Schizophrenia is a leading cause of global disability, and current treatments using dopamine D2 receptor blockade often have limited efficacy and poor tolerability. This highlights the necessity of understanding the disease’s etiology to develop better therapeutic approaches. Recent meta-analyses and studies on the neurobiology of prodromal, first-episode, and chronic schizophrenia reveal region-specific neurotransmitter alterations. Imaging evidence indicates higher levels of glutamate and dopamine in the basal ganglia and lower levels of glutamate, dopamine, and GABA in cortical regions, especially the frontal cortex, compared to healthy individuals.

Dysfunction in cortico-thalamo-striatal–midbrain circuits may disrupt brain information processing, contributing to psychotic symptoms. Understanding these dysfunctions can aid in developing new treatments and precision medicine approaches for psychotic, negative, and cognitive symptoms of schizophrenia. The review emphasizes the need for mechanistically based treatments that target specific neurotransmitter alterations and circuit dysfunctions to improve the efficacy and tolerability of schizophrenia therapies.

Reference: Howes OD, Bukala BR, Beck K. Schizophrenia: from neurochemistry to circuits, symptoms and treatments. Nat Rev Neurol. 2024 Jan;20(1):22-35. doi: 10.1038/s41582-023-00904-0. Epub 2023 Dec 18. PMID: 38110704.