Impact of Cardiometabolic Risk on Longitudinal Symptomatic and Functional Outcomes in Schizophrenia: A 4-Year Longitudinal Study

This PhD thesis investigated whether cardiometabolic burden is associated with the longitudinal clinical and functional course of schizophrenia. The study was based on a post hoc analysis of the Italian Network for Research on Psychoses, a multicenter prospective cohort in which 127 individuals with schizophrenia were assessed at baseline and after 4 years. Baseline cardiometabolic burden was operationalized as a composite index derived from routinely collected measures, including body mass index, waist circumference, systolic blood pressure, diabetes status, and cardiovascular/endocrine medical burden. Longitudinal associations with negative symptoms, disorganization, neurocognition, functional capacity, and real world functioning were tested using regression models adjusted for baseline outcome levels, demographic and clinical covariates, and antipsychotic metabolic liability. Higher baseline cardiometabolic burden predicted greater motivational negative symptoms, greater disorganization, and poorer real world functioning at follow up, while no clear associations emerged for neurocognition or performance based functional capacity. These findings suggest that cardiometabolic dysregulation may contribute not only to excess physical morbidity in schizophrenia, but also to worse symptomatic and functional outcomes over time. Overall, the thesis supports a more integrated model of care in which cardiometabolic assessment and treatment are considered part of routine psychiatric management, with potential relevance for both prevention and long term recovery