Furthermore, the RR in this study is within the 95% CI of that found in the previous investigation (1.27, 17.31). persons died of natural causes. The standardized mortality ratio was 2.80 (95% CI 0.89, 6.38). After adjusting for age and gender, mortality from natural causes was predicted in separate models by cigarette smoking (relative risk [RR] = 4.66, = DCHS1 .0029); lower cognitive score (RR = 0.96, = .013); level of antibodies to EpsteinCBarr virus (RR = 1.22, = .0041) and to Herpes Simplex virus type 1 (RR = 1.19, = .030); immunologic disease (RR = 3.14, = .044); and genitourinary disease (RR = 2.70; = .035). Because cigarette smoking confers an almost 5-fold risk of mortality, smoking cessation is an urgent priority. Having ARQ 621 an elevated level of antibodies to EpsteinCBarr virus and to Herpes Simplex virus type 1 are also significant predictors of death from natural causes. .007); in this age group, the odds of cardiac death were increased by 12-fold in smokers relative to nonsmokers (HR = 12.4, .0005). Smoking has also been found to be predictive of mortality in cohort studies of schizophrenia when adjusting for other relevant variables.6,8 In a study consistent with findings of increased mortality, we previously reported that persons with serious mental illness who smoked cigarettes had a significantly higher 10-year Framingham cardiovascular disease risk score than nonsmokers (13.2% vs 7.4%) and were more likely to have abnormalities in blood pressure and lipid markers.12 Recent studies have shown that some individuals with schizophrenia have increased rates of exposure to some microbial agents and increased levels of immune markers in the blood and in the central nervous system.13C15 However, the association between exposure to specific infectious agents and premature death in schizophrenia has ARQ 621 been the topic of only limited investigation. In an earlier version of the schizophrenia cohort described in this study, we found an association between serological evidence of and risk of dying of natural causes (HR = 4.7, = .02).16 The role of other infectious agents in schizophrenia mortality has not been previously investigated. The purpose of the current investigation was to identify the determinants of mortality in a cohort of individuals with schizophrenia assessed at baseline with an in-person clinical evaluation and a blood sample from which antibodies to infectious agents were measured. Mortality and causes of mortality were determined with data from the National Death Index (NDI) following a period of up to 11 years. We examined the role of demographic and clinical factors including cigarette smoking, exposure to infectious agents, and other potentially modifiable risk factors for mortality. Methods Participants Participants were individuals with schizophrenia who were enrolled by the Stanley Research Program at Sheppard Pratt in Baltimore, Maryland between February 1, 1999 and December 31, 2009 in a study directed at defining the association between antibodies to infectious agents and schizophrenia. At the time of their enrollment in the study, all participants were receiving services at treatment programs affiliated with Sheppard Pratt or at other psychiatric programs in central Maryland. All participants met the following additional inclusion criteria: (1) diagnosis of schizophrenia or schizoaffective disorder ARQ 621 made by a board-certified psychiatrist based on the Structured Clinical Interview for Diagnosis for Axis I disorders17; and (2) age 18C65. Exclusion criteria were (1) primary diagnosis of substance abuse or dependence, (2) any history of intravenous substance abuse, (3) mental retardation, (4) clinically significant medical disorder that would affect cognitive performance such as history of encephalitis or head trauma, (4) immunodeficiency condition such as HIV or cancer chemotherapy, and (5) onset of schizophrenia within the previous 2 years. All participants provided written informed consent, and the study was approved by the Institutional Review Boards of Sheppard Pratt and Johns Hopkins School of Medicine following established guidelines. Measures All participants were interviewed at study enrollment. Information was obtained about demographic variables including age, race, and education. Information about the participants age at the onset of the psychiatric disorder was obtained from self-report and medical records. Participants were also asked about the presence of.