The role of glutamatergic pathways in schizophrenia: From animal models to human imaging studies

Glutamate, a key excitatory neurotransmitter in the brain is implicated in the pathophysiology of schizophrenia. Animal and human studies have demonstrated that glutamate is involved in patterns of normal connective brain development and its specific receptors such as the N-methyl-D-Aspartate (NMDA) are associated with critical functions such as learning and memory. Therefore, there is a critical need to integrate animal studies of glutamate neurotransmission, human in vivo studies of structure and function relevant to the glutamate system, and the computational models of pharmacologic and behavioural processes. Such integrative approaches are needed to develop a clearer understanding of the role of glutamate in schizophrenia pathology. In this review, the authors selectively review relevant findings from the schizophrenia literature, as well as studies in animal and human experimental studies to motivate the need for a translational and integrative framework. Future experimental approaches to understanding glutamatergic neurotransmission in schizophrenia will benefit from considering this diverse collection of experimental literature and such knowledge will sharpen understanding of the precise role of glutamtergic neurotransmission in schizophrenia.