The prevalence of anxiety disorders is twice as high in women. The reason for this eleveated prevalence is unclear, partly because most animal research has used only males, and most human research has not considered sex as a variable of interest. This proposal will begin to examine the neurobiological basis for these differences by first studying how natural fluctuations of estrogen in healthy women may influence the resting-state activity and the extinction-induced reactivity of the fear extinction network, including the amygdala, hippocampus, and the ventromedial prefrontal cortex (vmPFC). Additional experiments will involve exogenous manipulations of estrogen in naturally cycling women to see how these manipulations may interact with the functional activation of the fear extinction network. Healthy women will participate in a well-established fear conditioning and extinction protocol at different points of their menstrual cycle. Functional MRI and psychophysiological tools wil be employed to test two overall hypotheses: 1) Naturally elevated estrogen levels during the menstrual cycle will facilitate the resting-state activity and extinction-induced functional reactivity of the fear extinction network, and will be associated with enhanced extinction retention, and 2) Exogenous administration of estrogen to women will enhance extinction retention, which will be associated with enahnced resting-state activity and extinction-induced functional reactivity of this extinction circuitry during extinction recall. Findings from his proposal may help develop sex-specific treatments for anxiety disorders, for example by using hormonal-based pharmacological adjuncts to facilitate the processes of safety learning during therapy.
The incidence of most anxiety and mood disorders is twice as high in women. This proposal will begin to examine the role of endogenous and exogenous estrogen levels on the functional activity and reactivity of the fear extinction network in healthy women. If successful, this approach could lead to developing sex-specific treatments to enhance the outcome of extinction-based therapies using estrogen as an adjunct to such therapies.
|Alexandra Kredlow, M; Pineles, Suzanne L; Inslicht, Sabra S et al. (2017) Assessment of skin conductance in African American and Non-African American participants in studies of conditioned fear. Psychophysiology 54:1741-1754|
|Maeng, L Y; Taha, M B; Cover, K K et al. (2017) Acute gonadotropin-releasing hormone agonist treatment enhances extinction memory in male rats. Psychoneuroendocrinology 82:164-172|
|Maeng, Lisa Y; Cover, Kara K; Taha, Mohamad B et al. (2017) Estradiol shifts interactions between the infralimbic cortex and central amygdala to enhance fear extinction memory in female rats. J Neurosci Res 95:163-175|
|Engman, Jonas; Linnman, Clas; Van Dijk, Koene R A et al. (2016) Amygdala subnuclei resting-state functional connectivity sex and estrogen differences. Psychoneuroendocrinology 63:34-42|
|Maeng, Lisa Y; Cover, Kara K; Landau, Aaron J et al. (2015) Protocol for studying extinction of conditioned fear in naturally cycling female rats. J Vis Exp :|
|Hwang, Moon Jung; Zsido, Rachel G; Song, Huijin et al. (2015) Contribution of estradiol levels and hormonal contraceptives to sex differences within the fear network during fear conditioning and extinction. BMC Psychiatry 15:295|
|Marin, Marie-France; Lonak, Sylwia Fowler; Milad, Mohammed R (2015) Augmentation of Evidence-Based Psychotherapy for PTSD With Cognitive Enhancers. Curr Psychiatry Rep 17:39|
|Maeng, Lisa Y; Milad, Mohammed R (2015) Sex differences in anxiety disorders: Interactions between fear, stress, and gonadal hormones. Horm Behav 76:106-17|
|Sierra-Mercado, Demetrio; McAllister, Lauren M; Lee, Christopher C H et al. (2015) Controlled cortical impact before or after fear conditioning does not affect fear extinction in mice. Brain Res 1606:133-41|
|Graham, Bronwyn M; Milad, Mohammed R (2014) Inhibition of estradiol synthesis impairs fear extinction in male rats. Learn Mem 21:347-50|
Showing the most recent 10 out of 13 publications