Study analyzes role of gender in relationship between genetics and subclinical expressions of schizophrenia microbiologystudy

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 link between schizophrenia and its subclinical expressions, but the results have been inconsistent.

A paper published in the journal Progress in Neuro-Psychopharmacology and Biological Psychiatry has addressed this question and also analyzed the role of gender in the relationship between genetics and subclinical expressions of schizophrenia in a sample of nearly 1,200 university students.

Researchers Araceli Rosa, from the Faculty of Biology and the Institute of Biomedicine (IBUB) of the University of Barcelona, and Neus Vidal-Barrantes, from the Faculty of Psychology of the Universitat Autònoma de Barcelona, both members of the Center for Biomedical Research in Mental Health Network (CIBERSAM), led the collaborative and interdisciplinary research team that carried out the study.

The study found no clear association between schizophrenia-related genetic load, as estimated through polygenic risk scores—a measure of individual risk for developing the disorder, caused by the presence of multiple schizophrenia-related genetic risk variants—and subclinical traits.

However, when analyzing sex differences, researchers found that in men, the genetic risk of schizophrenia is specifically associated with the positive dimension of schizotypy, which includes—for example—having 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.

Importance of considering gender differences

The results, which are part of the doctoral thesis carried out by Patricia Mas Bermejo (UB-IBUB), highlight the need to consider sex differences in future genetic and clinical studies. As the authors point out, “the specific association observed in men could be related to differences in non-genetic factors, such as the environment, which modulate the expression of genetic risk. In addition, these differences mirror patterns observed in patients with schizophrenia, where men tend to have different clinical symptoms than women, poorer premorbid functioning and earlier onset of the disease.”

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

A step forward in the research on schizophrenia

This study not only expands our understanding of the psychosis continuum, but also highlights the importance of addressing the impact of sex on genetic research. Exploring sex specificities in the shared genetic background between schizophrenia and its subclinical phenotypes “should be a priority in this field,” the authors conclude.

The study represents an example of the key role of interdisciplinary research in deciphering the complex mechanisms underlying psychiatric disorders and opens the door to more personalized approaches to understanding and treating them.