An understanding why women experience more stress-related mental disorders like depression and Post Traumatic Stress Disorder (PTSD) has eluded scientists but a new study in rat brains may help explain why women are more prone to mood and anxiety disorders than men.

In order to better understand this study, I found it helpful to look up a few key definitions:

  • stressor:   a stimulus that causes stress, can be physical, emotional or social
  • hormone:  a secretion of an endocrine gland that is transmitted by the blood to the tissue on which it has an effect
  • neurotransmitter:   a chemical that transmits signals from a neuron (nerve system cell) to a cell across an empty space called a "synapse"
  • receptor:   a protein molecule embedded in either the membrane or cytoplasm of a cell, to which one or more specific kinds of signaling molecules, such as a neurotransmitter or hormone may attach. Each cell typically has many receptors, of many different kinds.

Now, back to the study:

Corticotropin releasing factor (CRF), which acts as both a hormone and a neurotransmitter, is likely a key player.   In response to a stressor, CRF binds to receptors on cells in an alarm center deep in the brainstem, called the locus ceruleus.   This telegraphs heightened emotional arousal throughout the brain via the chemical messenger norepinephrine.   Such hyper-arousal can be adaptive for brief periods, but not if it becomes chronic.   Runaway CRF is a core feature of depression.

Previous studies suggested that this alarm system is more sensitive to CRF and stress in the female brain and researchers at Children's Hospital in Philadelphia developed an experiment to see how CRF receptors responded in male versus female rats, both unstressed and after exposure to a stressor (in this case, a swim).

Even in the absence of any stress, the researchers found the female stress signaling system to be more sensitive from the start.   CRF receptors had stronger connections or coupling in the female rats, so it took lower levels of CRF to activate proteins in the unstressed females compared to males.    CRF levels that had no effect in males turned on cells in female rats.

After stress, CRF receptors remained exposed on the neuronal membranes in the female rat, maintaining the CRF effect.   In the stressed male, the CRF receptors interacted with proteins in the cell that enabled some of the them to retreat and not be available to couple to the CRF.  This helped the male brain adapt its sensitivity to the stressor and thus the stress response was less than in the females.

What is the significance of this experiment?   Certain brain cells in females are more sensitive to CRF  and less able to adapt to too much CRF than male brain cells.

The next step is to examine the male and female CRF receptors for structural differences that might account for the functional differences (e.g., response to stress, depression).   Since most rodent models of mood and anxiety disorders use male animals exclusively, the new findings of sex differences in stress signaling mechanisms call for a more sex- and gender-balanced approach---especially for mental disorders that disproportionately affect females.   This sex-difference should also be factored in as medication treatments based on blocking CRF receptor are developed, say the researchers.

Source: Sex differences in corticotropin-releasing factor receptor signaling and trafficking:   potential role in female vulnerability to stress-related psychopathology.  Mol Psychiatry. 2010 Jun 15. (PMID:  20548297)



Interesting article. Interesting tidbit as well about male lab mice. I did not realize that! :)

I didn't know this about women before. I knew that women and men handled stress differently but I didn't know that certain brain cells in women were more sensitive to CRF. It's great to know this. Thank you.

That's very interesting. My experience has been that a larger number of women seem to suffer from anxiety than men.

Maybe this condition makes women more sensitive to emotion than men. We men at times tend to think everything is not a big deal when it should be. This condition women experience can be a curse but also may have its blessings.

It will be interesting to see if this sex differentiation plays out in humans. I know the CRH-1 receptor (CRF is now called CRH) is being looked at as a possible way to treat generalized anxiety disorder specifically in women. Certainly there is a relationship with anxiety disorders and stress. Through the lens of Chinese Medicine and we can see CRF/CRH as a manifestation of Kidney yang. Kidney yang has long known to be impacted by stress. By no coincidence CRH is secreted from the adrenal glands. The interaction of CRH and ACTH between the axis of the hypothalamus (an aspect of marrow- also kidney) and the adrenals further implicate water energetics. This type of research is exciting because I think it is through this kind of study that we will begin to integrate eastern and western medicines. Stress is such a huge factor in the manifestation and progression of many diseases. It's particularly great to see consideration being given to sex differences in this kind of research.

Yoga alleviates stress in both men and women. But maybe women experience more stress, so that's why more women are drawn to yoga?

Great article and an excellent study. I'm so glad I found this resource. Thanks so much.

great post to understand why women experience more stress-related mental disorders like depression than men

Come to think of it more women tend to become depressed compared to men. Wow. This article provides good insight and information. Now we know why some women have very weird mood swings during their period.

Very interesting study! It's amazing how much we can learn about ourselves through scientific studies. By the way, how big was their sample?

I’m still gaining knowledge from you, and I’m enhancing myself. I certainly loved reading through all that's written in your site.Keep your aarticles coming. I loved it!

Very interesting information! In fact I'm ineterested in the effects of hormones and neurotransmitters on moods, currently I'm teaching clients to sort of relieve their bad moods using behavioral means. Please share further information on these. Thanks!