Neurobiology of Depression – A Simplified Guide
The monoamine hypothesis of depression has guided pharmaceutical research into the development of antidepressants for decades. However, given the suboptimal efficacy of SSRIs and their delayed onset of efficacy, it is reasonable to presume that serotonin deficiency is too simplistic to account for the heterogeneity of depressive phenotypes. [Racagni and Popoli 2008]
- Contemporary research has failed to conclusively determine the role of serotonin in depression even though antidepressants are among the best-selling drugs in clinical practice. [Lecasse and Leo 2005]
- Stahl’s Essential Psychopharmacology states- “there is no clear and convincing evidence that monoamine deficiency accounts for depression, i.e., there is no “real” monoamine deficit”. [Stahl 2013]
- It has since been shown that serotonin transmission is elevated in multiple depressive phenotypes. [Andrews et al. 2015]
- Despite the absence of an alternative (and objective) diagnostic marker, research has identified various biological mechanisms with the discrete implication that these are all related. [Jentsch et al. 2015]
A unified theory of depression [Beck and Bredemeier, 2016] conceptualises MDD as a matrix of genetic, epigenetic, and environmental factors that interact with personality vulnerabilities that predispose an individual to information processing biases, stress reactivity, and belief formation that precipitate pathophysiological mechanisms across molecular, cellular, circuit, and behavioural levels.