Treating depression as brain damage

According to a recent article in the Boston Globe, the theory of depression as a chemical shortage in the brain is losing ground amongst scientists in favor of a new theory of depression as damage in the brain. It’s not nearly as out there as it initially sounds, and it actually does fit a lot of clinical evidence better. For instance, fluoxetine (the active ingredient in Prozac) raises the level of serotonin in the brain. Yet using other drugs to lower the level of serotonin in the brain does not cause depression, nor does it make depression worse. The release of serotonin caused by fluoxetine is thus probably doing something else to the brain: healing the neurons, not simply restoring a chemical balance.

Now, this only makes sense if depression is actually a mild, reversible neurodegenerative disorder as opposed to a chemical imbalance. The theory goes that people are depressed because their neurons are in bad shape due to a lack of regenerative trophic factors, and the proper treatments (fluoxetine and exercise are both highly effective) increase the production of trophic factors and cause injured neurons to recover/regrow. This explains the observed clinical phenomenon known as “Prozac lag” — serotonin levels go up within hours of starting treatment with the drug, yet it takes weeks for the depression to be alleviated. Well, guess how long it takes to repair/regrow neurons? Weeks, not hours. Fluoxetine is also being investigated as a treatment for lazy eye, which is caused by underdevelopment of the neural cortex. It works in rats, the theory being that the fluoxetine is fostering the growth of new neurons. It’s now starting to be used as a treatment for lazy eye in humans.

Now nobody’s sure if the new way of thinking about depression is completely correct, so don’t go jumping to any conclusions just yet, but it’s now looking more likely than the chemical imbalance theory of yesteryear. The new theory also explains the other factors that are so often coincident with depression — memory problems, smell and taste sensory deficits, and basic bodily process problems with weight control, sex drive, and sleeping. So under this new theory, we don’t think of depression as just sadness, but of an overall lowering in functioning in the brain caused by neural deterioration, of which sadness is simply the most notable symptom.

The new paradigm should make it easier to get people to accept treatment. Instead of telling people that they need chemical happiness (which some people refuse, because they don’t like the idea of a chemical in their brain making them something other than themselves), tell them that they need a chemical to repair minor neural damage. Phrased that way, it’s a lot less off-putting. Who would be opposed to fixing brain damage by taking a simple pill? It has a convenient explanation, too — in the modern world, humans are exercising a lot less often than we used to, and as a result, the trophic factors that promote neural regeneration aren’t being produced in the same quantities. If people aren’t getting enough exercise to replace those lost trophic factors, at least restore their equivalent brain function through the use of a convenient pill.

I wonder what ramifications this theory this will have on the future of neurology. We may soon find out that other psychiatric disorders are caused by some forms of damage to the brain (we already know about the obvious ones, like Alzheimer’s disease). Medical neuroscience may shift away from modifying neural chemical levels towards treating and rejuvenating neurons. It all goes to show how science is consistently digging up new truths and changing our world for the better. Science brought us fluoxetine and now it’s finally explaining how it actually works, creating a bridge of understanding that will hopefully help in the treatment of other disorders.

33 Responses to “Treating depression as brain damage”

  1. T2A` Says:

    I still say depression is psychological. I have every reason to be depressed but I am not. Therefore it must be bollocks. :]

  2. Cyde Weys Says:

    I don’t see how that follows, so I’ll assume you’re joking.

  3. Gregory Maxwell Says:

    It would help if the medical profession (not the researchers, .. but run of the mill doctors) would bother differentiating justified unhappiness, which is probably an adaptive response and not any form of imbalance/damage/malformation, from clinical depression.

    I don’t know that I’ll ever be able to shake the mental association of prozac with soma after the multitude of cases I’ve seen where friends and associates in abusive homes or with difficult lives have been pressured into a psychiatrists office (often by the very people mistreating them) where they are proscribed such drugs after nothing more than filling out a brain damaged screening form (Do you sometimes feel overwhelmed? have you ever though of suicide?) which would probably manage to identify Gus Godsey as in serious need of medication. … and of course the sucky factors in these peoples lives were never addressed.

    Of course, there are many real cases of depression that need treatment. But so long as we continue to over-proscribe, misdiagnose, and attempt to use drugs to make people stop complaining we’ll continue to produce a “chemical happiness” stigma which inhibits the truly needy from getting the treatment they need.

  4. drinian Says:

    Likewise, this is, I would guess, why many people with depression and anxiety disorders can discontinue SSRI use after a period of time. It also may be why can be tremendously beneficial in some cases.

