New research suggests that smoking can triple the chances of developing psychosis.
Previously the fact that people with psychotic mental illnesses are more likely to smoke has been put down to non-causal factors, such as obtaining relief from distress or self-medication.
But scientists now believe something in tobacco might be responsible, alongside genetic and environmental influences.
Researchers from King’s College London analysed data from 61 observational studies involving almost 15,000 tobacco users and 273,000 non-users.
They found that 57% of people treated for a first episode of psychosis were smokers.
Psychotic patients were three times more likely to consume tobacco than individuals without severe mental illness.
Dr James MacCabe said: "While it is always hard to determine the direction of causality, our findings indicate that smoking should be taken seriously as a possible risk factor for developing psychosis, and not dismissed simply as a consequence of the illness."
The study also showed that daily smokers became psychotic around a year earlier than non-smokers.
The scientists, whose findings are reported in The Lancet Psychiatry medical journal, acknowledge that causality is difficult to prove.
One theory is a possible link between smoking and excess dopamine, a brain chemical that plays a role in transmitting nerve signals.
Professor Sir Robin Murray, from the Institute of Psychiatry, Psychology and Neuroscience at King's College, said: "Excess dopamine is the best biological explanation we have for psychotic illnesses such as schizophrenia.
It is possible that nicotine exposure, by increasing the release of dopamine, causes psychosis to develop."
A proven link has already been found between cannabis use and psychosis in genetically vulnerable people.
Dr Sameer Jauhar, another member of the King's College team, said: "Longer-term studies are required to investigate the relationship between daily smoking, sporadic smoking, nicotine dependence and the development of psychotic disorders.
"In view of the clear benefits of smoking cessation programmes in this population every effort should be made to implement change in smoking habits in this group of patients."
Dr Michael Bloomfield, clinical lecturer in psychiatry at University College London, said: "It has been known for some time that patients who have schizophrenia are more likely to be cigarette smokers than people who do not have schizophrenia.
"Yet, a definitive explanation why this is the case has been lacking.
"This new study combines previously published scientific data into a statistical analysis which found that smoking cigarettes appears to modestly increase the risk of developing schizophrenia in later life.
"There are a number of plausible ways to explain how this may be happening, such as by heavy cigarette smoking increasing the ability to make the chemical dopamine in part of the brain called the striatum, which is in turn thought to play an important role in the development of schizophrenia.
"However, much more research is needed before scientists can say for certain that smoking definitely increases the risk of schizophrenia since it remains possible that people who would go on to develop schizophrenia are more likely to start smoking.
"Regardless of these findings, there is overwhelming evidence that nicotine use through tobacco smoking is one of the most dangerous drug problems in the world. Anyone who needs help in stopping smoking should speak with their doctor."