Why NMDA Enhancers May Not Be Producing Better Results

Hypofunction of the N-methyl-D-aspartate receptor (NMDAR) in the prefrontal cortex (PFC) has been implicated in positive, negative, and cognitive symptoms of schizophrenia. To clarify observations that NMDAR antagonists, such as ketamine, in normal people induce symptoms closely mimicking those of schizophrenia, researchers who received some industry support used functional neuroimaging.

First, ketamine-induced PFC hyperconnectivity was demonstrated in 19 normal subjects. Then, PFC connectivity was assessed in four groups — 96 healthy controls, 21 clinically well people at high risk for schizophrenia (HR), 28 patients who were early in the course of schizophrenia (EC), and 20 patients with chronic schizophrenia (CSZ). Compared with the healt…