Depression as an evolutionary adaptation: Anatomical organisation around the third ventricle

Currently available antidepressant treatments are no longer seen as the panaceas they once were. Only a proportion of the depressed population respond to them, they have a high relapse rate and a therapeutic lag of several weeks. The notable lack of progress in developing more efficacious drug-based antidepressant therapies over the past half century is a clear signal for the need to adopt new approaches. The current manuscript outlines the proposal that depression is an evolutionary adaptation that emerged where displaced dominants needed to make a transition to lower social status and that is now triggered, in those individuals that have this adaptation, by damage to reproductive potential from any source. The behavioural cluster associated with depression includes adoption of a hunched posture, avoidance of eye contact, loss of appetite for food and sex and sleep disruption. This behavioural cluster serves to reduce an individuals' attack provoking stimuli and so facilitates this social change. When viewed in this context, it becomes clear that many of the brain areas that mediate these behaviours (e.g. the pineal, hypothalamus and amygdala, whose main output, the stria terminalis passes through) all lie in close physical proximity to the third ventricle. In consequence, it is proposed that depression has its origins within this ventricle. Disruption of circadian rhythms, appetite for sex and food and fear/defence responses would all ensue if structures that border the third ventricle, or whose main connections pass through it, were damaged. Therefore, it is hypothesised that the behavioural expression of this adaptation is mediated by a single or pulsatile release of a yet to be identified noxious factor into the ventricular space. This extreme response reflects the severity of the emergency that was faced by our ancestral stock in this situation and has parallels with the development of other adaptations where the preservation of life (and hence the chance for further reproductive opportunities) takes precedence over all other concerns. The increased volumetric changes seen in the third ventricles of depressives and changes in other closely associated structures are in keeping with predictions based on the current hypothesis and it is hoped that this will be of heuristic value in the search for more effective drug-based antidepressant therapies. (C) 2009 Elsevier Ltd. All rights reserved.