Could brain inflammation be to blame for schizophrenia? People with the disorder seem to have more active immune cells inside their brains, and now this activity has been spotted even before the disorder develops. This link could be a breakthrough in developing new treatments that better target the causes of the disorder.

The idea that the immune system might play a part in schizophrenia was first floated 10 years ago. Since then, a couple of studies have found that people with schizophrenia seem to have more active microglia – the immune cells of the brain.

Peter Bloomfield at Imperial College London wondered if this increased immune system activity might be detectable before a person is diagnosed with schizophrenia. His team examined 14 people who had been identified as being at “ultra-high risk” of developing the disorder – they had already seen a doctor about symptoms like paranoia or hallucinations, but hadn’t yet had a psychotic episode. Typically, between 20 and 35 per cent of such individuals will go on to be diagnosed with schizophrenia.


By injecting a dye that labels active cells and using a PET scanner, Bloomfield’s team compared the activity of these people’s microglial cells with those of people with schizophrenia, as well as healthy people. They found increased microglial activity in both those who had schizophrenia, and those who had been classified as ultra-high risk.

“What’s interesting is that the level of activity correlated with the severity of symptoms,” says Bloomfield. During the study, two of the 14 at ultra-high risk went on to develop schizophrenia and schizotypal disorder – these people had the highest levels of microglial activity, says Bloomfield.

Old drugs, new tools

“This is potentially a game-changer,” says Peter Uhlhaas at the University of Glasgow in the UK. If the findings can be replicated in larger studies, it might be possible for doctors to identify which people will later develop schizophrenia, and offer them preventative treatments, he says. “It raises the possibility that we could intervene before psychosis and prevent the onset, which is a very promising prospect.”

At the moment, schizophrenia treatment tends to involve drugs that dampen down neuron activity in the brain. These drugs don’t work for everyone, and come with significant side effects, including weight gain, heart problems, and impotence. “They’re just nasty,” says Stephen Wood at the University of Birmingham in the UK. “A lot of people stop taking them.”

This suite of side effects makes these drugs unsuitable for use in people deemed to be at high-risk, but who may not necessarily develop the condition. If anti-inflammatory drugs can be shown to work in schizophrenia, not only could they offer a safer option to treat the disorder, they might also be benign enough to protect those at ultra-high risk, says Wood. Clinical trials are under way to test the effects of minocycline – an antibiotic that also has anti-inflammatory effects.

But even if anti-inflammatory drugs prove to be a useful treatment, the causes of schizophrenia will still be unknown. Highly active microglia could turn out to be a symptom of some other underlying trigger. In the meantime, health services could be doing more, says Wood. “One of the best things people with schizophrenia could do is exercise and eat better,” he says. Social support, and tackling sources of stress in a person’s life, is also vital, he says.

Journal reference: American Journal of Psychiatry, DOI: 10.1176/appi.ajp.2015.14101358

Brain activity during hallucinations in a person with schizophrenia (Image: Wellcome department of cognitive neurology/Science Photo Library)