Smoking could play a direct role in the development of schizophrenia and needs to be investigated, researchers say.
The team at King's College London say smokers are more likely to develop the disorder and at a younger age.
Published in the Lancet Psychiatry, their analysis of 61 separate studies suggests nicotine in cigarette smoke may be altering the brain.
Experts said it was a "pretty strong case" but needed more research.
Smoking has long been associated with psychosis, but it has often been believed that schizophrenia patients are more likely to smoke because they use cigarettes as a form of self-medication to ease the distress of hearing voices or having hallucinations.
The team at King's looked at data involving 14,555 smokers and 273,162 non-smokers.
It indicated:
- 57% of people with psychosis were already smokers when they had their first psychotic episode
- Daily smokers were twice as likely to develop schizophrenia as non-smokers
- Smokers developed schizophrenia a year earlier on average
The argument is that if there is a higher rate of smoking before schizophrenia is diagnosed, then smoking is not simply a case of self-medication.
Dr James MacCabe, from the Institute of Psychiatry, Psychology and Neuroscience at King's, said: "It's very difficult to establish causation [with this style of study], what we're hoping that this does is really open our eyes to the possibility that tobacco could be a causative agent in psychosis, and we hope this will then lead to other research and clinical trials that would help to provide firmer evidence."
Clearly most smokers do not develop schizophrenia, but the researchers believe it is increasing the risk.
The overall incidence of the condition is one in every 100 people normally, which may be increased to two per 100 by smoking.
The researchers said nicotine altered levels of the brain chemical dopamine, which has already been implicated in the psychosis.
Prof Michael Owen, the director of the Institute of Psychological Medicine at Cardiff University, said the researchers had made a "pretty strong case" that smoking may increase the risk of schizophrenia.
"The fact is that it is very hard to prove causation without a randomised trial, but there are plenty of good reasons already for targeting public health measures very energetically at the mentally ill."
The charity Rethink Mental Illness said: "We know that 42% of all cigarettes smoked in England are by people with mental health problems, and so any new findings about the link between smoking and psychosis is a potential worry.
"However, longer-term studies are needed to fully understand this potential link."
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