This review investigates the association between N-methyl-d-Aspartate receptor (NMDAR) hypofunction and somatostatin-expressing GABAergic interneurons (SST +) and how it contributes to the cognitive deficits observed in schizophrenia (SZ). This is based on evidence that NMDAR antagonists caused symptoms resembling SZ in healthy individuals. NMDAR hypofunction in GABAergic interneurons results in the modulation of the cortical network oscillation, particularly in the gamma range (30–80 Hz). These gamma-band oscillation (GBO) abnormalities were found to lead to the cognitive deficits observed in the disorder. Postmortem mRNA studies have shown that SST decreased more significantly than any other biomarker in schizophrenic subjects. The functional role of Somatostatin (SST) in the aetiology of SZ can be studied through its receptors. Genetic knockout studies in animal models in Huntington's disease (HD) have shown that a specific SST receptor, SSTR2, is increased along with the increased NMDAR activity, with opposing patterns observed in SZ. A direct correlation between SSTR and NMDAR is hence inferred in this review with the hope of finding a potential new therapeutic target for the treatment of SZ and related neurological conditions.
