26 March 2021

The gender problem

A major study has revealed the connection of mental illness with gender and genes

Georgy Golovanov, Hi-tech+

An international team of scientists has analyzed sex differences in the genetics of schizophrenia, bipolar disorder and major depressive disorder. Their findings indicate that although the genes of men and women are largely the same, there are also noticeable differences in how genes associated with blood vessels, nervous and immune systems affect people with these diseases. These differences are due to gender – the same genes in men can contribute to the development of mental illness, and in women prevent it. And other genes are the opposite.

A multinational consortium of more than a hundred researchers has done a tremendous job: scientists have studied the genome of 33,403 people with schizophrenia, 19,924 people with bipolar disorder and 32,408 people with major depressive disorder, as well as 109,946 people from the control group. Their goal was to understand why these psychiatric diseases manifest differently depending on the patient's gender, according to a press release from Large-scale genome analysis identifies differences by sex in major psychiatric disorders.

Article by Blokland et al. Sex-Dependent Shared and Non-Shared Genetic Architecture, Across Mood and Psychotic Disorders published in the journal Biological Psychiatry – VM.

For example, women have a significantly higher risk of major depressive disorder, while men are more likely to have schizophrenia. Bipolar disorder is about equally inherent in both, but the course of the disease and the prognosis are different.

"We are in the era of big data, and we are looking for disease–associated genes in order to identify drug-susceptible targets associated with this genotype and develop more effective therapies for diseases that may differ in women and men," said study leader Jill Goldstein, founder and director of the Innovative Center for Gender Differences in Medicine ICON.

Goldstein and her colleagues were looking for traces of single-nucleotide polymorphism, differences in the DNA sequence in the genome that distinguish one person from another and male representatives from female representatives.

By analyzing large databases of psychiatric diseases, the researchers were able to show that the risk of schizophrenia, bipolar disorder and major depressive disorder are subject, in addition to the influence of sex hormones, to the effects of sex-specific genes.

For example, scientists have found a link between schizophrenia or depression and gender in genes that control the production of vascular endothelial growth factor, a protein that ensures the appearance of new blood vessels. As it was established earlier, these mental illnesses very often appear simultaneously with cardiovascular diseases. Researchers believe they may have a common cause.

"There are gender differences in the frequency of chronic diseases, as well as cancer. They are widespread," Professor Goldstein said. – But medicine is mainly based on models of male health and male animals. We need to develop new models of precision medicine that take into account the influence of gender."

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