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You might be surprised to learn that the smoking rate for schizophrenic patients is 45 to 88 percent higher than the general population’s, according to “Co-Morbidity of Smoking in Patients With Psychiatric and Substance Use Disorders,” published in the American Journal on Addictions. And if you wonder what the underlying cause of such a pervasive habit might be, you’re not alone.  

Xiangning Chen and Jingchun Chen of the ���ӽ紫ý Nevada Institute of Personalized Medicine (NIPM) are looking to genetics for the answer.

“Genetics actually influences everything we are and do,” Xiangning Chen says. “Genetics defines your potential or capacity, and how you reach that capacity depends on the environment you’re in.”

People with schizophrenia can experience delusions, hallucinations, dissociations from reality, abnormal social behavior, erratic speech and behavior, and the inability to focus and recall information. Although environmental factors may contribute to the development of schizophrenia, the disorder has been linked to specific genetic variants that predispose a person to developing the condition.   

“Researchers have performed a lot of twin studies and family studies with respect to schizophrenia,” Jingchun Chen says. “The results show time and again that the more overlap people have in their genetic makeup, the greater their chances are for developing this disorder. For instance, if one twin sibling has schizophrenia, the other has a 50 percent chance of developing it as well. So there’s clearly a genetic component.”

Previous research has noted a strong correlation between heavy smoking and schizophrenia. A 2011 finding in the journal Psychiatric Services, for example, concluded that the “prevalence of smoking has remained alarmingly high among individuals with schizophrenia and bipolar disorder in routine psychiatric settings.” Although there is some dispute among researchers as to why, the most commonly cited explanation is that patients are attempting to “self-medicate.” In short, researchers have concluded schizophrenic patients smoke because it makes them feel better.

Xiangning Chen and Jingchun Chen wondered whether genetics might play a role in creating this analgesic effect.

Supported in part by separate grants from the National Institutes of Health, Xiangning Chen and Jingchun Chen examined genes associated with both schizophrenia and smoking to determine whether the disorder and nicotine dependence might be linked. Using sophisticated analytic techniques as well as data on the genetic components involved in the general population’s smoking behavior, the two discovered that while there was likely a genetic predisposition to smoking in schizophrenics, the cause of schizophrenic patients’ excessive tobacco use was not entirely due to nicotine dependence or addiction, as is often the case with smokers in the general population.  

“Schizophrenic patients have some unique behavioral factors that cause them to smoke, and smoke quite a bit,” says Xiangning Chen, a professor in both ���ӽ紫ý’s Department of Psychology and NIPM. “One of the challenges for schizophrenic patients is that they cannot remember things accurately, follow their thoughts easily, or concentrate effectively. Therefore, they use cigarettes to help them cope and overcome some of the symptoms caused by the disorder, as one effect of nicotine on humans is to improve cognitive function.”

Although schizophrenic patients are smoking for reasons that extend beyond what their genomes might predispose them to, the discovery of genetic liability between the schizophrenia and smoking has troubling implications.

“Schizophrenia and smoking are considered complex disorders, meaning that more than one gene contributes to them,” says Jingchun Chen, an assistant professor at NIPM. “Because we found some genes and pathways that are shared between schizophrenia and smoking, we now believe that smoking may actually increase the risk of schizophrenia developing in a person who has these genes, so the next step is to find out what the function of those genes are.”

The scientists say their work to pinpoint those genes could one day lead to personalized treatments aimed at improving patients’ quality of life or even preventing the condition entirely. The two researchers indicate that their plan to take advantage of the capacity of ���ӽ紫ý’s Cherry Creek II supercomputer, one of the fastest and most powerful supercomputers in the world, should enhance their ability to deliver results.

In the meantime, they say, they’ll be looking at genes associated with other disorders and diseases to see if these might also be related to schizophrenia. At this point, for example, the researchers know that schizophrenic patients have an increased chance of developing an autoimmune disorder — and vice versa — and are working to determine what genetic liability might link the two.

Another project involves using Cherry Creek II to look for genetic ties between smoking and lung cancer — that is, whether a gene or set of genes might predispose a person to lung cancer, nicotine addiction, or both. Contrary to popular belief, Xiangning Chen says, the relationship between cigarette smoking and lung cancer is much more complicated.    

“Smokers that develop or die of lung cancer are actually the minority,” Xiangning Chen says. “If smoking directly caused lung cancer, you’d expect to see more of it.”

Discovery of genetic roots in disease and disorder rests at the heart of NIPM’s mission. If research can determine which genes cause a particular condition, a “personalized” treatment strategy can be established. This would eliminate expensive guesswork associated with treatments that patients may or may not respond to, while increasing the likelihood of an individualized treatment’s success at the same time.

“I never expect that what I do will change the world,” Xiangning Chen says. “But what I can do is give people something to think about from the information I can give them. If you find out you carry a gene that predisposes you to lung cancer, for example, maybe you won’t smoke. That’s what NIPM and researchers like me are here for — to try to find a way to better treat people and help them make more informed decisions.”