind man who I still see.

One of the more interesting tasks I undertook to maintain my wellness was to write “My Eight Steps to Wellness” in my journal. They were:

  1. No pot.
  2. Exercise.
  3. Sleep well.
  4. Relax and meditate.
  5. Spend time with people I love and trust.
  6. Be aware of the beauty of the world.
  7. Eat well.
  8. One day at a time.

I guess these steps may seem obvious, but it was good for me to clarify them. I think they helped me handle the disruption of schizophrenia. I would recommend them to anybody as important steps to leading a good life, mental illness or not. When I read these steps to my psychiatrist, he added “stay on your medication” as number nine. Since that time, I have taken my anti-psychotic medication every single day. I am now 33 years old.

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Richard Schweizer volunteers at Eastside radio where he presents a weekly music show

Then came the drugs

The tale of my medication is interesting. As noted, my GP put me on Risperidone. My psychiatrist at the clinic immediately changed me to Zyprexa. This didn’t work so well, so he upped my dose considerably. I still was not responding well, so we switched to another drug. I can’t remember what it was. It may have been Serenace or Abilify. I was still having trouble maintaining my cognition. I had trouble concentrating on tasks requiring abstract thought. For example, in group therapy session I had to leave because it was too much to take in.

My doctor then pulled out the big gun, Clopine. Clopine has a significant side-effect profile. In one percent of people it can cause a major drop in white blood cell count, so you need to take a blood count test every month. It also makes you very sleepy. Aside from that, I responded well to it. I even remember coming out of the clinic to travel with my parents to Vanuatu for a holiday. While there, I was still experiencing symptoms though – I had that sense of fear and an over-whelming sense that my mind was being engulfed. It felt like my mind was a tiny island of rationality in an encroaching sea of fear. I had brought a guitar with me. I remember writing a song about how I felt, only to destroy it later, as I wished to forget what was happening to me. With the calm of the holiday, I also began imagining that voice again: “Ha ha, you’re going crazy”. When I got back I told my GP of how I felt, of suicidal urges, and she immediately booked me back into the clinic for another stay. I guess it must have been at about that time that my psychiatrist upped my dose of Clopine. I stayed on this dose for half-a-dozen years or so; after some time my psychiatrist and I agreed I could try cutting the dose, which I did successfully. The drug, even at this lower dose, has me sleeping 12 to 13 hours a night which, by the by, has meant I don’t think I will ever be able to hold down a full time job – I am just too sleepy to wake up at seven-thirty or eight.

Sometimes if you don’t laugh, you may cry

When I was first admitted, I, with my parents, had to answer a number of questions of an administrative nature. I recall the lady there asking me “any allergies?” I responded, “only lies”. An example of the quirky way my mind works. This, of course, was a joke, though no-one in the room felt like laughing. I still figure laughing is a valuable thing to have in life. I have since joked with friends and parents that if there is ever another military call-up in Australia I’ll be safe from harm: I have flat feet, bad eyes and a mental condition.

I also remember upon entering my room for the first time, the staff removed any objects that I might use to self-harm with – telephone wires, belts, sharp objects and so forth; I had told my psychiatrist that I was having specific suicidal ideas. Looking back on this time, I understood that all this commotion was important to make sure I did not self harm, though it also felt, to a frightened and confused man, as if there was some kind of degradation ceremony taking place. I never acted on the suicidal impulses (other than one night deliberately over-drinking at a family dinner, but that is another story…). I now know I never will. There is too much beauty in the world to cut short one’s time here.

The clinic was, remarkably, a very calm place. There were many people with problems, but few were happy to talk about their issues. I remember telling one girl I had schizo-affective disorder and she saying “Oh yeah, schizo-affective is a bitch to manage”. I realise now that she was commiserating with me. At the time though I thought she was saying there was no hope for me. I felt it was a judgment about the future of my mental illness.

I also recall a fellow in there dealing with bipolar disorder. He had had the illness for quite a time before he was diagnosed. I remember him as being a very real and strong man. He told me that his life had hung in the balance, but that he had chosen to be a “warrior for the light”; he would not give in to darkness and despair.

