Genetic Risk of Depression Linked to Increased Risk of Other Psychiatric Disorders

Recent research reveals that people who are hospitalized for depression are at an increased risk of developing conditions like substance abuse, bipolar disorder, schizophrenia, and anxiety, depending on their genetic predisposition to the individual disorder.

Genetic Risk of Depression Linked to Increased Risk of Other Psychiatric Disorders
With the help of, among other things detailed genetic scanning, the researchers have examined the genetic material of 1.3 million people—of which more than 370,000 have depression. It is the largest genetic study of depression to date, says Professor Anders Børglum. Image Credit: Lars Kruse.

Almost one in every five Danes suffers from depression at some point in their lives. According to a new study from Aarhus University, the genetic risk of depression is associated with increased genetic risk of other psychiatric diagnoses. The findings were recently published in Nature Medicine.

The scientists investigated the genomes of 1.3 million people, more than 370,000 of whom had depression, using a detailed genetic scan. This is the largest genetic study of depression to date, and it reveals that people with hospital-treated depression are more likely to develop diseases like substance abuse, bipolar disorder, schizophrenia, and anxiety disorders and that genetic analyses can anticipate the risk of developing these psychiatric disorders.

Image Credit: Ron Dale/Shutterstock.com

Image Credit: Ron Dale/Shutterstock.com

According to the study, people who have been hospitalized for depression and have a high genetic predisposition to bipolar disorder are 32 times more likely to develop the disease than the general population.

Individuals who have been hospitalized for depression and have a high genetic predisposition to schizophrenia are 14 times more likely to develop schizophrenia than the general population.

New Prevention and Treatment Options

Professor Anders Børglum of Aarhus University's Department of Biomedicine and iPSYCH (national initiative for integrative psychiatric research), who led the study, notes that the findings pave the way for future prevention and early treatment for high-risk people.

For example, targeted efforts that offer more frequent monitoring for the development of bipolar disorder, schizophrenia and anxiety among people with depression who have the highest genetic and clinical risk of being diagnosed with one of these disorders. This would enable early diagnosis and treatment, which we know can have beneficial effects."

Anders Børglum, Professor, Department of Biomedicine, Aarhus University

Anders Børglum believes that recognizing depressed people and a high genetic risk of developing substance abuse could make both the patient and the doctor aware of the problem. Preventative measures could then be introduced to avoid the development of substance abuse.

Individuals who have been hospitalized for depression and have a high genetic predisposition to substance abuse have a 21% chance of developing a severe substance abuse problem.

This is more than five times higher than the group with a low genetic predisposition for substance abuse and depression. And ten times higher than the general population in the absence of hospitalised depression. Over the same time period, this group has a 2% chance of being diagnosed with substance abuse.

Negative Effects on an Individual’s Brain Function and Level of Education

The scientists determined numerous new genetic risk variants and risk genes for depression in their study. These findings add to the understanding of the biological disease mechanisms at work and point to new molecular targets for treatment.

We found a number of biological systems and cell types that are affected by the genetic risk. The effects are seen in virtually all regions of the brain, but not in other organs. And mainly in the brain's nerve cells—neurons. The genetic risk can affect many different types of neurons. Overall, it can be said that the genetic risk affects the development and communication of brain cells.”

Thomas Als, Study First Author and Former Associate Professor, Department of Biomedicine, Aarhus University

According to the findings, a total of 11,700 genetic risk variants can illustrate 90% of the heritability of depression, making it one of the most complex and polygenic mental disorders. The significant proportion of the risk genes are still unknown.

The investigators discovered that nearly all of the 11,700 genetic risk variants for depression have an effect on the general population’s level of education. Some risk variants make it more likely to complete higher education, while others make it less likely. However, the genetic variants decrease a person’s chances of completing higher education.

In line with this, we found that genetic risk of depression is linked to reduced cognitive properties in the population. This particularly affects abstract thinking and mental flexibility, attention and verbal reasoning,” noted Anders Børglum.

Suggests that Depression to Some Extent is a Brain Development Disorder

Depression can be a serious and severely debilitating condition. The results of the study indicate that the seeds of the disease are already being sown in the embryonic stage.

We found evidence that part of the genetic risk is already influencing brain cells in the embryonic stage, and that depression to some extent is a neuronal developmental disorder. This tracks with the fact that we’re seeing a significant genetic overlap between depression and, for example, autism and ADHD.”

Anders Børglum, Professor, Department of Biomedicine, Aarhus University

Source:
Journal reference:

Als, T. D., et al. (2023). Depression pathophysiology, risk prediction of recurrence and comorbid psychiatric disorders using genome-wide analyses. Nature Medicine. doi.org/10.1038/s41591-023-02352-1.

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