Causes Of Endogenous Depression

Endogenous depression causes

It's caused by A! No, B.. Umm

Historical view of endogenous depression causes.

Historically, endogenous depression has been understood to be caused by an imbalance in brain chemistry. Specifically, it was thought that abnormally low neurotransmitter levels, perhaps due to low baseline production of them, were to blame. Endogenous depression was considered to be at least partially genetic and strongly hereditary; in other words, a family history of endogenous depression would mean that you were highly likely to have it as well and while this would be the case from birth, it was likely to first manifest post-puberty as with other types of depression. Speaking more broadly, endogenous depression (in the historical view) presupposes depression episodes that occur independent of external factors such as adverse life events as opposed to reactive depression, which is brought on solely or primarily by such factors, hence the common moniker of “situational depression“.

Modern view of the causes of endogenous depression.

The leading opinion in clinical and pharmacological psychiatry research circles holds that endogenous depression is caused by a dysregulation of the endogenous opioid system, but not the other systems such as the monoaminergic system, which is responsible for the well-known neurotransmitters dopamine and serotonin. The neurotransmitters implicated are beta-endorphin, dynorphins and met- and leu-enkephalins. Researchers and clinicians alike now use this view as the basis for classifying this sub-type of major depressive disorder.

The sufferer’s opinion on the nature and causes of endogenous depression.

Theory and research are great and, in the long run, are the only way we’re going to get anywhere in our understanding of mental health and mood disorders in particular. Without such understanding, our ability to get effective treatment that is safe, reliable and side-effect free is never going to get beyond where it is now, which is almost nowhere. However, such thorough understanding is a long way off and as such, anecdotal and experiential evidence is still equally if not more important. The view of endogenous depression currently being advanced by academics does not correspond particularly well with some sufferers’ experience.

It is a well-known fact that many undiagnosed mental health and especially mood disorder patients self-medicate with drugs available off the street. I’ve known one whose symptoms matched mine very well, so I am fairly confident that had he been diagnosed, the diagnosis would have been endogenous depression. If the research is to be believed, the only effective treatment would have been a course of synthetic opioids to compensate for the low production of the endogenous opioid system; in fact, while he did self-administer various equivalents of both artisanal and pharmaceutical origin, his symptoms did not abate sufficiently. From my own experience, I can tell you that on the few occasions when I have been prescribed pain medication containing synthetic opioid compounds, I did not feel any relief from my endogenous depression symptoms whatsoever.

In short, while the current research may be applicable to some endogenous depression cases, it is clearly not applicable to all of them and/or to varying degrees. We certainly don’t yet have a full picture of the causes, which makes diagnosis and treatment as difficult as it currently is.

The origin of the endogenous depression vs exogenous/reactive depression dichotomy.

In the early nineteen eighties, researchers and practicing psychiatrists alike were looking for ways to classify mood disorders in general and depression types in particular. This was driven by a number of considerations. Firstly, since there are no definitive clinical tests for the presence of depression (a urine or blood test that would confirm the presence of the disease) and the symptoms of depression can be varied, contradictory and the set of symptoms each patient presents with is rarely the same as another, it was thought that segmenting depression in this manner would make precise diagnoses easier and improve diagnostic consistency. Secondly, with some patients responding very well to tricyclic antidepressants or monoamine oxidase inhibitors and some not at all (or indeed adversely), this was expected to be helpful in both determining the cause of such inconsistencies in treatment outcomes and helping to identify the patients who would respond favourably to such treatment ahead of time.

Endogenous depression was then defined as related to the patient’s physiology and independent of external conditions, therefore being amenable to treatment with antidepressants  with talk therapy being no more effective for this type of depression than for a broken foot (the principle being that thought can not shape matter). Exogenous depression was considered to be reactive in nature – precipitated by life events and as such best treated with talking therapy, since you could scarcely expect the precipitating life event such as the death of a loved one and the consequent grief to go away after the patient swallowed some pills (the principle that pharmacology can’t influence the world outside the subject organism).

