Major Depressive Disorder and...Hypotension?

Feb 15 2012 Published by under Behavioral Neuro, Uncategorized

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!

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

Doğan Y, Onat A, Kaya H, Ayhan E, & Can G (2011). Depressive symptoms in a general population: associations with obesity, inflammation, and blood pressure. Cardiology research and practice, 2011 PMID: 22216414

<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Progress+in+neuro-psychopharmacology+%26+biological+psychiatry&rft_id=info%3Apmid%2F21453741& AF (2001). Association of hypotension with positive and negative affect and depressive symptoms in the elderly. The British journal of psychiatry : the journal of mental science, 178, 553-5 PMID: 11388973

Jorm AF (2001). Association of hypotension with positive and negative affect and depressive symptoms in the elderly. The British journal of psychiatry : the journal of mental science, 178, 553-5 PMID: 11388973

Kim BS, Bae JN, & Cho MJ (2010). Depressive symptoms in elderly adults with hypotension: different associations with positive and negative affect. Journal of affective disorders, 127 (1-3), 359-64 PMID: 20619901

Findley P, Shen C, & Sambamoorthi U (2011). Multimorbidity and persistent depression among veterans with diabetes, heart disease, and hypertension. Health & social work, 36 (2), 109-19 PMID: 21661300

Saboya PM, Zimmermann PR, & Bodanese LC (2010). Association between anxiety or depressive symptoms and arterial hypertension, and their impact on the quality of life. International journal of psychiatry in medicine, 40 (3), 307-20 PMID: 21166340

Briley, M., & Chantal, M. (2011). The importance of norepinephrine in depression Neuropsychiatric Disease and Treatment DOI: 10.2147/NDT.S19619

Hildrum, B., Mykletun, A., Stordal, E., Bjelland, I., Dahl, A., & Holmen, J. (2007). Association of low blood pressure with anxiety and depression: the Nord-Trondelag Health Study Journal of Epidemiology & Community Health, 61 (1), 53-58 DOI: 10.1136/jech.2005.044966

Goddard AW, Ball SG, Martinez J, Robinson MJ, Yang CR, Russell JM, & Shekhar A (2010). Current perspectives of the roles of the central norepinephrine system in anxiety and depression. Depression and anxiety, 27 (4), 339-50 PMID: 19960531

Itoi, K. (2008).
Ablation of the Central Noradrenergic Neurons for Unraveling Their Roles in Stress and Anxiety Annals of the New York Academy of Sciences, 1129 (1), 47-54 DOI: 10.1196/annals.1417.012

Getachew B, Hauser SR, Taylor RE, & Tizabi Y (2010). Alcohol-induced depressive-like behavior is associated with cortical norepinephrine reduction. Pharmacology, biochemistry, and behavior, 96 (4), 395-401 PMID: 20600245

Haenisch B, & Bönisch H (2011). Depression and antidepressants: insights from knockout of dopamine, serotonin or noradrenaline re-uptake transporters. Pharmacology & therapeutics, 129 (3), 352-68 PMID: 21147164

Andrews PW, Kornstein SG, Halberstadt LJ, Gardner CO, & Neale MC (2011). Blue again: perturbational effects of antidepressants suggest monoaminergic homeostasis in major depression. Frontiers in psychology, 2 PMID: 21779273

17 responses so far

  • Katie says:

    Very interesting topic

  • Pat says:

    I am not an expert in depression but one of the links between arterial hypotension and depression could be the presence of a low brain blood flow. On one hand, a reduction in cerebral blood flow has been associated with depression. On the other hand, when blood pressure is lowered below the cerebral autoregulation range (mean arterial pressure between ∼ 60 and 150 mmHg), blood flow to the brain becomes pressure-passive and a further reduction in blood pressure will lead to a reduction in brain blood flow. Also, if cerebral autoregulation is already jeopardized, a reduction in blood pressure (even if mean arterial pressure stays above 60 mmHg) could lead to reduced cerebral blood flow…

    It is probably more complex than that…but the reduction in cerebral blood flow could be one plausible underlying mechanism.

  • Kat says:

    This is VERY INTERESTING! My blood pressure tends to be low, and I experience bouts of orthostatic hypotension every now and again. As a relatively healthy 27 year old woman my doctor doesn't feel it needs treatment.

    I've also experienced a couple of depressive episodes since my 20s. I didn't respond well to Seroxat or Lexapro, but Efexor turned everything around for me. I wonder is it just coincidence that my blood pressure tends to be low, and that a serotonin-norepinephrine reuptake inhibitor helped my depression when SSRIs didn't.

