The contribution of proteomic studies in humans, animal models, and after antidepressant treatments to investigate the molecular neurobiology of major depression

The neurobiological basis of major depressive disorder (MDD) is only partially understood. The proposed hypotheses postulate dysregulations of monoaminergic and other neurotransmitter pathways, impaired stress responses, insufficient neurogenetic and neurotrophic processes generating maladaptive neuroplasticity, inappropriate inflammatory and metabolic responses. Proteomic approaches can provide useful contributions to the investigation of the molecular neurobiology of MDD due to their open-ended nature. Studies performed in brain regions of MDD patients which had received antidepressant (AD) treatment showed that affected proteins mainly belonged to energy pathways, transport of molecules, signaling, and synaptic transmission. Studies performed in animal models offer the advantage of more controlled experimental conditions at the expense of potential loss in relevance. The design of proteomic investigations included experiments carried out in MDD models, in naive animals treated with ADs, and in animal models subjected to AD treatments. A comparison of results suggested an overlap of several modulated pathways between MDD patients and animal models. Examples include the regulation of energy metabolism, especially oxidative phosphorylation and glycolysis, signal transduction pathways, including calcium-calmodulin kinase II, synaptic proteins, and cytoskeletal proteins. Nevertheless, the paucity of studies performed in human brains requires additional studies to confirm the correspondence.