In major depression, in both midbrain and hippocampus a hypoactivity of monoamines (serotonin, noradrenalin, dopamine) and a hypoactivity of presynaptic inhibitory neurotransmitters (GABA, glutamate) occurs. Serotonin hypoactivity, which is partly explained by polymorphisms of the serotonin transporter gene, could be as well due to an enhanced presynaptic inhibition carried out by glutaminergic neurons via m5Glu receptors. Noradrenalin hypoactivity is also due to an enhanced presynaptic inhibition exerted, via GABAB receptors, by GABAergic neurons. We derived neural networks from direct and reciprocal correlations between neurotransmitters. The neural networks presented here suggest a multimodal antidepressant pharmacotherapy by combining enhancing and antagonistic antidepressant drugs, for example noradrenalin reuptake inhibitors and GABAB antagonists.