<p>This is only one possible pathway.  There are many potential ones.  Further the fact that this is possible does not mean that it is the case always.</p>

<p>Stress activates the hypothalamic-pituitary-adrenal (HPA) axis.  For example, a meta-analysis by Dickerson et al. (<a href="http://dx.doi.org/10.1037/0033-2909.130.3.355">2004</a>) demonstrated that an acute laboratory based stressor reliably increased cortisol levels, a hormone downstream of the HPA.  That stress results in activation of the HPA is also well-demonstrated in animal models, where both physical (e.g., restraint or shock) and social stress (e.g., <a href="http://dx.doi.org/10.1016/j.yfrne.2004.09.001">Engelman, 2004</a>).</p>

<p>When stress occurs, various systems (e.g., amygdala implicated in threat detection) can lead to activation in the hypothalamus, where the paraventricular nucleus (of the hypothalamus) secretes corticotropin-releasing hormone (CRH).  The CRH acts on the pituitary gland resulting in a release of adrenocorticotropic hormone (ACTH).  ACTH is released into the blood, which allows it to reach the adrenal glands, specifically the adrenal cortex.  This stimulates the adrenal cortex to produce and release glucocorticoids (GCs) into the blood (in humans primarily cortisol, in animals corticosterone).  GCs in turn have broad ranging influences on the body.  For example, they seem to play role in immune regulation and function (although whether they are anti-inflammatory or pro-inflammatory seems to depend on quantity and time (there was a lively debate about this at a Psychoneuroimmunology conference.  For utterly inadequate notes on some of the presentation see <a href="http://blog.joshuawiley.com/?p=13">here</a>).</p>

<p>GCs also act in a negative feedback loop to shut off the HPA axis.  Finally, relevant for cognitive functioning, specifically memory, GCs can regulate the hippocampus.  This is believed to be adaptive in the short term, but when the hippocampus is chronically exposed to elevated levels of GCs, it can endanger cell function (for a review of GCs and the hippocampus, see <a href="http://dx.doi.org/10.1046/j.1365-2826.2001.00688.x">Joels, 2001</a>).</p>

<p>For example, using a longitudinal design, Huang and colleagues (<a href="http://dx.doi.org/10.1016/j.jocn.2008.12.026">2009</a>) demonstrated that in people with Alzheimer's Disease, basal plasma cortisol (cortisol levels in the blood, other major ways to measure cortisol are via saliva or urine) was predictive of a decline in cognitive function as well as atrophy in the hippocampus (specifically, the temporal horn).</p>

<p>Somewhere I have a slightly longer reference list on stress and aging, with an emphasis on stress effects in cognitive and physical function over time.  I do not have an answer for your final point, what can be done to minimize the effects.  The only clear suggestion would be to minimize stress.  I know there are some studies showing protective effects of physical activity for depression, physical function (that one's a no-brainer), and cognitive function.  One can speculate that if chronically elevated GCs released from the adrenal cortex are the cause, that administering an ACTH antagonist or the like may help, but to date, I know of no studies trying to block the effects of stress (in rodent models of cancer, stress effects on tumor progression and metastasis have been effectively blocked using beta blockers, but there the primary stress pathway was believed to be sympathetic nervous system activation rather than HPA).</p>

CC BY-SA 3.0
2012-07-13T16:10:52.460Z
2012-07-13T16:10:52.460Z
Joshua
<p><strong>Background:</strong> Ten years ago or so I went through a traumatic period which resulted in a lot of stress and anxiety. I initially assumed there was some depression but cognition and short term memory was gradually affected such that I had serious difficulty understanding new concepts at night class. At one stage I was practically "cut off" from emotions. I understand that this could be partly due to something happening on the hormonal or biological level.</p>

<h3>Questions</h3>

<ul>
<li>What does research show about the causal effects of stress on cognitive functioning?</li>
<li>How is the brain affected by stress? (e.g., chemical/physical, or  perhaps a "softer" level). </li>
<li>What could be done to minimise the negative effects of stress on cognitive functioning?</li>
</ul>

CC BY-SA 3.0
2012-07-12T00:24:09.387Z
Can you elaborate a bit more on what you mean by a "softer" level?
Chuck Sherrington
CC BY-SA 3.0
2012-07-12T00:28:54.490Z
I mean through a prolonged change in behaviour.
James P.
CC BY-SA 3.0
2012-07-12T00:44:45.703Z
Welcome to the site. A key thing with cogsci.se is that scientific questions are on topic, but self-help style questions are typically not on topic. Thus, the key is to ensure that the question is phrased at a sufficient level of generality that it would be beneficial to future readers. Thus, the background motivation is welcome, but it's also important to distil the scientific question. I think as it stands it's not too bad, but you might want to think about whether your question is about stress in general or about the effect of a particular type of traumatic event.
Jeromy Anglim
CC BY-SA 3.0
2012-07-13T17:25:07.847Z
Thank you for reformulating Jeromy. I do think stress in the physiological sense played a part in the condition but I'm obviously not a clinician. Also, this might be related: http://en.wikipedia.org/wiki/Clouding_of_consciousness
James P.
<abnormal-psychology><psychiatry><neurology><stress>
How can prolonged stress lead to a sustained reduction in cognitive functioning?
James P.
# How can prolonged stress lead to a sustained reduction in cognitive functioning?