    Not mentioned in the article was a study that came out a year or two ago that found many Parkinson’s Disease patients had been diagnosed with depression about a year being diagnosed with Parkinson’s. So, clearly, there is a role for degeneration in models of depression, and there are lots of different kinds.

  5. drinian Says:

    why exercise is beneficial, that is.

  6. Jeff V Says:

    Wow this article is really interesting. I think I’m going to go look up more about it, thanks!

    …but I probably won’t because life is meaningless and I’m no good.

  7. Amy Says:

    here’s a review of some research documenting the relationship between TBI and depression
    “Researchers found… that structural brain damage plays a large part in psychiatric illness.”

  8. heather (errantdreams) Says:

    It would help if the medical profession (not the researchers, .. but run of the mill doctors) would bother differentiating justified unhappiness, which is probably an adaptive response and not any form of imbalance/damage/malformation, from clinical depression.

    A good psychiatrist or psychologist will differentiate, and ask plenty of questions about what’s going on in your life before assuming clinical depression. Unfortunately, it’s like any other profession—plenty of cruddy and/or lazy doctors out there. It doesn’t help that a lot of general practitioners assume they know enough about psychiatry to prescribe psychotropic meds to people; they’re often the ones most guilty of handing out anti-depressants like candy. (How many general practitioners actually use the DSM when evaluating patients for depression?)

    I remember hearing once that it was thought that rather than there simply being a physical disorder called clinical depression, or a physical disorder called bipolar, there are probably actually a number of similar (but slightly different) disorders. Part of the reason for thinking this is that different people respond differently to different medications. One person with bipolar might respond great to lithium, while someone else doesn’t do well on it and needs depakote or even carbamazepine. Some folks do all right on just that one anti-spasmodic, while others need several other medications to control other aspects of the illness.

    And of course, there’s the fact that the combination of drug therapy and some sort of psychological therapy has been found to be twice as effective as either one alone.

    If there are different varieties of clinical depression, then I find myself wondering if it’ll turn out that some are inborn while others follow a ‘damage’ model. Or perhaps the damage is caused by something genetic. After all, last I heard it sounded like researchers were pretty sure that several things like bipolar and ADD were largely genetic.

    I have no idea how coherent this is, mind you, since it’s past my bedtime and I didn’t sleep well last night. :) Anyway, thanks for posting about this—it’s fascinating.

  9. Paul Jenskins Says:

    Truth be told – there is not enough evidence regarding depression and brain damage. The structural differences noted can possibly be accounted for many factors not yet identified.

    The one real frusturating aspect regarding treatment of depression lies in the descripiton of the action of an antidepressant. This is usually worded something to the effect of ” the mechanism of this medication is not truly known in how in interacts or treats the biochemical aspects of depression. I personally think that just one of the reasons for this is what incentive would a drug manufacurer have to further their study once the drug was approved. This goes in line with their disclaimer that ” beyond six months the effect of this drug is unknown” An incidence of depression lasts for at least 9 months and left untreated is likely to re-occur. However, why would a drug manufacturer concern themselves with that aspect.

    One final note is: what is the effect on a person who takes “prozac” *drug used only for illustration) for over twenty years. NO studies have been done.

    We talk about depression and brain damage and the possibility that antidepressants “may” assist in neuorgeneise.
    What else might they do? Who is in charge of studying that aspect?

  10. Paul Jenskins Says:

    It is very frusturating that there are no studies of long term use of antidepressants and a great percentage of individuals are taking antidepressants for years. However, if you look at the manufacturer’s drug information sheets – it usually states that their respective studies sometimes do not evan last as long as six months.

    When will the time come when drug manufacturers stop saying: “the actual mechanism regarding how this drug works is unknown?”

    If someone can be in a coma for a long period of time and come out of it with out brain damage – there is the possibility that depression is not always a cause or result of brain damage. Also, if anyone had dementia or alzheimers – wouldn’t it stand to reason that the frusurating aspects of that disease would lead to depression?

    The jury is still out. There is evidence of neurogenisis and so on and so on.

  11. Mark Says:

    “Science brought us fluoxetine and now it’s finally explaining how it actually works”, – I don’t know where this statement comes from because in actuality Science does not know how it works. The Drug Manufacturers do not know how it works.

    “The new theory also explains the other factors that are so often coincident with depression — memory problems, smell and taste sensory deficits, and basic bodily process problems with weight control, sex drive, and sleeping” How do we know that these spmtoms are not also the result of a “chemical imbalance” as opposed to brain damage?

