DECODING THE PLACENTA: MULTIOMICS INSIGHT INTO NEURODEVELOPMENT, PSYCHIATRIC RISK, AND CARDIOMETABOLIC COMORBIDITY

Overall Abstract Severe mental disorders show high rates of comorbidity and premature mortality, largely driven by metabolic and cardiovascular disease. Converging evidence suggests that these risks originate early in development, with the placenta playing a central role in shaping fetal brain and systemic physiology. Advances in high-dimensional “placentomics” now enable investigation of biological mechanisms linking prenatal biology to neurodevelopment, as well as shared metabolic and cardiovascular vulnerability across diagnostic categories. This symposium integrates genomics, transcriptomics, proteomics, and metabolomics to examine the placenta-brain-body axis in severe mental disorders. Ph.D. candidate Jonas Ø. Andersen will present our GWAS of placental efficiency, identifying genetic signals enriched in placental tissue and implicating regulatory pathways in the placenta. These include neurodevelopmental pathways (e.g., TSNAX-DISC1) and monoaminergic systems, linking placental gene regulation to early brain development and cross-disorder psychiatric risk. Dr. Andresen will present placental proteomic studies showing that protein signatures reflecting angiogenesis, inflammation, endocrine signaling, and metabolic regulation are altered in complicated pregnancies. These findings provide evidence of early biomarkers of adverse intrauterine environments that are linked to later cardiometabolic risk. Dr. Nerland will present findings on neurodevelopmental markers of brain morphology, with a focus on how these markers relate to genomic signatures of placental function in adolescent- and adult-onset psychosis. The talk will consider how these findings may clarify biological pathways linking early developmental disturbances to later psychosis risk. Dr. Garcia-Rizo will present metabolomic and clinical findings showing that early developmental factors such as birth weight are associated with later metabolic outcomes in psychosis, including antipsychotic-induced weight gain, glucose dysregulation, and broader cardiometabolic risk. Together, these presentations demonstrate how integrating placental omics across molecular layers can identify shared developmental mechanisms underlying psychiatric disorders and their comorbidities. By linking placental biology to both brain development and systemic metabolic and cardiovascular outcomes, this symposium highlights novel targets for early risk stratification and prevention aimed at reducing excess morbidity and premature mortality in severe mental disorders.