Abstract

Basic and clinical neurosciences have effectively advanced research on aetiology, pathogenesis and therapy options of psychiatric disorders. The objectives of the present short review were to summarise the key findings regarding the neurobiology of major depressive disorder (MDD) on the gene, cell as well as system level. Consistent with structural findings, which report alterations in regions of emotionally relevant networks of the brain in depressive disorders, findings of functional studies point to changes in an ordered interaction of ventral-limbic and dorsal-neocortical regions of the brain. Genetic and stress vulnerabilities as well as social rhythm disrupting interact to initiate a cascade of neurobiological alterations that disrupt this dynamic system. On the cellular level, monoamine as well as glutamate neurotransmission, circadian rhythm disturbance, glucocorticoids, inflammatory cytokines and brain-derived growth factors are relevant mediators of these pathological alterations. Progressive effects of recurrent and chronic MDD may then lead to further structural and functional abnormalities. Thus, treatment providers are directed to recog-nise that the factors that may initiate an MDD episode and those that maintain the illness are likely to be different. Given these long-term consequences, an essential objective of treatment must be to restore as early as possible normative functioning and prevent further neurobiological structural alterations.

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