Anxiety sensitivity, the menstrual cycle, and panic disorder: A putative neuroendocrine and psychological interaction

Abstract

The 2:1 female-to-male sex difference in the prevalence of Panic Disorder (PD) suggests that there is a sex-specific vulnerability involved in the etiology and/or maintenance of this disorder. The purpose of this paper is to present a new conceptual model, which emphasizes the interaction between a cognitive vulnerability for PD, anxiety sensitivity, and the effects of progesterone and its metabolite, allopregnanolone, on behavioral and physiological responses to stress during the premenstrual phase. This interaction is proposed to be a potential sex-specific pathway that may initiate and/or maintain panic and anxiety symptoms in women. This review paper presents preliminary evidence from both the human and animal literatures to support this new model. Specific topics reviewed include: psychopathology related to the menstrual cycle, anxiety sensitivity and its relationship to the menstrual cycle, PMS, and PMDD, anxiety-modulating effects of progesterone and its neuroactive metabolite, allopregnanolone, and how results from the neuroendocrine literature relate to psychopathology or symptoms associated with the menstrual cycle.

ADORA2A Gene Variation, Caffeine, and Emotional Processing: A Multi-level Interaction on Startle Reflex

“…Almost all of the female probands had been on hormonal contraceptives during participation in the present study. The actual hormonal status, however, was not considered in the present study, which might have introduced a potential confounder based on case reports suggesting oral contraceptives to potentially induce panic attacks (Deci et al, 1992;Ushiroyama et al, 1992) and animal as well as human studies providing evidence for gonadal hormones and menstrual cycle to modulate AS (Nillni et al, 2011;Toufexis et al, 2006). Furthermore, the functional relevance of the silent ADOR-A2A 1976T4C polymorphism is still unknown and therefore the mechanism by which this variant might confer susceptibility to anxiety remains to be elucidated.…”

Sex differences in anxiety disorders: Interactions between fear, stress, and gonadal hormones

“…This may be due to species differences; however, progesterone has been shown to suppress HPA axis activity via conversion to its metabolite allopregnanolone (Biggio, Pisu, Biggio, & Serra, 2014). In fact, a number of studies have reported anxiolytic properties of allopregnanolone (Nillni, Toufexis, & Rohan, 2011; Pibiri, Nelson, Guidotti, Costa, & Pinna, 2008; D. J. Toufexis, Davis, Hammond, & Davis, 2004).…”

Etiology, triggers and neurochemical circuits associated with unexpected, expected, and laboratory-induced panic attacks

“…The initiation of fluctuating sex steroid hormones over the menstrual cycle in women [see review (Nillni et al, 2011)] could be an important factor that contributes to the higher rates of PA and PD in women, but other factors such as early life stress or higher incidence of trauma such as sexual abuse or domestic violence in women could also account for this vulnerability. Evidence supporting a hormonal contribution includes a study demonstrating that female PD subjects with agoraphobia reported experiencing premenstrual exacerbations in anxiety symptoms, a pattern which could increase the rate of ePAs and contribute to the development of agoraphobia in these subjects (Breier et al, 1986).…”