We may have misunderstood the genetic basis of psychiatric conditions

CNRI/SCIENCE PHOTO LIBRARY

An analysis of gene variants in more than a million people diagnosed with neurodivergencies and mental health conditions – by far the largest study of its kind so far – has found that 14 conditions typically regarded as distinct actually fall into five underlying genetic groups.

The finding is encouraging for those diagnosed with multiple psychiatric conditions, says Andrew Grotzinger at the University of Colorado Boulder, a member of the research team behind the analysis. People can feel this means there is a lot wrong with them, he says, but there may be just one root cause.

“For the millions of people out there who are being diagnosed with multiple psychiatric conditions, this indicates that they don’t have multiple distinct things going on,” says Grotzinger. “I think it makes a big difference for a patient to hear that.”

When biologists started looking for genetic variants that are associated with a higher chance of developing a range of psychiatric conditions, they expected to find different variants for each. Instead, it became clear that there is a lot of overlap. A few researchers have even suggested that all such conditions have a single underlying cause, dubbed the p-factor.

This latest study suggests the reality is somewhere in between these two extremes. It doesn’t provide much support for the idea of a p-factor – while some gene variants were linked to all 14 conditions, they were involved in basic processes that cause many different problems beyond mental illnesses when they go wrong, says Grotzinger.

On the flip side, the team also found relatively few variants linked to a higher risk of just a single condition. Instead, the variants tended to fall into five groups, with an especially high overlap between schizophrenia and bipolar disorder, and between major depression, PTSD and anxiety.

Many of the variants linked to schizophrenia and bipolar disorder were in genes active in excitatory neurons – which make other neurons more likely to fire – whereas many of the variants linked with depression, PTSD and anxiety were in genes active in oligodendrocytes, the cells that produce the myelin sheaths around nerves.