    I know I'm only one data point, and correlation doesnt equal causation. But, still it's interesting! I'll be keeping an eye out for studies on this.

    Thanks for the exciting post!

  • Paul Winkler says:

    Make that *two* data points,Kat. I am on Effexor as well, and one result is that I have developed high blood pressure. There is no doubt whatever that the Effexor (venlafaxine) has a dramatic, positive effect on my mood.

    Interesting blog, Sci, and a topic I haven't seen discussed in this way before.

  • aek says:

    Thanks again, Sci, for this fascinating look at some of the complex mechanisms at work and play.

    There are differences in the character of hypotension, to be sure. Volume depletion is one cause - and can be the result of acute or chronic processes - anything from trauma (think amputations, gunshot wounds, stabbings and the like) to slow and insidious GI bleeds. Orthostatic hypotension is an intermittent, position sensitive condition, and the underlying BP may not be hypotensive at all. Constitutional hypotension, OTOH, is the state in which the BP is continually less than 110 systolic for males and less than 100 for females (the genders are indeed different). Diastolic pressures don't seem to be as strongly associated with the depression/anxiety/cognition/attention deficits seen with systolic hypotension.I didn't find studies looking at MAPs, but I wish there was one or two because Pat's points are important to consider.

    Clinically, the association seems to hold most strongly with mixed depression/anxiety, followed by depression and then anxiety. Given that cognitive deficits and poor attention are core symptoms of depression and often do not respond to medication (across all of the antidepressant classes), I wonder if Pat's points above don't figure in the picture. That would also explain the anxiety, whereby the HPA axis is signaling "danger" via anxiety. Clinically, when patients are beginning to get "shocky" - e.g. symptomatic, they almost always exhibit fretting like anxiety. The mechanism could be the same here in that the brain is trying to signal a need for increased blood flow.

    So maybe the first response you would see with an NRI is the decrease in anxiety type symptoms and the return of cognitive processing and attention, followed by a lifting of depressive symptoms. But you might also see this with an alpha or beta adrenergic agonist, no? Meaning that it might not be solely due to norepi, but a sympathetic blunting that would be responsive to agonists.

    /wild speculation

  • David says:

    I have battled major depression for years, in 2003 during a med change I was hospitalized. While in hosp. I was suffering from severe headaches, as they got worse my blood pressure went up. I was eventually put on Efexor & meds for high blood pressure.
    Now here is the strange part that my doctors, therapists, other sufferers, have never heard of. Sometimes when I am having trouble controlling my symptoms I experience a sudden & brief change in mood ( worse) when I stand. Has anyone else experienced this & does it tie in to the blood pressure/depression connection?

  • I am a 68-year-old overweight man with high blood pressure and type 2 diabetes.

    In my personal experience, my (extremely rare) episodes of depression have seemed to be the perfectly understandable results of outside stresses -- failure of a business in the 1970s, the resulting financial problems, the sudden death of my wife in 2003. Since I thought that the depression was a normal response to those events, I never would have considered taking anti-depressant drugs, since drugs would not have fixed external problems. With time, the external stresses -- and the depression -- went away. As the old saying goes, time heals all wounds.

    I am skeptical about blood pressure (either high or low) causing depression, but I would not rule out depression causing high blood pressure. I would think salt intake and weight would be much more important factors affecting blood pressure.

    After my wife died suddenly, I ate almost nothing for 2-3 weeks. I didn't check my blood pressure, but I bet it went down at the same time I was depressed. But in that case, the sequence would have been wife's death >> depression >> not eating >> weight loss >> lower blood pressure. The blood pressure and depression wold have been only loosely related.

  • turin says:

    Fascinating post. I think it is very very complicated issue, however. I have had lots of experience with different kinds of antidepressants (SNRI, SSRI, TCA, MAOI). Ones that boost norepinephrine do indeed have effect on the cardiovascular system (increased blood pressure, heart rate) and they also tend to be better at decreasing pain. But boosting just norepinephrine too much precipitated a severe depression and increased anxiety, in my case. But my pain and headaches were reduced significantly. Finding a balance of how the norepinephrine effects on the CNS (brain) and the autonomic nervous system (parasympathetic and sympathetic) is the key to some of this. But all the systems and neurotransmitters play a part in the balance of it all. Hard to isolate the cause and effect of one or the other.