Disputes about the difference between endogenous depression and reactive depression.

Since then, the fundamental assumptions on which the utility of differentiating between these two types of depression rests have been hotly disputed. There have been a growing number of claims, supported by research, that the likelihood of an endogenous depression sufferer experiencing an adverse life event prior to an episode is similar, if not identical, to the likelihood of that being the case for a reactive depression patient. Moreover, the efficacy of depression treatment with antidepressants does not appear to correlate anywhere as neatly as has been expected to the patients based on exogenous vs reactive diagnoses.

In addition to the above-mentioned empirically based critiques, some researchers held that this dualistic view of depression, when taken to its logical conclusion, would result in an irreconcilable conflict with what little we do know about the chemistry of the brain. Specifically, they claimed that this sort of classification necessarily implies that while some behaviours were all to do with brain chemistry (in the case of an endogenous depression diagnosis), others were somehow exempt (reactive depression diagnosis).

Additionally, some clinicians and quite a few sufferers have held that endogenous depression was being used as a default, catch-all diagnosis similar to ‘idiopathic’ diagnoses in other diseases. If a neurologist, for example, can’t figure out why someone is trembling, it’s diagnosed as idiopathic tremor. “Idiopathic”, of course, roughly means “arising spontaneously from no known cause” and as such is the absence of a diagnosis, but the Greek tag often misleads the patient into thinking that the doctor has finally put his finger on the problem. Similarly, when a talk therapist didn’t succeed in determining the circumstances which led to the depressive episode, the temptation was there to write it off as endogenous depression. This had long been a source of complaints from patients before the various bodies started discouraging the use of this classification.

Modern understanding of endogenous depression.

While it is widely accepted that the split classification of depression as either endogenous or reactive is not valid or useful for the original purposes for which it was conceived, there is a growing body of research that indicates it to be of value, albeit in a different way. Endogenous depression is viewed by these researchers as a disregulation of the endogenous opioid system.

The sufferer’s view of endogenous depression.

While researchers argue about things in theory, those of us in the trenches so to speak have an entirely different view. It may very well be that both reactive depression and endogenous depression sufferers can experience a depressive episode as a result of life events, but those of us with endogenous depression often experience episodes of depression not caused by life events or any other external factor. While this evidence is anecdotal and thus not appropriate for scholarly work, it is very appropriate indeed in other settings. Incidentally, the reason it is purely anecdotal at this time is both the lack of interest among researchers and the difficulty, length and expense involved in a statistically sound study to support this claim.

The existence of endogenous depression is important for the patients to determine the viability of treatment options, since we feel that talk therapy is not effective for us in the absence of exacerbating external facors. Secondly, it is important in raising both awareness and understanding of our condition. As difficult as coping with depression is, it is doubly difficult to deal with people disregarding our suffering and doubting the validity of our condition because they can’t see the “reason” for the depression. If we can’t differentiate between reactive and endogenous depression, we can’t inform and educate people on the idiosyncrasies of our subtype of depression.

The fact is, our understanding of brain chemistry and psychiatry today is somewhat akin to our understanding of the rest of medicine in the nineteenth century. We can’t penetrate the blood-brain barrier, measuring things in the brain non-intrusively has severe limitations no matter how much our technology improves and measuring intrusively is rarely a viable option. As a consequence, for a large number of compounds, we only know that they have certain effects without knowing why or exactly how they work. Antidepressants, for example, become bioavailable and start affecting neurotransmitter levels very quickly, yet they take quite some time to make a difference in the state of the patient being treated. We routinely discover that a certain compound has positive effects on brain function or mood when we test them for something else entirely (that’s how a lot of sleep medication was discovered). The reason I bring this up is that unlike the hard sciences or even the better understood fields of medicine, psychiatry does not currently have the last word on what is what and first-hand experience is not only valid and matters, but must always hold primacy. After all, it’s our mind and we darn very well know best if it’s messed up and in what way.

Depression-related (hopefully not depressing) quote of the day.

