Fig. 2.

 A) Pathophysiology of depression: Tryptophan (Trp) is converted to 5-hyroxytryptamine (5HT). Over-expression of pre-synaptic 5HT1A which inhibit the release of 5HT from presynaptic neurons or down-regulation of 5HT1A heteroreceptors which mediate action of 5HT at postsynaptic neurons, leading to the reduction of glutamate (Glu) and upregulation of N-methyl-D-aspartate (NMDA) receptors and upregulation of amino-methyl propionic acid (AMPA) receptors. These changes reduce expression of brain-derived neutrophic factor (BDNF) and impairment of neuronal plasticity. B) How insulin modulates the effect of 5-HT at the molecular level: insulin by binding to insulin receptors results in increase in the synthesis of BDNF and neuronal plasticity as mediated through protein kinase B and its action on m-TOR (mechanistic target of rapamycin) and glycogen synthase kinase 3