Project Summary/Abstract Grieving the death of a spouse is an extremely stressful life event. The grieving process may extend for a long period of time, taking a physical, mental, and emotional toll on the bereaved. Bereaved individuals are at an increased risk for morbidity and mortality, particularly within the first 6 months following the loss. Mortality rates are heavily imbalanced by cardiovascular-related deaths, which account for 20-53% of deaths following the loss of a spouse. However, researchers lack an understanding of the psychosocial aspects that may help explain why some bereaved individuals die of a “broken heart”, while others do not. Self-perceived burden, a psychosocial stressor, refers to a concern for the impact on others of one’s care needs resulting in guilt, distress, feelings of responsibility, and diminished sense of self. Psychosocial stressors promote transcription nuclear factor kappa B (NF-kB) activation, a prime pathway for upregulating proinflammatory cytokine production. Inflammation is central to all stages of CVD and our preliminary data identifies inflammation as a potential mechanism underlying CVD among the bereaved. Further, because self-perceived burden is a psychosocial stressor, it may impact bereaved individuals’ CVD risk by promoting systemic inflammation, thereby damaging the heart. Thus, it is important to understand when and if self-perceived burden develops during bereavement, and how it impacts CVD risk via inflammation. In the current study, we aim to investigate self-perceived burden, a novel psychosocial stressor, and its relationship to grief symptoms during the first year after losing a spouse. In addition, we will longitudinally investigate the relationship between self-perceived burden and inflammation, a marker of CVD risk. Last, we will explore which issues appear first in the time course during the grief trajectory; specifically, we will examine whether self-perceived burden partially mediates the relationship between earlier grief symptoms (2 months post-loss) and later inflammation (12 months post- loss). Concurrent with an R01 project funded by NHLBI, this project will examine grief symptoms, self- perceived burden, and inflammation among a sample of 160 bereaved individuals who recently lost their spouse. These associations will be examined longitudinally, with data collected at 2 months, 4 months, 6 months, and 12 months after the spouse’s passing. Investigation of the relationship between self- perceived burden and inflammation would further our understanding of who may be at risk for CVD. Importantly, self-perceived burden is a modifiable risk factor; results may yield important information related to the development or revision of existing clinical interventions for bereaved individuals targeting disease prevention.