Table 1.
Preclinical Studies on the Effects of KD on Animal Models of Schizophrenia
| Reference (author and journal) | Animals | Model | Schizophrenia-like behaviors/endophenotype | Findings |
|---|---|---|---|---|
| Kraeuter et al., 2015 Schizophrenia Res. | C57Bl/6 mice (males) | Std and KDa (3 wk) MK-801–induced (0.1, 0.2, and 0.4 mg/kg) hypo-glutamatergic state | Locomotor hyperactivity Stereotyped behaviors Ataxia Decreased sociability Spatial working-memory impairment | KD prevented MK-801–induced behavioral abnormalities |
| Tregellas et al., 2015 Schizophrenia Res. | DBA/2 mice | KDb only Auditory gating deficit in DBA/2 mice | Hippocampal P20/N40 gating in DBA/2 mice | Animals with highest blood ketone levels showed lowest P20/N40 gating ratios |
| Kraeuter et al., 2019c Schizophrenia Res. | C57Bl/6 mice (males) | Std and KDa (7 wk) MK-801–induced (0.25 mg/kg) hypo-glutamatergic state | Sensorimotor gating deficit (prepulse inhibition of startle) | KD prevented MK-801–induced sensorimotor gating deficit (independent of decreased caloric intake related to KD) |
| Kraeuter et al., 2019b Schizophrenia Res. | C57Bl/6 mice (females) | SD and KDa (6 mo) Olanzapine (2 mg/kg, 8 wk) MK-801–induced (0.25 mg/kg) hypo-glutamatergic state | Sensorimotor gating deficit (prepulse inhibition of startle) | Long-term KD and chronic olanzapine prevented MK-801–induced sensorimotor gating deficit in female mice No interaction between KD and olanzapine |
| Kraeuter et al., 2020 Psychopharmacology | C57Bl/6 mice (males) | BHB (3 wk) MK-801–induced (0.25 mg/kg) hypo-glutamatergic state | Sensorimotor gating deficit (prepulse inhibition of startle) | BHB prevented MK-801–induced sensorimotor gating deficit |
Abbreviations: BHB, beta-hydroxybutyrate; KD, ketogenic diet; Std, standard diet.
aKetogenic diet composition: carbohydrates: 9.4%, protein: 9.5%, fat: 77.6%.
bKD composition: carbohydrates: 0.6%, protein: 22.4%, fat: 77%.