I got a reader question in my inbox recently which caused me to go on an instant pubmed hunt: is there a link between hypotension and major depressive disorder, and if so, does increasing blood pressure help? And the more I dug, the more I realized that the answer is both very complicated…and pretty unknown. So today I’m going to talk a bit about hypotension and major depressive disorder. I’ve got a few papers in mind, but I’m not going to focus on a specific one. And if anyone has any better insights or information, please do chime in in the comments! This is an area to which Sci is not accustomed.
The link between the physiology of the brain (dysfunctions of which are thought to be behind depressive symptoms) and the physiology of the body is pretty well known. We know that bodily stress (using chronic mild stress paradigms in animals, for example) can produce depressiv-like symptoms, and most episodes of depression are preceeded by a period of outside stress (though in today’s world that’s usually not physical stress). We know that physical diseases, such as diabetes or heart attacks, can increase the risk for major depression as well. But what about blood pressure specifically?
Well, it kind of goes both ways. From what I can tell from the lit, it looks like depressive symptoms are associated with “altered vascular reactivity”, or rather, your blood vessels do not respond the way they are supposed to. It looks like this can go both ways. For example, chronic mild stress in mice reduces the ability for their blood vessels to react optimally to nitric oxide, which normally decreases blood pressure. Their blood vessels were less able to relax. This could be reversed with the application of fluoxetine (Prozac), an antidepressant. Similar studies have also shown that vascular reactions are impaired in stressed animals. In humans, people with hypertension are more likely to show depressive symptoms.
But that’s HYPERtension, or high blood pressure. What about HYPOtension, or low blood pressure? Well, that’s got associations, too. In this case, the associations are mostly in the elderly. Older people with very low blood pressure show lower “affect” and more symptoms of depressive-like behavior than those with higher blood pressure, who show fewer depressive-like symptoms by contrast. But again, this could be a failure of vascular reactivity, where the blood vessels do not respond as they are supposed to. In another study in elderly people, patients who had the biggest drop in blood pressure in testing (when your position is switched quickly, from lying down to standing, your blood pressure has to adjust. When it does this slowly it’s called orthostatic hypotension) were more likely to have depressive symptoms. Patients with major depression do not recover as quickly from exercise, and women with depression have lower blood pressure. There are other associations between depression, anxiety, and low blood pressure that have been found.
So where are we? Hypertension and prolonged inflammation appear to be associated with depressive symptoms in some patients, but hypotension is association with depressive symptoms in others. Is it peripheral monoamine levels like norepinephrine, which is known to constrict blood vessels? Is it changes in cytokine levels as a result of chronic stress? Is it the effects of chronic stress itself? I think most studies are needed in humans and animals to really determine how blood pressure affects mood in the long term, and whether blood pressure medications affect mood independent from their effects on blood pressure.
Does anyone else have ideas on this? Has the literature come down on one side or the other with regard to blood pressure and major depressive disorder? Inquiring minds want to know!
EDIT and UPDATE: This topic has continued on my mind all night. I did some more pubmed digging (with the help of the original question contact), and wanted to comment a little on depression, blood pressure, and norepinephrine specifically.
The idea here is that the neurotransmitter norepinephrine (noradrenaline to you Brits) has roles both in the brain and in your blood vessels. In the brain it plays a large role in depressive-like symptoms, fear, and anxiety like responding, and in the blood vessels it acts to constrict vessels (what we call a vasopressor) and increased blood pressure. So this makes us think logically that low levels of norepi might cause decreased blood pressure and depressive like symptoms along with them. There’s some animal support for this, depressive behavior induced by alcohol is associated with decreases in norepi, and if you knockout the norepi transporter, creating artificially high levels of the neurotransmitter, you get antidepressant like effects in mice. There is an idea that norepi plays a role in the regulation of stress via the HPA axis, and that dysregulation of norepi could lead in turn to dysregulation of stress, playing a role in depressive symptoms.
I personally think the potential role of norepi in stress regulation may be the most clinically interesting here. I don’t think low norepi alone is enough. Studies which decrease norpi production artificially in animals have had some very mixed results. Most important to me, while norepi influences blood pressure very quickly in humans, selective norepinephrine reuptake inhibitor drugs used as antidepressants increase blood pressure immediately, but still take 3-5 weeks to have a significant clinical effect on depressive symptoms. To me, this implies that norepi is affecting depressive symptoms more indirectly, and may be more of a side indicator rather than a cause, but again, I’m no expert here and would welcome some more expert opinions on this!
References
Gordon, J., Ditto, B., Lavoie, K., Pelletier, R., Campbell, T., Arsenault, A., & Bacon, S. (2011). The effect of major depression on postexercise cardiovascular recovery Psychophysiology, 48 (11), 1605-1610 DOI: 10.1111/j.1469-8986.2011.01232.x
Isingrini E, Surget A, Belzung C, Freslon JL, Frisbee J, O’Donnell J, Camus V, & d’Audiffret A (2011). Altered aortic vascular reactivity in the unpredictable chronic mild stress model of depression in mice: UCMS causes relaxation impairment to ACh. Physiology & behavior, 103 (5), 540-6 PMID: 21504753
Isingrini E, Belzung C, Freslon JL, Machet MC, & Camus V (2012). Fluoxetine effect on aortic nitric oxide-dependent vasorelaxation in the unpredictable chronic mild stress model of depression in mice. Psychosomatic medicine, 74 (1), 63-72 PMID: 22210237
Colloby SJ, Vasudev A, O’Brien JT, Firbank MJ, Parry SW, & Thomas AJ (2011). Relationship of orthostatic blood pressure to white matter hyperintensities and subcortical volumes in late-life depression. The British journal of psychiatry : the journal of mental science, 199 (5), 404-10 PMID: 21903666
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