It is widely accepted that there is an increased prevalence of cardiovascular risk factors in the schizophrenic population. There is also increasing evidence that some of the second generation antipsychotics may contribute additionally to a number of cardiovascular risk factors, particularly type 2 diabetes, obesity, and dyslipidemias. There is also some evidence that many of these factors may contribute risk to cognitive impairment, including dementia (Biessels et al 2006;Qiu et al 2005;Kivipeklto et al 2005) and more subtle cognitive decrements in non-psychiatric populations (reviewed by van den Berg et al 2008). Whether these factors are causal is less clear, but is a question that has obvious importance for public health.

We have become interested in this issue from the perspective of schizophrenia patients given their already impaired cognitive function and the greater prevalence of obesity and type 2 diabetes. Pilot data generated from subjects recruited for projects conducted by the Conte Center for the Neuroscience of Mental Disorders (CCNMD) at the Mount Sinai School of Medicine (a subset of which has been reported on previously, Friedman et al 2008) provides some evidence for association between increased weight and poor cognitive function. Analyses were conducted on 153 subjects (100 with schizophrenia, 53 non-psychiatric) with complete medical and cognitive data. Our analyses provided evidence for an inverse correlation between increased BMI and performance on delayed and immediate memory tasks. There was no evidence for caseness as an interaction term, suggesting the findings might generalize to the population. These pilot data provide some support for the hypothesis for a relationship between BMI and cognitive impairment. While the findings are preliminary, if correct may not reflect causality, and if they do, they may result from pathological changes that are not likely to occur to any appreciable extent, we are interested in exploring an alternative possibility of more direct causal links. Thus, we wish to use the ALSPAC data a) to explore relationships between BMI in childhood and cognition and b) to explore relationships between cognition and alleles that are known to be associated with increased BMI and T2D using the Mendelian randomization approach to test for possible causality.

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Friedman JI, Tang C, Carpenter D, Buchsbaum M, Schmeidler J, Flanagan L, Golembo S, Kanellopoulou I, Ng J, Hof PR, Harvey PD, Tsopelas ND, Stewart D, Davis KL. Diffusion tensor imaging findings in first-episode and chronic schizophrenia patients. Am J Psychiatry. 2008 Aug;165(8):1024-32.