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Neuroscience research

Case study:

Impact-driven research for healthier young minds

The mental health of our young people is at crisis point. Research involving the University of Exeter found that one in four teens aged 17-19 has a probable mental health disorder – up from one in six the previous year.

The University of Exeter’s neuroscience community is making great strides in understanding the mechanisms of how brains develop and how stress both occurs and impacts us in later life. Through innovative technology and a highly interdisciplinary approach, the University is building on this knowledge of mental health disorders including depression and anxiety, to create large-scale prevention studies.

Professor Ed Watkins has created interventions with a focus on reducing overthinking such as worry and rumination. These interventions build on experimental and neuroscience research that explores the mechanisms that underpin overthinking and worry, which in turn are proven to drive anxiety and depression.

Based on this research, the team have developed an innovative form of cognitive-behavioural therapy that targets overthinking, which has been found to be effective in multiple clinical trials, both in face-to-face and online therapy.

Professor Watkins said: “Most mental health problems occur for the first time between the ages of 12 and 24, which can be hugely disruptive during crucial years of social, academic and career development. Moreover, common mental health problems such as anxiety and depression tend to be recurring and the earlier they start in adolescence, the more likely they are to recur.  If we’re going to make any difference to reducing mental health problems in later life, it’s crucial that we intervene early. Understanding how the brain works is critical to developing effective intervention strategies.”

In adolescents with a history of depression, the team found that therapy changed patterns of brain activation and these changes were associated with reductions in over-thinking. The treatment reduced the elevated connectivity typically observed during over-thinking between the default mode network, which is active when individuals are not directly engaged in a task and is implicated in thinking about oneself, and the cognitive control network, the brain region involved in executive control. This reduced connectivity suggests that the treatment is either making it easier for young people to control their over-thinking or reducing the habitual nature of the over-thinking.

“It looks like the therapies with young people are changing the way the brain is working, and one possibility is that is making over-thinking less of a habit, so that young people don’t need to actively control it so much with the cognitive control network,” Professor Watkins said.

The team is using innovative methodologies and technology to increase access to these interventions, including a large-scale European study called ECoWeB, which developed an app for young people. This study found that a self-help cognitive behavioural therapy (CBT) app could prevent depression in young people who had elevated risk for depression. An ongoing study called Nurture-U is investigating how best to improve university student mental health through a whole university approach and will provide a blueprint for all UK universities to support good mental health for students.

The University of Exeter specialises in understanding brain development at both genetic and mechanistic levels. Professor Soojin Ryu has developed a unique model of genetically-modified zebrafish, in which stress hormones can be manipulated to examine the role of specific genes. She said: “Experiencing early life stress or trauma is the strongest risk factor for developing psychiatric conditions in later life, including depression. We look at how increases in stress levels influence brain development.”

Working with Exeter’s £12 million Aquatic Resources Centre’s 3,000 tank zebrafish unit, Professor Ryu’s team found that zebrafish who are exposed to high levels of stress hormones in early life exhibit a number of behavioural dysfunctions in later life, including poor social interaction and the ability to adjust to new environments. When they looked across the zebrafish brain's to examine genetic changes, they found dramatic differences in the way genes were expressed in adulthood in those who had experienced early life stress.

“This tells us that early life stress changes the brain, and especially alters the way animals - including humans - process stress in later life,” said Professor Ryu. “Using our model, we can see changes in specific genes caused by stress and see what impact that has. That’s a very exciting prospect for future drug discovery.”

Crucially, the genes in which the changes were found are known to be risk genes for psychiatric disorders in humans, including schizophrenia and depression.

Exeter hosts one of the world’s leading laboratories on epigenomics – which is investigating the way genes are expressed in the developing and aging brain and how this might influence disease. Through examining brains from foetal to old age, the lab has made major advances in understanding the gene changes implicated in disease. The lab works alongside the University of Exeter Sequencing Facility, which can read a much greater section of the genome in one go than was previously possible. Dr Rosemary Bamford said: “Our genome contains about 20,000 genes, but every gene can produce thousands of types of RNA, which code for different protein. Thanks to the new technology we’re able to examine this in a level of detail that has never been possible previously. For the first time, we’re discovering a huge number of versions of RNA never seen before. We’re finding implications in neurodevelopmental disorders including autism and schizophrenia. This rich level of diversity is important because it allows us to study the impact on making protein and the difference in healthy and diseased brains.”

This interaction between world-leading experts on genomics, molecular changes and human behaviour means the University of Exeter stands out on interdisciplinarity, with an active Children and Young People’s Wellbeing Exeter Research Network, Exeter Brain Network spanning through psychology, psychiatry, and statistics, and across the humanities where relevant. “It’s such a strength at Exeter that really benefits my work,” said Professor Ryu. “We’re incredibly collegiate. We span from examining how the brain develops at a molecular level, to understanding how the brain acts as a whole, and translating the mechanisms into the brain into trials that can really make a difference in human development.”

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