A collaborative research study from the University of Barcelona (UB) and the Autonomous University of Barcelona (UAB) has examined how genetic risk for schizophrenia correlates with mild, subclinical traits in the general population. The findings suggest that the genetic factors influencing schizophrenia risk manifest differently in men and women. The research, published in Progress in Neuropsychopharmacology & Biological Psychiatry, underscores the importance of considering gender differences in future schizophrenia research.
The study is rooted in the dimensional model of mental health, which views psychosis as a spectrum. This spectrum ranges from mild, subclinical traits—often seen in the general population as schizotypy—to the full clinical symptoms diagnosed in schizophrenia patients. While several studies have investigated the genetic link between schizophrenia and these subclinical expressions, results have often been inconsistent.
Led by Dr. Neus Vidal-Barrantes from UAB and Dr. Araceli Rosa from UB, the interdisciplinary research team focused on the role of sex in this genetic-subclinical relationship. The study, conducted at the CIBERSAM Mental Health Research Centre, involved a sample of nearly 1,200 university students. Despite the lack of a clear, overall connection between schizophrenia-related genetic risk (assessed via polygenic risk scores) and subclinical traits, sex differences were evident in the results. In men, the genetic risk for schizophrenia was specifically linked to the positive dimension of schizotypy, which includes traits like bizarre beliefs and unusual perceptual experiences. This pattern, however, was not observed in women, suggesting a possible gender-based difference in the subclinical manifestation of genetic risk.
The study’s findings, part of the doctoral thesis of researcher Patricia Mas-Bermejo, emphasize the necessity of factoring in sex differences in both genetic and clinical studies on schizophrenia. As the authors note, the specific association found in men could be influenced by non-genetic factors, such as environmental influences, which may interact with genetic predisposition. The results also align with observed clinical trends, where men typically exhibit earlier onset of schizophrenia, poorer premorbid functioning, and a distinct pattern of symptoms compared to women.
While the study did not find conclusive evidence for a shared genetic foundation between schizophrenia and its subclinical traits, it opens important avenues for future research. The interaction between genetic variants and environmental factors may differ by sex, a concept that warrants further exploration in the pursuit of more personalized approaches to schizophrenia diagnosis and treatment.
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