Abstract

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.

1. Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
2. Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
3. Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA.

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