Diagnosing schizophrenia and bipolar disorder
Research involves risk—and doesn’t always lead to reward. Neurologist and neuroscientist Emeritus Professor John Willoughby and electrical and electronic engineer Associate Professor Kenneth Pope were four years down a research rabbit hole before they stumbled across a dead-end. Now, they’re close to a breakthrough that could contribute importantly to how schizophrenia and bipolar disorder are diagnosed, treated and understood.
‘It was the worst moment. One of the worst periods of my life.’
This is how Emeritus Professor John Willoughby describes the moment his project with Associate Professor Kenneth Pope and psychiatrist Professor Tarun Bastiampillai started. He and Kenneth had been studying electrical brain activity they thought only existed in people with epilepsy. The discovery would’ve had huge ramifications for diagnosis. Years of lab work screeched to a stop when John and Kenneth ran their second trial—collecting electroencephalography (EEG) data from hundreds of people—and saw that the results they expected just weren’t there. There was no increased brain activity in people with epilepsy. They were distressed and anxious to understand why. There thoughts turned to contamination of EEG signals by electrical signals from muscles.
John and Kenneth reasoned that electrical muscle activity might still be to blame for the false clues they'd been following, even though they had taken steps to minimise the impact.
There is constant muscle activity in our bodies, including in our heads. It’s not just with swallowing, coughing or facial movements that muscle activity is produced, it is also required to simply maintain our natural facial appearance and hold our head up—and it is this activity that the sensitive EEG equipment picks up on. But no one knew the extent of the interference until John and Kenneth uncovered it.
While we knew electrical muscle activity was a known problem in interferring with the measurement of electrical brain activity, we thought we had dealt with it using the standard way.
They’re the type of people who need reliable answers. For themselves, for their project, they needed to know: ‘How much does electrical muscle activity influence the results measurement of EEG?’ There was one way to find out: by paralysing people (stopping all their muscle activity) and then measuring their EEG.
In order to completely remove muscle- activity- interference from their trial, John and Kenneth needed to temporarily paralyse people while they were awake and run the same tests. It sounds like a nightmare situation, like waking up during surgery and being unable to communicate, with a tube down your throat. Understandably, volunteers for this experiment were hard to come by. In the end they found eleven people who agreed: six men and five women. That number dropped to six when half of the volunteers couldn’t tolerate the intubation tube, which would allow them to breathe and keep them alive during the paralysis. But it didn’t matter. John and Kenneth only needed a handful of people to do the experiment just once.
The remaining six volunteers (including John himself) were fitted with an EEG cap and the breathing tube and tested with during different activities: eyes open, eyes closed, finger movements tapping, reading, memory memorising words, and other mental and physical tasks. They communicated their answers by tapping a finger when needed. Then the paralysis was administered, but with finger movements in one hand preserved by using a high-pressure cuff, which stopped the paralysis getting to one arm. And then they did the whole thing again.
John describes the experience as ‘relaxing’—as strange as that sounds. The brain doesn’t necessarily realise the body is paralysed. The trial took place in a darkened room, where he was unmoving and comfortable, so John barely noticed he’d been paralysed. He didn’t feel panicked because he knew it was completely safe. People go through the same procedure every day during surgeries; it’s just that patients are usually unconscious by the time the paralysis takes effect. Still, John went first to make sure the mechanics of the experiment worked. He was more apprehensive about the data and what it was going to say, than the paralysis. Not that his wife agreed. There was disagreement in his household the night he told her what he planned to do.
When asked about the results, John will shake his head and say that they were ‘just ghastly.’ In the high EEG frequencies they were interested in recording, the signals picked up 200 times more muscle activity than brain activity. His first thought on seeing the results was, ‘We’ll just have to give up.’
Kenneth had a more hopeful reaction, saying ‘Let’s see what we find after removing as much as we can of the muscle activity from the EEG signals.’ This approach led the research team down a new path.
Since this turning point, Kenneth and the team have developed signal- processing methods that mean they can get a much broader look at what’s going on in the brain using processed electrical signals. What they found was that there were no significant data or other differences (electro-encephalographically-speaking) happening in the background in people with epilepsy. That theory died for good. However, they did find a change in the high frequency EEG results in schizophrenia and bipolar disorder. In doing so, their initial failure led to a new and worthy direction.
Tarun Bastiampillai advises that there is no blood test for any mental illness. Until now, sScientists have not found any biomarkers (i.e. a molecule, gene or other clue in the body to point to a disease or disorder) or other biological indicators for schizophrenia or bipolar disorder. A biomarker would provide easier diagnosis and a better understanding of the basis of the illness. Schizophrenia and bipolar disorder could be caused by brain inflammation or rewiring or an electrical-signalling or (a receptor) problem. Some researchers theorise that these very similar conditions are the same disorder presenting differently. There’s so much we simply don’t know. Finding the cause could lead to new and more targeted treatments.
