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It has been over 50 years since the original serotonin hypothesis was proposed by the British Psychiatrist Alec Coppen. Recently, some authors have questioned the validity of the hypothesis. In this narrative review, we summarise the evidence for the serotonin hypothesis of depression, focusing on psychopharmacology and molecular imaging, as well as systems-level neuroscience. [ABSTRACT FROM AUTHOR]

Neuroendocrine and neurochemical theories of depression continued to be of importance in understanding pathophysiology and suggesting new kinds of pharmacological intervention. Monoamine theories still dominate the neurochemistry of depression and results from monoamine depletion studies suggest that in certain circumstances lowered activity of serotonin and noradrenaline pathways can indeed lead to clinical depressive symptomatology. More recent developments have implicated changes in the amino acid neurotransmitters, GABA and glutamate, in depressed patients; the ability of the NMDA receptor antagonist, ketamine, rapidly to relieve depressive symptomatology has been a spur to much basic research on the cellular mechanism of glutamatergic antidepressant action. The link between inflammation and depression has led to new kinds of immunological investigations in depressed patients and the possibility of targeted anti-inflammatory treatments. Finally HPA axis abnormalities remain a focus of interest, particularly from the point of view of the many medical co-morbidities which frequently complicate chronic depressive disorders. [ABSTRACT FROM AUTHOR]

Changes in emotional processing have been shown following acute administration of a range of monoaminergic antidepressants, and may represent an important common neuropsychological mechanism underpinning their therapeutic effects. Tianeptine is an agent that challenges the traditional monoaminergic hypothesis of antidepressant action, though its exact mode of action remains controversial. Healthy volunteers were randomised to receive a single dose of tianeptine (12.5 mg) or placebo, and subsequently completed a battery of tasks measuring emotional processing, including facial expression recognition, emotional memory and attentional vigilance, as well as working and verbal memory. Tianeptine-treated subjects were less accurate at identifying facial expressions, though this was not valence specific. The tianeptine group also showed reduced positive affective memory and reduced attentional vigilance to positive stimuli. There were no effects on emotional categorization or non-emotional cognition. The negative biases in aspects of emotional processing observed following acute tianeptine administration are at variance with the positive biases generally seen after acute administration of conventional antidepressant drugs, despite tianeptine’s putative antidepressant efficacy. This is an intriguing finding in the context of the lack of consensus regarding tianeptine’s mechanism of action; however, it may be consistent with the reported ability of acute tianeptine to increase the re-uptake of serotonin. [ABSTRACT FROM AUTHOR]