Other than that, I did not talk much with other people. When I was re-admitted, they put me in a shared room with another fellow who remained silent as he suffered through whatever it was that burdened him. I read magazines without taking anything in. I listened to a CD of classical guitar a friend had bought for me. I read Patrick White’s The Tree of Man (light reading for a clinic in-patient!). A dear friend brought me a mini-television one day when he visited. The darn thing only picked up the ABC, but perhaps it was best that I only watched the relatively somber line-up of our excellent public broadcaster whilst I waited for my meds to kick in.

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Prof Cyndi Shannon Weickert from NeuRA and Richard Schweizer at TEDx 2014 where Prof Weickert spoke on schizophrenia. The pair are good friends

My parents visited every day. They would always give me a huge hug when they left, even if this was out in the corridor. Close friends visited me, though at that time I had not decided to go public with my illness. Often my parents would bring me home during the day, but this ended upon the request of some of the nursing staff that wanted to keep me under observation.

I guess my final thought for the second part of ‘The World According to Richard’ would be that, as calm and restorative a place as the clinic was, perhaps the best place for a mentally ill person to get better is not in the surrounds of other people going through significant personal problems. Perhaps a farm surrounded by family would be better? But I don’t know for sure, I am no psychiatrist.

Editor’s note: Part Three of the series will be posted in the coming week.

‘The World According to Richard’ (Part One)

Richard Schweizer has schizophrenia. In this three part blog series he walks us through his journey from his initial symptoms to how he feels about the future…

I want to suggest to you an idea that may be a little confronting. It’s an idea that may take you a while to get your head around. And the idea is this:

Schizophrenia is normal.

It’s a simple idea, but a powerful one.

Now I know your immediate reaction is one of surprise, perhaps rejection, perhaps anger. How can a person who has schizophrenia, who has experienced its most terrible symptoms say it’s normal? How can I possibly say it is normal to hear voices, normal to suffer paranoia, normal to have bizarre delusions about yourself and your place in the world? How can I possibly say it is normal when so much brain science is discovering the abnormal brain conditions that give rise to mental illness?

I accept these questions. And yes, on one level, on an important level, schizophrenia is abnormal and deserves the care and support and resources that brain abnormalities require in their sufferers. Schizophrenia is quite abnormal.

But on perhaps a more fundamental level; I say that schizophrenia is normal.

When you look at the distribution of mental illness like schizophrenia in the population, when one looks at the history of madness in all cultures, schizophrenia regularly arises. Indeed, 1 in a 100 will suffer it in contemporary society. So, when you look at humanity more broadly, over populations and over time, we find that madness has always been with us, regardless of how it is treated.

Madness accompanies humankind, just like anger does, like fear, love and hatred do. Madness has always been there and, for the unfortunate among us that suffer, it always will be.

So what is the upshot of this idea? What does it mean if you come on my rhetorical journey and accept that schizophrenia is normal?

I believe deeply, that people with schizophrenia need the same support and love that people without mental illness need. I believe that people with schizophrenia should be approached as people suffering an illness, not as lepers of the mind. I believe people with schizophrenia deserve respect, not simply for living with a mental illness, but for being the people they are.

And it is to these ends that I dedicate this three-part blog:

‘The World According to Richard’

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Richard Schweizer hosts a music based radio program at Eastside radio in Sydney

Like most people, I was born at a very early age. My upbringing was stable and secure. I lived in a house of care and concern, with hard working, loving parents and grandparents. When I was in kindergarten I used to wear a Superman cape. When asked who I was, my reply was inevitably “Superman!” When I had to take the cape off for sleep-time my name was Richard again. Perhaps, at this young age, I was already looking for something greater in my life.

My record as a student was strong. I had received scholarships for school at Sydney Grammar and for an undergraduate in arts/law at Sydney University. I had plenty of friends. True, I was prone to bouts of depression, but I always got the job done. I enjoyed writing and playing music with a band; I read voraciously about Australian politics; I participated in the cultural life of the university; and I had girlfriends.

