Question
Asked 17th Dec, 2014
  • unaffiliated

Brain scans of severely depressed people show reduction of of grey matter in various areas of the brain but when does this degeneration begin?

Brain scans of severely depressed patients show reduction in grey matter volume in a number of areas of the brain associated with regulation of mood and cognition.
But what comes first? Is it the slow pre- depression build up of increasingly negative thinking that precipitates these reductions to the point where specific brain systems regulating mood and cognition suddenly fail to the point which tips the person into severe depression and then begin to degenerate further thus underpinning the illness?

Most recent answer

11th Jan, 2015
Anthony Frais
unaffiliated
Renzo's hypothesis regarding stress as a causative factor is plausible. However, the idea that excess cortisol and its effect on serotonin levels has a role to play in depression has been challenged - see
The British Journal of Psychiatry (2002) 180: 99-100 doi: 10.1192/bjp.180.2.99
EDITORIAL
Cortisol, serotonin and depression: all stressed out?†
P.J. COWEN, FRCPsych
Edward's hunch that epigenietic factors has a role to play is also entirely possible.I can only add that in addition to these factors, increasingly negative and often irrational  views on how  a person's life is going is the genesis of brain atrophy. This atrophy moves on a stage further causing the classic symptom of loss of interest in things usually enjoyed. This in turn accelerates the atrophy that triggers the 'tipping point' into the  often instantaneous  descent into severe depression..
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All Answers (24)

