Mitochondrial dysfunction as the cause of mood/psychiatric disorders

[wciarci]

I used to have really bad mood swings when I first became ill. I still do over react to stress and avoid stressful situations, arguments etc. whenever I can because I can't judge the appropriateness of my responses at times. After really working on methylation and mitochondrial support, I am better but not cured. Two of my sisters are bipolar and indeed it runs in the family but I do not have those symptoms and never had a mood problem until coming down with CFS/ME 10 years ago. Over the last few years there has been a lot of research into mitochondrial dysfunction and it is believed to be behind bi-polar as well as other illnesses. Since we have mitochondrial problems, I am posting some links for you to explore. CoQ10, Alpha Lipoic Acid and N-acetyl cysteine have been used in bi-polar to some success.

Mitochondrial dysfunction key to mood disorders: http://www.ncbi.nlm.nih.gov/pubmed/18979198

Trial using CoQ10 in bipolar: http://clinicaltrials.gov/ct2/show/NCT00327756

Higher CFS lactate: http://pn.psychiatryonline.org/content/44/7/17.2.full

CoQ10 reduces CFS lactate: http://www.mitochondrial.net/showabstract.php?pmid=1887756

Very good article on the science behind mitochondrial dysfunction and bipolar: http://www.nature.com/mp/journal/v10/n10/full/4001711a.html

Mitochondria key in mood disorders: http://findarticles.com/p/articles/mi_hb4345/is_10_37/ai_n42054297/?tag=content;col1

A good description of mitochondrial dysfunction, lactic acid build up in CFS: http://www.health-spy.com/mitochondrial.html

I am trying to get my sister to try some supplements. I hope this helps those who might be experiencing mood issues on top of this dreadful disease.

Wendy

 

[wciarci]

OK I am bumping myself. so sad.

 

[anciendaze]

very interesting connection

Hi Wendy,

This is a very interesting connection, but the mention of psychiatry probably scared people off. The connection with lactate levels made me think of the Light's results on perception of pain in CFS, with evidence of doubled numbers of lactate receptors. This sounds like an attempt by the body to down regulate exertion when there is some indicator of excess lactate.

I've been following a different trail through mitochondrial dysfunction recently, so that part of your post caught my attention.

I notice healthy functioning in bipolar patients is described as euthymic. Have you noticed any reference to cyclothymic variations? This is the pattern I see in many with CFS/ME: mornings resembling adrenal exhaustion followed by near hypomania in the evening, with difficulty falling asleep at appropriate times. I believe this correlates with cortisol levels.

 

[wciarci]

Anciendaze, very interesting post. I too am intrigued by the excess lactate, could account for the pain and fog? I know that the people in my family with bi-polar are up all night and tired, exhausted sleeping during the day, then around 7pm, watch out. I am thinking that if XMRV is proven that I and probably the rest of my family have it, just manifesting differently. By the way, in my family if you are not bi-polar you have another auto immune disease. I have CFS, my sister hashimoto's, my other two sisters, bi polar. Of two nephews and two nieces, one niece has bi-polar, the other lupus, my nephew cfs/fm and the last nephew, so far is clear. These health issues concern me. How could there be such ill health except for a virus that attacks the immune system and causes mitochondrial damage?

 

[wciarci]

OK looked up cyclothymic variations, many in my family have this when young. The full blown bi-polar generally doesn't hit them until they are in their 40's or 50's, around the time that CFS happens. Strange. They also have a 24 hour cycle. I remember being awakened at 2 or 3 am to clean the house (bi-polar mom).

Wendy

 

[alex3619]

virus, sleep and lactate

Hi wciarci

I will discuss your points in reverse order - the dominant hypothesis at this moment has to be a virus, with the leading candidate being XMRV. This could change quickly with new science, we have to wait till there is enough research to be sure. I consider many of the theories that have been proposed to be candidates not for the cause, but specific aspects of the phathophysiology. All of these issues interact to become a very very complex disorder, probably much more complex than type 2 diabetes, which is still perplexing scientists after most of a century of research. Finding a single cause will, however, let us focus on what to treat, regardless of the complexity of the pathophysiology.

The comments you made about those with bipolar are very interesting, especially about the up all night and asleep during the day. Many with ME or CFS (including me) have a very disturbed circadian rhythm that in its medium term stages looks just like what you describe, although it starts as insomnia. Now I am showing early signs of a complete loss of circadian rhythm, but then I am a very long term patient.

With respect to lactate, elevated lactate is a sign of mitochondrial or metabolic dysfunction, but it is not a cause. This myth arose because muscle fatigue is associated with high lactate. However, lactate is actually the result of the body fighting a deficient energy state, it doesn't cause fatigue. It is a very good thing to have, it helps you cope. When it is present, however, you know something is making demands of your energy system.

