The molecular interaction between the glutamatergic, noradrenergic, dopaminergic and serotoninergic systems informs a detailed genetic perspective on depressive phenotypes

The glutamatergic pathway has been consistently involved in the physiopathology of depressive disorder. However a complete dissection and integration of its role in the context of other known mechanisms is lacking. We summarized and integrated the evidence of various levels of interaction between glutamatergic and monoaminergic pathways (see videos). We identified six molecular pathways, some of which with specific regional distribution within the brain. From the six pathways we identified the key proteins and their coding genes, we then provided a detailed list of possible candidates with practical suggestions for association studies planning.

► Major depressive disease (MDD) is a disorder with undiscovered molecular basis. ► Consistently, the efficacy of antidepressant pharmacological treatment is incomplete. ► The molecular glutamatergic-monoaminergic interplay is analyzed to cover the gap. ► The molecular pathways regulating the glutamatergic-monoaminergic is described. ► For each of the pathways a list of genes and their variations are provided.