Ketamine administration produces transient psychopathological effects in both healthy volunteers and patients with schizophrenia, with the nature and severity of these effects varying according to experimental factors such as dose, route of administration, and participant characteristics. The meta-analysis quantifies these outcomes, showing that ketamine reliably induces psychotic-like symptoms, dissociation, and cognitive impairments in healthy individuals, while its effects in patients with schizophrenia are more complex and may involve both symptom exacerbation and potential therapeutic benefits depending on the context.
In people experiencing a first episode of psychosis, availability of N-methyl-D-aspartate receptors (NMDARs) in the hippocampus is lower than in matched healthy controls. Lower hippocampal NMDAR availability was linked to more severe overall, depressive, and general symptoms, and also to higher levels of the neurotransmitter glutamate in the striatum. No significant differences in NMDAR availability were found in other brain regions examined. These results support the hypothesis that reduced NMDAR function contributes to psychosis and point to the hippocampus as a key brain area involved.