Schizophrenia and bipolar disorder are widely socially misunderstood and stigmatised. While mental health campaigns are growing in frequency, they usually raise awareness for depression and suicide. People with psychotic illnesses who are homeless, in a compromised boarding house, or in jail, need more help and compassion. In Tarun’s opinion, this is the group that is suffering a great deal. He’s happy to put his attention where it is needed.
Billions of dollars have been spent looking for some biomarker or other sign in schizophrenia and bipolar disorder. If what our team has found is a true signal, it will be relatively groundbreaking.
When asked why they didn’t just give up when it all fell apart, Kenneth will say ‘Once you start finding out this kind of stuff, how could you stop?’ What they’re doing now could improve diagnosis for people with schizophrenia and bipolar disorder. It’s this sort of discovery that motivates researchers to be researchers and doctors to be doctors.
About 1% of Australians have schizophrenia and another 2% have bipolar disorder. Both schizophrenia and bipolar disorder usually manifest around 16 or 17 years old, but sufferers sometimes undergo a slow decline over several years until they are eventually diagnosed. John has seen this happen firsthand; his younger brother was diagnosed with schizophrenia. It’s a sixty-year illness—a chronic, lifelong condition. If there is a test for schizophrenia and bipolar disorder, diagnosis could be significantly easier, faster and more conclusive. It would take the guesswork out of reading symptoms.
With earlier diagnosis, patients could also start treatment when it has the greatest impact—vastly improving their quality of life. As it is now, to start treatment is not a straightforward process. Tarun must wait around three months before he concludes that a drug isn’t effective and try another. Many aren’t. A patient might spend five years trying to find a treatment that helps. If the brain activity John and Kenneth identified is affected by medication, this discovery could test not just for schizophrenia and bipolar, but also whether a treatment is working. It’s a tool that any doctor would wish for, and one that excites psychiatrist Professor Tarun Bastiampillai.
Tarun joined the team only a few years ago. He brings the clinical knowledge of bipolar disorder and schizophrenia, as well as connections to clinical services where he treats patients on a daily basis.
Because the team doesn’t know if medication will affect the results, they want to first test people who have been diagnosed with (or are strongly suspected of having) schizophrenia or bipolar disorder but are not being treated. That’s where Tarun comes into the project, connecting the team with people experiencing these disorders as they present to emergency departments in hospital settings.
I think interdisciplinary research is by far the most interesting. My understanding of medicine is very incomplete and their understanding of computing and analysis, and how hard or easy it is to do something, is incomplete. Together, it makes it much easier to come up with the kinds of projects that other people wouldn’t necessarily think of.
There’s a lot that can still go wrong, as John and Kenneth have experienced. For now, they’re happy with their new direction. They’ve made a discovery with huge potential and they’ve learned from the past. And this time, they’re hopeful the research will allow people with schizophrenia and bipolar disorder to get the help they need faster.
Emeritus Professor John Willoughby has retired from his roles as Professor in Medicine at Flinders University and consultant neurologist at Flinders Medical Centre. But he continues to teach medical students and undertake medical research on the use of EEG in the diagnosis of neuropsychiatric disorders. He is also involved in Doctors for the Environment Australia as secretary of the SA committee. Previously, Emeritus Professor Willoughby held roles in science administration as Chair of the Flinders Medical Centre Research Foundation, Convenor of the Centre for Neuroscience at Flinders University, and member and chair of various National Health and Medical Research Council (NHMRC) committees and the South Australian branch of the Australian Brain Foundation.
Associate Professor Kenneth Pope is an electrical and electronic engineer who has also studied computer science, mathematical physics and music. His research focuses on biomedical signal processing, particularly in EEG. He teaches biomedical and electronic engineers and has long held teaching administration positions, currently as Teaching Program Director for engineering, design and information technology at Flinders University. He volunteers for Engineers Without Borders.
Professor Tarun Bastiampillai is a consultant psychiatrist and a clinical academic at Flinders University. He has significant experience in senior mental health leadership roles as the previous SA Health Executive Director for Mental Health Strategy and as the Clinical Director of Southern Adelaide Local Health Network (SALHN). He has specific research interests in schizophrenia, mental health services research and e-mental health. He has published his work in high impact journals including: JAMA, The Lancet, Molecular Psychiatry, Lancet Psychiatry, Translational Psychiatry and the MJA. In 2013-2016, he was Chief Investigator for a Young and Well Cooperative Research Centre grant totalling $2.6 million.
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