The study, published November 6, 2019, in the journal Psychological Medicine, found that smokers had nearly double the risk of developing depression or schizophrenia compared with people who didn’t. “It is a very commonly held belief that individuals with mental illness smoke in order to ‘self-medicate,’ but most previous studies have not actually looked at causal effects," says Robyn E. Wootton, PhD, a senior research associate in the school of experimental psychology at University of Bristol in England and senior author of the study. “These findings are very compelling,” says Brian Barnett, MD, a psychiatrist at the Center for Behavioral Health at the Cleveland Clinic in Ohio, who was not involved in the research. “There’s been a lot of observational research showing the connection between smoking and schizophrenia, but it’s been difficult to determine which way the link goes,” says Dr. Barnett. The question is, do conditions like schizophrenia or depression make smoking more likely, or does smoking increase a person’s risk for mental illness, or both, asks Barnett. “Many of us in the field have had suspicions that the smoking itself does increase the risk for schizophrenia. This study uses a unique methodology to show which way the direction of causality is between the two,” he says.

Smoking and Mental Illness: It’s Complicated

People with schizophrenia and depression are especially at risk when it comes to smoking; individuals with severe mental illness, including schizophrenia, are 3 times more likely to smoke than the general population, according a paper published in May 2019 in Lancet Psychiatry. To try to determine which is the cause and which is the effect, investigators used a method known as Mendelian randomization, named after Gregor Mendel, the scientist who is considered the founder of the science of genetics. This method uses genetic variants to determine whether an observational association between a risk factor and an outcome is actually a cause and effect relationship, according to a paper published in November 21, 2017, in JAMA Guide to Statistics and Methods. At birth, some people may or may not inherit a genetic variant that impacts a risk factor; for example, a genetic variant that is associated with obesity. Investigators can follow the health outcomes between those individuals who have the specific variant and those who do not, and the difference in outcome is attributed to the variant.

Genetic Data Reveals Cause and Effect Relationship for Smoking and Mental Illness

To capture how many years people had been smoking and how many cigarettes they smoked per day, researchers examined data from 462,690 people of European ancestry from the UK Biobank. The Biobank is a major international health resource where over a half million people ages 40 to 69 years old agreed to provide blood, urine and saliva samples, as well as a detailed history for the purposes of research. Eight percent of the group were current smokers, and 22 percent were former smokers. The UK Biobank took self-reported information from participants about smoking status-current, former, never, age that the person started smoking, if they once smoked but stopped, age at cessation in years, and number of cigarettes smoked per day. Researchers used all the information collected to generate a “lifetime smoking index.” If a person was a former smoker, the impact on health was simulated through a half-life principle that calculated the decreasing effect that the past behavior would have over time. Depression was determined by a diagnosis that was confirmed by health medical records or self-reported cases of having a diagnosis or treatment, and schizophrenia was indicated by diagnosis or research-based assessments. Investigators found that smoking was associated with a 127 percent higher risk of developing schizophrenia, and a nearly doubled risk for developing depression. They also found that the relationship works the other way for depression; people who are depressed are more likely to smoke. The evidence that people with schizophrenia were more likely to smoke was less conclusive. “Our study fits amongst a growing body of research that goes against this self-medication hypothesis, suggesting that smoking can actually increase risk of developing mental illness,” says Dr. Wootton. The same research team used Mendelian randomization to show that smoking is likely a causal risk factor for bipolar disorder in a study published in September 2019 in the British Journal of Psychiatry.  These findings are supported by other research that suggests that quitting smoking can improve mental health symptoms, according to Wootton. Research on mental health symptoms after smoking cessation published in February 2014 in the BMJ found that quitting smoking was associated with reduced depression, anxiety, and stress, and improved positive mood and quality of life compared with continuing to smoke.

Why Could Smoking Contribute to Mental Illness?

It’s not clear why smoking could increase the likelihood of mental illness, says Barnett. “One thought is that when you smoke and inhale the nicotine, it activates the receptor for the neurotransmitter acetylcholine, which eventually leads to the release of dopamine and serotonin,” says Barnett. Because the dopaminergic system is heavily involved in schizophrenia, it could be that the nicotine or some other component in cigarettes could be disrupting the dopaminergic pathways in the brain that could ultimately contribute to schizophrenia, he explains. It’s kind of a crazy historical footnote, but doctors actually prescribed or recommended cigarettes for people with schizophrenia 50 or 60 years ago, says Barnett. “Patients found that smoking relieved some of their symptoms; we obviously don’t recommend that anymore,” he adds.

Findings Suggest That Smoking Could Cause More Immediate Health Risks

Often people are not as worried about smoking as they are about other kinds of substance abuse because the negative effects, such as lung cancer or cardiac problems, can seem far down the road, says Barnett. “These findings lend a little bit more immediacy to the problems that can arise from smoking,” he says. “Based on this research we can tell patients, particularly young patients in their teens or twenties, that smoking can increase your risk for schizophrenia or depression,” says Barnett. “These are conditions that can come on much more quickly and are disorders that can be first identified when a person is in their teens or twenties,” he says. This may help motivate patients to work on smoking cessation, he adds. According to the Centers for Disease Control and Prevention (CDC), mental illnesses such as depression are the third most common cause of hospitalization for people ages 18 to 44 years old. Adults living with serious mental illness die on average 25 years earlier than healthy adults. We already know that people should not take up smoking because of the detrimental effects on physical health, says Wootton. “This study shows that smoking also has detrimental effects on mental health, further stressing the importance that individuals should not smoke,” she says. These findings also reinforce the idea that individuals with mental illness who smoke need guidance and support to try and quit, she adds.