Bipolar, the Brain and Energy - Part Two

Okay, in this follow up to the first part on mitochondria and bipolar fatigue, let's look a little more about what's going in the brain with bipolar and energy.


First off, let's understand what an energy consumer the brain is to begin with. Your brain will consume twenty percent of all your body's total energy. Yes, you heard that right - twenty percent. That's approximately twenty percent of the oxygen that your lungs put into your bloodstream and about twenty percent of the nutritional energy that enters your bloodstream through the foods you eat (we'll get to this another time, but trust me, you want to pay a whole lot more attention to what you put into your body). All to that little three pound organ between your ears.


Now that's in a normally operating brain. Bipolar brains are far from "normal". I don't, by the way mean that to be in any way disparaging, but it's just a fact (albeit not a widely known or precisely understood fact); bipolar brains operate differently than that of the general population.


Bipolar brains tend to activate far more brain regions much more intensely when manic than non-bipolar brains. While I can personally attest to this, brain scans also bear this out.

The top is a normal control subject, the middle a hypomanic brain and the bottom depressed. The brighter yellow or red the region is, the more activated it is.


It is hard to understate just how active a manic or hypomanic brain is (I'll leave distinguishing between those two for another time). And again, without having experienced it, it is utterly beyond what anyone with a 'normal' brain can fathom. It really does feel like your brain is lit up like a blast furnace. Your brain feels like, and is running on all eight cylinders (usually, as we'll see, the brain actually limits the number of "cylinders" running at any one time). Massive amounts of neuronal real estate is fired up, regions that would not normally operate all at once (not all of this "fired up neuronal activity" is for the good, but again, for another time).


Not only is the brain more fired up, but it won't shut off. I once went thirty-five straight days with virtually no sleep. I've read reports of even longer stretches. Long periods of very little or no sleep is a hallmark of mania or hypomania (this, it must be clear, is not the same as insomnia and restless inability to sleep). Thoughts during this time are going to be happening at a breathtaking pace (not all necessarily for the good, either).


All of this means not only way above average numbers of neurons and various circuitry are activated, but for much longer durations than nature ever intended. In just a single thought there is an enormous amount of activity and energy requirements so one can well imagine how much demand there is being put on energy during manic phases. And here's the thing with brains: they are evolved to be highly efficient in energy conservation. Generally, a brain will only "bring on board" a limited amount of regions at any one time (other than for perhaps for brief bursts) for the simple reason of conserving energy. In times of crisis, for example, it will shut down parts of the frontal cortex (where deeper thought usually takes place) and fire up other regions (or put them on higher alert). It does this to make the most efficient and conservative use of available energy not only for the brain, but throughout the body.


In other words, it simply has not evolved to run at the energy outputs seen during manic/hypomanic phases for that long.


I have long considered bipolar disorder to be largely a disorder of brain energy allocation. I wrote this: "Whatever mania is - and as I said, I am scouring the earth looking for the neuroscience to this - it is energy at its core" in a post last December explaining bipolar disorder so it's nice to see serious researchers coming to the same conclusion:


"Bipolar disorder seems to be a disorder of energy; too little in depression and too much in mania," said Professor Michael Berk, who is leading the study. "This suggests that if we can usefully target energy, we might help depression in bipolar disorder"


[Professor Berk is leading the study cited below]


Energy is not in infinite supply. It does not just materialize out of thin air. As we saw in the previous post (albeit very briefly), mitochondria manufactures energy in all the cells in our body and brain. I personally believe, mitochondria and the neurons' energy are particularly at risk for damage (there's too much background to get into as to why I believe that but I can assure you it is a very well founded idea).


Mitochondria depends on numerous factors to manufacture that energy and when demand is high, those factors are not going to be able to keep up forever. That's just kind of cellular biology 101.


So just for starters, with high energy demands during a manic phase, those supplies are just simply going to be exhausted (in the literal sense of "running out") at some point. This is easily observable (and likely easier to understand) in muscle cells - put them under demand for too long, and they will burn out and you'll literally not be able to move a muscle.


So without going into a lot of long scientific explanation, I think we can fairly understand that aspect of the cyclical nature of bipolar - the brain simply, just like a cellular structure such as a muscle, needs recovery time after a high demand period. But this does not fully explain the long term debilitating fatigue that some bipolar patients (though not all) suffer through.


Now I have to remind that there is no single one thing going on in bipolar disorder and I don't mean to suggest that energy and mitochondria is the end all to be all in understanding and treating bipolar; it's just one piece of a very complex puzzle. Certainly dopamine is a major factor. I've written elsewhere a small amount on the huge role dopamine plays in all human behaviour and dopamine has long been thought to play a major role in bipolar. Dopamine, just briefly, is greatly involved in what controls our motivations and drives (and also is widely implicated in many addictions, such as compulsive gambling). When manic, our motivations and drives are on hyper-drive and the role of dopamine in this is why anti-psychotics are almost always prescribed (anti-psychotics are dopamine blockers at the synaptic level).


The "wakefulness" neurotransmitter norepinephrine is also thought to play a large role (which I touched on here).


These and other factors (that I hope to explore in more detail one day) are part of what gets manic brains so fired up. And these high energy demands are just part of what's going to burn out the cellular energy factories, mitochondria.


But there's more.


