Project Summary People with schizophrenia spectrum disorders have a shorter lifespan and higher morbidity and mortality than the general population, with cardiovascular conditions on top of the leading causes. Brain imaging research has revealed accelerated age-related brain changes in patients with schizophrenia spectrum disorders. However, neuroimaging studies of schizophrenia are typically brain-focused without system-level investigations on the risk factors. The causes of the exaggerated body and brain aging in schizophrenia is still largely unexplained, making it difficult to provide more effective screening and management for the devastating medical consequences for people suffering from schizophrenia. There are likely missing opportunities as vascular contributions to brain, especially white matter health, are well established in the general population. The goal of the current proposal is to utilize the standard but state-of-the-art vascular biology measures, combined with cutting-edge brain imaging that is informative of the underlying mechanisms, to study the potential vascular contributions to the accelerated age-related brain and cardiovascular diseases in schizophrenia. We will compare various vascular biomarkers and between vascular and stress factors, to identify the key body-brain paths that may explain the reason that schizophrenia spectrum disorders are associated with such high age-related medical and brain burden. The study may provide insights into the timing and mode for more effective screening, prevention and treatment effort.