Alterations in subpopulations of γ-aminobutyric acid (GABA) neurons appear to contribute to dysfunction of the dorsolateral prefrontal cortex (DLPFC) in schizophrenia. Indeed, lower expression of glutamic acid decarboxylase (GAD67), the enzyme responsible for most GABA synthesis, is consistently found in schizophrenia (1). The affected GABA neurons include basket neurons that express both the cannabinoid 1 receptor (CB1R) and the neuropeptide cholecystokinin (CCK) (2–4). For example, CB1R mRNA and protein levels are lower in the DLPFC of subjects with schizophrenia (5–7), and the magnitude of alterations in CB1R mRNA expression is significantly correlated with that for GAD67 mRNA (3,6). These findings suggest that both transcripts are lower in the same population of DLPFC GABA neurons in schizophrenia.