That sleep the brain doesn't get when manic? Bad news. I'll not get into this too deeply here but as I've written elsewhere, sleep is very critical to neuronal function. Briefly though, it has to do with neurons needing the down time of sleep for basic housekeeping such as "waste disposal". This is more cellular biology 101 - cells take in substances to produce energy, that process produces waste byproducts that have to be removed. That waste is toxic when build-up occurs. There is much research to suggest that neurons (along with all other cells in your body for that matter) need the sleeping state in which to perform this waste disposal and rid neurons of hazardous waste build up (I bet you never thought of it that way before, did you?).

But there's more yet and the news gets worse.

Mitochondria and Stress:

There is massive amounts of literature on the relation between stress and neuropsychiatric disorders so I can only hope to summarize this very briefly for now. There are also great bodies of literature on stress and cellular damage throughout the body, perhaps best summarized by Robert Sapolsky's lectures and books. While the stress response system is a complicated piece of business (and what isn't in the brain?), it more or less boils down to the effects the stress hormone glucocorticoid has on various brain systems and components.


Chronic stress - which essentially means chronically elevated levels of glucocorticoids - is really bad news for all of your health. While what particular part of your bodily systems it effects will be determined by genetics (a rather large subject in itself that we'll leave for perhaps another day), in the brain it's going to cause DNA to be changed this way or that, cellular damage, compromised immune systems, neuronal death (particularly in the hippocampus - hello, Alzheimer's and dementia) and, to get to today's topic, damage to mitochondria.


To get a bit of an understanding of the role of GCs (glucocorticoids) and mitochondria, we'll look at this excerpt from this paper:

Such work suggests that, under physiological conditions, GCs enhance (my emphasis - BGE) mitochondrial functions to provide cells with more energy for coping and adapting to acute challenges.

So far, so good. This is what all the literature on GCs will show - short term gains in times of, as they put it, "acute challenges". Which in evolutionary historical terms (IE: what our brains and bodies are most evolved/adapted for), means escaping a tiger attack or vigorously hunting for food. These are short term crisis situations though.


Further now from the excerpt:

However, chronic stress may lead to chronically elevated levels of GCs, which in turn may reduce cell functioning via the interaction between GRs/Bcl-2 and mitochondria. The decrease in proper cell function may contribute to the pathophysiology of several stress related mental health disorders, including major depression.

Sapolsky's work takes most of the "may lead to" out of that equation and establishes it almost without question as will lead to chronically elevated levels of GCs while furthermore documenting the cascading amounts of damage they will have in neuronal circuitry and neurons (which I summarized in an earlier post).


So what that latter excerpt is saying, in layman's language, is that chronic exposure to GCs will go past the short term energy boost and instead - pardon my French - fuck up mitochondria's mechanisms for converting various substances into energy.


How bad this damage may be and how repairable it may or may not be are matters of ongoing research and study. For now though, I think we have to take "subject A" - the well observed (and experienced by moi) aspect of bipolar depression - the chronic and debilitating fatigue, add it to our now deeper understanding of mitochondria's vital role in producing the mental and physical energy we experience and need and then add these two to what appears to be growing evidence for that role being damaged or compromised by chronically elevated levels of GCs and make a conclusion that damaged mitochondria are in large part responsible for the fatigue suffered by many people with bipolar depression and major depressive disorder (and, some literature suggests, schizophrenia).


There are other factors in the lethargy and lack of motivation experienced during depressive phases - and I will get to those in other posts - but for understanding the worst of the fatigue, I do think we have our smoking gun.


But I always like to include multiple sources, so there's more. The role of mitochondria dysfunction is becoming more widely known and is the subject of more and more research. A reader of this blog brought the following research to my attention. This is from a university group in Australia and New Zealand. The nature of this research is to test a special cocktail of nutrients meant to boost mitochondrial function, an outline of which can be found here.


What I found of interest is support for the theory that stress is the source of damage to mitochondrial functioning and furthermore, this is the basis for bipolar fatigue.


There is a growing body of evidence supporting the presence of oxidative stress states in bipolar disorder. With high levels of oxidative stress comes mitochondrial dysfunction.


Oxidative stress is outside my body of reading so I'll leave an understanding of that to what appears to be a well written and sourced entry in Wikipedia. (I don't like relying on Wikipedia for a source but often it really does summarize various bodies of research as well as anywhere). While I cannot claim an understanding of the exact mechanisms of oxidative stress (gads, yet more reading for my 'to-read' list), it does appear to me that oxidative stress damage (and the world of anti-oxidants to combat it) is different than GC stress damage.


So to summarize, mitochondria are responsible for all cellular energy generation. Their functionality comes under attack in bipolar, it would appear, via four possible means:


- plain exhaustion (again, in the literal sense of supplies running out) due to chronic overuse during manic phases (in the brain, this is just as in any over-taxed cell that simply shuts down due to overuse).


- build up of toxic cellular waste products as a result of lack of sleep during manic phases


- grave, long term damage due to chronically elevated levels of glucocorticoids which comes from chronic stress (which will arise from a wide variety of sources both within the brain of a bipolar person and from external stressors)


- oxidative stress damage

Stress and Bipolar Disorder:

So what does stress have to do with bipolar disorder? Well, almost everything. And in better understanding what stress is and how it affects brain components, we can better understand not only what triggers bipolar episodes, but more importantly, what to do about it.


