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.

This is what you will be saying when Ultimate Depression Relief takes effect. What a tremendous feeling it will be for you to feel happier and depression-free throughout the day. You willl discover something new and wonderful every day when you use Ultimate Depression Relief. You will be able to enjoy work because you will be depression-free, mentally-focused, and ready to win the day. You will most likely outperform your co-workers because you will be able to focus and concentrate much better. Every minute of the day and night it will gently relax, comfort, and relieve you from depression. Gesundheit, Santé, Salute

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

Endogenous Depression Vs Exogenous/Reactive Depression

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

What Is Endogenous Depression?

What is endogenous depression then? (the boring part)

The term “endogenous” comes from the Greek “endo“,meaning roughly “from within”, and “gen“, meaning “producing”.  If we put it all together, an endogenous depression  - properly fully termed endogenous major depressive disorder or mood disorder, endogenous clinical depression - simply means that the depression is caused by factors internal to the organism rather than external factors such as life events, trauma or environmental influences. This is juxtaposed with an exogenous depression (also termed reactive depression), which is brought on by one or more of the external factors listed above. The difference between the two will be the subject of an upcoming article. (You can now read the article “Differences Between Endogenous and Exogenous/Reactive Depression“.)

Endogenous depression is, briefly speaking, caused by dysregulation of one or more systems involving neurotransmitters which are responsible for, among others, euphoria, sense of well-being and energy. It is believed to be a genetic, hereditary condition in most cases. Read Causes Of Endogenous Depression if you’d like more detailed, if boring to some, information.

What is endogenous depression like really?

Endogenous Depression Painting

Endogenous depression through the eyes of a symbolist painter

For a sufferer, it means being a slave to neurotransmitter production and reuptake in his or her brain. No matter how great the weather, how beautiful the surroundings or how pleasant, friendly and cheerful people around him or her are, the sufferer can feel subdued, groggy and emotionless or conversely irritable and anxious. What makes things worse is that those wonderful people can’t understand why the sufferer is carrying on in such an unsociable, grumpy manner when there’s every reason in the world to be jolly and enjoy life. Humans are social animals and as such find it difficult to sustain a good mood if one of the members of the group is behaving in such an abnormal way. Not knowing the reasons for such behaviour on the part of the sufferer and attributing it, at least subconsciously, to his or her contrarian nature or inability to place the well-being of the group ahead of his or her own, many members of the group are likely to exhibit overt signs of displeasure in various forms, none of which are easy to deal with for the sufferer and which invariably make the situation worse. Others will react by attempting to uncover the reasons behind the sufferer’s bad mood, either by asking him or her things like “what’s wrong” and assuring him or her that “you can talk to me”, ad infinitum, or by doing random things to remove perceived impediments to the sufferer’s being happy, the list of which is of course arrived at through infuriatingly inappropriate guesswork. The sufferer will often think “If my problem weren’t in my head, there’s no way this would have been it – do you even know me?”.

It’s a feeling of being trapped inside your own head – willing yourself to feel better so your friends and family can have a good time, wishing and hoping beyond hope that relief will come and no one will realize just how badly the sufferer is capable of functioning in society. Of course, relief doesn’t come and both the irritating fussing over the ‘grumpy’ sufferer by some and the disapproving looks from the rest make matters even worse. Saying “don’t mind me, I’m just under the weather today, it’s nothing to do with you guys or anything, really” doesn’t help one iota and you wish you could say what’s really wrong, but you can’t – because you don’t know yourself, can’t find the words or can’t live with the stigma.

Read Endogenous Depression Signs And Symptoms for more, as this deserves its own article (one I can write on a better day than today).

Depression-related quote of the day.

I don’t mean to be a Pollyanna, but whenever I’ve felt helpless in a battle with my own brain and despaired at the futility of fighting my own body, I’ve come back to this:

“If you don’t like something, change it; if you can’t change it, change the way you think about it.”

- Mary Engelbreit

The new way I choose to think about my predicament is different each time, but I distinctly remember one from childhood. My mother’s colleagues, after hearing me play several Chopin preludes, couldn’t believe that a 7 year old boy could understand enough about the depths of sadness, melancholy and hopelessness to play them in the manner I did. I felt a certain hint of satisfaction at thinking that I’ve plumbed the depths of despair no adult in the room has, enabling me to make music, rather than just elicit sound from my instrument.

Why I started EndogenousDepression.NET

Why did I start “Endogenous Depression Help“?

I started this site as a result of being frustrated by what’s out there on the web, or rather what isn’t. All the large health sites have plenty of articles about depression, even whole sections, but they are all written by people who don’t know what it’s like. All this dry prose, regurgitated from textbooks, medical journals and ‘crazy people for dummies’-style books is great if you’re trying to please the search engines and sell ads (which is what these sites want to do) or if you’ve heard the term and are curious about what it means. Even Wikipedia isn’t much help. If you’re a sufferer or think you might be one, they’re worse than useless – they’re depressingly useless. If you are a friend or family member of someone who is or you think might be a sufferer, differential diagnoses in medical jargon won’t tell you much about the signs in practice and definitely won’t help you understand how your loved one might feel and how you can help.

How do I want “Endogenous Depression Help” to be different?

I won’t just list endogenous depression symptoms, I’ll write about how they feel to the person experiencing them and what they look like to his or her loved ones. I won’t just talk about endogenous depression treatment options in general, I’ll explain what the experience is like and what the pros and cons are. I won’t just push pharmaceutical treatment options, as important and effective as they can be, and will instead also present alternatives including things anyone can do on their own without having to pay doctors at every step of the way with money you might not have.

I’d also like to put together information for family members and friends to help them cope (the sufferer is never the only one affected by depression), understand, take charge and regain some hope. A community for everyone affected, which I hope to build together with you, the readers, is long overdue.

In short, I intend to actually help everyone involved with genuine information informed by my and others’ first-hand experiences without any concealed agenda or one eye on profits.

Depression-related quote of the day

In my many times of trouble and internal strife, I’ve often found solace in quotes, fables and haiku that made my mind acquire a different perspective on both my own plight and the world in general. I’d like to make it a tradition to conclude each article with one of them, so without further ado, here is an Arab fable which persuaded me that I can’t possibly be the most unfortunate human being that ever lived at a time when I felt certain that I indeed was.

I never lamented about the vicissitudes of time nor complained of the turns of fortune except on the occasion when I was barefooted and unable to obtain slippers. Yet when I entered the great temple at Kufa with a sore heart and beheld a man without feet I offered thanks to the bounty of God, consoled myself for my want of shoes and said:  ’A roasted fowl is to the eyes of a satiated man less valuable than a blade of fresh grass on the table, but to him who has no means nor power, a burnt turnip is a roasted fowl’.