New research from NORMENT finds that people with schizophrenia have a genetic propensity to smoking and a reduced genetic risk of obesity. The study highlight the importance of including lifestyle interventions in treatment for schizophrenia.
Schizophrenia is a severe mental illness characterized by hallucinations and delusions. People with schizophrenia have 10 to 20 years shorter life expectancy than the general population, largely due to a high risk of cardiovascular disease.
Previous research has shown that there are genetic links between schizophrenia and cardiovascular disease. However, the link has been unclear.
In a new study, researchers have found that there is a significant genetic overlap between schizophrenia and several cardiovascular disease risk factors, particularly obesity and smoking.
“Our findings indicates that people with schizophrenia have a genetic tendency to smoke and a reduced genetic risk of obesity”, Linn Rødevand says. She is a postdoctoral fellow at NORMENT - the Norwegian Center for Research on Mental Disorders at the University of Oslo.
The study is published in the American Journal of Psychiatry.
Highlight the importance of lifestyle interventions for people with schizophrenia
According to Rødevand, the findings have several important implications for the treatment of people with schizophrenia.
«This research underlines the importance of lifestyle interventions in the treatment of schizophrenia. These interventions should include diet, physical activity and smoking cessation”, the postdoctoral fellow says.
“In addition, this underscores the need for more personalized medical treatment for each individual patient with schizophrenia”, she says.
Such interventions may help minimize weight gain and reduce other risk factors for cardiovascular disease. This in turn, may help extend the lives, and contribute to a higher quality of life, of people with schizophrenia.
Are people with schizophrenia more affected by nicotine’s addictive properties?
A widespread risk behavior among this group is smoking. Previous research suggests that people with schizophrenia smoke at high rates.
According to this study, this may be due to a genetic explanation. There is a genetic overlap between some of the same genes in both schizophrenia and the propensity for smoking.
«The genetic overlap between schizophrenia and smoking may indicate that people with schizophrenia are more affected by the addictive properties of nicotine than others”, Rødevand says.
Smoking - a form of self-medication?
Perhaps smoking represents a form of self-medication when life is difficult. People with schizophrenia may lose touch with reality during symptom episodes. This can be distressing and frightening for them.
“It is possible that smoking to some extent is an attempt to compensate for a genetic dysfunction in nAChRS”, Rødevand says.
NAChRS is a particular receptor affected by nicotine. The receptor contributes to some of the stimulating effect you experience from smoking nicotine. Therefore, some people experience reduced discomfort and anxiety in the moment. Thus, for some, smoking can partly be an attempt to compensate for distress or unpleasant symptoms.
“For this reason, it is important to take into account this vulnerability to smoking, when implementing lifestyle interventions as part of treatment”, she adds.
Obesity is frequent in schizophrenia
Another risk factor for cardiovascular disease linked to schizophrenia is obesity. This occurs when an individual have an abnormal or excessive fat accumulation on the body and a body mass index over 30. Obesity is more frequent in schizophrenia than in the general population.
However, this study suggests that the genetic link with obesity differs from that with smoking. Gene variants that affect schizophrenia are linked to a reduced risk of obesity.
“This is in line with previous research which shows that people with schizophrenia have a lower body mass index before the onset of schizophrenia and treatment”, the postdoctoral fellow, says.
There must therefore be other factors than genetics, which play an important role in weight gain and obesity in schizophrenia.
“Given that schizophrenia on average is associated with reduced genetic risk for obesity, environmental factors are likely to be the main drivers of the development of obesity seen in many patients", Rødevand says.
Antipsychotic drugs can induce weight gain
Environmental factors that contribute to an unhealthy lifestyle are important to include in a treatment plan for schizophrenia, the researcher believes. In addition to smoking and diet, loneliness, socioeconomic challenges and adverse effects of antipsychotics should be targeted.
Treatment of schizophrenia often includes antipsychotics. One of the most common adverse effects of these medications is weight gain.
“The findings in this study indicates that there are non-genetic factors that contribute to the development of obesity in this patient group. However, genetic factors may play a role in how vulnerable individuals are to weight gain induced by medications”, the researcher says.
Analyzed data from hundreds of thousands of individuals to identify genetic variants
The aim of this study was to better understand the genetic overlap between schizophrenia and cardiovascular disease, using various statistical methods and models.
“We have analyzed data from hundreds of thousands of individuals to identify different genetic variants that are linked to both schizophrenia and risk factors for cardiovascular diseases”, Rødevand says.
She explains that they wanted to estimate the number of shared genetic variants between schizophrenia and cardiovascular diseases, as well as the genetic variants that are unique to the diseases.
They also wanted to pinpoint shared genetic locations between schizophrenia and risk factors for cardiovascular disease.
“The findings support the importance of more targeted interventions for this patient group”, Rødevand says.
“The study also provide more insight into the mechanisms behind the diseases, which in turn can lay the foundation for more personalized and effective treatment of people with schizophrenia”, she adds.
Further knowledge is needed to develop more effective treatments
The relationship between schizophrenia and cardiovascular disease is complicated, and further research is needed to better understand this connection.
“There is a particular need for more knowledge to develop more effective treatments. This applies to both medications with improved effects and reduced side effects, and more targeted lifestyle interventions”, says the researcher.
Rødevand and her colleagues aim to gain a better understanding of the link between severe mental disorders and lifestyle factors.
“Lifestyle factors are often referred to as "environmental factors", but lifestyle is behavior that is influenced by genetics. The question is whether gene variants linked to lifestyle also affect severe mental disorders”, says Rødevand.
Rødevand, L., Rahman, Z., Hindley, G. F. L., Smeland, O. B., Frei, O., Tekin, T. F., Kutrolli, G., Bahrami, S., Hoseth, E., Shadrin, A., Lin, A., Djurovic, S., Dale, A. M., Steen, N. E., Andreassen, O. Characterizing the Shared Genetic Underpinnings of Schizophrenia and Cardiovascular Disease Risk Factors. American Journal of Psychiatry. https://doi.org/10.1176/appi.ajp.20220660