O104 - Rethinking sex effects in schizophrenia: continuous brain sex-scores and their clinical correlates
O104
Rethinking sex effects in schizophrenia: continuous brain sex-scores and their clinical correlates
N. Hostalet 1 2 3,*, D. Vosberg 4 5, C. Almodóvar-Payá 1 2 3, M. Latorre-Guardia 1 3, M. Giralt-López 6 7 8, A. Guerrero-Pedraza 9, S. Sarró 1 3, R. Salvador 1 3, E. Pomarol-Clotet 1 3, T. Paus 4 10, M. Fatjó-Vilas 1 2 3
1FIDMAG Germanes Hospitalàries Research Foundation, 2Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona , Barcelona, 3CIBERSAM, Instituto de Salud Carlos III, Madrid, Spain, 4Centre de Recherche du CHU Sainte-Justine, 5Departament of Neuroscience, University of Montreal, Montreal, Canada, 6Servei de Psiquiatria Infantil i de l’Adolescència, Hospital Universitari Germans Trias i Pujol, Badalona, 7Departament de Psiquiatria i Medicina legal, Universitat Autònoma de Barcelona, Barcelona, 8Institut Recerca Germans Trias i Pujol , Badalona, 9Fundación Hospitalarias Sant Boi, Sant Boi, Spain, 10Department of Psychiatry and Addictology, University of Montreal, University of Montreal, Montreal, Canada
Introduction: Sex differences in schizophrenia (SZ) are well-documented in terms of age of onset, symptoms, and treatment response. However, sex is often treated as a covariate rather than a primary variable of interest. Continuous “sex-scores” have been proposed to quantify the “maleness/femaleness” of multiple traits, as a complement to biological sex.
Objectives: We aimed: i) to compute brain sex-scores in healthy individuals (HC) and SZ patients and; ii) to examine the association of brain sex-scores with SZ symptoms.
Methods: In Sample A (215 males, 211 females HC), sex effect coefficients were obtained for 34 cortical regions (Desikan-Killiany atlas) through linear regressions of cortical thickness (CT) and surface area (SA). In Sample B (237 SZ patients), individual-level CT and SA values were summed and weighted by the sex effect coefficients obtained from Sample A to compute sex-scores ranging from 0 (maximum maleness) to 1 (maximum femaleness). We assessed correlations between sex-scores and Positive and Negative Syndrome Scale (PANSS) in SZ patients, separately for males and females.
Results: CT sex-scores showed significant correlations with PANSS-Negative symptoms in females (r2 =-0.4; pFDR=0.017). In males, CT sex-scores were associated with PANSS-Positive symptoms (r2=-0.18;pFDR=0.033) and general psychopathology (r2=-0.24;pFDR=0.009).
Conclusions: Our data suggest that lower CT sex-scores (associated with greater maleness) are related to more severe symptoms, highlighting the importance of considering sex-related variability in a quantitative manner. Then, sex-scores emerge as a useful tool to study sex- and gender-related variability in the neurobiology and clinical expression of schizophrenia.
Acknowledgements:ISCIII project-PI20/01002,grant-FI21/00093-NH,grant-CP20/00072-MFV co-funded by ERDF/ESF;AGAUR-2021SGR01475;Beca Santander-Estades formatives Espanya i estranger 2024 doctorands UB-NH;Beca de Recerca Bàsica de l’Acadèmia 2025.
Disclosure of Interest: None Declared