    We need to be cautious and remember what the word “theory” means.

  12. knacker Says:

    I’m waiting for the completely engineered intelligent systems. Then we won’t have to worry about crap like this; we’ll just redesign minds so they don’t have these problems.

    Then again, that might suck more with all the lack of humanity and junk.

    I don’t know what to think, so I’ll stop.

  13. William (green) Says:

    You saw Equilibrium, right?

  14. knacker Says:

    Hahah, I love it when people point to fiction to determine how any particular idea would work in real life.

  15. William (green) Says:

    That’s not quite what I was going for. I just thought it was a good movie, and it’s vaguely relevant, so… “Why not”, you know?

  16. knacker Says:

    But anyway, what I was talking about was something like, or maybe a precursor to, the singularity. A time when all inteligence chooses it’s own path.

    There will probably still be some depression, because some depression will definitely come from the ghost in the shell… And while I think that most people will just choose to live in an ultra-real world of warcraft world to get out of it, it’ll be better than our current reality, where anyone with a mental problem is going to start causing problems for everyone else, shooting up schools, starting fights.

    I don’t think we’ll lose our humanity. It’ll enable us to be more human than ever before, in both bad and good ways.

  17. William (green) Says:

    I’m going to point to fiction here, but as you said, the Ghost in the Shell. At that point, what’s to stop some emo-goth-hacker kid with an Internet trenchcoat from doing the same thing? People who no longer value themselves are dangerous to the society whose members do, and I don’t think that will ever change.
    Well, not for a long, long, long time. Loooong.

  18. knacker Says:

    By “ghost in the shell”, I meant the factors in one’s consciousness that can’t be accounted for by the meat, the extremely complex inter-workings that may be impossible to penetrate, like it’s original context, but yeah… GitS was a really good series.

    The difference was that Ghost in the Shell is actually VALID fiction for thinking about the future. It doesn’t prescribe a certain ending for the technology, it just introduces the possibilities, both bad and good.

    And I think the difference will be that the poor helpless hopeless idiot kid will turn to a fictionalized world rather than the harsh reality, effectively sealing himself off. I think that the fiction will be that seductive.

    And I honestly think that it’ll be easier for the government to just give these kids an IV, maybe give some limp pretense of trying to draw them out of their hikikomori-like trance, and shut them off from society forever. Sort of like putting old people in nursing homes because it’s too much trouble to try and fix them, but unethical to just let them die.

    In fact, the idea of them being dangerous to society may make it easier for the other members to accept this state of affairs as well. All it’ll take is the equivalent of one columbine style attack and everyone will be sealing these dangerous kids off on their own. Hell, it may even become the de-facto method of dealing with troublesome kids. Send them off to Candy Land! Where they can dance and sing with the mushroom club and we don’t have to keep their little asses in line anymore.

    Humanity is a sad species, becoming more and more selfish by the decade.

    Hell, some tech or political change may happen a month from now making this scenario impossible, but it’s still fun to think about.

  19. Richard Hartman Says:

    Try cpc-choline &/or hyperbaric oxygen.

  20. werner Says:

    Could it be possible that people feel depressed for good reasons? … perhaps a sense that you have done something wrong or made major mistakes in your life. No one wants to accept the idea that the ultimate solution, suicide, may sometimes be justified. What is currently referenced as a clinical illness was at one time called “conscience” or “guilt”. There is no pill available here.

  21. joe Says:

    Werner, your ignorance is so severe let me tell you that I hope a family member of yours falls to depression and you see the toll it takes. I hope you die.

  22. Diane Says:

    All my life I’ve suffered with mental illness. I was severely abused as a child and was showing signs of mental illness even then. So which came first? Did the abuse create the mental illness or was I genetically predisposed since my Dad was bi-polar and my mother a malignant narcissist. I have been suffering with fibromyalgia for thirty years and now after being denied for decades that the disorder is even real new brain scans reveal a significant loss of brain mass as well as reduced blood flow to key areas in long term fibro sufferers. I’ve been on 9 different psych meds for the depression as well as the fibro, none of which have had any significant difference in my daily life. I’m now a medical marijuana patient and of all the meds I take except for the vicodin it has give me the most relief with many of my symptoms.
    I’m excited by the new brain research as I’ve often wondered if I had a damaged brain. I look forward to some definitive answers as well as some vindication.

  23. Jane Says:

    I don’t know about brain damage causing depression, but I very strongly believe that depression, long-standing suffering or mental illness can cause brain changes which I would refer to as “damage.”

