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 & Biological Psychiatry has addressed this question and also analysed 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 Centre for Biomedical Research in Mental Health Network (CIBERSAM), lead 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 analysing sex differences, researchers found that, in men, 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 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.
The study involved the participation of researchers Patricia Mas Bermejo and Araceli Rosa, from the Department of Evolutionary Biology, Ecology and Environmental Sciences (UB and IBUB), and Neus Vidal-Barrantes, Pilar Torrecilla and Valeria Lavín, from UAB's Department of Clinical and Health Psychology, with the participation of the IBUB and the CIBERSAM, and the collaboration of researcher Sergi Papiol, from the Institute of Psychiatric Phenomics and Genomics (IPPG) and the Max Planck Institute of Psychiatry (Munich, Germany), and Professor Thomas R. Kwapil from the University of Illinois at Urbana-Champaign (United States). The paper is part of the Barcelona Longitudinal Investigation of Sensitivity and Schizotypy (BLISS-2; ref. PID2020-119211RB-I00) project, funded by the Spanish Ministry of Science, Innovation and Universities and led by Neus Vidal-Barrantes (UAB).
Reference article
Mas Bermejo, Patricia; Papiol, Sergi et al. "Sex-specific association between schizophrenia polygenic risk and subclinical schizophrenia-related traits". Progress in Neuro-Psychopharmacology & Biological Psychiatry, October 2024. DOI: 10.1016/j.pnpbp.2024.111161
