Depression contributes substantially to disease burden worldwide; however despite of this, the progress in understanding its pathophysiology has been extremely slow and the discovery of new therapeutic mechanisms is at a near standstill. The molecular targets of current major classes of antidepressants were all reverse engineered from drugs previously discovered by serendipitous clinical observations. Since the existence of adult-born neurons was unequivocally documented, adult neurogenesis

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... me a very promising, but also very hyped target for antidepressant drugs. Introduction of corticotrophin releasing hormone inhibitors aimed to exploit a prospective reduction of glucocorticoid-mediated inhibition of adult neurogenesis with the aim to produce antidepressant effect. Although these drugs failed to demonstrate efficiency in phase three clinical trials, they provided the following valuable lesions for the future: (1) Inter-species differences between animals and humans should be considered very carefully, (2) Animal model phenotypes mimicking depression should be more robust, preferably shown by multiple behavioral paradigms, and (3) variability between different subgroups of depression should be taken into consideration because of the pronounced heterogeneity of the disease.