The Neurotrophic Hypothesis of Depression: Treatment Implications for Erythropoietin

  • Lea Julia Mertens


A purely neurotransmitter-based explanation of major depression and antidepressant action, such as the monoamine hypothesis, falls short to explain the delayed clinical onset of most agents in reference to the immediate neurochemical effects. Recently, in attempts to understand the psychobiological underpinnings of depression, the focus shifted to an involvement of intracellular signaling cascades, gene expression and protein translation. This review discusses evidence for the so-called neurotrophic hypothesis of depression, which emphasizes stress-induced disruption of brain-derived neurotrophic factors (BDNF), second messenger systems, gene expression and subsequent neural atrophy and network changes that manifest as depressive symptoms in the etiology of depression. Additionally, within the framework of the neurotrophic hypothesis, the treatment potential of the cytokine Erythropoietin is discussed.


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