Although serotonin modulators are currently first-line treatment for MDD and anxiety disorders, other neuronal populations are believed to have a role. For example, dysregulation of GABAergic neurons has also been implicated in depression and anxiety.48 Patients with MDD have reduced GABA receptors in the parahippocampal and lateral temporal lobes.49 Depressed patients showed a reduction in the number (50%) and size (18%) of GABAergic neurons in the dorsolateral prefrontal cortex and orbitofrontal cortex compared with control patients.50 Indeed, long-term treatment with different types of antidepressant therapies leads to enhanced GABAergic transmission through a GSK3β-mediated mechanism.51, 52 GABAergic cell therapy has already been applied to animal models53, 54 and may have a role in the treatment of MDD (for more on GABAergic based disease modeling and therapy, refer to the SCZ section of this review).
