Biological Evidence for Depression – Proof Mental Illness Exists

April 11, 2011 Natasha Tracy

Discussion of the clinically-relevant evidence for the biology of depression. Depression is real and treatment works. Here's some of the proof.

In my last article on the biological evidence for depression I discussed evidence in genes, hormones, monoamines (like serotonin) and neuroimaging. Today I’ll finish off the research areas for the biological evidence of depression and suggest what I think all this biological evidence means.

Brain Shrinkage in Depression

As mentioned, it has been consistently shown brain volume loss is seen in those with untreated major depressive disorder (MDD) and antidepressants stop (and may reverse) this volume loss. It is thought this brain volume loss may make people more sensitive to stress and increase the likelihood of future depressions.


It is not known why the volume loss occurs as there is no way to study the suspected processes in a living brain. However, very early research suggests brain derived neurotrophic factor (BDNF) – one of the most active substances to promote neuron growth (neurogenesis) – may be decreased in depression and increase with antidepressant treatment.

Neurotransmission and Depression

Dysfunction in the glutamate system, key for neurotransmission, learning, and memory, has been found in those with MDD. Inhibitors in glutamate release have shown antidepressant properties. Neurotransmission is an extremely challenging area of study and it’s likely currently known drugs don’t target specific dysfunction adequately.

Circadian Rhythms and Depression

Sleep-wake patterns are often problematic in those with depression and it has been shown that manipulation of the sleep-wake cycle (circadian rhythm) can produce antidepressant effects. However, the genetic and biological reasons for this dysfunction and effect are unknown.

What Does this Biological Evidence Mean?

Biological evidence for depression means two things for those fighting the notion mental illness isn’t real:

  1. Depression, as a biological disease, exists
  2. Treatment for the disease has corrective, biological effects

Yes, neurology is a science. Yes, psychiatry is a science. No, they aren’t just coming up with random chemicals to put into bottles.

Biological Evidence has Limitations

All this evidence shows while we do have biological indicators of depression, many in fact, we are unable to personalize a treatment for an individual’s biology.

Right now “depression” is a disease with essentially two treatable categories – unipolar or bipolar. These are useful distinctions in terms of treatment but are inadequate in terms of biology. It is clear to me that the human brain is far too complex to make only this single distinction.

I think many things can go wrong in the brain and lead to the symptoms of depression, but we aren’t diagnostically sophisticated enough to pinpoint an individual brain’s problem and give an individual treatment.

And while we do know many things about the biology of depression there are still so many things we don’t know. It’s clear that we can detect system dysregulation, but it’s likely only a part of that system is actually broken and we aren’t able to pinpoint that part. We don’t even have a name for that part yet.

Depression is real. Treatment works.

While I, and I think any researcher or doctor, would admit we’re miles away from complete understanding, what we do know grows by leaps and bounds each year. Much of what’s in this article couldn’t have been written 10 years ago.

And while what we do not know may outweigh what we do know, we do know this: depression is real and treatment works.

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.

Handy table of clinically relevant neurobiological hypotheses of MDD with their strengths and weaknesses.

Natasha Tracy is a mental health writer. You can find Natasha Tracy on Facebook or @Natasha_Tracy on Twitter.

APA Reference
Tracy, N. (2011, April 11). Biological Evidence for Depression – Proof Mental Illness Exists, HealthyPlace. Retrieved on 2024, July 14 from

Author: Natasha Tracy

Natasha Tracy is a renowned speaker, award-winning advocate, and author of Lost Marbles: Insights into My Life with Depression & Bipolar. She's also the host of the podcast Snap Out of It! The Mental Illness in the Workplace Podcast.

Natasha is also unveiling a new book, Bipolar Rules! Hacks to Live Successfully with Bipolar Disorder, mid-2024.

Find Natasha Tracy on her blog, Bipolar BurbleX, InstagramFacebook, and YouTube.

Natasha Tracy
April, 17 2011 at 2:33 pm

Hi Gledwood,
What you're experiencing is typical for many with bipolar disorder.
In my opinion, sleep regulation is _key_ in stabilizing bipolar disorder. I would suggest talking to your doctor about your sleep issues. Again, in my opinion, I prefer to take a sleeping pill to sleep when hypomanic then to stay awake. I find this is _much_ more stabilizing.
Believe me, there are therapies for your sleep disturbances.
First, there are medications both to help you sleep at night and promote wakefullness during the day. There are many ways to accomplish this and your doctor can tell you more about that.
There is also light therapy, social rhythm therapy and dark therapy as non-medication options.
Usually a combination works the best.
Read this - Light and darkness is bipolar disorder:
You would likely have to talk to a professional to learn about social rhythm therapy, but basically it's just a fancy way of saying having a strict routine every day.
Do not undertake any treatment without talking to your doctor.
Good luck.
- Natasha

Natasha Tracy
April, 17 2011 at 2:24 pm

Hi Johnny,
You're welcome.
The evidence in bipolar disorder is much more complex than that of depression.
First, it's very difficult to estimate brain volume loss based on mania or depressive episodes. Some researchers feel bipolar depression and unipolar depression have the same effect on the brain, some don't. There's no clear answer here.
Second, researchers have taken an interest in brain abnormalities in schizophrenia and bipolar disorder. There appears to be an overlap in abnormalities between the two disorders but schizophrenia appears to show more substantial brain volume loss.
Third, it appears that volume loss can be seen in many different places in bipolar disorder, but not in every part of the brain.
Fourth, brain white matter appears to be correlated to positive bipolar disorder outcomes (as does IQ)
Basically, what I'm saying is, yes, I think there is brain volume loss in bipolar disorder, but it's trickier to be specific than for unipolar depression.
Also, we know that many of the medications taken by those with bipolar disorder increase neurogenesis and thus work to reverse or at least stop this volume loss, just like with depression. And yes, just like depression, this loss may be one of the reasons bipolar disorder is degenerative.
- Natasha
(Those were just the first few studies I pulled. There are 254: )

April, 16 2011 at 11:42 am

There's definitely some link between mood cycles and the circadian rhythms. When I'm manic or cycling my sleep shrinks down to an average of just over two hours per night, though I'm only going to bed every other night. Then as soon as I wake up for any reason I'm UP and do not bother trying to sleep again. Then when I'm depressed I sleep a minimum 12 hours on a good day. On a bad week I can sleep 16 hours or more every single day. 12 hours at night, 4 hours in the afternoons. No way could I hold down a job. I never have periods of normal mood lasting anything longer than a couple of days, so I'm basically fucked by this disease and don't know if or when I will ever be able to lead anything aproaching a "normal" life.

April, 14 2011 at 6:50 am

First off, I just wanted to thank-you for creating such a wonderful site! :) I can relate to all of the issues you speak about quite well!
In regards to your note on "Brain Shrinkage in Depression"...
I have been told by doctors that when an individual who has bipolar disorder experiences a manic or depressive episode, a small portion of their white brain matter shrinks. Do you see any validity to this claim in the research you have done!? I was told this is a reason why bipolar disorder is such a degenerative disease because then as one gets older, so do the episodes. I thought you may have come accross something due to your note.

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