Effects of beta-hydroxybutyrate administration on MK-801-induced schizophrenia-like behaviour in mice.

RATIONALE: Impaired cerebral glucose metabolism is a core pathological feature of schizophrenia. We recently demonstrated that a ketogenic diet, causing a shift from glycolysis to ketosis, normalized schizophrenia-like behaviours in an acute N-methyl-D-aspartate (NMDA) receptor antagonist model of the illness. Ketogenic diet produces the ketone body, ß-hydroxybutyrate (BHB), which may serve as an alternative fuel source in its own right without a strict dietary regime. OBJECTIVE: We hypothesized that chronic administration of BHB replicates the therapeutic effects of ketogenic diet in an acute NMDA receptor hypofunction model of schizophrenia in mice. METHODS: C57Bl/6 mice were either treated with acute doses of 2 mmol/kg, 10 mmol/kg, or 20 mmol/kg BHB or received daily intraperitoneal injections of 2 mmol/kg BHB or saline for 3 weeks. Behavioural testing assessed the effect of acute challenge with 0.2 mg/kg MK-801 or saline on open field behaviour, social interaction, and prepulse inhibition of startle (PPI). RESULTS: Acute BHB administration dose-dependently increased BHB plasma levels, whereas the 2 mmol/kg dose increased plasma glucose levels. The highest acute dose of BHB supressed spontaneous locomotor activity, MK-801-induced locomotor hyperactivity and MK-801-induced disruption of PPI. Chronic BHB treatment normalized MK-801-induced hyperlocomotion, reduction of sociability, and disruption of PPI. CONCLUSION: In conclusion, BHB may present a novel treatment option for patients with schizophrenia by providing an alternative fuel source to normalize impaired glucose metabolism in the brain.

Health risk behaviours and allostatic load: A systematic review.

Health risk behaviours (HRB) across the lifespan have been associated with higher cumulative physiological burden as measured by allostatic load (AL). This study examines the contribution of HRB and their effects on multisystem biological risk associated with morbidity and early mortality. We systematically reviewed the literature to assess the links between HRB and AL. Twenty-six eligible human studies were included in our assessment of the current literature investigating the association of different HRB that included overeating/obesity, alcohol, smoking, drug use, physical inactivity and sleep impairments in relation to AL. We found that 50 % of obesity and substance abuse, 75 % of sleep and 62.5 % of combined HRB studies showed a significant association with AL. Lifestyle coping behaviours therefore have a significant contribution to AL. This study is among the first to explore multiple domains of HRB in relation to AL. Further research should focus on evaluating lifestyle factors that adapt HRB as a strategy to cope with chronic stress to help decrease AL and resulting long-term negative health consequences.