My onset of schizophrenia occurred at a time of a number of stresses in my life. I had law exams and was in the process of breaking up with my girlfriend of two years. I had developed a bad eye condition that required me to become accustomed to hard contact lenses (they are still a pain in the neck), I was smoking a bit – though not too much – pot, and I was about to start a Summer placement with the NSW Attorney-General’s office.

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Richard Schweizer on stage with his band

I don’t remember much of this period, so bear with me if my account is fragmented.The first symptom I recall happened while I was sitting in class during my law degree. A blanket seemed to come down over my senses. I felt detached; distant from the world. If you are a movie lover, think of the scene in Trainspotting where Ewan McGregor overdoses and looks at the world down a lengthy corridor.

I also experienced bizarre thoughts. I can recall, at one time, thinking my friend was the devil. I knew then that that was a bizarre thought, but it popped into my head regardless. Much later, my GP said that symptoms of schizophrenia often concern themselves with things we love or hate. Some months later whilst in the Sydney Clinic and reading a magazine article about Bob Dylan (whom I idolize) a thought popped into my head… kill Bob Dylan. This disturbed me greatly.

I also remember having visual and conceptual ‘flashes’. This is hard to describe. Say, for example, on television I would see a cartoon character get banged on the head and have stars rotate around their head. That image would ‘flash’ out for me, almost as if there was a coincidence, or as if something more, going on. I refer now to another movie, this time ‘A Beautiful Mind’. Think of the scenes where Russell Crowe stares at newspapers and hidden messages flashed out at him. That’s what it felt like.

There was a darker side to this too. I would see/think flashes of violence when I saw certain people. I remember with distress a time when I saw my then girlfriend mutilated by violence. I remember, too, an occasion when I was being introduced to staff in the Attorney General’s office and I saw a reflection through the window on an accompanying building. For some strange reason I kept thinking the reflection was a gun, pointing at me. I knew, rationally, that it was a reflection, but I kept thinking it was a gun.

And then there was the voice. At least, I think it was a voice. It may have just been the artifact of an audible imagination. Reading later of other people’s experiences, I am not sure if my voice was as clear and strident as what many experience. Nevertheless, I did imagine some kind of voice, and it would tease me mercilessly about my greatest fears. Perhaps my greatest fear has always been losing my mind – my most valuable quality. The voice would say “ha ha, you’re losing your mind”. Just imagine it – some sort of phenomena arising from deep out of your mind, knowing all your fears and weaknesses.

With experiences like these perhaps it’s normal (there’s that word again) that I became emotionally unstable. I became paranoid, depressed and anxious. The strongest emotion I felt was fear – fear that I would hurt myself or someone else.

At some point in this downwards trajectory I went to my parents with a plea for help. I can’t remember how it started but I had been taking advantage of a free counselling service, and my counsellor had promised me I did not have and would not have schizophrenia. I guess I was able to cover things up pretty well, as they didn’t pick it up.

I arrived an hour late for my first day at the Attorney General’s office, saw the gun, and was feeling deeply unstable. I visited that same counselling service for an emergency walk-in session, but my normal counsellor wasn’t there. Instead I met with a lady who, after hearing me out, gave me two excellent pieces of advice: “keep yourself grounded, literally on the ground, and tell your mum”.

Around about that same time I had clambered up on my house’s backyard pergola to climb into my brother’s room as I had forgotten my key. My mum was immediately concerned by what I told her about how I was feeling and also by my risky behavior climbing onto the pergola. She booked an appointment for me to see my GP the next day. The GP listened to my story and told me to take Risperidone, and to come back and see her the next day. She also said not to look up what the drug was given for.

Of course, that night my mum looked up Risperidone on the Internet, and it said “for the treatment of schizophrenia”. Mum showed me.

My first reaction was to go numb. I didn’t know where I was. I went up to my room and immediately searched the Internet for non-pharmaceutical treatments for schizophrenia. I had a strong belief before then that drugs altering the brain’s chemistry should be avoided at all costs. (I now realise they are all but inevitable for certain serious conditions).

