Letter to the EditorKetogenic diet reverses behavioral abnormalities in an acute NMDA receptor hypofunction model of schizophrenia
Section snippets
Conflict of interest
The authors declare no conflict of interest.
Contributors
ZS conceived the idea, designed the study and analyzed some of the data. AKK carried out the behavioral studies, analyzed the data and wrote the first draft of the manuscript. HL and BCL assisted with behavioral data analysis and DR helped with the biochemical assays. All authors contributed to and have approved the final manuscript.
Acknowledgements
We thank Mr. Scott Blyth and Ms. Jennifer Stanford, who kindly provided support and assistance in the animal facility and members of the Laboratory of Psychiatric Neuroscience for the helpful discussions.
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2021, Neurobiology of StressCitation Excerpt :The ketone bodies acetoacetate (AcAc) and beta-hydroxybutyrate (BHB) are small molecules catabolized in the liver via fatty acid oxidation during times of starvation or metabolic stress, when carbohydrates are scarce (Achanta and Rae 2017; Newman and Verdin 2014). Metabolic shifts toward ketone body catalysis have been reported in patients with schizophrenia (Yang et al., 2013), and increasing circulating ketones, through either ketogenic diets (Sussman et al. 2015; Phelps et al. 2013; Kraeuter, van den Buuse, and Sarnyai 2019; Kraft and Westman 2009; Palmer 2017; Palmer et al. 2019; Kraeuter et al., 2015; Murphy et al., 2004; Ahn et al., 2014; Evangeliou et al., 2003; Ruskin et al., 2017; Murphy and Burnham 2006) or exogenous ketone supplementation (Ari et al., 2016; Kashiwaya et al., 2013; Brownlow et al., 2017), have demonstrated therapeutic effects in psychiatric disease in both rodents and humans. AcAc and BHB freely cross the blood-brain barrier and enter the mitochondria, where they are converted to acetyl-CoA, driving ATP synthesis (Achanta and Rae 2017; Newman and Verdin 2014).
Gut-brain axis: A matter of concern in neuropsychiatric disorders…!
2021, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :A growing body of evidence has shown that diets (e.g., DHA, PUFAs, EPA/DHA mixture, and 3′Sialyllactose (3′SL) or 6′SL) that modify the gut microbiota composition can reduce stress-related behavior and HPA activation (Davis et al., 2017; Pusceddu et al., 2015; Tarr et al., 2015). The ketogenic diet may normalize the behavior which supports the existing links between the GI tract and schizophrenia (Kraeuter et al., 2015). It has found that fermented foods improved cognitive function (Kim et al., 2016).
Ketogenic therapy in neurodegenerative and psychiatric disorders: From mice to men
2020, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :Ketogenic diet showed promising effects in individuals with psychosis. We demonstrated that ketogenic diet normalised positive, negative and cognitive symptoms of schizophrenia in an NMDA-receptor antagonist mouse model of schizophrenia (Table 2) (Kraeuter et al., 2015; Kraeuter et al., 2019). DBA/2J mice, an inbred strain, show spontaneously schizophrenia-like behaviours and metabolic abnormalities (Sarnyai et al., 2015).
Ketogenic diet and olanzapine treatment alone and in combination reduce a pharmacologically-induced prepulse inhibition deficit in female mice
2019, Schizophrenia ResearchCitation Excerpt :We hypothesised that a ketogenic diet may provide an alternative fuel source to glucose by causing a metabolic shift to fatty acid utilisation (Paoli et al., 2013). We recently reported in an acute N-methyl-d-aspartate (NMDA) receptor hypofunction model in male mice, that a ketogenic diet exerts antipsychotic-like effects (Kraeuter et al., 2015; Kraeuter et al., 2019), suggesting that it may provide an adjunct therapy to commonly used antipsychotics. Indeed, recent clinical case studies have shown encouraging results with ketogenic diet being used as an adjunct therapy (Palmer, 2017; Gilbert-Jaramillo et al., 2018; Palmer et al., 2019; Sarnyai et al., 2019).