19th Dec, 2014
Béatrice Marianne Ewalds-Kvist
Stockholm University University of Turku Finland
Dear Anthony,
Check this recent paper out:  
Neurosci Bull. 2014 Dec 11.
Grey matter volume abnormalities in patients with bipolar I depressive disorder and unipolar depressive disorder: a voxel-based morphometry study.
Cai Y, Liu J, Zhang L, Liao M, Zhang Y, Wang L, Peng H, He Z, Li Z, Li W, Lu S, Ding Y, Li L.
Abstract
Bipolar disorder and unipolar depressive disorder (UD) may be different in brain structure. In the present study, we performed voxel-based morphometry (VBM) to quantify the grey matter volumes in 23 patients with bipolar I depressive disorder (BP1) and 23 patients with UD, and 23 age-, gender-, and education-matched healthy controls (HCs) using magnetic resonance imaging. We found that compared with the HC and UD groups, the BP1 group showed reduced grey matter volumes in the right inferior frontal gyrus and middle cingulate gyrus, while the UD group showed reduced volume in the right inferior frontal gyrus compared to HCs. In addition, correlation analyses revealed that the grey matter volumes of these regions were negatively correlated with the Hamilton depression rating scores. Taken together, the results of our study suggest that decreased grey matter volume of the right inferior frontal gyrus is a common abnormality in BP1 and UD, and decreased grey matter volume in the right middle cingulate gyrus may be specific to BP1.
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19th Dec, 2014
Maria Bettencourt Pires
Universidade NOVA de Lisboa
How very interesting!
I begin to wonder wether what came first: severe depression, or grey matter reduction?
Could any of those lead to another? 
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19th Dec, 2014
Béatrice Marianne Ewalds-Kvist
Stockholm University University of Turku Finland
Post Scriptum
Genetics come first but could pass unrevealed in case no serious reactions towards negative life events would happen.
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19th Dec, 2014
Anthony Frais
unaffiliated
Hi everybody.
Re.J Affect Disord. 2008 Oct;110(3):241-7. doi: 10.1016/j.jad.2008.01.022. Epub 2008 Mar 5.
Life events and hippocampal volume in first-episode major depression.
Kronmüller KT1, Pantel J, Götz B, Köhler S, Victor D, Mundt C, Magnotta VA, Giesel F, Essig M, Schröder J.
This study suggests that 'results do support the hypothesis that the hippocampus plays a crucial role in the pathogenesis of major depression especially in the early phase of the disorder'
Also, 'results also support the stable finding of life event research that life events taking place within 3 months prior to the onset of depression are more significant than life events in other time intervals'
For convenience, lets say then that the study findings are accurate.
So adverse life events kick starts the insidious reduction of volume in specific areas of the brain. Some people may either be genetically pre- disposed to suffering from depression or lack resilience in coping with adverse life events or both are at high risk of lapsing in to severe depression. So it may only take one more adverse life event that suddenly tips the person in to severe depression - this can happen overnight. Another way of putting it is the English saying ' the straw that breaks the camels back'
The study states that this effect sets in 3 months before the descent into severe depression - for some it could be a bit longer. One study suggests that reduction in volume can be demonstrated in younger people
Lupien, S.J., Evans, A., Lord, C., Miles, J., Pruessner, M., Pike, B.,
Pruessner, J.C., 2007. Hippocampal volume is as variable in young as in old adults: implications for the notion of hippocampal atrophy in humans. NeuroImage 34, 479–485.
So if this study is accurate, this could account for cases where a person gets severely depressed and who may have been abused as a child.
All this is very much an over-simplification but the conclusion is that loss of volume in brain regions are the pre -curser to severe depression and not as a result of the illness its self?
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19th Dec, 2014
Béatrice Marianne Ewalds-Kvist
Stockholm University University of Turku Finland
I would not dare to say that
19th Dec, 2014
Anthony Frais
unaffiliated
Hi Beatrice,
Why not?
19th Dec, 2014
Béatrice Marianne Ewalds-Kvist
Stockholm University University of Turku Finland
Not all old people are depressed although
"Normal aging causes atrophy of the brain. The aging brain shrinks by an average of 1.9 percent every 10 years. It begins in young adulthood, but becomes more prominent when individuals reach their sixties. People can reportedly lose a half percent to 1 percent of brain volume per year after the age of 60. This is due to the number of cells in the brain decreasing with age, thus resulting in generalized atrophy. Some areas of the brain may shrink more than others, like the hippocampus, which is involved in memory."
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19th Dec, 2014
Anthony Frais
unaffiliated
Hi Beatrice,
I accept what you say, But I think it's a safe bet that the authors of the two studies I quoted from have taken your points in to account. It seems they are noticing an abnormal loss of volume in excess of the accepted percentage of loss noticed in ageing?
19th Dec, 2014
Béatrice Marianne Ewalds-Kvist
Stockholm University University of Turku Finland
Hi Anthony,
Nothing is simple and easily understood by the human mind. From 2014
PLoS One. 2014; 9(7): e102692.
Insular and Hippocampal Gray Matter Volume Reductions in Patients with Major Depressive Disorder
Mirjam Stratmann et al.
Results
Compared to healthy control persons, patients showed a strong gray-matter reduction in the right anterior insula. In addition, region-of-interest analyses revealed significant gray-matter reductions in the hippocampal formation. The observed alterations were more severe in patients with recurrent depressive episodes than in patients with a first episode. The number of depressive episodes was negatively correlated with gray-matter volume in the right hippocampus and right amygdala.
Conclusions
The anterior insula gray matter structure appears to be strongly affected in major depressive disorder and might play an important role in the neurobiology of depression. The hippocampal and amygdala volume loss cumulating with the number of episodes might be explained either by repeated neurotoxic stress or alternatively by higher relapse rates in patients showing hippocampal atrophy.
20th Dec, 2014
Béatrice Marianne Ewalds-Kvist
Stockholm University University of Turku Finland
Anthony,
As you can see from results from 2014 episodes of depression affect certain areas in hippocampus in other words, your statement that " loss of volume in brain regions are the pre -curser  (precursor) to severe depression and not as a result of the illness its self" is contradicted.
Deleted profile
It seems to me this question requires a model of how the brain relates to conscious experience. Can a thought / experience cause changes in the gray matter of the brain? If it can, how does it do it? What is a thought? Is it part of an electromagnetic field, for example and if it is how does that electromagnetic field influence the gray matter that is producing it? Why does a negative thought reduce the volume of gray matter and how does that reduction change the subsequent production of the e.g. Electromagnetic field   That is thought. There is a long way to go!
20th Dec, 2014
Béatrice Marianne Ewalds-Kvist
Stockholm University University of Turku Finland
Stahl's book on psychopharmacology presents the hypotheses that exist on how mood and levels of transmittors correlate.
20th Dec, 2014
Edward E. Stambaugh II, Ph.D.
Family Medicine Associates, Broomfield, CO
One of the most promising current hypotheses is the inflammation approach which sees depression as an inflammatory process that involves the brain in its entirety  as cytokines lay down inflammation markers that initiate the destruction of healthy neurons.
Deleted profile
That is really interesting- could this be the reason Muliple sclerosis is often associated with depression?.
22nd Dec, 2014
Béatrice Marianne Ewalds-Kvist
Stockholm University University of Turku Finland
Dear Anne,
MS is associated with depression for several reasons and the psychological are not the least ones. The prospective of MS's progression and to spend the rest of your life in a wheel chair does not seem to entise many. Also the lack of a good option for cure and the lack of convincing results from stem-cell treatments contribute to a lower mood for these patients. Chronic disorders usually go with a certain psychological expression.
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Deleted profile
This comes back to my point about consciousness and the brain. If you are a materialist, which I think Anthony seems to be, everything psychological has a material base so something in the brain must come before the experience of depression. Whether this is nanoseconds before or 3 months is of course a big question. Inflammation in the brain is the cause of white matter lesions in the brain in MS. what I am suggesting and what Edward says about inflammation of the brain leading to depression suggests that it may also be the cause of depression in MS. There may be other mechanisms but the principle of the brain before experience remains the same - if you are a materialist that is. What do you think?
23rd Dec, 2014
Béatrice Marianne Ewalds-Kvist
Stockholm University University of Turku Finland
Dear Renzo,
Since when is it revealed that hippocampus plays a primary role in the HPA axis?
23rd Dec, 2014
Béatrice Marianne Ewalds-Kvist
Stockholm University University of Turku Finland
The role of the hippocampus in the inhibition of the HPA axis is in my opinion not the primary role, the primary role till now of hippocampus has been realetd to memory although of course stress affects memory
Deleted profile
For some reason I was thinking the same about chronic stress and also insomnia maybe?
10th Jan, 2015
Edward E. Stambaugh II, Ph.D.
Family Medicine Associates, Broomfield, CO
An excellent question. I am only aware of depression from a bipolar variant perspective and know of research that there is thinning in the right precentral gyrus which recovers to normal thickness with treatment with lamotrigene. Inasmuch as we find an 80% genetic determinism in bipolar illness it would appear that genetics, perhaps upregulated by epigenetic factors represents the chicken in the classic question.

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