BA-2025-03 - Mar Fatjó-Vilas

Beyond the binary categorization of biological sex: redefining sex differences in schizophrenia and its neurobiological correlates

Sex is a determining factor in the health-disease binomial. However, the variability associated with biological sex has been understudied, generating clear biases in the etiological and clinical knowledge of human diseases, also in mental illnesses such as schizophrenia.
Going beyond the comparison between men and women from a binary perspective, we propose an innovative approach to the assessment of biological sex: calculating quantitative sex scores (called sex-scores, where 1 represents “maximum femininity” and 0 “maximum masculinity”).
The first objective of the project is to calculate sex-scores based on different traits (cerebral, anthropometric and metabolic) and study their relationship with clinical heterogeneity in schizophrenia. The second objective is to study the biological mechanisms associated with sex differences by analyzing the genetic and cellular determinants of sex-scores, using genomic and transcriptomic data. Both objectives will allow us to answer questions about the origin of sex differences observed in schizophrenia in epidemiological, genetic, neurobiological and clinical aspects (see graphic summary).
With a multidisciplinary team we will work on two independent case-control samples already collected (from FIDMAG Research Foundation and UK-Biobank), in which we will be able to develop and validate the proposed objectives. In addition, we will use open access transcriptomic data from different human brain atlases.
Having a quantitative and multi-trait assessment of biological sex has high potential for applicability in the design of clinical strategies that facilitate the establishment of etiological and predictive markers of interest not only in the field of precision medicine in mental health but also across many medical disciplines.

30.000,00 €

L'Acadèmia - Fundació Privada de l'Acadèmia de Ciències Mèdiques i de la Salut de Catalunya i de Balears