Multivariate analysis of immune-molecular profiles for patient stratification in psychotic and affective disorders

Multivariate analyses of immune-molecular data are increasingly shifting the understanding of psychotic and affective disorders away from purely categorical models and towards biologically informed stratification. Paolo Enrico will discuss how immune dysregulation may help define clinically relevant subgroups that cut across conventional diagnoses and relate more closely to symptom dimensions, neurobiological alterations, and treatment responsiveness. In psychosis, data-driven studies have identified inflammation-associated subgroups, with evidence of differential neuroanatomical patterns and, in some cohorts, cognitive correlates [1,2]. Transdiagnostic evidence further indicates that immune-related signatures may map onto dimensions such as anhedonia across psychosis and depression [3]. Emerging multi-omics approaches reinforce this perspective by showing that integration across biological layers can refine stratification beyond single-marker models [4]. In parallel, the concept of an inflammatory subtype of depression is gaining relevance, with potential implications for future nosology, biomarker-informed prognosis, and targeted treatment development [5]. Early biomarker-enriched and inflammation-stratified intervention studies further support the clinical relevance of this framework, although findings remain mixed. The lecture will also consider why these biological signals have not yet translated into clinically usable stratification, particularly in light of persistent heterogeneity in biomarker panels, sampling procedures, analytic pipelines, and outcome definitions.

[1] Enrico et al. Mol Psychiatry 2023; [2] Lizano et al. Mol Psychiatry 2021; [3] Lalousis et al. Biol Psychiatry 2024; [4] Hagenberg et al. Brain Behav Immun 2025; [5] Miller Am J Psychiatry 2025.