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Biological Evidence for Depression – Mental Illness Exists

Common messages spread by certain special interest groups are that “mental illness doesn’t exist” and “there is no biological evidence for mental illness.” It’s not surprising I take great exception with these claims. So do most doctors.

But the brain is an extremely complex organ and refuting the above notions is hard. It’s not a two-word response. So, I’m going to attempt to give a two-part overview, in plain English, of some of the research around the biology of major depressive disorder according to a meta-analysis done in 2010 (see below).

There are several promising areas in the research of the “pathophysiology” (the physical changes stemming from a disease) of major depressive disorder (MDD), all with strengths and weaknesses.

Depression, Genes and Stress

Studies consistently show genetic factors affect 30% – 40% of cases of MDD. The other 60% – 70% of cases are closely linked to stressors both in the present and in childhood. A wide array of genes have been found to be associated with MDD.

[Note: the Mayo Clinic now offers a gene test to assess how your body would react to particular antidepressants.]


Depression and Stress Hormones

Elevated levels of cortisol (a stress hormone) is associated with times of stress. Cortisol levels typically decrease to normal levels once the stress has passed, however, in depressed patients, cortisol levels appear to be permanently elevated. Elevated cortisol is more prominent in those with childhood trauma.

[Note: cortisol levels have been linked to other mental illnesses such as anxiety and PTSD as well.]

Cortisol can be measured in saliva and elevated cortisol levels are almost exclusively found in patients with severe and psychotic depression. The corticotropin-releasing hormone (which stimulates cortisol release, among other things) has been repeatedly shown to play a major role in depression (and other diseases).

Serotonin, Dopamine and Noradrenaline (Monoamines)

Monoamines like serotonin, dopamine and noradrenaline have been widely studied and almost everything that increases the concentration of monoamines has been shown to have antidepressant effects.

While reduced central serotonin has been associated with “mood congruent memory bias, altered reward-related behaviors, and disruption of inhibitory affective processing,” testing of serotonin levels in people with MDD shows inconsistent results.

Research is increasingly showing the role of dopamine in MDD. Dopamine levels are consistently low in depressed patients and experimentally reducing dopamine levels is associated with an inability to feel pleasure and decreased performance on a reward-driven task in those with an increased risk of depression.

It is thought the monoamine effects seen are likely downstream effects of the primary abnormality, which is unknown. New drugs that affect dopamine appear to have promising antidepressant uses, particularly in hard-to-treat depression.

[Note: some dopamine altering drugs are on the market but are often not covered for mood disorders due to lack of FDA-approval in those disorders.]

j0385807Neuroimaging of Depression

Because of the cost of neuroimaging studies, only small-scale study data is available and most studies don’t have overlapping results due to subjects and neuroimaging methods selected.

However, structural abnormalities and decreased brain volumes have consistently been found in several areas of the brain of those with MDD. Brain volume in those with untreated depression decreases with length of depression.

At this time, the volume loss cannot be explained but can be stopped or possibly reversed with treatment. (Many mental illness treatments have been shown to promote neuron growth, neurogenesis.)

Biological Evidence for Depression – Part Two Next Week

Next week I will discuss the three remaining biological depression areas of research and bring together what this information means.

Notes on Information Source

This information is a concise synopsis of “Pathophysiology of Depression: Do We Have Any Solid Evidence of Interest to Clinicians?” by Gregor Hasler at the Psychiatric University Hospital, University of Berne, Switzerland. Published: World Psychiatry. 2010 October; 9(3): 155–161.

Hasler has published in a number of reputable journals. I believe this work was completed without outside funding, but I can’t find any information confirming that.

Yes, I have massively condensed this article and explained it in plain English, so for all the details, refer directly to the article.


Comments are welcomed as always; however, please be aware comment moderation has become stricter. Comments that are not on topic or that disparage others will not be allowed. Thank-you for your cooperation

You can find Natasha Tracy on Facebook or GooglePlus or @Natasha_Tracy on Twitter or at the Bipolar Burble, her blog.

Author: Natasha Tracy

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33 thoughts on “Biological Evidence for Depression – Mental Illness Exists”

  1. There are those who want to treat the brain as a separate organ from the rest of our body, especially in regards to mental illness. Maybe it is the feeling of lack of control” or maybe because there is little environmental causation. Again like always would these folks say cancer does not exist? There are some who say that but are usually publicly mocked.
    Now that you show that there is “Real” science from “Real Institutions” the anti psych crowd can only go personal. Science removes their argument so like a child they get personal. Keep fighting them with science, shine a light into their empty theories.

  2. Hi Steven,

    Yes, the article references 88 other publications. It’s a pretty good overview of where mental illness is right now. We’re far from knowing enough, but we do know some things.

    – Natasha

  3. Hi Natasha!

    Thanks for this article. Lot’s of insights, resources, links and the like that dispel the myths of depression as something that’s “all in the mind”, tantamount to eliciting preconceived (and erroneous) notions from people about how “easy” it may be to handle.