The significance of what I was realising washed over me – a rising flood.

I came back downstairs. I don’t remember a great deal after that. Perhaps my mind has blanked out the terrible experience.

I remember two things; one, crying tears, so many tears with my parents. I wailed like a baby. The other thing was asking my parents “Why did Omi and Opi [my grandparents] survive the Holocaust, only for this to happen?” I do not know why I asked that question. I guess the Holocaust was the deepest historical event affecting my family. Perhaps I thought this was an injustice that they should be spared, to see my life shattered. I still don’t know why I said it.

It was the worst night of my life.

Later my parents told me, that my brother had heard me crying that night and asked “What’s wrong with Richard?” I felt terrible that I should burden him too. “Richard has schizophrenia” they told him.

That night I saw hideous black ghosts flying above my bed. I left my bedroom and crawled into bed with my parents; a deep reversion to the childlike.

The next day I entered the Clinic.

Editor’s note: Part Two of the series will be posted in the coming week.

Of squiggly lines and schizophrenia

Dr Jason Bruggemann is investigating new ways of identifying children at risk of developing schizophrenia.

I am relatively new to schizophrenia research, so I was surprised by the sheer diversity of people I have met who have schizophrenia – men and women from a wide variety of backgrounds with distinct personalities who don’t conform to any particular stereotype. While the disease affects them in different ways, however, they have all described the significant challenges that schizophrenia has posed for them and their families.

Schizophrenia is a neurodevelopmental disorder that typically begins during late adolescence or early adulthood. Healthy development during adolescence involves large-scale reorganisation and restructuring of the brain, including changes to the delicate excitatory/inhibitory balance of the brain’s neurotransmitter systems and underlying brain structure. This process seems to go awry for people with schizophrenia. Environmental factors like stress also appear to contribute to the onset of the disease.

Dr Jason Bruggemann

Dr Jason Bruggemann holds an EEG ‘net’, made up of wires and electrodes.

We know that early diagnosis and treatment can significantly improve long-term outcomes and help minimise the damaging effects of schizophrenia. Hence, current research is focused on potential ways of identifying children at risk of developing schizophrenia. Our colleague Dr Kristin Laurens and her team from Kings College London are currently evaluating a combination of factors as potential early markers, including subtle peculiarities of speech and movement, lower IQ and poorer academic achievement, disturbances in social, emotional, and behavioural functioning, and subclinical psychotic-like experiences such as occasionally hearing voices that nobody else can hear.

At NeuRA, we are conducting research into another potential marker of schizophrenia risk called the mismatch negativity (MMN). The MMN is an index of the brain’s electrical response to changing patterns of sounds. It’s derived from a measure of the electrical activity of the brain called the electroencephalograph (EEG), more commonly known as ‘brainwaves’. The raw EEG signal may look like just a bunch of squiggly lines running across the computer screen but, once analysed, the resulting data can help us better understand patterns of normal and abnormal brain function.

An example of a raw EEG

The squiggly lines of a raw EEG read out.

In adults with schizophrenia, the size of the MMN has been related to disease severity, ability to function in the wider-community (functional outcome), and grey matter volume loss in the frontal and temporal brain regions. The MMN is usually smaller in adults with chronic schizophrenia compared with typical individuals. In light of this, we recently investigated whether a group of children who may be at increased risk of schizophrenia (based on having some of the risk factors described above or having a first-degree relative with schizophrenia) also have a smaller MMN relative to typically developing children.

Our results showed that although the MMN exhibited by the children at risk of schizophrenia was unlike that of their typically developing peers, it also differed from the smaller MMN observed in adults with schizophrenia. In fact, we found a relative increase in the MMN over the frontal brain region, rather than a decrease!

“If we can reliably identify at-risk children then perhaps we can reduce the burden of schizophrenia for future generations.”