(Asked by: username_0 on 2012-07-12)

**Background:** Ten years ago or so I went through a traumatic period which resulted in a lot of stress and anxiety. I initially assumed there was some depression but cognition and short term memory was gradually affected such that I had serious difficulty understanding new concepts at night class. At one stage I was practically "cut off" from emotions. I understand that this could be partly due to something happening on the hormonal or biological level.

### Questions

* What does research show about the causal effects of stress on cognitive functioning?
* How is the brain affected by stress? (e.g., chemical/physical, or perhaps a "softer" level).
* What could be done to minimise the negative effects of stress on cognitive functioning?

**Tags:** abnormal-psychology, psychiatry, neurology, stress

> **Comments:**
> **username_1**: Can you elaborate a bit more on what you mean by a "softer" level?  
> **username_0**: I mean through a prolonged change in behaviour.  
> **username_2**: Welcome to the site. A key thing with cogsci.se is that scientific questions are on topic, but self-help style questions are typically not on topic. Thus, the key is to ensure that the question is phrased at a sufficient level of generality that it would be beneficial to future readers. Thus, the background motivation is welcome, but it's also important to distil the scientific question. I think as it stands it's not too bad, but you might want to think about whether your question is about stress in general or about the effect of a particular type of traumatic event.  
> **username_0**: Thank you for reformulating Jeromy. I do think stress in the physiological sense played a part in the condition but I'm obviously not a clinician. Also, this might be related: http://en.wikipedia.org/wiki/Clouding_of_consciousness  

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## 1 answers

### Answer by username_3 on 2012-07-13. Score: 8

This is only one possible pathway. There are many potential ones. Further the fact that this is possible does not mean that it is the case always.

Stress activates the hypothalamic-pituitary-adrenal (HPA) axis. For example, a meta-analysis by Dickerson et al. ([2004](http://dx.doi.org/10.1037/0033-2909.130.3.355)) demonstrated that an acute laboratory based stressor reliably increased cortisol levels, a hormone downstream of the HPA. That stress results in activation of the HPA is also well-demonstrated in animal models, where both physical (e.g., restraint or shock) and social stress (e.g., [Engelman, 2004](http://dx.doi.org/10.1016/j.yfrne.2004.09.001)).

When stress occurs, various systems (e.g., amygdala implicated in threat detection) can lead to activation in the hypothalamus, where the paraventricular nucleus (of the hypothalamus) secretes corticotropin-releasing hormone (CRH). The CRH acts on the pituitary gland resulting in a release of adrenocorticotropic hormone (ACTH). ACTH is released into the blood, which allows it to reach the adrenal glands, specifically the adrenal cortex. This stimulates the adrenal cortex to produce and release glucocorticoids (GCs) into the blood (in humans primarily cortisol, in animals corticosterone). GCs in turn have broad ranging influences on the body. For example, they seem to play role in immune regulation and function (although whether they are anti-inflammatory or pro-inflammatory seems to depend on quantity and time (there was a lively debate about this at a Psychoneuroimmunology conference. For utterly inadequate notes on some of the presentation see [here](http://blog.joshuawiley.com/?p=13)).

GCs also act in a negative feedback loop to shut off the HPA axis. Finally, relevant for cognitive functioning, specifically memory, GCs can regulate the hippocampus. This is believed to be adaptive in the short term, but when the hippocampus is chronically exposed to elevated levels of GCs, it can endanger cell function (for a review of GCs and the hippocampus, see [Joels, 2001](http://dx.doi.org/10.1046/j.1365-2826.2001.00688.x)).

For example, using a longitudinal design, Huang and colleagues ([2009](http://dx.doi.org/10.1016/j.jocn.2008.12.026)) demonstrated that in people with Alzheimer's Disease, basal plasma cortisol (cortisol levels in the blood, other major ways to measure cortisol are via saliva or urine) was predictive of a decline in cognitive function as well as atrophy in the hippocampus (specifically, the temporal horn).

Somewhere I have a slightly longer reference list on stress and aging, with an emphasis on stress effects in cognitive and physical function over time. I do not have an answer for your final point, what can be done to minimize the effects. The only clear suggestion would be to minimize stress. I know there are some studies showing protective effects of physical activity for depression, physical function (that one's a no-brainer), and cognitive function. One can speculate that if chronically elevated GCs released from the adrenal cortex are the cause, that administering an ACTH antagonist or the like may help, but to date, I know of no studies trying to block the effects of stress (in rodent models of cancer, stress effects on tumor progression and metastasis have been effectively blocked using beta blockers, but there the primary stress pathway was believed to be sympathetic nervous system activation rather than HPA).


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