Why are more men diagnosed with schizophrenia?

Why are more men diagnosed with schizophrenia?

New research has found a link between the genetic differences in men and women and their likelihood of developing certain psychotic and mood disorders.

In a study recently published in Biological Psychiatry, researchers looked at the underlying genetic differences between the sexes for the reason why bipolar disorder, schizophrenia, and depression affect the two sexes in different ways and at different rates.

After examining the genomes of 85,735 people with schizophrenia, bipolar disorder, or depression, and 109,946 people without any of those conditions, the researchers found almost a dozen single nucleotide polymorphisms (SNPs) that differed between men and women diagnosed with one of the three disorders.

What are the impacts of SNPs?

The four nucleotides - Adenine, Thymine, Cytosine, and Guanine - that are used to make DNA are compared in particular orders to make specific proteins.

SNPs are a kind of mutation where a single nucleotide - either A, G, T, or C - is swapped for another in a specific spot in the genome. These substitutions can affect our risk of getting certain diseases. 

In the study of mental disorders in the different sexes, the team found that these mutations would have different impacts on the different sexes. Some SNPs were only linked to disease in one sex, while others decreased the likelihood of the disorder occurring in one sex but increased it in the other.

The researchers also found that these mutations occurred in genes that are linked to vascular, immune, and neuronal development pathways, suggesting cardiovascular and neurological health are affected by each other in some way.

“We found a SNP in the IDO2 gene,” Jill Goldstein, a clinical neuroscientist at Harvard Medical School and the senior author of the study, told The Scientist

This particular gene is associated with immune tolerance in humans, meaning it helps suppress the immune system so it doesn’t attack bodily tissues and other substances. The gene is also linked to and has different effects on different disorders.

“The SNP [in the IDO2 gene] increased the risk of bipolar disorder in women and decreased the risk in men, but it also decreased the risk of major depression and schizophrenia,” she said. “With that same genetic SNP, we found a lower risk of depression and schizophrenia in women, but a higher risk in the men.

“And what was even more exciting was that the pathways that were implicated - vascular pathways and immune pathways - fit with what has been found and mapped by neurobiology,” Goldstein said.

In their studies of the shared abnormal changes between the brain and heart, Goldstein and her team found schizophrenia has a high comorbidity with cardiovascular disease.

“I was thrilled to see we actually found these genes with shared sex differences in areas that we’ve been studying,” she said.

Why this matters

Though these differences are small, they can have implications for how treatment can be tailored to different patients.

Gendered differences in the presentation and effectiveness of treatments have been previously identified in other diseases including cardiovascular disease and lung cancer.

“There are real-life consequences if we do not develop sex-dependent therapeutics, and I think it is critical for precision medicine,” she said.

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