Lack of neuron ‘pruning’ may be behind many brain-related conditions

Many disparate conditions, such as depression, phobias and attention deficit hyperactivity disorder (ADHD), may have the same underlying cause: a delay in “pruning”, a process in which unneeded connections between brain cells disappear.

The finding comes from one of the largest brain-scanning studies done in adolescents and has been confirmed in several other data sets, including people of other ages. “We’ve been able to show that these different [conditions] are all related to a single underlying neurobiological factor,” says Barbara Sahakian at the University of Cambridge.

The results lend weight to a controversial recent idea in neuroscience that many disparate conditions share a common cause – a concept known as the p factor.

Until now, this was mainly based on the fact that many people have more than one such condition or may be diagnosed with different conditions at different times in their lives, as well as DNA studies finding that the same set of gene variants predispose people to multiple conditions.

Now Sahakian and her colleagues are proposing a neurobiological basis for the p factor, which they call the “neuropsychopathological (NP) factor”.

The researchers did their first analysis using an existing set of brain scanning images for nearly 2000 teenagers assessed at 14, where there was also information about various psychiatric symptoms.

Participants or their parents completed questionnaires to produce scores for symptoms of mental health conditions such as depression, anxiety, eating disorders and phobias. They were also scored for ADHD and assessed for symptoms of autism traits.

People who had the highest scores for these conditions, indicating stronger symptoms, were more likely to have greater density of tissue in the prefrontal cortex, an outer region of the brain at the front of the head. This, say the researchers, indicates a lack of, or delay in, pruning in their brains.

Pruning is a mysterious process that starts in young childhood, although increases dramatically in adolescence. It is thought to happen because synapses – connections between brain cells – that aren’t used very much are lost. “As you’re learning and your brain is getting more efficient, you get rid of the extra synapses you don’t want,” says Sahakian.

It wasn’t possible to quantify the pruning delay or the difference in tissue density in this study, nor is it known whether those who had a greater density of tissue in the prefrontal cortex at this stage catch up with the rest of the population, at least to some extent, later, says Sahakian.

The finding was confirmed in four other sets of brain scanning data, including a second collection of brain scans and symptom scores for nearly 2000 adolescents, and two studies that included people in their 20s with ADHD. This indicates that the lack of brain pruning correlates with brain function in adulthood too.

A lack of pruning has previously been proposed as a cause of schizophrenia, ADHD and autism, but not other conditions.

Robert Plomin at King’s College London, who has been involved in genetic studies that support the idea of a p factor, says the new proposed explanation is plausible as a contributor, but may not be the whole story. “You are looking for something that’s a general mechanism,” he says.

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