Schizophrenia May Be the Result of Teenage Brain Pruning Gone Wrong

Out-of-control pruning of brain connections could trigger the development of mental illness.

Elijah Henderson

Our brains are born with more connections than it needs. The body has developed a mechanism for trimming it down, a process that happens in adolescence called “synaptic pruning,” which, in most people, results in a normal adult brain. But when that process goes awry, it could lead to the beginnings of schizophrenia.

It hasn’t been easy to pin down the causes the elusive brain disorder, largely because it’s such a variable condition. Recently, a breakthrough study, the results of which were published in Nature, made headway, identifying 108 genes that were more active in schizophrenic brains. A large number of these genes, it seems, are involved in synaptic pruning.

There was one gene in particular that intrigued Steven McCarroll, Ph.D, who led the Nature study: C4, which is involved with the immune system, is both commonly activated in schizophrenic brains and involved with the immune system. And if the immune system is good at anything, it’s bringing destruction down on unwanted molecules.

McCarroll’s team hypothesized that the protein produced by C4 was involved in targeting the brain’s synapses — the connections between neurons in the brain — for termination:

In mice, C4-mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.

The C4 molecule, it seems, allows synaptic pruning to go overboard, causing the brain to lose many more connections than it should. And since pruning largely takes place during adolescence, it makes sense that signs of schizophrenia tend to surface during the teenage years.

It’ll take more work to confirm exactly what role C4 and the other schizophrenia-related genes play in the development of this mental illness. At the very least, McCarroll’s focus on synapses gives future researchers a sense of direction — the immune system was long suspected to play a role, but nobody knew for sure — and a potential new drug target.

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