“Brain Connection Pruning Problems Linked to Adolescent Mental Disorders”

Problems with the brain’s ability to prune itself of unnecessary connections may be linked to adolescent mental health disorders, a new study suggests.

The findings could help explain why people are often affected by more than one mental health disorder and could in the future help identify those at greatest risk, the researchers say.

According to the World Health Organization (WHO), one in seven adolescents (aged 10 to 19) worldwide suffer from mental disorders.

It also says depression is a leading cause of illness and disability among adolescents, with half of all adult mental disorders starting by age 14, but most going undetected and untreated.

Another mental health disorder that can emerge during adolescence is anxiety which, along with depression, appears as internalizing symptoms, including low mood and worry.

Other conditions like attention deficit hyperactivity disorder (ADHD) manifest as externalizing symptoms, such as impulsive behavior, experts say.

Professor Barbara Sahakian from Cambridge University’s department of psychiatry said: ‘Young people often experience multiple mental health disorders, starting in adolescence and continuing – and often transforming – into adult life.

“This suggests that there is a common brain mechanism that could explain the onset of these mental disorders during this critical period of brain development.”

In the new study, led by researchers in the UK, China and Germany, the scientists identified a characteristic pattern of brain activity among these adolescents, which they termed the ‘neuropsychopathological factor’ (NP).

Finding this factor could help identify young people at higher risk of exacerbating mental health problems.

Professor Jianfeng Feng of Fudan University in Shanghai, China, and the University of Warwick, UK, said: ‘We know that many mental health disorders start in adolescence and that people who develop a disorder have a risk more likely to develop other disorders as well.

“By looking at brain activity and looking for this NP factor, we may be able to detect those at higher risk earlier, giving us more opportunities to intervene and reduce this risk.”

The researchers looked at data from 1,750 14-year-olds from the Imagen cohort, a European research project examining how biological, psychological and environmental factors during adolescence can influence brain development and mental health.

Specifically, they looked at brain scans taken while adolescents took part in cognitive tasks to see how different brain regions communicate with each other.

According to the findings, adolescents who experienced mental health problems showed similar patterns of brain activity.

This was regardless of whether their disturbance was one of the internalizing or externalizing symptoms, or whether they experienced multiple conditions.

The study found that these patterns – the NP factor – were largely evident in the area in the front of the brain responsible for executive function which, among other functions, controls flexible thinking, self-control and emotional behavior.

The researchers confirmed their findings by replicating them in 1,799 people in the US ABCD Study, a long-term study of children’s brain development and health, and by studying patients who had received psychiatric diagnoses.

Genetic data from the Imagen group indicated that NP was strongest in those who carried a particular IGSF11 gene variant that has previously been associated with multiple mental disorders.

This gene plays an important role in synaptic pruning, a process by which unnecessary brain connections, synapses, are discarded.

Because the frontal lobes are the last brain areas to complete development in adolescents and young adults, the researchers suggest that problems with pruning may particularly affect these regions.

Dr Tianye Jia of the Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China and King’s College London, said: ‘As we grow, 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 brain activity isn’t drowned out by “white noise.”

“Our research suggests that when this important pruning process is disrupted, it affects how brain regions communicate with each other.

“Because this impact is seen more in the frontal lobes, this has implications for mental health.”

The study, funded by the National Natural Science Foundation of China, the European Union, the National Institute for Health and Care Research (UK) and the National Institutes of Health (US), is published in Nature Medicine.

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