Brain 'pruning' problems linked to adolescent mental health disorders

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.

That’s according to an international collaboration led by researchers in the UK, China and Germany, which may help explain why people are often affected by more than one mental health disorder. Their work has been published in the journal Nature Medicine.

Many mental health problems emerge during adolescence — including depression and anxiety, which manifest as ‘internalising’ symptoms including low mood and worrying, as well as attention deficit hyperactivity disorder (ADHD), which manifests as ‘externalising’ symptoms such as impulsive behaviour. Indeed, young people often experience multiple mental health disorders, beginning in adolescence and continuing 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,” said Professor Barbara Sahakian from the University of Cambridge. Now, Sahakian and her colleagues have identified a characteristic pattern of brain activity among these adolescents, which they have termed the ‘neuropsychopathological factor’ (NP factor).

The team examined data from 1750 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 1799 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.

“As we grow up, our brains make more and more connections. This is a normal part of our development,” said Dr Tianye Jia, from Fudan University and King’s College London.

“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 and the University of Warwick, said, “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.”

This is a modified version of a news item published by the University of Cambridge under CC BY-NC-SA 4.0. This version is similarly licensed under CC BY-NC-SA 4.0.

Image credit: iStock.com/Lazy_Bear