Newswise — Problems with the brain’s ability to ‘prune’ itself of unnecessary connections may underlie a wide range of mental health disorders that begin during adolescence, according to research published today.
The findings, from an international collaboration, led by researchers in the UK, China and Germany, may help explain why people are often affected by more than one mental health disorder, and may in future help identify those at greatest risk.
One in seven adolescents (aged 10-19 years old) worldwide experiences mental health disorders, according to the World Health Organization (WHO). Depression, anxiety and behavioural disorders, such as attention deficit hyperactivity disorder (ADHD), are among the leading causes of illness and disability among young people, and adolescents will commonly have more than one mental health disorder.
Many mental health problems emerge during adolescence. Among these are disorders such as depression and anxiety, which manifest as ‘internalising’ symptoms, including low mood and worrying. Other conditions such as attention deficit hyperactivity disorder (ADHD) manifest as ‘externalising’ symptoms, such as impulsive behaviour.
Professor Barbara Sahakian from the Department of Psychiatry at the University of Cambridge said: “Young people often experience multiple mental health disorders, beginning in adolescence and continuing – and often transforming – into adult life. This suggests that there’s a common brain mechanism that could explain the onset of these mental health disorders during this critical time of brain development.”
In a study published today in Nature Medicine, the researchers say they have identified a characteristic pattern of brain activity among these adolescents, which they have termed the ‘neuropsychopathological factor’, or NP factor for short.
The team examined data from 1,750 adolescents, aged 14 years, from the IMAGEN cohort, a European research project examining how biological, psychological, and environmental factors during adolescence may influence brain development and mental health. In particular, they examined imaging data from brain scans taken while participants took part in cognitive tasks, looking for patterns of brain connectivity – in other words, how different regions of the brain communicate with each other.
Adolescents who experienced mental health problems – regardless of whether their disorder was one of internalising or externalising symptoms, or whether they experienced multiple disorders – showed similar patterns of brain activity. These patterns – the NP factor – were largely apparent in the frontal lobes, the area at the front of the brain responsible for executive function which, among other functions, controls flexible thinking, self-control and emotional behaviour.
The researchers confirmed their findings by replicating them in 1,799 participants from the ABCD Study in the USA, a long-term study of brain development and child health, and by studying patients who had received psychiatric diagnoses.
When the team looked at genetic data from the IMAGEN cohort, they found that the NP factor was strongest in individuals who carried a particular variant of the gene IGSF11 that has been previously associated with multiple mental health disorders. This gene is known to play an important role in synaptic pruning, a process whereby unnecessary brain connections – synapses – are discarded. Problems with pruning may particularly affect the frontal lobes, since these regions are the last brain areas to complete development in adolescents and young adults.
Dr Tianye Jia from the Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China and the Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK said: “As we grow up, our brains make more and more connections. This is a normal part of our development. But too many connections risk making the brain inefficient. Synaptic pruning helps ensure that brain activity doesn’t get drowned out in ‘white noise’.
“Our research suggests that when this important pruning process is disrupted, it affects how brain regions talk to each other. As this impact is seen most in the frontal lobes, this then has implications for mental health.”
The researchers say that the discovery of the NP factor could help identify those young people at greatest risk of compounding mental health problems.
Professor Jianfeng Feng from Fudan University in Shanghai, China, and the University of Warwick, UK, said: “We know that many mental health disorders begin in adolescence and that individuals who develop one disorder are at increased risk of developing other disorders, too. By examining brain activity and looking for this NP factor, we might be able to detect those at greatest risk sooner, offering us more opportunity to intervene and reduce this risk.”
Funders included: the National Natural Science Foundation of China, European Union, National Institute for Health and Care Research (UK) and National Institutes of Health (NIH, USA).*
Reference
Chao Xie et al. A shared neural basis underlying psychiatric comorbidity. Nat Med; 24 Apr 2023: DOI: 10.1038/s41591-023-02317-4
ENDS
*A full list of funders can be found in the paper.
Once the paper has been published online, it will be available at the following URL: https://www.nature.com/articles/s41591-023-02317-4
About the University of Cambridge
The University of Cambridge is one of the world’s leading universities, with a rich history of radical thinking dating back to 1209. Its mission is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence.
Cambridge was second in the influential 2023 QS World University Rankings, the highest rated institution in the UK.
The University comprises 31 autonomous Colleges and over 100 departments, faculties and institutions. Its 20,000 students include around 9,000 international students from 147 countries. In 2022, 72.5% of its new undergraduate students were from state schools and more than 25% from economically disadvantaged backgrounds.
Cambridge research spans almost every discipline, from science, technology, engineering and medicine through to the arts, humanities and social sciences, with multi-disciplinary teams working to address major global challenges. In the Times Higher Education’s rankings based on the UK Research Excellence Framework, the University was rated as the highest scoring institution covering all the major disciplines.
The University sits at the heart of the ‘Cambridge cluster’, in which more than 5,200 knowledge-intensive firms employ more than 71,000 people and generate £19 billion in turnover. Cambridge has the highest number of patent applications per 100,000 residents in the UK.
About King’s College London and the Institute of Psychiatry, Psychology & Neuroscience
King's College London is one of the top 35 universities in the world and one of the top 10 in Europe (QS World University Rankings, 2021/22) and among the oldest in England. King's has more than 33,000 students (including more than 12,800 postgraduates) from over 150 countries worldwide, and 8,500 staff. King's has an outstanding reputation for world-class teaching and cutting-edge research.
The Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s is a leading centre for mental health and neuroscience research in Europe. It produces more highly cited outputs (top 1% citations) on psychiatry and mental health than any other centre (SciVal 2021), and on this metric has risen from 16th (2014) to 4th (2021) in the world for highly cited neuroscience outputs. In the 2021 Research Excellence Framework (REF), 90% of research at the IoPPN was deemed ‘world leading’ or ‘internationally excellent’ (3* and 4*). World-leading research from the IoPPN has made, and continues to make, an impact on how we understand, prevent and treat mental illness, neurological conditions, and other conditions that affect the brain.
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About the National Institute for Health and Care Research (NIHR)
The mission of the National Institute for Health and Care Research (NIHR) is to improve the health and wealth of the nation through research. We do this by:
- Funding high quality, timely research that benefits the NHS, public health and social care;
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NIHR is funded by the Department of Health and Social Care. Its work in low and middle income countries is principally funded through UK Aid from the UK government. www.nihr.ac.uk
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