A landmark study cofunded by the National Institute of Mental Health (NIMH), the Broad Institute, and other NIH components has shown that the risk of schizophrenia is increased in people who inherit a “suspect gene” that may affect the maturing adolescent brain.
Versions of the gene C4 may trigger “runaway pruning” of synapses, eliminating connections between neurons. People with schizophrenia show fewer neuron connections. “Normally, pruning gets rid of excess connections we no longer need, streamlining our brain for optimal performance,” says Thomas Lehner, PhD, director of the Office of Genomics Research Coordination at the NIMH. But overpruning can impair mental function, he says. The time of streamlining, during late teens and early adulthood, corresponds to the usual age-of-onset of schizophrenic symptoms.
In this study, researchers analyzed the genomes of 65,000 people and 700 postmortem brains. They found that the gene C4 switched on more in people with the suspect versions; those people faced a higher risk of schizophrenia.
Although it affects only about 1% of the population, schizophrenia is as much as 90% heritable. But just how the genes work to confer risk has been a mystery, say the researchers. Lead investigator Steve McCarroll, PhD, says, “Understanding these genetic effects on risk is a way of prying open that black box, peering inside and starting to see actual biological mechanisms.”