  24. M_b Says:

    Werner, I wonder if you could tell me how that stunning logic of yours applies to any of my former fellows at the Children’s Psychiatric Hospital, please? I knew, among many, an eight year old who tried very hard to cut his own throat with a kitchen knife, another who attempted to break his glasses in order to slit his wrists, a thirteen year old girl who had her death meticulously planned out. Could you tell me please what terrible thing they’d done in order to be consumed with such “guilt” that they would attempt to end their lives like that? And should we have let them, as a form of “justice?”

    The world is not as clean cut as merely punishment and crime, friend.

  25. Generative Says:

    Does depression actually kill neurons or does it only damage/weaken them (along with slowing neurogenesis)? Also, are there any studies indicating how long it does for the damage (or death) to start?

    Now that people begin to learn more about harnessing the power of neural regeneration then….is it likely that directing the birth and integration of new neurons in all major areas of the brain awaits in the somewhat near future? How much cognitive boost could occur by doing this?

  26. v_manman Says:

    and what about the studies that show placebos are about as effective as real anti-depressants?

  27. CHRIS Says:


  28. u_mad_bro Says:


  29. sdf Says:

    This is a no-brainer to me. I hate the word ‘depression’. It insinuates so much less than the clinical version of it is.

    I’ve felt for long that I have some form of brain-damage which led me to google for results, as this vacuum in answers is driving me nuts.

    When I wake up after a long sleep there’s this deep, degenerative feeling headache. I feel vulnerable outside as it virtually impossible to feel in control. Trying to focus on controlling myself often results in forgetting my footsteps, and I hit curbs and almost people. Sometimes my hands shake, but mostly when the brain feels very depressed. I walk aroud trying to hide the mess, and doing so takes away from walking straight. And concentraion and reaction are poor, that I’m worried about walking into people, which happens, and I don’t know what to say. There are no answers, since not even science knows, let alone ordinary folk.

    Sometimes that deep headache leads to vomiting. I swear it’s that vomiting releases endorphins and is the body’s way of restoring mood somehow. It’s like you hit the rock bottom, emotionally, and the body reacts brutely to try to recouperate. Nothing else helps at that point that i know of.

    When things are ‘better’, there’s mainly a dominant sad mood that makes it very difficult to interact with people. It feels as if the parts of the brain that generate joy have died. Thus the sad feeling doesn’t go away. And avoiding people more or less is a natural consequense, since it’s so far from normal that it can’t be ignored and people ask if your on drugs. Processing what they say is diffuclt. It’s as if there’s a face just staring at me, and I have to make a concerted effort to focus on the talking part of the ‘face’. Can’t simply date, having friends is challenging, etc. It leads to existential problems on top of a neurological degenerative mess. There’s no room for to deal with other problems on top, so your teeth and other health aspects take a toll, as there’s simply no energy to deal with them.

    It’s fucked-up. There are no answers, even after years. I hate it. It’s just a naked existence, that I swear most people wouldn’t have survived. They’d likely kill themselves or big-time despaire after just 2 hours. I remember, being more fully experiencing, and trying to imagine something like this would’ve been almost impossible, it’d be just too off and uncomfortable to do. Only having hope keeps you going. But not hope alone, not without working toward something, but it often seems futile. It’s a joke.

  30. amy Says:

    I’ve suffered from depression coupled with eating disorders for several years…I had spent most of my days at the gym, running up to 14 hours a week, nevertheless I was extremely depressed….

  31. wew Says:

    Brain damage sounds a lot more sensible than ‘chemical imbalance’. Memory and thinking problems to the point of a handicap are supposed to be caused by a lack of serotonin? What a joke. Serotonin is readily available in several foods for one. It sounds more like with muscle atrophy, in that perhaps the brain doesn’t produce enough of needed brain chemicals to function and feel normal, which causes it to shrink. Muscle atrophy also happens when not using them for long. What if they said that limping legs were caused by a muscle based ‘chemical imbalance, it’d be insulting. Atrophy more matches the severity in symptoms, and the impossibility to control them by effort or will power.

  32. Andy Says:

    Its underdevelopment of the VISUAL cortex not the neural cortext — second paragraph, third to last line

  33. Kelly Says:

    When one doctor began to treat me with this theory in mind, I woke up. After 20 years, I am functional. Now I work in a field that helps children recover from their injuries and lead their own lives.
    I have been self-sufficient for 5 years without relapse.
    This theory deserves further investigation. It is not a “joke.” It is not an “excuse.” It is a possibility.