Bye
Alex

Anciendaze, very interesting post. I too am intrigued by the excess lactate, could account for the pain and fog? I know that the people in my family with bi-polar are up all night and tired, exhausted sleeping during the day, then around 7pm, watch out. I am thinking that if XMRV is proven that I and probably the rest of my family have it, just manifesting differently. By the way, in my family if you are not bi-polar you have another auto immune disease. I have CFS, my sister hashimoto's, my other two sisters, bi polar. Of two nephews and two nieces, one niece has bi-polar, the other lupus, my nephew cfs/fm and the last nephew, so far is clear. These health issues concern me. How could there be such ill health except for a virus that attacks the immune system and causes mitochondrial damage?

 

[glenp]

Ty for those links wciarici.

http://vch.eduhealth.ca/PDFs/FL/FA.500.Un21.pdf

 

[ramakentesh]

Elevated cerebral lactate levels occur for one or two reasons; either there is an impairement of glucose metabolism at the cerebral mitochondrial level (less likely) or there is a reduction in blood flow to the brain or certain areas of the brain causing cerebral hypoxia, which in turn reduces glucose metabolism and results in an increase in lactate levels. Increased cerebral lactate levels are neuro-protective - a safeguard against hypoxia.

 

[ramakentesh]

However, lactate is actually the result of the body fighting a deficient energy state

Cerebrally, no its actually released when there is impairement of glucose metabolism. Cerebral mitochondria require oxygen to convert glucose into energy - when there is an impairement in blood flow or tissue hypoxia, lactate is released to protect the brain.

 

[anciendaze]

beware of systems with feedback

ramakentesh has brought in another legitimate point of view. One problem we have in dealing with not only disease, but also medical professionals, is that a high percentage have been trained to look at levels of biomarkers and ignore most other things. Any system with feedback will have dynamic behavior which becomes abnormal long before any level stays consistently out of range. I am not trained in medicine or related fields. I do have considerable experience with dynamics, including some very complicated non-biological cases.

Concentrating on levels and ignoring dynamics is like waiting for the oil light in your car to come on before you take it to a mechanic, instead of taking it in as soon as you notice it is losing oil. (One friend had the light come on while he was doing 60 mph. He got the clutch in, but had not slowed to a stop before the engine seized.)

This question of mitochondrial damage looks like a good place to probe deeper. For one thing, mitochondria have their own DNA, and my untrained impression is that this is not as well-defended as nuclear DNA. One wild idea on my mind is that even a failed attempt to reproduce virus particles by inserting genes in mitochondria might result in production of junk without replicating virions. Mitochondria can die without triggering apoptosis or immune response. This would match the low viral load, limited immune response and loss of energy in infected tissues.

If we are dealing with mitochondrial disease, we have to consider reduced functioning in tissue with lots of mitochondria, including the liver. If the liver is not clearing toxins adequately, we have another way to increase demands on other weakened parts of the metabolism. Recent reports of reduced expression of CD26/DPP4, which cleaves neuropeptide Y, would also increase loads of a neurotoxic molecule.

Various mechanisms in the body do detect metabolic disturbances and attempt to respond without any clear 'idea' of the cause. It looks to me like much of the problem is an attempt to down regulate a 'presumed' cause - overexertion. If the damage comes from a different cause, this will not solve the problem.

Virtually all cellular metabolism involves mitochondria, so it is not surprising to find multiple biochemical pathways converging here. One part of the picture that I'm seeing are double or triple impacts from several relatively-minor separate insults to metabolism. There is something weird about glucose metabolism and lactate response in CFS/ME.

It is now part of the folklore of CFS/ME that we become hyper when we eat sugar. (My own friends observed this before CFS was an official diagnostic category for anyone.) We crash when the sugar high ends, as if we were using amphetamines. This is one example of abnormal dynamics.

Allergies form yet another broad field of problems connected to CFS/ME. One aspect of biochemical dynamics hit me long ago when my allergic rhinitis plugged up my sinuses so badly I was afraid to get on a scheduled flight to Europe, because I could not clear my ears. I went to my doctor, who said, "no problem, I'll fix you up." He gave me a shot which did clear up my allergies. It also kept me awake for 48 hours! When I came down, and came back, I asked what on earth he gave me. It was simply prednisone, a steroid. So, one aspect of peculiar biochemical dynamics in my case is an exaggerated response to steroids.

Orthostatic intolerance is a third example of strange dynamic behavior in CFS/ME. As long as I lie flat during an EKG, nothing appears to be wrong with my heart. Immediately after getting a clean EKG I have to be careful not to stand up too fast.

The positive spin on all this bad news is that finding a single place where many causes of illness converge suggests that fixing problems at that one place may solve more than one problem. Dr. Cheney's experimental treatments with stem cells derived from placental tissue could be an example, as these cells bring their own healthy mitochondria.

In dealing with your unfortunate relatives, I can only say to do what you can when you can. There are many times when good advice will be useless. You have to wait for opportunities, and be very, very patient. Admit that you have limitations yourself.

If you have not already read it, I recommend "An Unquiet Mind" by Kay Redfield Jamison. It won't tell you how to treat such problems, it will give you an unusual insight into how an exceptional person deals with them.

 

[wciarci]

Thanks for the replies, very detailed and thought provoking. My only purpose though in posting this was that mitochondrial dysfunction, be it in bi-polar or CFS can cause mood disorders. So, supporting the mitochondria would help at least with these problems.

Wendy