Genetic risk of schizophrenia impacts men and women differently

A Spanish research team has analysed the relationship between the genetic risk of having schizophrenia and mild subclinical traits in people of the general population. According to their study, the way the genetic risk of having this disorder affects these subclinical traits is different in men and women. The research has been published in the journal Progress in Neuro-Psychopharmacology and Biological Psychiatry.

According to the dimensional view of mental disorders, psychosis is expressed on a continuum ranging from mild subclinical traits and experiences present in the general population (schizotypy) to clinical symptoms in patients diagnosed with the disorder. Numerous studies have explored the genetic relation between schizophrenia and its subclinical expressions, but the results have been inconsistent.

Researchers from Universitat de Barcelona (UB), Universitat Autònoma de Barcelona (UAB) and the Network Centre for Biomedical Research in Mental Health (CIBERSAM) tackled this question by analysing the role of sex in this relation between genetics and subclinical expressions of schizophrenia in a sample of almost 1200 university students. The study found no clear association between schizophrenia-related genetic load (estimated through polygenic risk scores, an individual risk measurement in developing the disorder given by the presence of multiple schizophrenia-related genetic risk variants) and subclinical traits. However, when analysing sex differences, researchers observed that in men, genetic risk of schizophrenia was specifically associated with the positive dimension of schizotypy, which includes aspects such as bizarre beliefs and unusual perceptual experiences. This pattern was not observed in women, suggesting that the subclinical expression of genetic risk may differ by sex.

These results, which form part of the PhD thesis of UB’s Patricia Mas-Bermejo, highlight the need to consider differences between men and women in future genetic and clinical studies. According to the study authors, the specific association observed in men could be related to differences in non-genetic factors, such as the environment, which would modulate the expression of genetic risk. In addition, these differences reflect patterns observed in patients with schizophrenia, in which men tend to present different clinical symptoms from women, poorer premorbid functioning and earlier onset of the disease.

Although no conclusive evidence was found of a strong shared genetic basis between schizophrenia and its subclinical phenotypes, this study opens new questions and directions for researching how genetic variants and environmental factors interact differentially according to sex.

This work not only increases our understanding of the psychosis continuum, it also highlights the importance of addressing the impact of sex on genetic research, with the authors stating that exploring sex specificities in the shared genetic background between schizophrenia and its subclinical phenotypes should be a priority. The research represents an example of the key role of interdisciplinary research in deciphering the complex mechanisms underlying psychiatric disorders, opening the door to more personalised approaches in their understanding and treatment.

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