INTRODUCTION: Previous studies investigating the relationship between obesity 
and cognition as well as gender differences in these relationships reported 
equivocal results. Here, we examined age, years of education, schizophrenia, and 
gender differences which might affect the relationship between obesity and 
cognition.
METHODS: 1012 healthy controls and 707 participants with schizophrenia were 
recruited. Information on body mass index (BMI) was obtained and a 
neurocognitive battery was administered. Structural equation modeling (SEM) was 
performed to examine the relationship between BMI, schizophrenia, cognition and 
its covariates.
RESULTS: No significant direct effect of BMI on cognition was found when 
cognition was regressed on age, years of education, diagnosis of schizophrenia 
and BMI. Instead, two SEM models indicated that indirect effects between BMI and 
cognition exist. The indirect effect of BMI on cognition through schizophrenia 
was present in both genders, while the indirect effect of cognition on BMI 
through schizophrenia was only found in females. BMI affecting cognition through 
age, years of education and schizophrenia appears to be the most plausible model 
that explains the data. This indirect effect was larger in females and was 
masked by diagnosis of schizophrenia.
CONCLUSION: With increased rates of obesity in schizophrenia, it is important to 
highlight the potentially deleterious effect of obesity on cognition. BMI could 
be used as a candidate risk marker to identify people at higher risk of 
cognitive deficits, and as an intervention target for modifications of cognitive 
outcomes.