  4. Natasha,

    Thank you for the update. I can respect your enthusiasm with the theories. If lack of mental heath or stability is proven biologically it is a brave new world indeed. However, I am on the other side of the aisle on this. I will rant and muse now on these things. What would change if a bipolar disease gene was actually discovered?
    Would medical, legal, and political laws change? How so? To what degree? Would civil and religious authorities be more merciful to diseased offenders and as a consequence less so to their healthy victims? By what percentage? Who would decide?
    What new tests would apply? What old tests would be validated? “Maybe he/she is just an undiagnosed or untreated bipolar?” Would a cruel act by someone with a mental disease diagnosis now be less cruel? Would a kind or courageous act be even more kind or courageous? Would a contract signed by someone with mental disease now possibly be less legal?
    Would having such a gene make one less mature or less responsible or excuse poor hygiene or table manners or bad debts or social graces or watering flowers or patience with children? Maybe a lack of confidence or excessive pride is just due to a bipolar disease gene. Is there a gene marker for that? A graded difficulty factor? How about with exercise or volunteering or vitamins figured in?
    What test can currently be applied to prove conclusively someone has a bipolar disease? Would the test hold up in a bar room discussion or in a court of law? Are unhappy or abusive or abused people less stable generally and more rude more often than happy people simply because of a gene?
    Does a bipolar disease gene possibly contribute to make you sad or angry or greedy or jealous? Does another gene than make you joyful or loving or kind?. Does another one make you a quitter or lazy or fat? More apt to make impulsive choices with unhappy consequences? Is it a question of personal behavior or of social conduct or is it mainly biology? Is there a “scientific cure” for the way some people relate to or respect others or themselves? Could a medical drug or a surgery fix this. If so, prescribe me one please.

  5. Hi rsl,

    I think you’re missing my point.

    While yes, I’m the kind of person that finds research interesting, it’s not terribly useful to me. If it doesn’t help me personally get better, it’s of limited personal value.

    This information is less for me than it is for every person with a mental illness who has to stand up to people saying mental illness isn’t real. It doesn’t exist. Mental illness is just “normal emotion.” And so on.

    Legally, mental illness is already an illness, legality has nothing to do with it. What it has to do with is dispelling myths. Brain scans don’t change my life one whit.

    – Natasha

  6. Natasha,

    Thanks so much for this article! I have always wondered if cortisol levels were elevated in patients with depression. I have OCD and Bipolar and wondered why I always felt stressed. I guess that explains it!

  7. It is evident that neuroscience investigation, the last two decades, have made great inventions, that will contribute in successful treatment of mental disorders. Depression as the most frequent mental illness isn’t exception. The researches have confirmed that mental diseases are descended from disorders of brain as organic substratum of psychological functions. It seems simply to agree with this ascertainment, but in clinical psychiatric workout we face with many difficulties and primitive attitudes as well. In this antipsychiatric movement, unfortunately, are included patient and doctors. By me, the main reason for this sceptic state in Mental Health Service is overload inheritance in century-old mistreatment of psychiatric entities. It should to constrain for a substantial promotion of mental health; its maintain and its current treatment. Otherwise, depressive patient as others mentally ill patient wouldn’t take required medication, even this is in disposal. There are many misunderstandings that should to explore in concordance with epochal achievement of biological evidence for mental illnesses.

  8. Psychiatry is about treating behavior that society does not approve of so if I refuse to get out of bed to work and go to a job I detest then I must be clinically depressed. People who openly challenge the status quo are doomed to a diagnosis of some sort. Look at the list of behaviors of any psychiatric label and you’ll see what I mean. Psychiatry is about making people compliant. All people who suffer serious mental illness have been abused or traumatized at some point. If you actually look into their backgrounds whatever they’re going through has been triggered by some event or events, however that’s not what psychiatry is about, getting to the heart of the matter rather, it’s about ticking off a list of behavioral symptoms diagnosing and medicating.

    As for genes even if in Van Goghs case if they were to identify the set of genes that made him stand out from the norms what would that gene be, a biopolar gene or a gene for artistic creativity? What then? Give someone like van Gogh a drug that switches off the respective bipolar/creative genes so he can be like everyone else and spent his life working 9-5 as an office clerk.

  9. Elpenor,

    You are certainly welcome to that opinion. If you do not wish to get out of bed and get a job, that’s your business, but it seems like you would be homeless fairly quickly. If you don’t have a problem with that, then that’s up to you.

    Some people have trauma in their background and have a mental illness, some do not. Some people do not have a trauma and do not have a mental illness, some do. People are unique. Trauma doesn’t equal mental illness. Many people with a mental illness work very hard at dealing with whatever their particular life experiences have been, that doesn’t necessarily make a mental illness disappear.

    Well, if you would rather lose an ear and paint, well again, that’s up to you, but I rather like my ears. Keeping my ears isn’t about “society” or “convention” it’s about the fact that I want my ears. And arms. And pretty much everything else I was born with.

    And for all the people who committed suicide, that isn’t about “fitting in” either, it’s about saving their lives. If you would rather have a dead brother, or mother, or friend, than a medicated one, well, again, that’s your business, but mot people wouldn’t make that choice.

    I wrote that mental illness is only a problem when it causes problems in your life. http://www.healthyplace.com/blogs/breakingbipolar/2011/03/mental-illness-is-only-a-problem-when-mental-illness-is-a-problem/

    – Natasha

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