Delusions, the persistent bizarre beliefs characteristic of psychosis, may arise from disturbances in prediction error-dependent learning. In a placebo-controlled study with 18 human subjects, ketamine—an NMDA receptor antagonist that induces aberrant prediction error signals—was administered during re-exposure to a conditioned fear stimulus. This led to stronger subsequent fear memory compared to placebo, with the degree of strengthening correlating with individual vulnerability to ketamine's psychotogenic effects and with prediction error brain signals. A partial replication in an independent sample with an appetitive learning procedure (8 subjects) supported these findings. The results suggest a link between altered prediction error, memory strength, and psychosis, potentially explaining both the emergence and persistence of delusional beliefs.
LSD can be beneficial as an adjunct to psychotherapy for carefully selected patients, but concerns exist about potential chromosome damage in people who take the drug.
Long-term use of drugs like phencyclidine (PCP), which block NMDA glutamate receptors, can produce schizophrenia-like symptoms in people and abnormal behavior in animals. This review evaluates how well PCP-induced animal behaviors model human psychotic disorders and presents a hypothesis about PCP's effects on the prefrontal cortex. The behavioral and neurochemical changes caused by PCP suggest that altered interactions between glutamate and dopamine systems in the prefrontal cortex may contribute to the cognitive problems seen in schizophrenia.