Abstract
Dietary sugar in humans has increased dramatically in the modern era. However, it is unclear whether and how high sugar diets affect the pathogenesis of psychiatric disorders. Here we first investigated causal relationship between excess sugar intake and development of psychiatric disorders using mice. We demonstrate that a high sugar diet induces expression of schizophrenia and bipolar disorder‐associated phenotypes in mice deficient for glyoxalase‐1, an enzyme associated with psychiatric disorders and involved in the detoxification reaction in glycation processes. We found that a high sugar diet increased nondiabetic vascular damage in glyoxalase‐1 mutant mice, and reduced glucose uptake into the brain parenchyma. Chronic aspirin treatment protected vascular damage, increased glucose uptake into the brain, and prevented development of several psychiatric‐associated phenotypes. Postmortem analysis of brains from patients with schizophrenia and bipolar disorder revealed similar vascular damage to what we observe in our mutant mice. Our results indicate that schizophrenia is associated with vascular damage likely caused by metabolic dysfunction.
