DURING his PhD Steven McCarroll was surprised to get a phonecall from an old classmate 鈥� and startled to find he was making the call from prison. His friend had been walking down the street when he was gripped by the conviction that people were chasing him, and broke into an apartment to hide.
McCarroll鈥檚 friend was in the throes of schizophrenia. Symptoms of the condition include hallucinations, like hearing voices, and paranoid delusions.
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The event set the stage for McCarroll鈥檚 career. Now in Boston, his latest work offers tantalising clues about the cause of the condition, which is poorly understood and can affect people for life. It suggests schizophrenia can result from a normal stage of teenage brain maturation gone wrong.
鈥淚t鈥檚 really exciting because it could lead to new ways of treating the disorder,鈥� says , who studies psychosis at King鈥檚 College London.
鈥淭he discovery could lead to new drugs to tackle symptoms such as deterioration of memory鈥�
The work builds on a recent landmark study that pointed to of schizophrenia. The one is a large region of the genome that encodes proteins involved in the immune system, on the face of it a puzzling find for a brain disorder.
McCarroll鈥檚 team has now found that people with the risky variants of this region have higher levels of a molecule called complement component 4. In the blood, C4 binds to microbes to signal that they should be eaten by immune cells. By genetically engineering mice that lack C4, the team showed it has a second role 鈥� in the brain. Here C4 binds to neurons at the points where they connect with other neurons, and signals that these connections, or synapses, should also be engulfed by immune cells. 鈥淚t targets things for swallowing,鈥� says McCarroll.
As teenagers鈥� brains mature they go through a developmental stage called pruning, in which they lose synapses. Post-mortem studies show that . McCarroll speculates that the risky C4 gene variants cause too much pruning. 鈥淚t would make a lot of sense,鈥� he says.
One theory is unlikely to explain all cases, as schizophrenia is such a variable condition, says Robin Murray of King鈥檚 College London. But it may explain why, for some people, the first signs appear in adolescence, when pruning peaks.
These initial symptoms include problems with memory and attention, emotional withdrawal and lack of motivation. These get much less attention than psychotic symptoms but tend to precede psychosis by a few years. Unlike psychosis, there are no drugs to alleviate them.
McCarroll thinks that a lack of synapses may be key to explaining these lesser-known aspects of the schizophrenia. If so, his work offers a way to tackle them. For example, drugs that work against a molecule related to C4 are already being tested for the eye disease .
鈥淧eople make the mistake of equating schizophrenia with psychosis,鈥� McCarroll says. 鈥淚f you ask patients what are the hardest things to endure, [many] would say the fact they can no longer hold down a job.鈥�
This article appeared in print under the headline 鈥淭een gene link in schizophrenia?鈥