skip to main content

NMDA hypofunction model — MRCPsych Paper A MCQ

Instant feedback + full explanation. One question, done properly.

EasyNeurophysiology and neurochemistryNMDA hypofunction modelMRCPsych Paper A

A 21-year-old man develops transient hallucinations and disorganised thinking after recreational ketamine use. His symptoms resolve when he is sober. Which observation best explains why ketamine is used to support the NMDA receptor hypofunction model of schizophrenia?

Educational content. Not a substitute for clinical judgement or local policy.

Reveal the answer and explanation

Correct answer: A — NMDA receptor antagonism can produce schizophrenia-like symptom domains

Explanation lettering: C = shown as A · A = shown as B · D = shown as C · B = shown as D

C is correct. Ketamine is an NMDA-type glutamate receptor antagonist. In experimental and recreational settings, NMDA receptor blockade can cause transient positive symptoms, such as hallucinations and disorganisation, as well as cognitive and negative-symptom-like changes. This overlap with several schizophrenia symptom domains supports the NMDA receptor hypofunction model, although ketamine effects are not identical to schizophrenia. Ketamine is not a direct dopamine D2 agonist (A), and NMDA receptors are excitatory ionotropic glutamate receptors rather than GABA receptors (B). NMDA–dopamine interactions vary by neural circuit, so activation does not uniformly suppress dopamine in every pathway (D). The psychotomimetic effect is pharmacodynamic and is not caused by inhibition of antipsychotic metabolism (E).

Reference: Frohlich J, Van Horn JD. Reviewing the ketamine model for schizophrenia. Journal of Psychopharmacology. 2014;28(4):287–302. https://pubmed.ncbi.nlm.nih.gov/24257811/