Genetic differences between men and women may explain why mental illnesses affect genders differently

BOSTON, Mass. — When it comes to your genes, there are significant similarities between men and women. However, when it comes to mental illnesses such as bipolar disorder, schizophrenia, and clinical depression, the differences between the genders may lead to different symptoms. Researchers from Massachusetts General Hospital (MGH) say this points to these illnesses vary according to a patient’s gender.

During their study, researchers discovered that genes with a link to the brain, brainstem, vasculature, and immune functions, expressed themselves differently in people with mental illnesses, depending on gender. Psychiatric experts believe this research might pave the way for new therapies for serious mental illnesses.

Does your gender influence mental illness progression?

For this study, over 100 researchers and scientific organizations worked together to examine the genomes of nearly 200,000 people. From that group, 33,403 individuals had schizophrenia, 19,924 individuals suffered from bipolar disorder, and 32,408 individuals had a case of clinical depression. The remaining 109,946 individuals were part of the control group, consisting of mentally healthy individuals.

Investigators wanted to know why there were gender differences in these severe mental illnesses. There is a large gender difference in the prevalence of mental illnesses such as clinical depression and schizophrenia. Women and men have nearly the same chance of developing a bipolar illness, however, the start, progression, and outcome of these cases are vastly different for the two sexes.

“We’re in the era of Big Data, and we’re looking for genes that are associated with illnesses to identify druggable targets associated with the genotype, in order to develop more effective treatments for that illness that may differ by sex,” says senior author Jill M. Goldstein, Ph.D., founder and executive director of the Innovation Center on Sex Differences in Medicine (ICON) at MGH, in a media release.

A ‘snip’ to blame for genetic differences?

Single nucleotide polymorphisms (SNPs) can be to blame for many genetic differences. Referred to as “snips,” they are differences in a singular nucleotide or “letter” in DNA. The team scanned the genetic sequences of each individual to check for SNPs.

“There are sex differences in the frequency of chronic diseases and cancers as well. It’s pervasive,” Goldstein explains. “But medicine, essentially, has been built on models of men’s health and male animals. We need to develop our precision medicine models incorporating the effect of sex.”

Although the specific cause for these variations is unknown, Goldstein and her team found a specific protein in blood vessels that affects depression and schizophrenia based on gender. This protein regulates the development of new blood vessels and is present in both men and women.

Previous studies have shown that sex hormones like testosterone and estrogen can have a major impact on the body. However, this study found that sex hormones did not affect the protein. Instead, distinct genetic variations caused a difference in the way it interacted according to gender. This difference may be the reason for gender-based differences in certain mental illnesses.

Women at risk for further health issues

With the help of vast psychiatric records, the team revealed that probabilities for developing schizophrenia, bipolar illness, and clinical depression are dependent upon connections between certain genes and gender.

“My lab is studying the substantial 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 there are shared causes between psychiatric and cardiovascular diseases that are not due to the effects of medication,” Goldstein says. “In addition, the co-occurrence of depression and cardiovascular disease is twice as high in women as in men, and this may, in part, be associated with our finding in depression of sex differences in a gene controlling vascular endothelial growth factor.”

“Our study underscores the importance of designing large-scale genetic studies that have the statistical power to test for interactions with sex. Dissecting the impact of sex, genes, and pathophysiology will identify potential targets for sex-dependent or sex-specific therapeutic interventions creating more effective therapies for both men and women,” the researcher concludes.

The study appears in the journal Biological Psychiatry.