And in understanding the role of stress - or the stress response system - we'll better understand why some people get hammered more by the down cycles of bipolar and why some develop the debilitating chronic fatigue well documented to plague many people who are bipolar (and is the main reason, IMO, it IS a disorder for many).


But that is a longish subject and will have to wait for the next installment.


Sources:


Academic publications, books and university lectures of Robert Sapolsky


Searching for the Mind with Jon Lieff (which was recently named one of the most comprehensive sources of neuroscience information on the web)


Mapping the Mind by Rita Carter


The Willpower Instinct by Kelly McGonigal


Numerous academic research articles supplied to me via neuroscience acquaintances linking acute stressful events or chronic stress to neuropsychiatric disorders which, while not represented in detail here, laid the groundwork for establishing stress as a key factor in not only triggering psychiatric episodes (schizophrenia, bipolar, various forms of depression, anxiety, ADHD among others) but also in determining their long term outcomes.


Please continue to Part Three of the series.

Testimonials Page - Reader Feedback on Taming the Polar Bears

I first got to know Brad in the "Brain Cafe" on Facebook. It's a pubic group designed for discussion about science, psychology, creativity and education. Members include neuroscientists, professors, researchers and people like -- me, no credentials and just interested in learning. The are many discussions going on at once, but I am drawn in particular to the study of the human brain. I quickly noticed that Brad was the resident expert in the group and was tremendously well-respected. I was, and continue to be, amazed by his knowledge of neuroscience and the relationship between the brain and behavior. He has studied it all - more than I will ever fully comprehend. After listening for a good while, I finally got up my courage, put aside my fear of looking foolish, and engaged Brad in one of the neuroscience discussions. To my relief, he treated my pedestrian questions with respect and filled my brain with answers. We have continued our conversations outside the confines of the Brain Cafe, and I continue to learn from him. Now I know where to go as I wonder down the path of learning and am abruptly stopped by a burning, yet complicated question. Thanks Brad!

• Cynthia Witkin – Washington, DC Political Analyst

 

For the very first time in my life
I actually look forward to tomorrow
Even though nothing is perfect
And I still have tears
I just caught myself looking forward
To tomorrow. Not dreading it. Not wishing I won't wake up. But ready
To take on tomorrow. It is a strange feeling I have never felt before. It is new and exciting.

You did that Brad. This is your work. This would not have happened in a million years if it wasn't for you.

• Via email from an anonymous Polar Bears reader with whom I've been working with privately for some months

There can be no other closer connection, no closer bond than that of a twin. It is with this understanding, that I want to share with you my impressions of Brad’s remarkable journey from being often a ward of the state due to a chronic suicidal state, to now, where he has regained his passion for life, and helping others.

Under the care of the provincial mental health system, Brad was kept heavily drugged, that while this may have kept him safe from himself, this treatment gave him little, if any, hope of recovery. It was this lack of hope, a lack of a path forward, that spiraled him ever further into a deeper state of depression.

Something had to change, something significant had to change.

It was at this point, Brad made the biggest, most courageous decision of his life--to turn his back on the provincial mental health system, and forge his own path to recovery. This path was rooted in the belief that there had to be a better way to regain a positive mental state of health.

With the help of close family and friends, Brad set out on this amazing journey. Always keenly intelligent, he pursued all the latest research on neurology with a vigor I hadn’t seen from him in years, and that would have been impossible in his previous drugged state.

It was by no means easy, nor a straightforward path. The ups and downs were many, and at times disheartening. But together, with his “Team”, he made it through the troughs, and gradually built some plateaus of encouraging accomplishment.
In time, Brad began to get connected with some of the top leading researchers of the mind, and with this ever increasing acquisition of knowledge, he began to formulate his own system to recovery.

It has been nearly two years since that courageous choice, and as Brad’s twin brother, I can unequivocally state that the transformation has been nothing short of miraculous. While there is a long ways to go, the spiral is unquestionably up, and a man who this world was in grave danger of losing, has now regained one that has a zest for life again. More so, the world  regained a man who is a positive force for the millions of others who suffer from mental health challenges.

All of this was only possible because of Brad’s own self designed program, based on the very best research and minds available. Without this program, and his dedication to it, and to helping others like him, I have no doubt I would have by now lost  

•  Gregory Esau - The Glia Custom Auto Manufacturing Company

I am just stunned at what a difference in change of food and eating habits has made in my life. If Brad had not insisted a change in diet, I might never have known how much better, more alert I am during the day, but also, as a sided effect, the weight I am losing. And because I am using superfoods every day now, and making smoothies, I have more (much more) energy and am never hungry. Thank you so much! Who would have thought that food, influences the brain. Not me. 

• N.A. - Taming the Polar Bears follower

You don't know what a relief it was, to finally come across a person, that does not only understand what it is to live with BPD (Borderline Personality Disorder), chronic depression and PTSD, but at the same time can explain to me, how my brain works during different mood swings or episodes. I have been in therapy with several psychiatrists and psychologists for 20 years and none of them actually knew what it felt like, or how this works in my brain. You do. And that makes all the difference to me. 

