According to the Anxiety Disorders Association of America, 40 million Americans suffer from anxiety disorders—over twice the number of people who suffer from alcoholism,1 and nearly three times the number who suffer from depression.2 Of these 40 million people, two-thirds are female. While culture and environment might play contributing roles, science suggests that women may be chemically predisposed to “stress out.”

Corticotropin-releasing factor (CRF) is a neurotransmitter that is released due to stress and binds to neurons in the locus ceruleus, the “alarm center” of the brainstem. CRF’s ability to set off “alarms” in this area of the brain (that is, to stimulate neurons) is affected by:

1. the amount of neurotransmitter released in the brain, and
2. how readily neuroreceptors bind to it.

In a study published this past summer in Molecular Psychiatry, a team of researchers at The Children’s Hospital of Philadelphia investigated the latter phenomenon by comparing how CRF receptors responded in male vs. female rats. They found that even before the rats were stressed, lower levels of CRF were necessary to activate neurons in female rats than male rats. Then, after the rats were put through a stressful swim, the male rats’ neurons pulled their CRF receptors inside the neuronal membrane, effectively preventing the receptors from accepting the CRF neurotransmitter. Female rats’ neurons, however, left their CRF receptors exposed and ready to bind with the neurotransmitter, thereby making those neurons more susceptible to the effects of stress.

These results seem to suggest that females are at a considerable disadvantage when it comes to dealing with stressful situations. However, the results of an earlier study published in Psychological Review4 suggest that oxytocin—a hormone secreted in response to stress—actually gives females a physiological advantage when coping with the effects of stress. Oxytocin mediates stress; it typically makes people less anxious and more social (known as the “tend-and-befriend” pattern of behavior). Researchers at the UCLA found that male hormones reduce the effect of oxytocin, while female hormones amplify it.

These two studies may seem to contradict one another; however, they are only contradictory when asking, “Who is more affected by stress, males or females?” In response to the question, “Why do males and females respond differently to stress?” they provide compelling answers:

• Male bodies suppress oxytocin, so they experience the initial CRF-induced “fight or flight” response to stress.
• Females are more likely to “tend or befriend” in response to stress, thanks to oxytocin mediation of the immediate CRF-induced response.
• Female CRF receptors are more sensitive to the CRF neurotransmitter and, under stress, their neurons leave those receptors exposed. This may explain why females are twice as likely to suffer from anxiety disorders as males.

More Resources from Wiley on This Topic
	Stress – From Molecules to Behavior: A Comprehensive Analysis of the Neurobiology of Stress Responses by Hermona Soreq, Alon Friedman, Daniela Kaufer
	Stress, Neurotransmitters, and Hormones: Neuroendocrine and Genetic Mechanisms by Richard Kvetnansky, Greti Aguilera, David Goldstein, Daniela Jezova, Olga Krizanova, Esther Sabban, Karel Pacak
	Molecular and Biophysical Mechanisms of Arousal, Alertness and Attention edited by Donald W. Pfaff, Brigitte Kieffer

1. National Institute on Alcohol Abuse and Alcoholism (NIAAA), 2007. http://www.niaaa.nih.gov/FAQs/General-English/Pages/default.aspx

2. National Institute of Mental Health (NIMH), 2004/2005. http://www.nimh.nih.gov/health/publications/the-numbers-count-mental-disorders-in-america/index.shtml#MajorDepressive

3. Bangasser, D., Curtis, A., Reyes, B., Bethea, T., Parastatidis, I., Ischiropoulos, H., Van Bockstaele, E., & Valentino, R. (2010). Sex differences in corticotropin-releasing factor receptor signaling and trafficking: potential role in female vulnerability to stress-related psychopathology Molecular Psychiatry, 15 (9), 896-904 DOI: 10.1038/mp.2010.66

4. Taylor, S., Klein, L., Lewis, B., Gruenewald, T., Gurung, R., & Updegraff, J. (2000). Biobehavioral responses to stress in females: Tend-and-befriend, not fight-or-flight. Psychological Review, 107 (3), 411-429 DOI: 10.1037//0033-295X.107.3.411