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Researchers have found that there is a significant genetic overlap between schizophrenia and several cardiovascular disease risk factors, particularly obesity and smoking.

People with schizophrenia have a genetic predisposition for smoking and a reduced risk of obesity

Nevertheless, many people in this patient group struggle with obesity. This suggests that non-genetic factors contribute to the weight gain.

Julie Nybakk Kvaal
COMMUNICATIONS ADVISER
Presented by: University of Oslo
Published

Schizophrenia is a severe mental illness characterised by hallucinations and delusions. People with schizophrenia live on average 10 to 20 years shorter than the general population. 

This is largely due to a high risk of cardiovascular disease.

Previous research has shown that there are genetic links between schizophrenia and cardiovascular disease. However, what this link is has been unclear.

Researchers have now found that there is a significant genetic overlap between schizophrenia and several cardiovascular disease risk factors, particularly obesity and smoking.

Linn Rødevand is a postdoctoral fellow at NORMENT.

“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 researher at NORMENT - the Norwegian Center for Research on Mental Disorders at the University of Oslo.

Lifestyle interventions are important

“This research underlines the importance of lifestyle interventions in the treatment of schizophrenia. These interventions should include diet, physical activity, and smoking cessation,” Rødevand says. 

In addition, she says it is important for doctors to better tailor medical treatment to each individual patient with schizophrenia.

The researcher believes that such interventions may help minimise weight gain and reduce other risk factors for cardiovascular disease. 

This, in turn, may help extend the lives and quality of life of people with schizophrenia.

Are people with schizophrenia more addicted to nicotine?

Smoking is a widespread risk behaviour in this group. Previous studies have shown that there are very many people with schizophrenia who smoke.

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.

Is 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.

“It's 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 effects one gets from smoking nicotine. Many therefore experience reduced discomfort and anxiety in the moment. Thus, smoking for some may partially be an attempt to compensate for distress or unpleasant symptoms.

“For this reason, it's important to account for this vulnerability to smoking when implementing lifestyle interventions as part of treatment,” she adds.

Many with schizophrenia struggle with obesity

Obesity is another risk factor for cardiovascular disease linked to schizophrenia. Obesity is when the amount of fat on the body is abnormally high and the body mass index, commonly known as BMI, is 30 or above. 

Many people with schizophrenia struggle with obesity.

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,” Rødevand says.

Therefore, there must be factors other than genes that come into play when they struggle with weight gain and obesity.

“Given that schizophrenia 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,” she 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, it may be important to look at loneliness, socioeconomic challenges, and side effects of antipsychotic drugs.

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.

Analysed data from hundreds of thousands of individuals

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 analysed 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 provides more insight into the mechanisms behind the diseases, which in turn can lay the foundation for more personalised and effective treatment of people with schizophrenia."

More knowledge is needed

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 medications with improved effects and reduced side effects, and more targeted lifestyle interventions,” Rødevand says.

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 behaviour that is influenced by genetics. The question is whether gene variants linked to lifestyle also affect severe mental disorders,” she says. 

Reference:

Rødevand et al. Characterizing the Shared Genetic Underpinnings of Schizophrenia and Cardiovascular Disease Risk Factors, American Journal of Psychiatry, 2023. DOI: 10.1176/appi.ajp.20220660

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