• Nina - Taming the Polar Bears follower

Now, I've been interested in neuroplasticity for ages but didn't really actually get to sit down and pay attention to it consistently until now. Thanks for another great post, Brad, you're an incredible inspiration to me. I'm hoping to fix up things in my life and completely transform them.

• Anonymous Taming the Polar Bears follower in the Brain Cafe Facebook group

[ more to come ]

Bipolar Disorder, the Brain and Energy - Part I

This three part series on the brain and energy is going to be the opening salvo in what I am going to hammer away at length – how much you are your energy and how much I think brain and body energy play critical roles – perhaps the role – in disorders such as bipolar, major depression and perhaps even more minor bouts of depression and important roles in almost every major neuropsychiatric disorder.

As well, recently I have been drawn more into the worlds of Traumatic Brain Injury and Chronic Traumatic Encephalopathy, having been diagnosed with the latter and having many new followers of Taming the Polar Bears who suffer with the former. While quite distinctly different brain injury disorders, both share some common defining symptoms - brain fatigue and/or brain fog. Brain and body fatigue symptoms in both of these disorders will have an at least somewhat different pathology to what I present in this series. Nonetheless, the experience of the brain fatigue and fog is essentially the same and just as troubling and frustrating so there's a lot to relate to here. As well, I feel strongly that brain injuries - whether acute as in TBI or cumulative over long periods like in CTE - will affect mitochondrial function as well. This will take further and deeper research on my part, however. In any case, if you are reading here as a sufferer of either TBI or CTE, I feel this series will be of some value to you. 

While what I'm going to explain about mental energy and body energy in this series is not all that's involved in brain and body energy (and how that's allocated), it will form a very large foundation for understanding how important energy is to brain functions and for what happens when the ability to produce that energy has been impaired.

Now, by “energy” I do not mean “pep”, “vim and vinegar” and things we generally think of when we think of having “energy” or not.

No, I'm talking about the very fundamentals of how your cells and brain cells generate energy. You are made up of trillions of cells, have around eighty-six billion brain cells and what you experience as “energy” is the collective energy created by those trillions of bodily cells and billions of brain cells.

And I'm going to demonstrate – through my own story and other evidence – what happens when “the power goes out”.

I first wrote this series in May of 2014, now three years ago (as of this update of early June 2017). I started off then stating “the depressive phase continues” because it had gone on since August of the previous year. Thank god I had no idea that a full three years later I'd often still be experiencing a crippling lack of energy or I'd have done myself in back then. Back then, I felt that surely the end must be just around the corner and some semblance of normal energy would return.

For the longest time it seemed apparent that I was in the “depressive phase” of a classic – and monstrously long – manic-depressive cycle, with the manic phase starting at the beginning of 2013 through approximately late June of that year (six weeks of full blown no sleep mania, months of classic hypo-mania). I kept my hopes up that with the end of the cycle (and they can be as long as two years) my energy would normalize. However, as the months have stretched into years with no improvement, I am beginning to accept that this is "it". I need to write in more specifics about the great impacts this has one one's life but that will have to wait for a separate piece. 

People generally don't understand what a bipolar "depressive phase" means. The usual assumption is that you sit around feeling negative and sad and sorry for yourself which, while it describes a good deal of the kind of depression most people experience, isn't what we're talking about with bipolar depression. It's not that emotional issues may not be a part of the picture, it's just that these kinds of depression involve severe and debilitating physiological symptoms (elsewhere I'll compile the argument that what are regarded as "emotional issues" are rooted in stress induced brain energy depletion and how energy is allocated throughout the brain though this series will look at the chronic and acute stress plays).

Without getting into all the symptoms of bipolar depression, what I and many others consider to be the defining feature is an absolutely stupefying lack of energy. Reports among anyone who's been through the worst of the depressive phase of bipolar describe an inability to do almost anything physically, mentally or emotionally. The renowned authority on bipolar disorder - and bipolar sufferer herself - Kay Redfield Jamison in her best selling book An Unquiet Mind describes the crippling lack of energy of the depressive phases quite well. I've read many case histories that also describe the debilitating nature of bipolar depression and have heard the stories from people in group therapy or that I met in my research. Just getting out of bed is a major accomplishment. Even simple routines of personal hygiene require the greatest effort. Most day to day activities taken for granted by most people can be out of the question. Furthermore, there are all kinds of cognitive impairments. I've come to see the great mental fatigue as the greatest and most harmful impact. It is increasingly my main hypothesis that the majority of depressive symptoms arise from brain and body cells being unable to adequately produce energy.

Other symptoms (or other ways to think of the fatigue) can be:

• anedonia (the inability of or difficulty with experiencing pleasure)
• catatonic or vegetative states
• psychomotor retardation

But as much as I suffer from it and understand that it's part of the condition, I still can't help feeling like a "wimp" and that there's more that I could do. And the barbed comments I hear about not doing anything all day (or not appearing to do anything in their eyes), the veiled comments about "laziness" and "just being lazy" will always ring in my ear. So it's hard physiologically and psychologically. It just really beats down on your self esteem. An enormous amount of the stigma we will get will be from how people perceive our crippling fatigue. 

And then there are the occasional "lectures" I receive in which people tell me, in effect, if I just pushed past it, if I just exercised enough, if I "just dug down", I'd work my way past the fatigue or I'd find the energy.

