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Open Access Highly Accessed Review

Sex differences, gonadal hormones and the fear extinction network: implications for anxiety disorders

Kelimer Lebron-Milad and Mohammed R Milad*

Author Affiliations

Department of Psychiatry, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA

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Biology of Mood & Anxiety Disorders 2012, 2:3  doi:10.1186/2045-5380-2-3

Published: 7 February 2012

Abstract

Convergent data from rodents and human studies have led to the development of models describing the neural mechanisms of fear extinction. Key components of the now well-characterized fear extinction network include the amygdala, hippocampus, and medial prefrontal cortical regions. These models are fueling novel hypotheses that are currently being tested with much refined experimental tools to examine the interactions within this network. Lagging far behind, however, is the examination of sex differences in this network and how sex hormones influence the functional activity and reactivity of these brain regions in the context of fear inhibition. Indeed, there is a large body of literature suggesting that sex hormones, such as estrogen, do modulate neural plasticity within the fear extinction network, especially in the hippocampus.

After a brief overview of the fear extinction network, we summarize what is currently known about sex differences in fear extinction and the influence of gonadal hormones on the fear extinction network. We then go on to propose possible mechanisms by which sex hormones, such as estrogen, may influence neural plasticity within the fear extinction network. We end with a discussion of how knowledge to be gained from developing this line of research may have significant ramifications towards the etiology, epidemiology and treatment of anxiety disorders.

Keywords:
menstrual cycle; sex hormones; estrogen; progesterone; estrus cycle; fear extinction