Smoking causes… schizophrenia?

By Dr. Liji Thomas, MDNov 7 2019

Yes, we all know smoking is the cause of lung cancer, throat cancer and many other deadly conditions, but it turns out that smoking also puts a person at risk of depression and schizophrenia as well, according to a new study published in the journal Psychological Medicine on November 6, 2019.

The researchers found that there is evidence that smoking has a negative impact on mental health. It is already known that the prevalence of smoking among schizophrenics and depressive patients is higher than in society at large.

Image Credit: Srdjan Randjelovic / Shutterstock

The study

The researchers looked at the genetic data of smokers with mental illness, to see if smoking was in any way responsible for the other condition. Many previous studies have examined smokers to test for any genetic tendency towards mental illness, but such a finding does not indicate that one causes the other.

The study included data from almost 463,000 individuals of European origin, and examined the genetic data using an approach called Mendelian randomization. In other words, they tried to link genetic differences with specific traits, such as whether a specific gene variant occurred in a person with a particular trait like depression.

They retrieved 378 gene variants associated with an increased risk that the individual would begin smoking, from genome-wide association studies (GWAS) data from the GSCAN consortium. A genome-wide association study (GWAS) is a genetics research method that helps to find associations between specific disease conditions and genetic variants. The genomes from a number of people are scanned and examined to find common genetic markers in people with common conditions.

They also did their own GWAS to identify 126 genes linked to lifetime smoking behavior, including the duration, heaviness and cessation of smoking. They made sure these genes were validated by testing for positive outcomes not related to the study, such as lung cancer.

They obtained genes linked to schizophrenia and depression from GWAS from the PGC consortium.

Once they had a set of associations, they tested to see what happened if individual with a genetic risk for schizophrenia or depression was exposed to smoking. This could tell them if there was a cause-and-effect relationship between smoking and the other conditions. For instance, if people with genes associated with schizophrenia risk and smoking risk began to smoke, would they have a higher rate of schizophrenia than those with the same genes who did not smoke? Conversely, if people with both sets of genes developed schizophrenia, would they be more likely to smoke?

They used two samples to test the relationship between smoking and both the mental health traits in both directions.

The findings

The scientists found that there was evidence of an increased risk both ways. In other words, smokers were more likely to develop depression or schizophrenia, but people with these traits were also more likely to smoke – though this effect was smaller than the first.

Beginning to smoke, and smoking heavily, were both independently linked to a higher risk of both conditions compared to never-smokers – even when they later stopped. By way of example, they quote a more than doubled odds of schizophrenia and almost doubled odds of depression in an ex-smoker who formerly smoked heavily (20 a day for 15 years) but quit for 17. The cause-and-effect relationship of smoking was slightly stronger with schizophrenia than with depression.

As a fallout of the study, they advised that psychiatric treatment facilities be smoke-free so that they would not have a negative effect on the mental health of patients. They suspect that nicotine might possibly affect brain circuits that are also linked to mental illness.

Smoking was also found to increase the risk of bipolar disorder in an earlier study by the same team published in September 2019. Earlier, in January 2018, another study found that marijuana use or smoking was linked to an increased chance of adolescent psychosis-like experiences. Cannabis is more often and more heavily used by smokers, and this could be another factor that increases the odds of mental health issues in smokers.

Implications

Some experts disagree with the report’s conclusions. Psychiatrist David Curtis says he doesn’t think smoking directly induces schizophrenia by its action on the brain, but rather that smoking in pregnancy has already been proved to increase the risk of schizophrenia. His interpretation has it that mothers of schizophrenic patients had genes which increased their tendency to smoke, and therefore smoked during pregnancy, passing on a higher risk of schizophrenia to their offspring. The genetic risk of smoking, meanwhile, passed down through the mother to the offspring independently. This is why the association of smoking and schizophrenia shows up at gene level.

Nonetheless, people who have mental conditions are at a greater risk of early death, up to 20 years earlier than the population at large, as reported by the Lancet Psychiatry Commission in July. The researchers noted that mentally ill people were often not targeted during anti-smoking campaigns, which led to a poorer state of health among this group. This tendency would promote health inequality, they said. To protect their mental health, smoking initiation should be discouraged and smokers should be encouraged to quit, irrespective of existing mental problems – because smoking only makes everything worse.

Researcher Robyn Wootton sums up, “Our work shows that we should be making every effort to prevent smoking initiation and encourage smoking cessation because of the consequences to mental health as well as physical health.” Addiction and mental health specialist Ian Hamilton adds, “While the physical harms of smoking are well known, this research points to the mental health risks of using tobacco. This risk should be communicated widely but particularly to school-age children who might be tempted to try smoking.”