Boy, as if I haven't tried pushing myself past it. As if somehow during the now three years of living with this while maintaining great ambitions I somehow forgot to try and dig down for energy when I really needed it.

Personally, I find the fatigue impossible to explain to friends and family. Like many things about human experience, it's very hard to measure and quantify and thus hard to put in perspective for people. Hey, everyone gets fatigued sometimes, so what's my problem?!

The depth of bipolar fatigue, the absolute inability to do anything physical or mental for more than an hour or two and how this persists for months and months (or years) is just beyond the ability for most people to comprehend. Like many aspects of a severe mental health disorder, only those that have been there truly understand (most psychiatrists are particularly clueless about the fatigue). You really do have to go through it to understand how broadly it affects everything you do or can even plan to do.

And I do try push past it. There are periods where I'll feel better for a few days and I'll think, "yippee, my energy is back!". I'll rush to use that energy to get a bunch of stuff done, make plans, and just try to move my freaking life forward but I'll quickly burn out and be absolutely floored by total mental and physical fatigue for a week or weeks afterward. I'm talking days of just being being in near vegetative or catatonic states (catatonic states are a long observed in severe or advanced phases of bipolar type 1) , being able to nothing more than sit by the window listening to music virtually unable to think whatsoever and just able to get through very basic things like getting up and getting clothes on, preparing meals and things like that. Even something completely enjoyable and uplifting like hosting a dinner party or a photography excursion out in nature can leave me exhausted and immobile for days afterward. It can be extremely discouraging and dispiriting.

I've made great strides in overcoming many of the most terrible symptoms of bipolar and suicidal depression. I have at times regained hope and a love of life. I live in less fear and am no longer as governed by my emotions and vicious distorted thoughts. I am less reactionary to events around me.

But I cannot escape the incredible fatigue. For me, just the fatigue is the most debilitating part of the disorder. I am no longer able to hold a job. I am no longer able to even think about holding a job. There is no known cure or treatment for bipolar fatigue. I've learned to accept and live with its limitations much better and get about my days without having to spend great deals of time in bed (though I still have those days), but it is still a devastating part of the illness for me. I am fueled by great ambitions and my mind is often alive with ideas, but I absolutely literally do not have the energy to pursue even a fraction of them. The reading, research and writing that I put even into this little blog have often grind to a halt. I have to carefully "budget" anything that requires physical or mental energy so that I can accomplish at least little steps in a few key goals. I have to set aside the vast majority of things I'd love to pursue. 

And in the last several years I've spoken with numerous people - both bipolar or with depression and/or anxiety disorders - who experience very similar fatigue symptoms and the impacts these have had on their lives.  

Which is why I continue to be driven in my quest for the answers to "why?" That's all I want to know - why?

I email anyone and everyone I can in my search. Top research hospitals, famous professors and researchers; you name it. Not too many answer back but Jon Lieff of the excellent science blog Searching for the Mind has. And to make a long story short, while he didn't want to offer any answers, he did give me the clue that mitochondria was a target of much bipolar research.

So your intrepid researcher made it a prime target of his research.

Now there are many possible factors in bipolar depression or major depressive disorder involving (particularly in the former), neurotransmitters, hormones such as the stress hormone glucocorticoid, hyper or under activated limbic regions, certain brain regions that are too "locked on", among others. I touched on some of these in past (now under construction) posts and it seems quite certain that all of these are involved. And as I've also written, there appears to be actual structural change or damage. According to research, both structural and functional MRI studies have identified specific brain regions in BD patients, namely the prefrontal cortex and limbic regions, which both appear to be altered in size and their functions impaired. So fairly serious stuff.

But today we're going right down to the cellular level in our search for understanding the terrible fatigue and exhaustion of the depressive phase.

First of all, what is mitochondria? Mitochondria are the energy factories of cells. All cells in animal bodies (plants are a different matter as you'll see) - as part of their complex inner workings - have mitochondria.

The website HyperPhysics (which has since been taken down, unfortunately) just happened to have a fairly simple straightforward description of mitochondria:

Mitochondria are the energy factories of the cell. The energy currency for the work that animals must do is the energy-rich molecule adenosine triphosphate (ATP). The ATP is produced in the mitochondria using energy stored in food. Just as the chloroplasts in plants act as sugar factories for the supply of ordered molecules in the plant, the mitochondria of animals act to produced the ordered ATP molecules as the energy supply for the processes of life.

A typical animal cell will have on the order of 1,000 to 2,000 mitochondria. So the cell will have a lot of structures that are capable of producing a high amount of available energy. This ATP production by the mitochondria is done by the process of 'respiration', which in essence is the use of oxygen in a process which generates energy. This is a very efficient process for using food energy to make ATP. One of the benefits of "aerobic exercise" is that it improves your body's ability to make ATP using the respiration process.  

Mitochondria look something like this:

As you can see, there's a lot going on in there (which I won't even attempt to address here). Let's have a look at how they fit into a neuron.

That illustration is of course highly simplistic and just representative of what's contained in a neuron. It shows two mitochondrion while in fact there are thousands of them (as you can see in the above clip).

Now, did we just establish mitochondria as the "energy factories" of all cells, including (of course) neurons? Why yes we did. I think you can see where I'm going with this and why these little guys are vitally important to our understanding of the debilitating fatigue in the depressive phase of bipolar or of major depressive episodes or chronic depression.

