Major depressive disorder (MDD) is a common psychiatric disorder effecting approximately 121 million people worldwide and recent reports from the World Health Organization (WHO) suggest that it will be the leading contributor to the global burden of diseases. At present, the most commonly used treatment strategies are still based on the monoamine hypothesis that has been the predominant theory in the last 60 years. Clinical observations show that only a subset of depressed patients exhibits full remission when treated with classical monoamine-based antidepressants together with the fact that patients exhibit multiple symptoms suggest that the pathophysiology leading to mood disorders may differ between patients. Accumulating evidence indicates that depression is a neural circuit disorder and that onset of depression may be located at different regions of the brain involving different transmitter systems and molecular mechanisms. This review synthesises findings from rodent studies from which emerges a role for different, yet interconnected, molecular systems and associated neural circuits to the aetiology of depression.
Keywords: Circadian rhythm; Depression; Epigenetics; Homeostasis; Immune; Molecular signalling; Neural circuit; Neurogenesis; Sleep deprivation.