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Biological Evidence for Depression – Mental Illness Exists

'Depression is all in your head' say some who claim there is no proof mental illness. Here are biological, testable indicators of depression proving it 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) are 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.]

Neuroimaging 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 the length of the 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

Natasha Tracy is a renowned speaker, award-winning advocate and author of Lost Marbles: Insights into My Life with Depression & Bipolar.

Find Natasha Tracy on her blog, Bipolar Burble, Twitter, Google+ and Facebook.

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

  1. You’ve been highly selective in how you have reported the findings of a single meta-analysis. The analysis itself contains phrasing that is easily misinterpreted. It points out that while genetic predisposition (sensitivity which is not specific to depression) may have a minor influence, the overwhelming contribution is environmental and therefore psychosocial intervention has the greatest potential for ‘treatment’. It also points out that while some physiological changes are evident in some sufferers it is not evident in the majority. It clearly states that there is huge variability and no unifying theory of pathophysiology exists.

    The problem with meta-analysis is that they rely on studies already carried out which themselves have inherent flaws and biases. The major flaw being being confirmation bias (you see what you want to see and downplay contradictions ) and that correlation is not causation. Our mental states influence our physiology, long term exposure to stressful environments causes adverse affects and changes on our physiology. That physiological changes are evident in some subjects and not others does not imply causation.

    Presenting selectively chosen phrases from a single meta-analysis without presenting any qualification for the points you are making is misleading and potentially harmful. The truth is that the evidence shows (and is stated repeatedly in the study) that no single varifiable biomedical abnormality can be proven to cause depression.

    There is a huge body of evidence, not just from special interest groups but from within the psychiatric field itself and from clinical psychologists and therapeutic practitioners, not to mention experiences of ‘service users’ that shows that treating mental distress as biological illness is unfounded and potentially very harmful.

    If the purpose of your site is to support and inform sufferers of mental distress you have a responsibility to present informed unbiased information. Statements such as “biological evidence for depression – mental illness exists” are misleading and supported by the paper you are quoting

    Given that the scientific understanding of these issues is likely to beyond most readers of your article it is likely to simply cause more distress and alienation.

  2. At this time, medical science alleges “knowledge” based on it research, the majority of it of very poor quality and funded by the pharmaceutical industry. Whether mental illness is genetic, environmentally caused, and/or a combination of these two and/or a combination of other factors is not yet definitely established and is as of yet unknowable. At this point, based on the uncertainty of an accurate diagnosis in most patients I think medicine does more harm than good. I think some rare patients do benefit and do need help and benefit from pills. I am not anti medication–only for those who benefit from it However, I think many vulnerable children are inaccurately diagnosed by highly paid physicians who are paid by Big Pharma to place them on expensive pills. Many of these children recover without pills. Therefore, at present considering the economic incentives for over-medicating, I think for the majority of the public, medicine and Big Pharma do more harm than good. Science, I think, at this time too biased, greedy, and political to be accurate and fair.

  3. Elopenor and others trauma doesn’t always play a part in mental illness, look at the 1980s documentary “Children of Darkness” Brian a schizophrenic and moderately intellectually disabled may or may not had trauma but had a very loving father

    Some children seem to be born with mental illness, how do you explain that? And some with very loving families

    I agree, however, at times trauma play a part in mental illness and there is even one illness PTSD where trauma is a ‘criteria’

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