Don't go breaking my heart: protecting cardiometabolic health in psychosis

Background People with psychotic disorders experience markedly elevated rates of cardiometabolic disease and premature cardiovascular mortality. While antipsychotic and antidepressant medications contribute substantially to metabolic risk, growing evidence suggests that psychosis itself is associated with early abnormalities in cardiac structure, metabolism, inflammation, and autonomic function, often evident before or shortly after treatment initiation. Understanding the relative and interacting contributions of illness-related and treatment-related mechanisms is essential to developing effective preventive and therapeutic strategies. Aims & Objectives This presentation aims to synthesise evidence from multimodal cardiac imaging, genetic studies, and large-scale meta-analyses to examine how psychosis and its pharmacological treatment jointly contribute to cardiometabolic risk. Specific objectives are to: Method The talk integrates findings from several complementary research approaches. These include cardiac MRI and spectroscopy studies examining myocardial structure, function, and bioenergetics in schizophrenia; imaging studies combined with genetic and polygenic risk approaches to disentangle illness-related from treatment-related effects; meta-analyses of metabolic and inflammatory alterations in drug-naive first-episode psychosis; and network meta-analyses comparing the cardiometabolic side effects of antipsychotics and antidepressants. Evidence from translational and clinical studies is synthesised within a mechanistic framework encompassing inflammation, insulin resistance, autonomic dysfunction, and altered energy metabolism. Results Across methodologies, converging evidence indicates that cardiometabolic vulnerability is present early in psychosis, including subtle myocardial dysfunction, systemic inflammation, and insulin resistance prior to substantial medication exposure. Antipsychotic and antidepressant treatments further modify risk, with marked heterogeneity between agents in their effects on weight, glycaemic control, lipid profiles, and cardiovascular outcomes. Network meta-analytic data highlight clinically meaningful differences between drugs, while imaging and genetic studies suggest overlapping biological pathways linking psychosis, metabolic dysregulation, and cardiac dysfunction. Discussion & Conclusions Cardiometabolic risk in psychosis arises from the interaction between intrinsic illness-related mechanisms and medication-induced effects, rather than pharmacotherapy alone. These findings underscore the need for early risk stratification, informed prescribing, and proactive cardiometabolic monitoring. Integrating psychiatric and physical healthcare, alongside emerging metabolic interventions, offers a realistic opportunity to reduce cardiovascular morbidity and mortality in this high-risk population.