So to get this very straight and clear, if mitochondria (or mitochondrion) are impaired or damaged, then cells cannot produce energy. If cells cannot produce energy, then cells cannot perform their jobs. As we are essentially just a collection of trillions of cells, if our collective cells cannot produce energy and do their jobs, then we will not have energy or be able to count on the function of cells to do the work we need to - including physical work or mental work. Hence the debilitating physical and mental fatigue.

This is not something you can "will" yourself past or overcome with plucky perseverance and chipper enthusiasm. If these crucial parts of our very cells are compromised or damaged, then energy is not happening in those cells, pure and simple. And thus whatever you require those cells to do in your daily functions is not going to be happening, at least not at normal levels. And thus - tra-la! - debilitating mental and physical fatigue.

And the role of mitochondria and bipolar depression is - again, this is according to top science researchers like Jon Lieff - becoming a huge area of research.

And having defeated or learned to control virtually every other aspect of what I suffered during depressive phases and having been left with only the fatigue, it has given me very unique insight into just how much brain and body energy affects our mental states, something I am going to further establish as we go along.

Bipolar, the Brain and Energy - Part II

Bipolar, the Brain and Energy - Part III

Why I Question the Disease Model for Depression (and Why You Should Too)

Why I Question the Depression as

a “disease” Model

(and why you should too)

With large events like the Germanwings incident and the subsequent discovery that the copilot who commandeered the craft into a mountainside suffered from "depression" (clearly something else was amiss with the young copilot other than depression) as well as celebrities committing suicide and it being revealed that they had battled depression, we get the calls to understand that depression is a disease. Even one my favourite neuscientists Robert Sapolsky wrote an impassioned piece for the LA Times imploring that mental illness was a terrible disease

But is it? Is depression a disease that runs some terrible inevitable course? Is any mental illness necessarily a disease?

I can assure you that I completely understand how hard a bout of depression is. I know deeply well how difficult my various disorders are (very advanced bipolar disorder type I with severe depressive episodes, Borderline Personality Disorder, at times Major Anxiety Disorder). It is not possible for the vast majority of the population to have suffered depression any worse than the worst of bipolar depression or major depressive disorder (both of which together make up only a small percentage of depression cases) so yeah, I do understand how hard it is. Trust me, I DO. To the point I was willing – nay, driven - to take a knife to my throat or jump in front of a train to make it all stop. So yeah, I get how hard it is to suffer through. I get that it is suffering.

Yet there are several problems with the disease model. Chief among them is that there exists no scientific evidence for depression starting out as a disease in the sense that, say, MS does. Literally tens of thousands of researchers around the globe doing the most advanced brain research in the history of mankind and yet no proof, no smoking gun for a disease marker or any biological marker that leads to a single cause or root for depression. So sorry, until you have a solid biological and physiological marker, it is simply not true nor scientifically or medically valid to state that depression is a “disease”.

An enormous part of the problem, I've found is the semantics of the word "depression" itself. 

There is a whole spectrum to this largely psychological phenomenon that we experience as "depression" with a wide variety of possible causes or triggers. We don't have the time or space to get to that today but it is essential to understand there is no one single experience or physiological or neurological basis for this mental experience. 

Another huge issue I have with the disease model as it is generally understood is that it's largely a construct of the alliance (yes, it is an alliance) between the psychiatric industry (yes, it is an industry) and the pharmaceutical industries. And in the grand tradition of capitalist “marketing” (propaganda and misinformation are more accurate but those terms tend to be too provocative), the “disease” model has been sold as a vehicle to put money in the pockets of pharmaceutical companies, their executives, their sales reps and the doctors who flog their products to an unsuspecting public that is desperate for answers to their suffering. 

Sorry, but I have a huge issue with corporations (or any of the quacks out there for that matter) profiteering off of the suffering of others. Or, as I like to say, you may as well trust McDonald's research and models for "nutrition". The odds are about the same that massive multi-billion dollar corporations really give a shit about your mental health (or nutritional needs). What corporations care about is that they do - and sell - anything, and I mean anything, to meet their quarterly sales projections, satisfy their shareholders and make Wall Street happy. Don't for a moment kid yourself that they give a shit about what you're going through (nor the sales reps trying to make their sales quotas and make their house payments).

But the biggest reason I vehemently oppose the “disease” model of depression or mental illness isn't because there's no scientific proof, nor even that massive multinational corporations are profiteering off of our suffering (and regular readers here will know what a massive bee in my bonnet that is). No, it's neither of those two things. It's for the simple reason that, ironically, it's causing more people to suffer. It's causing more people to suffer longer. And – worst of all – it's causing more people to die.

And that is my biggest issue of all.

Like any decent human, I hate to see suffering and death. I hate even more to see completely needless suffering and death.

There is no question that depression is a major and widespread problem (and again I'll outline why as we go along). Those of us who follow the issue all know the numbers – one in four will suffer a significant depressive episode (not to be confused with the clinical definition of major depressive disorder) in their lives, all the thousands of lost work days, all the billions of dollars of lost wages and so on. And worst of all, the suicide deaths (to the tune of over 35,000 a year in the US and Canada combined).