“Well, it may be all right in practice, but it will never work in theory.”

- Warren Buffett talking about how academics view his investment approach

I thought this was appropriate to sum up our discussion of how to sum up the dispute around whether endogenous depression exists (and we with it).


  • “Endogenous Versus Exogenous: Still Not the Issue”, Medscape Psychopharmacology Today Journal Article,  Thomas AM Kramer, MD
  • “Does the antidepressive response to opiate treatment describe a subtype of depression?”, European Neuropsychopharmacology Journal Article

What’s the difference between endogenous depression and exogenous depression (aka reactive depression)?

Endogenous Depression Results


An endogenous depression is there regardless of events in the outside world, although they can definitely exacerbate it. An exogenous depression is caused by adverse life events, environmental factors (nasty weather does it to some extent for most of us, for example) and has nothing to do with neurochemistry. The term “reactive depression” is perhaps more telling, in the sense that it helps one to put one’s finger on the main difficulty endogenous depression sufferers have to deal with in their relationships with the people around them.

Why reactive depression sufferers have it easy compared to endogenous depression sufferers.

People who don’t suffer from mood disorders only know that which they’ve experienced themselves and since their moods are, in the vast majority of cases, influenced by things happening to them and/or certain things in their environment, they can’t conceive of the concept that someone might be depressed independently of or indeed despite external events and environmental influences. To them, someone suffering from a depression on a balmy, sunny day, after they’ve just left their fulfilling, prestigious and well-paying job to go home to a beautiful and open-minded spouse via a bar where everyone knows their name and a short stop at their lover’s place (who, incidentally, is as physically attractive as he or she is unassuming) is beyond comprehension – after all, he or she is depressed ‘for no reason’. According to them, the sufferer just needs to get his or head ‘right’ – realize how good he or she has it and voila – problem solved, no more depression, because how can anyone ever be depressed about having such a fairy-tale life? To them, depression for ‘no reason’ (in fact, there is a reason, it just isn’t either identifiable, tangible or corrigible in the outside world they share with the sufferer) is no depression at all, it isn’t valid and the sufferer’s very real suffering isn’t real at all.

All types of depression are tough and I wouldn’t wish any of them on anyone. It isn’t a competition either, in the style of ‘my depression is worse than your depression‘. With that said, as difficult as it is to deal with the mess in your own head, its even more difficult to deal with the lack of support from those around us (if we’re lucky) and active disdain and derision for our weak-mindedness (if we’re not). Reactive depression sufferers can usually count on others to say ‘give the guy a break, his wife has just left him, his house has burnt down together with his incredible collection of rare bonsai trees his grandfather, whom he loved dearly, had brought back from Japan to be passed down through generations as a family heirloom and he now lives under a bridge with an ugly, old woman and has to suck stones for money’, which will usually grant them all kinds of leeway in social settings, but the best an endogenous depression sufferer can hope for is ‘leave that guy alone, he’s a moody so-and-so’.

How to explain that you don’t have reactive depression and what that means.

What I’ve found helpful is to draw parallels with an experience non-sufferers may have had. In a not particularly sunny climate, light seasonal depressions are quite common. The lack of sunlight in the winter causes a vitamin D deficiency, which in turn (it is thought) negatively affects a person’s baseline sense of well-being. How severe this is depends on each person’s individual sensitivity, but it is common enough to be noticed. Ask them to remember what the difference between the last gloomy day of the winter and the first really sunny day of the spring was in terms of how they felt; now explain to them that for you, it isn’t as simple as a sunny day or a vitamin D supplement.

Depression-related quote of the day.

It isn’t cheerful or helpful this time, but it underscores what I’ve written above:

Depression can seem worse than terminal cancer, because most cancer patients feel loved and they have hope and self-esteem.
- David Burns

Can’t leave it at that, can we, so here goes:

Curiosity endows the people who have it with a generosity in argument and a serenity in their own mode of life which springs from their cheerful willingness to let life take the form it will.
- Alistair Cooke