Understanding sex differences in the genetic basis of schizophrenia

A joint research study conducted by the UAB and the UB has analyzed the relation between the genetic risk of having schizophrenia and mild subclinical traits in people of the general population. According to the study, the way the genetic risk of having this disorder affects these subclinical traits is different in men and women. The research, published in Progress in Neuropsychopharmacology & Biological Psychiatry, highlights the importance of considering gender differences in this relation.

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.

A collaborative and interdisciplinary research team led by Dr Neus Vidal-Barrantes from the UAB and Dr. Araceli Rosa from the UB, researchers at the CIBERSAM Mental Health Research Centre, has tackled this question by analyzing 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.

Importance of considering sex differences

These results, which form part of the PhD thesis Patricia Mas-Bermejo, highlight the need to consider differences between men and women 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 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 than 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.

A step forward in the research into schizophrenia

This work not only increases the understanding of the psychosis continuum, but also highlights the importance of addressing the impact of sex on genetic research. As the authors conclude, "exploring sex specificities in the shared genetic background between schizophrenia and its subclinical phenotypes should be a priority in this field." 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 personalized approaches in their understanding and treatment.

The work, published in the journal Progress in Neuropsychopharmacology & Biological Psychiatry, involved researchers Patricia Mas-Bermejo and Araceli Rosa, from the Department of Evolutionary Biology, Ecology and Environmental Sciences of the University of Barcelona (UB), and Neus Vidal-Barrantes, Pilar Torrecilla and Valeria Lavín, from the Department of Clinical and Health Psychology of the Universitat Autònoma de Barcelona (UAB). It also included the involvement of CIBERSAM, the Institute of Biomedicine of the University of Barcelona (IBUB) and of researcher Sergi Papiol from the IPPG and the Max Planck Institute of Psychiatry in Munich (Germany), as well as Professor Thomas R. Kwapil from the University of Illinois at Urbana-Champaign (USA).

The research forms part of the Barcelona Longitudinal Investigation of Sensitivity and Schizotypy (BLISS-2; ref. PID2020-119211RB-I00) project funded by the Spanish Ministry for Science and Innovation and directed by Dr. Neus Vidal-Barrantes, from the UAB.