It may be possible to prevent schizophrenia by calming the brain's immune system, say scientists.
Brain scans found an overactive immune system in patients as well as in those at high risk of schizophrenia.
The UK Medical Research Council team wants to test anti-inflammatory drugs to treat or even prevent the disease.
Other experts in the field said the study, in the American Journal of Psychiatry, was "important" and furthered understanding of the illness.
There has been mounting evidence that the immune system and inflammation play a key role in schizophrenia and other psychiatric conditions.
The researchers analysed microglia, which are like the brain's own gardeners weeding out infection but also "pruning" unwanted connections between brain cells.
A chemical dye which sticks to microglia was injected into 56 people to record their microglia activity.
The highest level was found in patients with the condition, but those deemed at high risk of developing schizophrenia also showed heightened activity levels.
Dr Oliver Howes, the head of the psychiatric imaging group at the MRC Clinical Sciences Centre, told the BBC News website: "This is a real step forward in understanding.
"For the first time we have evidence that there is over-activity even before full onset of the illness.
"If we could reduce activity [before full-blown illness] then we might be able to prevent the illness - that needs to be tested, but is one key implication [of the research]."
He thinks the microglia become like a gardener too keen with the shears and sever the wrong connections in the brain leaving it wired incorrectly.
"You can see how that would lead to patients making unusual connections between what is happening around them or mistaking thoughts as voices outside their head and causing the symptoms we see in the illness," Dr Howes added.
Some small trials have suggested that anti-inflammatory drugs may help patients when they have been given alongside traditional medication.
However, further studies are now needed including on anti-inflammatory drugs that target only the microglia rather than those, such as Ibuprofen, that have a wider effect on the body.
Dr Howes advised patients not to self-prescribe the drugs and added that any decisions about medication should be made with a doctor.
It is not yet clear why some people have overly active microglia.
Analysis of patients' DNA - their blueprint of life - has implicated genes that control the immune system.
It suggests some patients are predisposed to having a more sensitive immune system, but events later in life such as times of high stress have also been implicated.
The head of psychiatry at the University of Edinburgh, Prof Stephen Lawrie, commented: "This is an important paper, which both confirms and extends previous findings, in a carefully controlled and state-of the-art study."
He said the findings "suggests the possible amelioration or even prevention of one of the worst illnesses affecting mankind" through drugs to tame the immune system in the brain.
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