Brain development patterns in early adolescence can predict mental health problems up to four years before symptoms emerge. In a large-scale study conducted in the United States, researchers followed nearly 12,000 adolescents over six years and analyzed almost 30,000 magnetic resonance imaging (MRI) scans.
The paper, published on the preprint server bioRxiv, notes that the cerebral cortex — the brain’s outer layer — gradually becomes thinner with age. The researchers found that sensory regions develop and thin first, followed by regions responsible for complex thinking.
The findings challenge the widely held theory that mental disorders are caused by defects in specific brain circuits. Instead, the results suggest that vulnerability to mental health symptoms is associated with disruptions in the timing of brain development, potentially rooted in genes that are active even before birth.
How does the brain “prune” and develop?
Cortical thinning during childhood and adolescence is a natural process. Neuroscientists associate it with the “pruning” of unused connections between neurons, a process known as synaptic pruning, which helps the brain function more efficiently.
Jacqueline Claus, a child psychiatrist at the University of Iowa, and her colleagues studied data from children beginning at age nine. The children underwent brain scans every two years, while their parents completed mental health questionnaires annually.
The analysis showed that brain regions do not thin at a uniform rate. Instead, the process follows an S-shaped curve: thinning initially accelerates, then proceeds at a relatively steady pace before slowing as development nears completion.
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By age 13, thinning begins to slow in primary sensory regions, such as the visual cortex.
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By age 16, the developmental wave reaches the frontal lobes, which are responsible for planning, concentration and emotional regulation.
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Cortical thinning occurred more rapidly in girls than in boys across nearly all brain regions.
The link between anxiety and depression
The researchers identified a clear association between delayed cortical thinning and mental health:
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Children who had a thicker cortex in sensory regions at age nine — indicating that the developmental process was lagging — were more likely to develop symptoms of anxiety and depression by age 13.
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The same pattern was observed in the prefrontal cortex, a region involved in complex cognition. Adolescents with a thicker cortex in this area at age 11 were more likely to show signs of mental health problems by age 13.
“The key question is not what a particular brain region does, but when it develops,” explains study co-author Joshua Roffman, a psychiatrist at Mass General Brigham in Boston. Beatriz Luna, a cognitive neuroscientist at the University of Pittsburgh, suggests that a thicker cortex may indicate delayed brain plasticity, potentially making it more difficult for children to adapt to their environment.
Furthermore, comparisons with genetic brain atlases revealed that the regions whose cortical thickness most accurately predicted adolescent symptoms closely corresponded to gene networks active during prenatal development.
Avram Holmes, a neuroscientist at Rutgers University who was not involved in the study, notes that the paper provides one of the clearest pictures yet of brain development. However, he emphasizes that the statistical effects identified were small and detectable only in a large population. Consequently, the method is not yet suitable for predicting an individual child’s mental health outcomes in clinical practice.
