Our research is opening a whole new avenue of exploration to improve brain function for those with schizophrenia

While on my research journey at NeuRA, I discovered unexpected biological changes in the brain of those with schizophrenia, and we were the first to share this with the world.

We find hostile immune cells are invading the brain, escalating inflammation and creating an unhealthy environment for the neurons needed for language, learning and reasoning. What does this insight mean? It’s an important discovery, because it opens a whole new avenue of exploration to improve brain function for those with schizophrenia.

This also leads us to ask why do hostile immune cells enter the human brain in the first place? We don’t yet know the answer, and it’s proving difficult to pinpoint. Research tells us that there is not one single cause of schizophrenia, there are many. So, we suspect that there are multiple reasons why more hostile immune cells are found in the brains of people with schizophrenia. Are the origins of schizophrenia linked to the immune system? Yes, there is evidence to support this. However, there’s much more investigation to be done.

Searching for the origins of schizophrenia
Some research groups around the world are focused on foetal development and even on the placental origins of schizophrenia. It is thought that maternal stress and maternal infections increase the risk of offspring developing schizophrenia.

At NeuRA, our group is zoning in on changes that may trigger schizophrenia at the age of onset – which is typically during adolescence. This is a time when hormonal changes dominate. Oestrogen has neuro-protective effects and is anti-inflammatory, while testosterone triggers increased dopamine, which is toxic in high amounts. Another major change happens in the thymus, which is an important immune organ that shrinks during adolescence. This thymus educates immune cells to distinguish self from non-self and ensures that only foreign cells (bacteria) are attacked. Without proper education, the immune cells can produce antibodies against oneself (autoantibodies). This is important, as we know that autoantibodies can cause hallucinations and delusions if they get into the human brain. A third major change occurring in teens, is increased recreational drug use and this is known to trigger neuronal damage and inflammation, and can increase the risk of developing schizophrenia. So, there are many possible routes to the same outcome – which is inflammation in the brain of people with schizophrenia.

There are still a lot of unknowns but investing in research into the potential origins and causes of schizophrenia is so important. That’s what will reveal the road to better treatments and even potentially preventing the development of full-blown schizophrenia. But it is also time consuming and extremely costly – that’s why we need your help.

Doing better for people with schizophrenia right now

While we keep working on uncovering the origins and causes, we also want to do better for our friends, relatives and community members who suffer from schizophrenia today. So we also research alternative treatments based on these new insights, in the hope that we can deliver for people suffering from schizophrenia right now.

Current schizophrenia medications involve many undesirable side-effects. We have recently discovered a biological underpinning for schizophrenia, namely neuroinflammation, that offers the promise of finding better ways to manage positive symptoms like hallucinations and delusions or negative symptoms like depression and cognitive deficits. Dampening neuroinflammation may allow people with schizophrenia to recover, and to find more meaning in life through maintaining part-time employment or building some strong social relationships.

Inspired by my brother, and his battle with schizophrenia, I have chosen to focus my life’s work on identifying what actually happens in the brains of people with schizophrenia. Right down to the cellular and molecular levels. It is my passionate and deeply-held belief that this is the very best way I can help. It is only by illuminating the events which take place inside the brain at different times – leading up to onset of schizophrenia, during psychotic episodes, and when people are in a less active stage of disease – that we can hope to discover how to better treat it. Depending on the stage of disease each person with schizophrenia is experiencing at any given time, they may very well need different treatments for different stages – instead of just one blunt instrument, like anti-psychotics that are most commonly used. But we need to keep working, and your support plays a big part in keeping our research alive.

Finding echoes of our own experience of schizophrenia
I draw inspiration from meeting and working with people with schizophrenia and their families, as well as other scientists and clinicians in New South Wales, around Australia and around the world. I also love to read, and there are many fantastic non-fiction books that share raw and captivating real life experiences, at least some of which relate to my own and possibly your trials with schizophrenia.

One of my favourite books is ‘Brain on Fire: My Month of Madness’, by New York Post writer Susannah Cahalan. Susannah found herself hospitalised after psychotic breaks and was offered many different diagnoses, including schizophrenia. As it turned out, she had a rare form of encephalitis (anti-NMDA) – but the key point was that her brain was grossly inflamed with an infiltration of immune cells. Once this inflammation was properly treated, she recovered and her ‘schizophrenia’ was cured.

Another favourite book of mine is ‘Hidden Valley Road: Inside the Mind of an American Family’ by Robert Kolker. This is about the Galvin family in Colorado, a mid-century family with a dozen children – 10 boys and two girls – and in which six of the boys had schizophrenia. The family partnered with researchers to investigate the genetic origins of the disease and with donors, help build a world recognised research centre in Boulder. The research on this one family taught us so much about the complex interplay between genetic and environmental factors in schizophrenia. Many genes are involved – it’s not a straightforward relationship like it is with the one gene that causes cystic fibrosis. Sadly, none of these boys were cured of their schizophrenia.

My take-home from ‘Hidden Valley Road’ is just how significant the partnership between those affected by the disease (directly or indirectly) and researchers is. Our collaboration in research – for example through participation in clinical trials and donating to keep research alive – is what will get us to the end goal, together.

The more people know about schizophrenia and how it impacts those in its orbit, hopefully the more support we will receive for research and the closer we get to developing more effective treatments. My end goal is to arrive at a point where we have the ability to understand schizophrenia at both the cellular and molecular level, so that we can:

  • Treat people who are in an active state of disease on a personalised basis (no one size fits all anymore).
  • Lead clinical trials with novel treatments
  • Test if blocking inflammation can prevent relapse for those who are in remission.
  • Identify those at high risk of the disease early, and prevent them their progression to full-blown schizophrenia by blocking inflammation early on

This will take time and we have our work cut out of us, but I believe it is possible through research, with every fibre of my being. With your generous support, we can make a difference.

Thank you,

Professor Cyndi Shannon Weickert.

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