Genetic analysis identifies gender-dependent differences in major psychiatric disorders

A study of gender differences in the genetics of schizophrenia, bipolar disorder and major depressive disorders shows that while genetic transmission is substantial between males and females, there are obvious gender-dependent differences. in terms of how genes related to the central nervous system, immune system, and blood vessels affect people with these disorders.

The findings, from a multinational consortium of psychiatric researchers including researchers and a senior author at Massachusetts General Hospital (MGH), could encourage better treatment for major problems. mind-boggling. They are published in the journal Biological Psychology.

The findings were made possible only through collaboration with more than 100 researchers and research groups, which combed through the genomes of 33,403 individuals with schizophrenia, 19,924 with bipolar disorder, and 32,408 with dys- major depression order, as well as 109,946 controls (people without any of these studies).

Their goal was to understand why these major psychiatric problems differed between the two sexes. For example, women have a much higher risk for major depressive disorder, but the risk for schizophrenia is significantly higher among men. The risk of bipolar disorder is about the same for women and men, but disease onset, course, and prognosis are quite different between the two.

We are at the time of Big Data, and we are looking for disease – related genes to identify drug targets associated with the genotype, in order to develop more effective treatments for that disease. may vary by gender. “

Jill M. Goldstein, PhD, senior author, founder and executive director of the Center for Innovation on Sexual Differences in Medicine (ICON) at MGH

Goldstein and colleagues sought clusters in the form of single nucleotide polymorphisms, or SNPs (“snips”), in which one “letter” of DNA (nucleotide) differs from one individual to the next and between sexes.

“There are gender differences in the frequency of chronic diseases and cancers as well. It’s dangerous,” says Goldstein, who is also a professor of Psychology and Medicine at Harvard Medical School. “But medicine is, in large part, built on models of male and animal health. We need to develop our detailed treatment models that incorporate the impact of sex.”

By taking advantage of large psychiatric databases, the researchers were able to show that the risks for schizophrenia, bipolar disorder and major depressive disorder are influenced by the interaction of specific genes. with sex, as well as the effects of sex hormones such as estradiol or testosterone.

For example, the researchers found interactions with schizophrenia and depression and sex in genes that controlled the production of vascular endothelial growth factor, a protein that stimulates the growth of new blood vessels.

“My lab is studying the co-occurrence of depression and cardiovascular disease. It turns out that both depression and schizophrenia have a very high co-occurrence with cardiovascular disease. We ‘believe that there are shared causes between psychiatric and cardiovascular diseases that are not due to the effects of medication, “she says. “Furthermore, the co-occurrence of depression and cardiovascular disease is twice as high in women than in men, and this may be related to what we found in depression between sex differences in a gene that controls vascular endothelial growth factor. “

The researchers confirm that, while the specific causes of the diseases they have studied are not yet known, “our study confirms the importance of designing large genetic studies at has statistical power to test for interaction with sex.Disclosing the effects of sex, genes, and pathophysiology identifies potential targets for sex- or gender-dependent therapeutic interventions creating more effective treatments for both men and women, “she says.