So no, nobody - least of all, me - is arguing that it's not a problem and you can trust me when I say that I take depression or other mental health disorders more seriously than 99.9% of the people on the planet. But the number one worst way to make a serious problem hundreds of times worse and to prolong solving or alleviating it a hundredfold is to completely misunderstand the problem and stubbornly and steadfastly apply the wrong solutions.

That, folks, is the definition of insanity. And insane is exactly what the present day “mental health care” system and approach is.

If you study the history of mental health, you'll discover that depression as we know it today was very rare as recently as the fifties. Prior to that, the numbers of severely depressed people requiring hospitalization was very, very low and the numbers of people who never came out of it almost unheard of. And no, the medical and psychiatric establishments weren't so unsophisticated that they didn't recognize severe cases of depression. And prior to the fifties it's not like they didn't, you know, have things to get depressed about. I mean in the several decades prior to the fifties (from whence psychiatric problems began to skyrocket) there were only two world wars, the 1918 flu endemic (that took more lives than both world wars combined), the Great Depression, massive amounts of social injustice, no social safety nets and so on.

No, if you examine the history of depression (and there is very good literature on it going back to the genesis of Western medicine of Hippocrates' time), it never existed to the depth and breadth that does now. Depression is not getting better under the psychiatric/pharmaceutical disease model, it's exploding.

Then we're sold on the idea that it's a disease and that it's endemic. And the corporations and pill pushers laugh all the way to the bank. And we continue to suffer.

So yeah, I have a problem with that (and you should too). And the disease model is contributing to the problem becoming worse.

How is that?

I thought you'd never ask.

When people are convinced their depression is a “disease”, two things are likely to happen.

One is that they're going to be put on a merry-go-round of drugs or are subjected to ineffectual and potentially brain damaging treatments like electro convulsive therapy (or ECT as it's commonly known).

There are two problems with this approach. One is that no scientific proof for either the neurochemical basis for all anti-depressants exists nor are there any studies that show improved long term outcomes for drug therapy nor has any anti-depressant in history been able to outperform a placebo. (you can scour the world's scientific data banks and you'll find none of these).

So to begin with, people are being prescribed and are taking medications that are by all objective and scientific measures, completely ineffectual.

We may as well be performing blood letting to cure illnesses. Seriously, it's just like that.

Secondly, what you will find if you dig enough is all kinds of health problems – mental and physical – that are caused by anti-depressants (and virtually all psychotropic or psychoactive pharmaceutical drugs). I cannot possibly summarize the vast amounts of data and evidence that has been compiled over the past several decades but it is extensive, very well compiled and very, very real.

So that is a huge contributor to our “endemic” right there.

The other is very simple. If you keep following a certain model and applying the wrong solutions, that means you're not applying the right solutions.

Now it turns out that the vast majority of symptoms and causes of those symptoms are psychological in nature.

Now please keep in mind that I suffer from the worst form of bipolar there is and the defining feature of the worst form of bipolar is that it generates nuclear powered depressive phases. 

And when I got off the drugs that were killing me and started working – note that word working – on my depression, I realized that the vast majority of symptoms were being generated by my mind (one of the reasons bipolar is so tenacious and pernicious is that it's particularly “good” at generating nuclear powered thoughts).

What I found was that virtually everything I was suffering from was stuff I could work on (the one thing that is most outside the control of major bipolar or major depression sufferers and which is physiological in nature I outline in a highly acclaimed three part series starting here).

And I can one hundred percent guarantee that if you do not work on these things, then your chronic depression is very unlikely to get better.

The truth is that one the greatest contributor to depressive feelings is cognitive distortions, or distorted thoughts. And it is these distorted thoughts that set off the cascade of physiological symptoms and distorted dark "realities" in our minds.

And there are reasons for you experiencing these distorted thoughts (which is going to take a separate column to get into). If you are not exploring and becoming aware of what these reasons are (or triggers in psychology parlance), you are literally going to be their bitch.

So that's a huge problem with taking pills to solve emotional/psychological problems – they mask the real problems which means you don't work on the real problems which means depressive episodes will continue to make you their bitch no matter how much of the pharmacy you gobble down every day. Trust me, I have closets full of “been there, done that t-shirts” for that. And in the number of years I've been in the mental health care system I've seen hundreds of others going through the same thing. Lots of doctors, lots of pills, NOT getting better. I've seen very, very good people go through this and personally witnessed their stunning decline. It's sickening to watch (unbearable almost).

The other problem with the “disease” model is – and here's a new word for you – the very, very real nocebo effect. Now I need you to really, really understand the concept of nocebo. It's very real. And very deadly.

Nocebo, briefly, is the opposite of placebo and is tied to our very powerful belief generating neuronal networks. Both are incredibly powerful. And very well scientifically and medically studied and documented. There is no shortage of literature available on it.

Placebo is the more widely known of the two. Placebo is the MASSIVE elephant in the boardrooms of pharmaceutical companies (contrary to what you might think, they are painfully aware that none of their drugs can outperform placebos (and hence their misinformation marketing campaigns). Placebo is the belief of a positive outcome for something. Believe a pill or medication will make you better, and poof, it very well might. This is not just true for psychological problems, it's true for even serious medical problems. The placebo effect is so powerful that surgery can be performed with a placebo anesthetic and the patients will experience no pain. Placebo knee surgeries have been performed and the patients were thrilled with how their painful symptoms “disappeared”. This is all very well studied and documented.