It was difficult for us to interpret this result in the context of what we know about MMN in adults with chronic schizophrenia. We looked at MRI data from an overlapping sample of children, which revealed differences in grey and white matter volume in the same brain regions that produce the electrical activity seen in the MMN. Also, the developmental literature indicates that the MMN tends to be larger in young children compared to adults. This has led us to speculate that perhaps the ‘at-risk’ children are on a different developmental trajectory than their peers. It is possible that this unusual MMN result may reflect the complex interplay between developmental changes and the factors placing these children at higher risk of developing schizophrenia.

It’s essential to conduct long-term follow-up of these potentially at-risk children to establish who goes on to develop schizophrenia and how their MMN changes as they mature. This follow-up work, being completed by our colleague Dr Kristen Laurens, will tell us whether the increased MMN we found in this study may indeed be a useful way of identifying children at risk of developing schizophrenia.

The unique people with schizophrenia that I have met currently live their lives as best they can despite the challenges raised by this condition. If we can reliably identify at-risk children then, with appropriate early treatment, perhaps we can reduce the burden of schizophrenia for future generations.

Rethinking schizophrenia

I work in the field of schizophrenia research; specifically, I study schizophrenia by looking at the brain. Up until about 25 years ago, this way of studying schizophrenia was considered a dead-end career path for pathologists and researchers like me; many doubted that measurable differences between the brains of people with schizophrenia and those who don’t have a mental disorder even existed.

NeuRA’s Dr Vibeke Catts

In the past few decades, however, modern and sophisticated techniques have revealed the existence of differences at a sub-cellular level in the brains of people with schizophrenia. These differences are subtle and cannot be detected with a brain scan.

“Our research raises the possibility that altered development during childhood and adolescence plays a part in the development of schizophrenia – challenging the dogma that the developmental defect occurring in schizophrenia is restricted to foetal life.”

A focus of our research group at NeuRA has been to consider how and when these subtle differences arise. To do this we first need to understand normal brain development: what happens in the brain as a foetus develops, as a baby is born and as a child matures into an adult? Only when we’ve answered these questions can we understand how brain development is disrupted in schizophrenia.

The main events during normal brain development are the birth of neurons (neurogenesis), the movement of neurons from their birthplace to their final position in the adult brain (migration), the establishment of fast communication tracts between brain regions (myelination) and the setting up of connections between neighbouring neurons (synapse formation). Different types of neurons add sophistication to the system (the timing of the development of these varies).

This enhanced image of a neuron shows the cell body (right), and a long thin axon projecting out to the left. The axon enables the neuron to communicate with other neurons.

Our work, and that of others, also tells us that communication and connections between neurons is impaired in people with schizophrenia. In particular, the chemical communication (called signalling) from small inhibitory neurons, which help shape the appropriate response patterns of the more prevalent information-carrying excitatory neurons, appears to be affected. Several findings converge to suggest that the inhibitory interneurons fail to mature properly, resulting in a brain that is unable to amplify and contrast relevant signals, while at the same time filter out background signal noise.

Perhaps most interesting, however, is our finding that neurons develop over a long period; while a lot of brain development and change occurs before a baby is born, many dynamic changes continue to take place in the brain well into the teenage years.

The pre-adult brain is at its most vulnerable when neurons are developing and undergoing change; this is when there is an increased potential for something to go wrong and when deleterious environments can be the most damaging.

Our research raises the possibility that altered development during childhood and adolescence plays a part in the development of schizophrenia – challenging the dogma that the developmental defect occurring in schizophrenia is restricted to foetal life. It’s important to note here that the first signs of schizophrenia typically appear during adolescence.

An important implication of this is that by intervening early in adolescence it may be possible to stabilise the brains of those adolescents at risk of psychotic disorders by targeting and preventing some or all of these changes at the sub-cellular level. Any disruption in brain development may then be only transitory. The hope is that we could prevent people from developing chronic schizophrenia, a disease that has a profound effect on people’s lives and which is currently very difficult to treat effectively.

References 

Catts, V. et al (2013) Rethinking schizophrenia in the context of normal neurodevelopment. Front Cell Neurosci. 2013 May 15;7:60.  

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