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From Chaos to Consilience: Part IIWhat the New Mind-Body Science Tells Us About the Pathophysiology of Major Depression: Page 2 of 3

From Chaos to Consilience: Part IIWhat the New Mind-Body Science Tells Us About the Pathophysiology of Major Depression: Page 2 of 3

Depression is an analogue of this phenomenon, which should come as no surprise given its evolutionary origins. Thus, in addition to the anxiety, fear, and internal pain produced by danger pathway activation/dysregulation, depression is also characterized by a loss of pleasure that can be profound. This reflects the fact that in addition to danger pathway activation, depression is typically associated with hypoactivity in “pleasure pathways” running from midbrain into anterior areas of the basal ganglia (ie, nucleus accumbens). Not surprisingly, many recent studies show that chronic activation of danger pathways—such as the innate immune inflammatory system—compromises dopaminergic signaling in pleasure pathways.18

Why are the genes for depression so common?
Short answer: Because genes identified thus far that increase the risk of depression are not depression genes per se but rather play more general roles in regulating systems that are responsible for multiple physiological functions essential for survival and reproduction. In general, they are genes for operating and regulating danger/ adaptation/pleasure pathways in the brain and body. Most often, risk alleles for depression increase/dysregulate activity in danger pathways and/or reduce activity in pleasure and executive pathways in the face of environmental adversity.19,20 In good times or when exposed to supportive early environments, these alleles contribute to individuals who are perhaps more successful and happier than most.21-23 Even in bad times, these genes probably promote reproductive success by engendering creativity and intelligence24—how else could they survive the threshing of natural selection if they did not confer occasional high pay-off selective advantages to counter their more frequent detrimental effects?

Nonetheless, these ideas are not settled science, and alternative views exist about potential adaptive advantages of depression or even whether genes that promote depression must confer some type of adaptive advantage to be retained in the human genome. Although genes that are specific for depression or that always cause depression regardless of environmental conditions have yet to be identified, this does not prove that such genes may not yet await discovery. If such genes were ever found, it would be expected that they would be very powerful but also very rare and therefore would account for only a tiny fraction of individuals with depression.

Would it surprise you to learn that genes reported to increase the risk of developing depression in the face of psychosocial stress also seem to increase the risk of depression in the context of sickness?25,26 Would you predict that these risk alleles might enhance survival in the face of infection early in life and that this might also account for their high prevalence in the human gene pool?27

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