The genes that cause mental disorders may also control weight
People with severe depression or bipolar disorder may be at greater genetic risk of obesity, while people with schizophrenia may be protected from becoming overweight, a Norwegian study shows.
It is well known that people with severe mental disorders, such as severe depressive disorder, bipolar disorder and schizophrenia, are much more likely to die early, compared to healthy people. On average, their lifespan is 10 to 20 years shorter than that of the general population.
One of the important causes of this increased mortality is cardiovascular disease.
These patients are particularly prone to being overweight or obese, which is a major risk factor for heart disease.
In the past, medicines and lifestyle have often been blamed for this connection. But recent research suggests there is a deeper link.
Genes are important in mental disorders
Over the past 15 years, a number of studies have shown that genes have a lot to say when it comes to serious mental disorders. Researchers have found a number of gene variants that increase a person’s vulnerability to these disorders.
If a person with high genetic vulnerability is exposed to adverse environmental factors, such as an infection or mental trauma, that person can develop a mental illness — in the same way that genes can predispose a person to physical illnesses, such as obesity and heart disease.
This made Nils Eiel Steen from the University of Oslo and his colleagues wonder: could there be an overlap in genetics when it comes to the relationship between serious mental disorders and weight?
In other words: Can certain gene variants cause both mental illness and obesity?
Found several genes linked to both weight and mental illness
Steen and his colleagues used data from large registers containing information on genes, BMI and mental illness in almost 1,400,000 people.
The researchers analysed the data to search for genes that appear to be linked to both BMI and mental illness.
They found a number of gene variants that met these criteria. In all, 63 gene variants were associated with both BMI and schizophrenia, 17 variants were associated with both BMI and bipolar disorder, while 32 variants were associated with both BMI and severe depression.
But not all these genes affected weight in the same way. Some gene variants increased the risk of being overweight and obese, while others reduced the risk.
Schizophrenia genes associated with lower risk
In the case of schizophrenia, several of the gene variants were linked to a lower risk of being overweight. This is consistent with the fact that low weight is actually one of the risk factors for schizophrenia.
“This also suggests that when schizophrenia patients are overweight, it is mainly due to environmental factors such as lifestyle and medicines,” Steen says.
However, in bipolar disorder and especially depression, most gene variants were associated with a higher risk of obesity. That means it will be easier for many people with these mental disorders to become obese.
“This is an important study,” says Anne Høye at the Department of Clinical Medicine at UiT - The Arctic University of Norway. She herself studies the relationship between mental and physical illness, but was not involved in Steen's research.
“It shows that there is a genetic link between mental illness and BMI, but that the relationship is very complicated and that it can go in different directions for the disorders in question,” she says.
Høye notes that the study doesn’t provide clear answers, but does provide valuable information that provides more knowledge in a very complicated field.
“This is a big puzzle, and they’ve found some important pieces,” she said.
Steen himself is quite clear that it’s not possible to draw any simple conclusions about obesity and mental disorders from this work. In fact, each new piece of research only makes the picture more complex. Each patient has his or her own unique background related to their physical and mental problems.
“This will always reflect a combination of genes and environmental factors,” he says.
Thus, hundreds of gene variants can make you more or less vulnerable to mental illness. But the significance of each of the variants is quite small. It is your own very personal combination of genes that determines how vulnerable you are and in what way.
Perhaps your particular composition of gene variants may even determine how vulnerable you are to very specific environmental factors. One person may be more at risk of having a harmful number of infections. A different person may be vulnerable to traumatic life events.
On top of this complicated picture comes the risk of being overweight and obese.
Difficult to study
Most people with schizophrenia may have many genes that protect them from being obese. However, some may have inherited schizophrenia genes that are linked to an increased risk of being overweight. At the same time, a person with the protective version of the genes can still become overweight due to medication and lifestyle.
In other words: Two people with fairly similar mental and physical symptoms may have completely different underlying causes for their problems.
This makes it challenging to study and treat the diseases. But this kind of knowledge can also open up opportunities for better treatment, says Steen.
Better customized treatment
Although major advances have been made in the treatment of cardiovascular disease in recent decades, these advances don’t seem to have prevented heart disease in patients with mental disorders. This could be because doctors are mainly concerned with mental health problems, meaning that physical problems are less of a focus.
If this new gene research shows that certain patients have a high genetic risk of obesity, it may become more natural to adjust their treatment so they also get help controlling their weight.
“This new knowledge can also have consequences for the development of new medicines,” says Steen.
For example, it’s conceivable that drug companies could make medications that are tailored to different genetic subgroups of patients.
The new results are also another piece in the puzzle in understanding the mechanisms behind serious mental disorders.
Related to stress system
Several of the gene variants the researchers found are linked to mechanisms that are likely to be important in mental disorders, such as central nervous system development.
“I find it particularly interesting that some of the gene variants are linked to the cortisol system — the body's stress response system. We know that cortisol has metabolic effects and is linked to schizophrenia, depression and bipolar disorder, so that makes sense,” Steen said.
Other genes were linked to the signal substance glutamate, which also appears to play a role in mental disorders.
Research shows that inflammation in the body can play a role in both cardiovascular disease and mental disorders. Some of the gene variants that are most strongly linked to schizophrenia are linked to the immune system, says Steen.
He believes this is one of the questions he and his colleagues will pursue in the future.
Because there is much, much more to find out.
“Most of the genetics have not been mapped yet. We are only at the very beginning of this research,” Steen said.
S. Bahrami et.al: «Shared Genetic Loci Between Body Mass Index and Major Psychiatric Disorders A Genome-wide Association Study», JAMA Psychiatry, January 2020. Summary