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, say researchers.
Many mental health problems emerge during adolescence, highlighted the authors of a new study, published in Nature Medicine. 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, they explained.
Worldwide, 1 in 7 adolescents aged 10-19 years experience mental health disorders, according to the World Health Organisation (WHO). Amongst the leading causes of illness and disability among young people are depression, anxiety, and behavioural disorders such as ADHD. "Adolescents will commonly have more than one mental health disorder," the authors pointed out.
Professor Barbara Sahakian, from the department of psychiatry at the University of Cambridge, and one of the study's authors, said: "Young people often experience multiple mental health disorders, beginning in adolescence and continuing – and often transforming – into adult life."
She said that this suggests there's a "common brain mechanism" that could explain the onset of these mental health disorders during this "critical time of brain development".
Notably, many mental health disorders have their approximate peak onset in adolescence, coinciding with the emergence of comorbidity.
The authors explained that studies had proposed a "general psychopathology factor" underlying common comorbidities among mental health disorders, and that the high prevalence of comorbid mental disorders suggested "shared neurobiological origins" among different psychopathologies. However, the neurobiological mechanisms and generalisability remained "elusive", they said.
Brain Activity Pattern Linked to Adolescent Mental Health Disorders Identified
For the study, an international collaboration of researchers, led by those in the UK, China, and Germany, examined data from 1750 adolescents aged 14 years from the IMAGEN cohort. This is a European research project examining how biological, psychological, and environmental factors during adolescence may influence brain development and mental health.
The researchers examined imaging data from brain scans taken while participants took part in cognitive tasks, looking for patterns of brain connectivity. They identified a characteristic pattern of brain activity among adolescents with mental health disorders, which they termed the 'neuropsychopathological factor', or NP factor for short.
"Regardless of whether their disorder was one of internalising or externalising symptoms, or whether they experienced multiple disorders, adolescents who experienced mental health problems showed similar patterns of brain activity," reported the authors. They pointed out that the patterns, or the NP factor, were largely apparent in the frontal lobes.
By studying 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 mental health diagnoses, the researchers were able to replicate and confirm their findings.
Having examined genetic data from the IMAGEN cohort, the researchers identified that the NP factor was strongest in individuals who carried a particular variant of the gene IGSF11, which had previously been 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," they said.
Pruning Predicaments
The NP factor might represent a "unified, genetically determined, delayed development of prefrontal that further leads to poor executive function", proposed the authors. The NP factor could serve as a "reliable neuropsychopathological biomarker" of psychiatric comorbidity, they postulated.
Study author Dr Tianye Jia, from the Institute of Science and Technology for Brain-Inspired Intelligence at Fudan University in China and the Institute of Psychiatry, Psychology & Neuroscience at King's College in the 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'."
The authors explained: "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 Jia stressed that when the "important pruning process is disrupted", it affected how brain regions talk to each other. She added that since this impact is seen most in the frontal lobes, it has "implications for mental health".
The researchers said that the discovery of the NP factor could help identify those young people at greatest risk of compounding mental health problems.
Contributing author Professor Jianfeng Feng, from the Fudan University in China and the UK's University of Warwick, 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."
Those with comorbid psychiatric diagnoses often experience poorer outcomes and severe deficits in various cognitive and behavioural domains. "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," he said.
The authors added that they hoped the findings of the study may in future help identify those at greatest risk, and help to develop new therapeutic interventions for psychiatric comorbidities.
Funding for the study was provided by the National Natural Science Foundation of China, European Union, National Institute for Health and Care Research (UK) and National Institutes of Health (NIH, USA). A full list of funders can be found in the paper. Dr Banaschewski served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, and Shire. He has been involved in clinical trials conducted by Shire and Viforpharma, and has received royalities from Hogrefe, Kohlhammer, CIP Medien, and Oxford University Press. Dr Barker has received honoraria from General Electric Healthcare for teaching on scanner programming courses. The other authors declare no competing interests.
