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.

“Help me, I’m terrified of falling!”

Being afraid of falling is very common – and not something you should have to live with, says NeuRA researcher Joanne Lo.

Last week I went to visit an eighty-year-old woman who was terrified of having a fall and ending up in a nursing home. ‘Florence’ loves her sunny unit and enjoys the independence of living in her own place and, until recently, was a very active and confident woman.

Earlier this year, however, she had a particularly bad fall on the stairs to her apartment block. She now lives with a fear that weighs on her every day. Her fear of falling is so overpowering that she avoids any activity that might be the least bit risky, such as walking the short distance to her local shops.

Meeting people like Florence reminds me how far we’ve come in the last decade in terms of what we can offer to older people at risk of falling. Not so long ago, if you were elderly and fearful like Florence, you might not have dared to venture outside and possibly become more frail, depressed and socially isolated.

NeuRA researcher Joanne Lo is part of the falls and balance research group.

But as a result of research from around the world – in which NeuRA’s Prof Stephen Lord and his team have played an important and active role – we have gotten better at helping people fall less. At the heart of these improvements is a simple battery of tests developed at NeuRA, known as FallScreen.

We use FallScreen to test a person’s physical function; for example, we measure how much a person’s body sways while they attempt to stand still on a foam mat. We use the results to predict a person’s risk of having a fall in the next year.

In the postural sway test, the patient attempts to stand as still as possible while we measure how much their body sways.

We know what to test for because, early in his research career here at NeuRA, Prof Lord assessed hundreds of older adult volunteers to see what was different about those who fell during the subsequent year. He identified five primary areas of physical function that contributed to an individual’s risk of falling: their vision, the speed of their reactions, leg sensation, muscle strength and balance. He then devised simple methods of assessing these different areas and the assessment tool known as FallScreen was born.

Studies have found that FallScreen allows us to predict future fallers with an accuracy of 75%. Why is this important? Because if you know you’re at risk, then you can do something about it.

In Florence’s case, I assessed her as being at moderate risk of falling in the next year. She was surprised; in her fearful state, she had felt she was at very high risk. I was able to show her specific exercises to strengthen her leg muscles and talked about ways of addressing her fear so that she could continue to exercise confidently.

The FallScreen assessment tool is now being used in hospitals and clinics around the world. This means that health practitioners have a scientifically-validated way of testing where the potential deficits are in their patient’s physical function and are better able to target these areas in their treatment. This is good news for maintaining the patient’s independence and helping them to prevent a fall in the future.

If you think you are at risk of falling, or have a fear of falling, I can’t urge you strongly enough ask your GP for a referral to a falls clinic for an assessment. There are many things you can do to reduce your risk; being assessed is just the beginning.

For example, at NeuRA we are currently looking into ways of improving exercise programs, such as using an iPad app as a digital personal trainer. This is just one of many ways we are trying to reduce falls in older people. If you’d like to find out more, please visit our website.

Credit or savings?

When I tell people I manage a Brain Bank they usually look quizzical and joke about making deposits and withdrawals. The reality is, they’re not so far from the truth. People make the decision to donate their brain for medical research every day and when they do, a Brain Bank is where their brain goes. Continue reading