Unravelling the pathophysiology of depression is a unique challenge. Not only are depressive syndromes heterogeneous and their aetiologies diverse, but symptoms such as guilt and suicidality are impossible to reproduce in animal models. Nevertheless, other symptoms have been accurately modelled, and these, together with clinical data, are providing insight into the neurobiology of depression. Recent studies combining behavioural, molecular and electrophysiological techniques reveal that certain aspects of depression result from maladaptive stress-induced neuroplastic changes in specific neural circuits. They also show that understanding the mechanisms of resilience to stress offers a crucial new dimension for the development of fundamentally novel antidepressant treatments.
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Work in E.J.N.'s laboratory was supported by grants from the National Institute of Mental Health.
E.J.N. receives income for consulting for Merck Research Laboratories, Neurologix, and PsychoGenics, as well as research support from AstraZeneca.
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Krishnan, V., Nestler, E. The molecular neurobiology of depression. Nature 455, 894–902 (2008). https://doi.org/10.1038/nature07455
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