Is there a genetic link between the risk of schizophrenia and the surface of the brain?

The genes that influence the risk of developing schizophrenia appear to be the same genes that affect the thickness and size of the surface of the brain.

According to a new study from the Norwegian Center for Mental Disorders Research, NORMENT, there is a genetic link between the risk of schizophrenia and the surface of the brain. The above images of the human brain are taken with neuroimaging techniques. Illustration image: Colourbox.com.

Schizophrenia is a serious brain disorder. It affects approximately one in a hundred people in their lifetime worldwide. Nobody knows exactly why some people develop schizophrenia, but a combination of biological and environmental factors are known to contribute to the condition. Among the biological factors, genes play an important role. Twin studies have shown that genetic factors account for approximately 80% of an individual’s risk of developing schizophrenia.

Image by Weiqiu Cheng
Weiqiu Cheng is a postdoctoral researcher at NORMENT. Image: Øystein Hormo, UiO.

However, do the same genes that influence the risk of developing schizophrenia also affect the biological characteristics of the brain that we can measure? According to a new study, there is indeed a genetic association between the risk of schizophrenia and the surface of the brain.

– The results of our study demonstrate that a group of genes that contribute to the risk of schizophrenia also affect the thickness and size of the surface of the brain, says Weiqiu Cheng.

She is a postdoctoral fellow at the Norwegian Center for Mental Disorder Research, NORMENT.

Study paves the way for new insights into the brains of people with schizophrenia

The brain surface is the outermost layer of the brain. This layer is called the cerebral cortex, which is mainly made up of gray matter. It consists of around 20 billion nerve cells which are tightly packed together. This area is involved in many high-level brain functions, such as emotion and reasoning.

What are we referring to when we talk about the thickness and size of the surface of the brain?

Imagine that our brain looks like a crumpled up piece of paper. When we talk about the thickness of the brain surface, we are referring to the thickness of the sheet itself. The size of the brain surface is the surface of the sheet, which is the same whether the sheet is laid flat or rolled up.

These brain characteristics therefore appear to be influenced by a group of genes that also contribute to the risk of schizophrenia.

– In previous studies, researchers have found that schizophrenic patients have significant differences in the thickness and size of the surface of the brain, compared to healthy people. Our study may provide biological insights into these findings, Cheng says.

X-ray image of the human brain.
Images of the human brain taken with neuroimaging. Illustration image: Colourbox.com.

Brain surface thickness and size could be promising biomarkers

For a long time, researchers have tried to find out if there are so-called biomarkers for mental disorders such as schizophrenia. A biomarker for schizophrenia would mean that we could determine a person’s risk for schizophrenia based on one or more measurable biological characteristics.

– Today, it is not possible to conclusively determine whether someone has schizophrenia based on medical examinations. We want to know if there is a reliable and objective biomarker, ie one or more biological characteristics, which are associated with the risk of schizophrenia, says Weiqiu Cheng.

She adds:

– The thickness and size of the surface of the brain can potentially be such biomarkers.

The results of this study could be a small step towards that endeavour.

– The genetic overlap we found helps us understand the genetic relationship between schizophrenia and brain surface thickness and size. This could pave the way for future studies of schizophrenia biomarkers, Cheng points out.

Cortical folding and furrow depth are also hereditary

Photo by Dennis van der Meer
Dennis van der Meer is a researcher at NORMENT. Image: Private.

Researcher Dennis van der Meer also works at NORMENT. He recently published a study in which he looks at another parameter, namely the folding of the human cerebral cortex measured by the depth of the sulci.

To explain what sulci depth means, we have to go back to the example where we look at the brain as a sheet of paper. When we crumple the sheet like a ball, there will be creases and bumps. Sulcal depth is the depth of the various creases and bumps in the ball.

“Surprisingly, few researchers have looked at this parameter so far,” says van der Meer.

van der Meer and his colleagues discovered that the depth of furrows is largely determined by our genes.

– This suggests that the depth of the furrows may be an interesting characteristic to investigate. I’m very excited about what we might discover in the future, he says, and adds:

– We have already discovered that some of these genes are also implicated in brain disorders, including schizophrenia. This indicates that this understudied brain feature may provide many clues as to how these disorders arise.

Biomarker may help improve prevention, diagnosis and treatment in the future

Today, the diagnosis of schizophrenia is made on the basis of systematic interviews and questionnaires.

– Schizophrenia is a very heterogeneous mental disorder. That means patients with schizophrenia vary widely in their symptoms, disease course and outcomes, Cheng says.

People with schizophrenia also suffer from an increased prevalence of other mental disorders.

– Today’s diagnostic methods are therefore demanding and time-consuming for both patients and clinicians. If, on the other hand, the diagnosis can be formulated from a biomarker, linked for example to the brain or to genes, then it is more objective and less demanding, explains Weiqiu Cheng.

She thinks a biomarker for schizophrenia could also contribute to better prevention and treatment.

Image of a patient with a therapist filling out a questionnaire
Today, the diagnosis of schizophrenia is made on the basis of systematic interviews and questionnaires. This is demanding and time-consuming for both patients and clinicians. If, on the other hand, the diagnosis can be formulated from a biomarker, then it is more objective and less demanding, according to Weiqiu Cheng. Illustration image: Colourbox.com.

NORMENT study is the first to demonstrate genetic overlap

Researchers have long believed that there is a genetic link between different brain structures and schizophrenia. Nevertheless, the NORMENT study is the first to be able to prove the genetic overlap.

– In previous studies, which I referred to earlier, researchers looked at MRI images of the brains of people with schizophrenia. They revealed that people with schizophrenia had unusual changes in brain structure. It was then that the researchers discovered that the thickness and size of the surface of the brain was different from that of healthy people. However, the researchers were unable to statistically prove the genetic overlap, says Weiqiu Cheng.

Cheng and his colleagues at NORMENT therefore chose to use a different analytical method than those used in previous studies. In total, they analyzed the genes of more than 40,000 people with schizophrenia and nearly 65,000 healthy people, using large European databases. This is how they proved the genetic link.

– I want to continue in this area and I believe that genetic studies of this type can ultimately help us understand why some people become schizophrenic and how the disorder develops over time, concludes Weiqiu Cheng.

Dennis van der Meer adds:

– We are working in a very complex field, but also very promising. The results of our studies are all small steps, but it is good to see that we are slowly making solid progress towards identifying the biology underlying brain disorders. They are no longer such a mystery.

/Public release from the University of Oslo. This material from the original organization/authors may be ad hoc in nature, edited for clarity, style and length. The views and opinions expressed are those of the author or authors. See in full here.

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