Genetic link between mental disorders, cardiovascular disease and metabolic disorders

Breaking new ground 24. feb 2022 2 min Senior Researcher Daniel S. Quintana Written by Kristian Sjøgren

New research shows that oxytocin system dysfunction contributes to both mental disorders and cardiovascular and metabolic health. A researcher says that oxytocin has the potential to treat mental disorders and the associated risk of cardiovascular disease and metabolic disorders.

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People with a severe mental disorder such as schizophrenia or bipolar disorder have an increased risk of developing cardiovascular disease and metabolic disorders such as type 2 diabetes.

Oxytocin is a versatile and multifunctional hormone and neurotransmitter associated with social cognition and behaviour and therefore also with the social dysfunction associated with severe mental disorders. Recent evidence also indicates that the oxytocin system is linked with metabolic regulation and how this affects cardiovascular health.

Now a new study shows that oxytocin is associated with the shared genetic risk factors for schizophrenia, bipolar disorder and metabolic risk factors, including the quantity of whole-body fat, body mass index and sugar intake.

This discovery is important in understanding the links between mental disorders and metabolic disorders and may form the basis for developing treatments for both the physical and mental conditions.

“Our data emphasise the importance of oxytocin in developing both mental disorders and metabolic disorders. Many researchers are already considering using oxytocin to treat severe mental disorders, but that research might be extended to develop drugs to improve the metabolic functioning of people with a severe mental disorder,” explains a researcher behind the study, Daniel Quintana, Senior Researcher, Department of Psychology, University of Oslo, Norway.

The research has been published in Translational Psychiatry.

Oxytocin has several roles in maintaining good health

Oxytocin probably plays an important role in social cognition.

For example, the region around the eyes frequently displays signals that people experience through social cognition. When people smile, are sad or are angry, this is visible around the eyes. This is an important way of understanding what other people are thinking or feeling.

Experiments have shown that administering a nasal spray with oxytocin increases the amount of time a person spends looking at the region around the eyes in interacting with other people.

Oxytocin has therefore been proposed as a way to treat social dysfunction, one characteristic of people with mental disorders, including schizophrenia and bipolar disorder.

“In addition, research on mice has shown that oxytocin plays a role in metabolism. For example, giving rats oxytocin reduces their food intake. This has also been observed among people. Further, research has shown that blocking the oxytocin signalling pathway leads to overweight despite normal food intake in rodents,” says Daniel Quintana.

Researchers have investigated the link for years

The link between severe mental disorders and cardiovascular health has been studied for many years, since cardiovascular disease reduces the life expectancy of people with a mental disorder compared with the general population.

Some antipsychotic drugs are known to contribute to metabolic disorders, but metabolic disorders have also been frequently observed among non-medicated individuals with mental disorders.

Since the relatives of people with mental disorders also have an increased risk of cardiovascular disease and metabolic disorders, researchers have thought that genetics probably plays an important role.

The researchers behind the new study investigated this genetic role.

Compared genes from databases

The researchers thoroughly explored databases to identify the 150 genes associated with how the oxytocin system functions. Variants in these genes can affect the secretion of oxytocin and how it functions.

The researchers then investigated which variants in these oxytocin genes were associated with schizophrenia and bipolar disorder. They thus found the gene variants that most strongly link the oxytocin system to these mental disorders.

By identifying these oxytocin gene variants linked with severe mental illness, the researchers could then examine how these gene variants are linked to various metabolic markers among almost 500,000 people.

The results showed that the oxytocin genetic variants that were associated with increased risk of developing schizophrenia and bipolar disorder also affected the risk markers for metabolic disorders, including whole-body fat, body mass index and sugar intake.

“We conclude that genetic variants for the oxytocin-specific risk of developing schizophrenia and bipolar disorder are also linked to metabolic risk factors, which may be a potential link between the two types of health conditions,” explains Daniel Quintana.

Improving treatment

Daniel Quintana says that the researchers had expected to find an association between metabolic disorders and mental disorders, so the most useful discovery is finding the metabolic risk markers that are most strongly associated with schizophrenia and bipolar disorder.

“Our results provide evidence of how dysfunction of the oxytocin system influences the development of both mental disorders and metabolic disorders. Based on this, future research should examine not only whether oxytocin can strengthen cognition and behaviour but also whether oxytocin could improve metabolic regulation among people with a severe mental disorder,” says Daniel Quintana.

Oxytocin-pathway polygenic scores for severe mental disorders and metabolic phenotypes in the UK Biobank” has been published in Translational Psychiatry. In 2016, the Novo Nordisk Foundation awarded a grant to Daniel Quintana for the project Investigating Oxytocin System Dysfunction as a Common Link between Metabolic and Psychiatric Symptoms in Severe Mental Illness.

Daniel S. Quintana is a researcher in biological psychiatry at the University of Oslo. His research interests include social behavior, the oxytocin sy...

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