Angiopathy with impaired glucose logistics observed in schizophrenia-like model mice

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 demonstrate that a high sugar diet induces expression of schizophrenia-associated positive, negative, and cognitive symptoms in mice deficient for glyoxalase-1, an enzyme associated with schizophrenia involved in the detoxification of carbonyl compounds. 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 reduced vascular damage, increased glucose uptake into the brain, and prevented development of several schizophrenia-associated phenotypes. Postmortem analysis of brains from patients with schizophrenia 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.