Objectives People who have bipolar disorder or schizophrenia are at greater risk for obesity and other cardio-metabolic risks and several prior studies possess linked these risks to poorer cognitive ability. = 417) we investigated the association of self-reported body mass index and current use of medications for hypertension or diabetes with overall performance on a comprehensive neurocognitive battery. We examined sociodemographic and medical factors as potential covariates. Results Patients with bipolar disorder were less likely to be overweight or obese than patients with schizophrenia and also less likely to be prescribed medication for hypertension or diabetes. However obesity and treated hypertension were associated with worse global cognitive ability in bipolar disorder (as well as with poorer performance on individual tests of processing speed reasoning/problem-solving and sustained MK-0457 attention) with no such relationships observed in schizophrenia. Obesity was not associated MK-0457 with symptom severity in either group. Conclusions Although less prevalent in bipolar disorder compared to schizophrenia obesity was associated with substantially worse cognitive performance in bipolar disorder. This association was independent of symptom severity and not present in schizophrenia. Better understanding of the mechanisms and management of obesity may aid in efforts to preserve cognitive health in bipolar disorder. CD2 effect of obesity may not be linear gradations within BMI must be investigated (19). In this study we examined the relationship of overweight and obesity as well as pharmacologically treated diabetes and hypertension with performance-based assessments of cognitive abilities in bipolar disorder and schizophrenia. In a large ethnically homogenous sample (persons of Ashkenazi descent) of 804 adults with schizophrenia or bipolar I disorder we assessed the relationship between commonly defined categories of BMI (defined as normal: 18.5-25.0 kg/m2 overweight: 25-30 kg/m2 and obese: > 30 kg/m2) (20) and global cognitive ability and individual cognitive domains measured by a comprehensive and well-normed neuropsychological test battery adjusting for demographic/socioeconomic clinical and medication exposure covariates. We hypothesized that there would be significant relationships between BMI treated hypertension and diabetes and global cognitive functioning that would persist after adjustment for relevant covariates in both bipolar disorder and schizophrenia. We explored whether this relationship differed across diagnoses and whether BMI was differentially associated with individual cognitive domains that were examined as part of the overall cognitive assessment. Methods Sample All participants were originally enrolled in a parent study focusing on the genetics of schizophrenia and bipolar disorder. Participants were of full or mixed Ashkenazi Jewish descent determined on the basis of ancestry of four grandparents. The purpose of restriction to this population subgroup was to take advantage of potential founder effects in this population MK-0457 for genetic studies (21). Participants were recruited via advertisements websites and publications marketed toward Jewish people. Enrollment in the parent study which took place between 1996 and 2006 included the completion of an in-person clinical interview [the Diagnostic Interview for Genetics Studies (DIGS) (22)] blood draws and a family history interview. Most of MK-0457 the participants in the parent study were evaluated in their homes with only a small subset being evaluated in an institutional setting. The in-person assessment was completed by Ph.D.-level clinical psychologists. Previous reports have described the purpose and methodology of the parent study in detail (23 24 Between 2007 and 2012 subjects diagnosed with bipolar I or schizophrenia in the parent study were re-contacted to participate in a follow-up study that involved administration of a battery of neurocognitive and functional capacity measures. All participants signed written informed consent to participate in this follow-up study which was approved by the Johns Hopkins Medicine Institutional Review Board. Participants were once again seen in their place of residence for administration of the follow-up study measures. In the present analysis data were available for a total of 368 participants with bipolar disorder and 436 participants with schizophrenia. For the present study we only included participants who completed the neurocognitive.