APR 19, 2021

Fear Processing Depends on Estrogen Levels, not Sex

WRITTEN BY: Annie Lennon

While unusual fear-memory processing has been thought for some time to contribute to anxiety disorders, its underlying neurobiology has remained poorly understood. Now, though, researchers from Germany have found that estrogen levels may influence fear-memory processing. 

Medical literature shows that women are twice as likely as men to suffer from anxiety disorders. While some studies have also suggested that female sex hormone estradiol (E2) may have a role in fear recall and extinction (eradication of fear-associations), until now, this connection had not been studied in terms of neural oscillations. 

For the new study, the researchers examined 20 men, 20 women using oral hormonal contraceptives and 20 free-cycling women during the middle of their cycle. Oral contraceptives suppress levels of female sex hormone estradiol (E2), meaning that those on the medications had lower levels of this hormone than free-cycling women. 

Participants underwent a fear-conditioning exercise in which they were exposed to four photographs of neutral male faces. While being shown two of these photographs, a loud noise was played to encourage a ‘fearful’ association with them.

Afterwards, participants underwent ‘fear extinction' training. This involved showing two neutral photographs- one previously presented with the noise and the other without. This time though neither were shown with the noise. To see how well associations had been learned, remained or were removed, the next day, the participants were once again shown all four photos, including the two from the extinction part of the exercise. 

During this part of the experiment, the researchers also measured participants' skin conductance responses (SCR) and brain oscillations via electroencephalography (EEG). In doing so, they found that free-cycling women in the middle of their cycle (with higher levels of E2) had lower peripheral fear expression from SCR during fear recall and extinction recall than both men, and women taking contraceptives. 

The researchers also noted enhanced theta oscillations in the medial prefrontal cortex and the dorsal anterior cingulate cortex (dACC) in men, and women taking oral contraceptives than free-cycling women. This builds upon other research showing that theta oscillations in the dACC positively correlate with fear expression. 

While interesting findings, the researchers note that subjects were not randomized to have experimentally manipulated estrogen levels and so causal links between estrogen levels and fear processing should not be drawn. They do say however that their findings suggest that fear memory may depend more on E2 status than sex per se. 

 

Sources: Neuroscience NewsBiological Psychiatry: Cognitive Neuroscience and Neuroimaging