  • jm says:

    Intriguing post.

    I was wondering what blood pressure range is considered to be hypotension, as opposed to being just "the low side of normal."

  • Marie says:

    Patient 17 years presenting with orthostatic hypotension, first treated with Gatorade which brought the bp to normal as long as it was maintained. Patient developed severe migraine , assuming it was menstral cycle related, was prescribed Lolestrin Fe which occurred the same month she has four wisdom teeth extracted and was prescribed Vicodin for pain. Near the end of her first month's dose of harmones the patient went into severe panic attacks and was hospitalized. Now 4 months later, off the harmone, patient continues to have orthostatic hypotension and has been treated with decreasing doses of depokote and abilify. She became severely depressed so the doctor added 2.5mg of lexapro which cleared her thinking to get her through mid terms. She was still incapacitated being overwhelmed by the advanced workload. Her dose of lexapro was raised to 5mg. She seems more positive and I am hopeful that she continues to improve. I don't know what is first the chicken or the egg. Her headaches have improved since the lexapro but the bp has been down with2.5mg and she was lethargic facing apgov and politics which she did not want to do.
    She has been to the heart doctor twice and all has checked out .

  • Sarah says:

    I have no scientific information about this, but thank you for writing the article and for your interest in the topics. I and many others rely on people like you to further advance medical treatments, and I really greatly appreciate it.
    I visit this page because today, my doctor tried to tell me my orthostatic hypotension is caused by my depression. A cardiologist has already diagnosed vasovagal syncope. I may likely have postural orthostatic hypotension syndrome. I also have had Hashimoto's since childhood and so I was asking about tests for related gladular problems, such as adrenal insufficiency. But because I have depression, I am constantly made to felt uncared for. My depression is fairly under control, but I have all of these physical symptoms and no answers, yet they don't want to test further; just throw other antidepressants at me even though I've tried several for long amounts of time and they just don't do anything. Anyway, thank you again.

  • Devin says:

    Addressing the underlying cause permits you to get rid of lots of anxiety out of your everyday life.

    Slow your breathing down to about 10 deep breaths
    per minute. It is being utilized, not only to control anxiety levels, but also as an exercise after surgeries, and when a client experiences difficulty of breathing.

  • Quint says:

    I have dealt with blood pressure issues for years. This site has had some highly beneficial tips. Thank you for your work!

  • Terry says:

    Hi, I Just found this site after some people who had been diagnosed with depression issues notably bipolar who I have supported with personalisd exercise techniques commented on a light headed feeling with one of the exercises which combined focus on balance and breathing technique to fully engage the diaphragm.

    Being as none of the comments here consider one of natures own data points namely how weather changes are now known to be a factor, most notably with an increased risk of heart attacks as found in the 'Athens study' and also the 10 year WHO Monica study, why not let nature help provide some of the answers needed here.

    My research gives consideration to the 1016mb identified as the optimum for lowest risk of heart attack noting that risk increases the further, up or down, from 1016mb the local air pressure is (give or take 11mb)
    A weather system as we know varies in time taken to pass over and ones location and altitude will obviously affect 'the background local air pressure. So if meds have not resolved the problem a daily log of how you feel may be helpful in providing a natural benchmark with which you can pin down any psychological triggers that become more sensitive in the person with depression issues when the weather pattern changes. If anyone is interested in exploring this further wants to compare notes feel free to email me. troyterry15@gmail

  • terry says:

    One study of interest:

    J Neurol Neurosurg Psychiatry. 2006 April; 77(4): 552–553.
    Published online 2005 December 14. doi: 10.1136/jnnp.2005.074369
    PMCID: PMC2077524
    Stress induced hypotension in pure autonomic failure

  • The other medication in the works is named Udenafil or trademarked
    name is Zydena(R). Pharmacy technicians are faced with new
    things every day; from customer service to new medications to insurance issues,
    the pharmaceutical field changes daily. In some cases, doctors can advise on safe and appropriate over the counter (OTC) medications that can be used.

  • Lori says:

    My blood pressure is typically 120/70, when not depressed I tend to exercise more and I think this maintains my blood pressure. After reading some research I learned of the possibility of a correlation between B/P and major depression. My B/P lowers to 100/60 during depressive episodes of which there are external and internal etiology (back/neck pain w/ slower mental processing). It is interesting to note the lack of blood flow to the brain due to this drop in B/P. I hope there can be more clinical trials on this before trying new medications.

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