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.

How very interesting!

I begin to wonder wether what came first: severe depression, or grey matter reduction?

Could any of those lead to another? 

Post Scriptum

Genetics come first but could pass unrevealed in case no serious reactions towards negative life events would happen.

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?

I would not dare to say that

Hi Beatrice,

Why not?

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."

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?

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.

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.

Stahl's book on psychopharmacology presents the hypotheses that exist on how mood and levels of transmittors correlate.

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.

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.

Dear Renzo,

Since when is it revealed that hippocampus plays a primary role in the HPA axis?

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

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.

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..