Disrupted Synaptic Pruning a Key Factor in Teen Mental Health at Risk

Summary: According to research, problems with the brain’s ability to prune itself of unnecessary connections may be behind a wide range of mental health disorders that begin during adolescence. This could explain why people are often affected by more than one disorder. The discovery of a characteristic pattern of brain activity called the “neuropsychopathological factor” (NP factor) could help identify those at greatest risk of mental health problems and facilitate earlier interventions to reduce the risk.

Source: University of Cambridge

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 shows a brain
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. Image is in the public domain

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.”

Funding: Funders included: the National Natural Science Foundation of China, European Union, National Institute for Health & Care Research (UK) and National Institutes of Health (NIH, USA).

About this mental health and neuroscience research news

Author: Craig Brierley
Source: University of Cambridge
Contact: Craig Brierley – University of Cambridge
Image: The image is in the public domain

Original Research: Open access.
A shared neural basis underlying psychiatric comorbidity” by Barbara Sahakian et al. Nature Medicine


A shared neural basis underlying psychiatric comorbidity

Recent studies proposed a general psychopathology factor underlying common comorbidities among psychiatric disorders. However, its neurobiological mechanisms and generalizability remain elusive.

In this study, we used a large longitudinal neuroimaging cohort from adolescence to young adulthood (IMAGEN) to define a neuropsychopathological (NP) factor across externalizing and internalizing symptoms using multitask connectomes.

We demonstrate that this NP factor might represent a unified, genetically determined, delayed development of the prefrontal cortex that further leads to poor executive function.

We also show this NP factor to be reproducible in multiple developmental periods, from preadolescence to early adulthood, and generalizable to the resting-state connectome and clinical samples (the ADHD-200 Sample and the Stratify Project).

In conclusion, we identify a reproducible and general neural basis underlying symptoms of multiple mental health disorders, bridging multidimensional evidence from behavioral, neuroimaging and genetic substrates.

These findings may help to develop new therapeutic interventions for psychiatric comorbidities.

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