The Madrid Manic Group (MadManic) Cohort: Multi-Omics and Digital Phenotyping For the Studies of Severe Mental Disorders and Suicidality

ABSTRACT Severe mental disorders (SMDs), including bipolar disorder, schizophrenia, and major depressive disorder, are highly complex conditions associated with a substantial clinical burden and an increased suicide risk. Here, we present the Madrid Manic Cohort ( MadManic ), a large-scale initiative from Spain designed to integrate genomic, multi-omics, clinical, and digital phenotyping data to investigate the biological basis and clinical heterogeneity of SMDs. The cohort is still expanding and currently includes over 4,400 participants (∼2,300 psychiatric patients and ∼2,100 controls) and >11,000 biospecimens. Genotyping, transcriptomic and epigenetic data are available for different subsets of the cohort. By establishing the MadManic cohort we aim to integrate molecular data with detailed clinical and longitudinal digital information, allowing a more precise characterization of patient subgroups based on biological and phenotypic profiles. The MadManic cohort is well positioned to contribute to major international efforts in psychiatric genetics by enhancing the representation of Southern European populations, and advancing the identification of genetic risk, clinical predictors, and pharmacogenomic markers of treatment response. This cohort represents a valuable resource for advancing precision psychiatry, with the potential to improve risk prediction and guide personalized interventions in SMDs.