The diagnosis of mental disorders remains a major challenge due to the absence of objective diagnostic biomarkers. The search for clinically useful biomarkers has been hindered by shared neurodevelopmental mechanisms across conditions-resulting in reduced specificity of risk factors and overlapping manifestations among different disorders-as well as by limited understanding of the biological and pathophysiological mechanisms underlying specific outcomes. In addition, although evidence shows that biological sex and gender influence the prevalence, clinical presentation, therapeutic response, and prognosis of many psychiatric conditions, most mental health studies fail to incorporate these differences adequately.
Therefore, our goal is to identify biological and clinical patterns that can improve understanding of psychiatric heterogeneity, adopting a sex and gender-informed perspective. Accordingly, the objective of this project is to investigate sex- and gender-related effects on genomic, neuroanatomical and phenotypic dimensions allowing to identify complex, multilevel patterns underlying mental disorders heterogeneity.
To meet these objectives, analyses will follow a progressive strategy, beginning with sex-pooled samples, advancing to categorical sex and gender comparisons, and ultimately applying continuous sex/gender scores that position individuals along a continuum of variation based on the generated sex/gender-specific multilevel patterns (PMID: 33139896 and 37277458). The analyses will be performed in the general population sample (controls) as well as between patients and controls, and among patients with specific psychiatric diagnoses.
Given the neurodevelopmental basis of many psychiatric disorders, the project will incorporate critical developmental windows and associated environmental and biological risk factors, supporting refined patient stratification and precision psychiatry approaches.