January's Article of the Month: Sex Differences in Genetic Risk for Schizophrenia
The “Article of the Month” initiative, led by the Research and Communication Committee of the Department of Clinical and Health Psychology throughout 2025, kicks off with the selection of “Sex-specific association between schizophrenia polygenic risk and subclinical schizophrenia-related traits” as January's article of the month.
This study, led by predoctoral researcher Patricia Mas-Bermejo and Dr. Araceli Rosa, from the Department of Evolutionary Biology, Ecology, and Environmental Sciences at the University of Barcelona, is part of the Barcelona Longitudinal Investigation of Sensitivity and Schizotypy (BLISS-2; ref. PID2020-119211RB-I00) research project, funded by the Spanish Ministry of Science and Innovation. This project is led by Dra. Neus Vidal Barrantes del Departamento de Psicología Clínica y de la Salud de la Universitat Autònoma de Barcelona, who co-authored the article along with Dra. Pilar Torrecilla y la investigadora predoctoral Valeria Lavín, from the same department. This study provides new insights into how genetic risk for schizophrenia influences subclinical psychosis-related traits, emphasizing the importance of considering sex differences in this field.
From the dimensional perspective of mental disorders, psychosis exists on a continuum ranging from mild traits and experiences in the general population to clinical symptoms in diagnosed patients, such as those with schizophrenia. The set of mild subclinical manifestations is referred to as schizotypy. However, previous studies exploring the genetic link between schizophrenia and its subclinical expressions have yielded inconsistent results. This research, published in the journal Progress in Neuropsychopharmacology & Biological Psychiatry, with an impact factor of 5.3 (first decile in the Psychiatry category of Journal Citation Reports), addresses this issue by analyzing the role of sex in this relationship.
Main Results
This study found no clear association between genetic risk for schizophrenia (measured through polygenic risk scores) and subclinical traits such as positive, negative, or disorganized schizotypy. However, when the analysis was stratified by sex, a key result emerged: in men, genetic risk for schizophrenia was specifically associated with the positive schizotypy dimension, which includes unusual perceptual experiences and odd beliefs. This pattern was not observed in women, suggesting that the subclinical expression of genetic risk may differ by sex.
Implications of the Study
These findings underscore the need to consider sex differences in future genetic and clinical research. As the authors note, the specific association found in men may be linked to non-genetic factors, such as environmental influences, that modulate the expression of genetic risk.
While no conclusive evidence was found for a universal genetic link between schizophrenia and its subclinical phenotypes, this study opens new questions and research avenues to explore how genetic variants and environmental factors interact differently by sex.
A Step Forward in Schizophrenia Research
This study highlights the importance of sex-specific approaches in genetic research. As the authors conclude, “exploring sex differences in the genetic background shared between schizophrenia and its subclinical phenotypes must be a priority in this field.”
This research represents a crucial step in understanding psychiatric disorders, paving the way for more personalized approaches to their study and treatment.