The flip side is nocebo in which you believe in negative outcomes and those negative outcomes materialize for no other reason than the negative power of belief.

Take, for example, the belief system built up around a simple bone in a remote aboriginal tribe in Australia.

The man who discovers he is being “boned” by the shaman is indeed a pitiful sight. He stands aghast, with his eyes staring at the treacherous pointer, and with his hands lifted as though to ward off the lethal medium, which he imagines is pouring into his body. His cheeks blanch and his eyes become glassy and the expression on his face becomes horribly distorted ... He attempts to shriek but the sound chokes off in his throat, and all that one might see is froth at his mouth. His body begins to tremble and the muscles twitch involuntarily. He sways backward and falls to the ground, and after a short time appears to be in mortal agony.

After a while he becomes very composed and crawls to his wurley (hut). From this time onward he sickens and frets, refusing to eat and keeping aloof from the daily affairs of the tribe. Unless help is forthcoming in the form of a counter charm administered by the village medicine man, his death is only a matter of a comparatively short time.

• anthropologist Herbert Brooks in a 1925 account witnessed in his earlier observations of Australian tribes people

So nothing has been done to the man, merely a bone being waved in his direction and some words uttered. But he so firmly believes in the shaman and the "deadly" curse of the bone that he did indeed get sick and die.

Ha-ha, I know what you're thinking! You're thinking we in the West are much more clever than that and would never fall for something like that. Guess again.

Take the case of “Mr. A”.

Mr A had been depressed for several months after his girlfriend broke up with him. He had a chance to take part in clinical trials for a new anti-depressant that was being tested at the time and decided to enter the trial. During the first month he felt that his mood had improved considerably and he experienced no troubles from the capsules.

During the second month he had another fight with his girlfriend and he decided to commit suicide by swallowing 29 of the capsules. But after doing so, he changed his mind and asked a neighbour to take him to the hospital.

He arrived there shaking and pale. His blood pressure was low and he was breathing rapidly. He was injected with a normal saline solution to maintain an adequate arterial tension, and his blood pressure rose; but it dropped again when the infusion was slowed. Lethargic, he received nearly two hundred ounces of saline over a period of four hours. At this point, a doctor from the clinical trial, who'd found out what had happened, arrived and told Mr A that he had taken a placebo. Mr. A expressed surprise followed by tearful relief. Within fifteen minutes, he was fully alert and his blood pressure and heart rate returned to normal. 

All these symptoms – and even death – and there is not a single physiological basis for either of them whatsoever.

And so this is what often (though not always) happens with the disease model of depression; the more people believe they have an “illness” that's “permanent” the more they'll a) believe they are more sick than they have any medical or physiological basis for and b) they'll refuse to recognize and work on the things they need to work on. ("These are not just “thoughts”, this is a serious illness!!”, etc).

And you'll almost always see worsening outcomes over time, a worsening outcome because a) they believe they are helpless because it's a “disease”, b) they leave "treatment" up to demonstrably ineffectual antidepressant medications and c) because they think it's disease, they ignore or do nothing about the real underlying causes.

Now it's true – and I can certainly vouch for this – what we experience in the worst throes of depression feels “real”. But it's not. It's virtually all created by our minds and the distorted thoughts we become subject to. (At some point I'll get to what is real when we're depressed – it's not all just thought distortions. I do get to the physiological basis for one symptom - the mental and physical fatigue - in that three part series I linked to above plus there are a number of other possible factors that I briefly outline in my post debunking quick fixes for psychiatric and mood disorders).

During my worst period of “mental illness” - a thirty month hell between July of 2010 when I was first diagnosed as bipolar and put on medications and the end of 2012 - a great deal of my worst suffering was, I discovered afterward, my full and complete belief that I had an “incurable” mental “illness”. Vast amounts of my hopelessness were because of this. And meanwhile I wasn't identifying or working on any of my triggers and underlying issues.

Everything I do now revolves around being aware of and controlling my thoughts. And again, there is no more powerful distorted thought generator than severe bipolar (more severe than even schizophrenia because of the sheer variety and polar opposite thoughts and beliefs).

And this is what I find tragic about so many cases of mental health breakdowns. People's outcomes become far worse because they're applying the wrong solutions to the wrong problems and are not aware of their real problems and real, doable solutions. All because they're so sure they have a "disease" and, like the nocebo examples we looked at, the more they believe this, the worse they get.

And the thing that I find empowering by not assuming the disease model is that it gives the power to turning around my depressive mental states to me. Not an uncaring doctor, not a harmful chemical compound in a pill, but me.

And this is what I see in the vast majority of depressive cases – people feeling totally disempowered to do anything about it and, as I'll outline in another column, the more disempowered we feel about our lives, the worse we'll suffer depression.

And THAT is a tragedy.

So look, I am NOT telling you that what you or a loved one are going through isn't serious. It absolutely is and I take it very seriously.

But I am a) sickened when I see worsening outcomes for no good reason at all (and even deaths by suicide) and b) I want you to feel empowered and inspired by the knowledge that you can do something to live a life not being depression's bitch.

For further reading along the same vein, please see the piece Is Depression an Illness?  by an acquaintance of mine, Dr Jeffrey Rubin.