Johansen B. Amin

Desde mediados del siglo XX, el tratamiento de la esquizofrenia ha experimentado una transformación significativa, pasando de un enfoque institucionalizado a un modelo de atención basado en la comunidad. En los primeros modelos de tratamiento, la atención se centraba principalmente en el manejo de los síntomas psicóticos, ya fueran positivos (como alucinaciones y delirios) o negativos (como apatía o aislamiento).

Highlights • NMDARs transition through two distinct structural conformations before opening • The efficiency of NMDAR opening depends on which intermediate pathway is entered • Fast NMDAR opening requires glutamate-induced displacement of the GluN2 pre-M1 helix • Glutamate-induced displacement of the S2-M4/M4 axis also facilitates rapid channel gating Summary NMDA receptors (NMDARs) are glutamate-gated ion channels that mediate fast excitatory synaptic transmission in the nervous system.

At present, 23 patients with neurological disorders have been identified with de novo missense mutations in the M4 segments of NMDAR subunits (Fig. 1). The clinical phenotype for these patients is typically severe, encompassing epileptic encephalopathies and intellectual disabilities (Supplementary Table 1). For the majority of patients, the mutations occur at glycines (15 out of 23 patients).