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Does chronic occupational stress cause brain damage?

During the last decade, Western societies have been facing increasing reports about a new work-related phenomenon. It affects healthy, productive, and highly functional individuals typically working long hours for many years without a normal weekend recovery. These persons complain of stereotyped symptoms, including memory and concentration problems, sleeplessness, profound fatigue, and a feeling of being emotionally drained, which they attribute to occupational stress. This condition is frequently misinterpreted as depression because of partially shared symptoms. However, it is seldom helped by anti-depressant medications and seems to represent a separate construct. The underlying mechanisms are unknown, and there is an ongoing discussion whether the described disabilities are caused by stress, if they could be associated with cerebral changes, or if we are confronted with a new medical condition.

Psychosocial stress, initially defined by Lazarus and Folkman (1987), is thought to result from an “imbalance between demands and resources.” An adequate coping with stress stimuli involves specific networks in the brain, which encompass the structures processing emotion (primarily the amygdala), and parts of the frontal lobe that are involved in cognitive modulation of emotion (the anterior cingulate cortex (ACC) and the medial prefrontal cortex (mPFC).

Brain, (viewed from side) showing mid-brain structures. The amygdala (marked in red), which is the first relay in the processing of stress stimuli, has tight and reciprocal connections to the medial prefrontal cortex (mPFC, marked in blue). Combined inhibitory and excitatory, so called top-down modulation, of the amygdala is necessary for normal stress coping. We believe that repetitive stress stimulation of the amygdala may lead to damage of the mPFC via targeted neurotransmitter release from the amygdla to mPFC, impaired stress modulation. This, in turn, causes further amygdala stimulation of the mPFC, leading to a cortical thinning in this region (as shown in figure 1), as well as the described cognitive symptoms.
Brain, (viewed from side) showing mid-brain structures. The amygdala (marked in red), which is the first relay in the processing of stress stimuli, has tight and reciprocal connections to the medial prefrontal cortex (mPFC, marked in blue). Combined inhibitory and excitatory, so called top-down modulation, of the amygdala is necessary for normal stress coping. We believe that repetitive stress stimulation of the amygdala may lead to damage of the mPFC via targeted neurotransmitter release from the amygdla to mPFC, impaired stress modulation. This, in turn, causes further amygdala stimulation of the mPFC, leading to a cortical thinning in this region (as shown in figure 1), as well as the described cognitive symptoms.

We hypothesized that repeated, chronic stress could lead to damage of the brain areas which modulate stress perception, leading to a vicious cycle with impaired ability to cope with stress and a further facilitation of stress perception. To measure whether such damage could exist, we used measurements of the cortical thickness and of the volumes of specific brain structures known to be involved with the processing of psychosocial stress stimuli, including the amygdala. These measures were carried out using brain MRIs compared between 40 subjects reporting symptoms of chronic occupational stress (on average 38 years old) and 40 matched controls. We found that in stressed subjects, there was a significant thinning of the mesial prefrontal cortex (see below). Furthermore, in the frontal cortex, which is essential for our cognitive functions, the normal thinning effect of age was more pronounced than in the controls. In addition, the amygdala volumes were increased in subjects with occupational stress and the increase was positively correlated with the degree of perceived stress.

Blue cluster shows significant reductions in Cth in stressed subjects. The calculation is corrected for age and gender. The projection of cerebral hemispheres (MR images of the Freesurfer atlas) is standardized. Scale is logarithmic and shows –log10(P). Warm colors indicate positive contrasts (higher values in stressed subjects), cool colors negative contrasts (lower values in stressed subjects). Reproduction from Savic I. 2013, Cerebral Cortex bht348.
Blue cluster shows significant reductions in Cth in stressed subjects. The calculation is corrected for age and gender. The projection of cerebral hemispheres (MR images of the Freesurfer atlas) is standardized. Scale is logarithmic and shows –log10(P). Warm colors indicate positive contrasts (higher values in stressed subjects), cool colors negative contrasts (lower values in stressed subjects). Reproduction from Savic I. 2013, Cerebral Cortex bht348.

Together, these data suggest that chronic occupational stress may indeed be associated with specific changes in brain regions involved with the processing and modulation of stress stimuli.

Are the observed changes a cause to the increased stress sensitivity (and hence, the described symptoms), or an effect of excessive occupational stress?
The cross sectional study design used does not permit conclusions about the causality, but considering that stress perception was correlated with structural enlargement of the amygdala, it is plausible to believe that we are dealing with an effect of stress.

Are the changes reversible?
Our very preliminary results from follow-up investigations after treatment suggest that the observed cerebral changes may be reversible, which further argues that they might have been caused by stress.

Although several issues remain to be done for a better comprehension of the described condition, the already available findings indicate that it may well be a stress-related illness. Of note is that the locations of the observed cerebral changes in several aspects correspond to the locations of structural changes detected through MRI in persons suffering from other stress-related disabilities, such as post-traumatic disorder or early life traumas. Therefore, one may hypothesize that psychosocial stress affects our brains in a rather stereotyped manner, regardless of the underlying cause, and that cerebral changes occur not only in response to exposure to extreme and life threatening situations, but could also be an effect of accumulated everyday stress. Extreme occupational stress needs to be coped with at an early level, and if becoming associated with maladaptive coping effort and strategy, the result may be a drastically reduced recuperation, sleep problems, fatigue, and subsequently cognitive disability.

Headline image credit: Brain. CC0 via Pixabay

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