Abstract
Depression is a major health problem with a high prevalence and a heavy socioeconomic burden in western societies. It is associated with atrophy and impaired functioning of cortico-limbic regions involved in mood and emotion regulation. It has been suggested that alterations in neurotrophins underlie impaired neuroplasticity, which may be causally related to the development and course of depression. Accordingly, mounting evidence suggests that antidepressant treatment may exert its beneficial effects by enhancing trophic signaling on neuronal and synaptic plasticity. However, current antidepressants still show a delayed onset of action, as well as lack of efficacy. Hence, a deeper understanding of the molecular and cellular mechanisms involved in the pathophysiology of depression, as well as in the action of antidepressants, might provide further insight to drive the development of novel fast-acting and more effective therapies. Here, we summarize the current literature on the involvement of neurotrophic factors in the pathophysiology and treatment of depression. Further, we advocate that future development of antidepressants should be based on the neurotrophin theory.
Highlights
Depression has emerged over the past decades as a major debilitating disease with a high prevalence in occidental populations, resulting in profound social and economic burden (Lopez and Murray 1998; Nestler et al 2002; Pincus and Pettit 2001; Wittchen et al 2011)
Recent clinical studies showed that electroconvulsive therapy (ECT) promoted structural plasticity including increased volume and morphometric changes in the hippocampus and the amygdala along with improved clinical responses, especially in patients with a smaller hippocampal volume (Joshi et al 2016; Nordanskog et al 2010; Tendulkar et al 2013)
Growth factors have been proven to be strongly involved in regulating plasticity by impacting upon almost all of the neuroplasticity processes mentioned in section BNeuroplasticity changes in major depressive disorder (MDD) and the effects of antidepressant therapies,^ including neuronal survival, differentiation, and proliferation (Crutcher 1986; Lu et al 2014)
Summary
Depression has emerged over the past decades as a major debilitating disease with a high prevalence in occidental populations, resulting in profound social and economic burden (Lopez and Murray 1998; Nestler et al 2002; Pincus and Pettit 2001; Wittchen et al 2011). While a decrease in basolateral amygdalar volume has been associated with an increase in both fear and stress reactivity in mice (Yang et al 2008), an enhanced dendritic arborization, elongation, and spine density, providing evidence for increased synaptic connectivity within the amygdala, were reported after chronic stress exposure in rats (Vyas et al 2006; Vyas et al 2002) These data were in line with those showing an enhanced activity of the basolateral amygdala and long-lasting anxiety-like responses in rats that received repeated injections of urocortin, an agonist of corticotropin releasing factor (CRF) receptors (Rainnie et al 2004). These findings provide further evidence of the crucial role of the hippocampus in depression
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
