Menstrual Cycle Effects on Psychological Symptoms in Women With PTSD

Nillni, Yael I.; Pineles, Suzanne L.; Patton, Samantha C.; Rouse, Matthew H.; Sawyer, Alice T.; Rasmusson, Ann M.

doi:10.1002/jts.21984

Cited by 75 publications

(47 citation statements)

References 24 publications

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“…14 Further, women with PTSD report more severe psychological symptoms based on the phase of their menstrual cycle. 15 Consistent with this observation, female rodents also show more fear and anxiety-related behaviors in phases of their estrous cycle characterized by low estrogen levels, specifically the metestrous or diestrous phases. 16–19 …”

Section: Introductionmentioning

confidence: 53%

Estrogen-dependent association of HDAC4 with fear in female mice and women with PTSD

et al. 2017

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Women are at increased risk of developing post-traumatic stress disorder (PTSD) following a traumatic event. Recent studies suggest that this may be mediated, in part, by circulating estrogen levels. This study evaluated the hypothesis that individual variation in response to estrogen levels contributes to fear regulation and PTSD risk in women. We evaluated DNA methylation from blood of female participants in the Grady Trauma Project and found that serum estradiol levels associates with DNA methylation across the genome. For genes expressed in blood, we examined the association between each CpG site and PTSD diagnosis using linear models that adjusted for cell proportions and age. After multiple test correction, PTSD associated with methylation of CpG sites in the HDAC4 gene, which encodes histone deacetylase 4, and is involved in long-term memory formation and behavior. DNA methylation of HDAC4 CpG sites were tagged by a nearby single nucleotide polymorphism (rs7570903), which also associated with HDAC4 expression, fear-potentiated startle and resting state functional connectivity of the amygdala in traumatized humans. Using auditory Pavlovian fear conditioning in a rodent model, we examined the regulation of Hdac4 in the amygdala of ovariectomized (OVX) female mice. Hdac4 mRNA levels were higher in the amygdala 2h after tone-shock presentations, compared to OVX-homecage control females. In naturally cycling females, tone-shock presentations increased Hdac4 expression relative to homecage controls for metestrous (low estrogen) but not the proestrous (high estrogen) group. Together, these results support an estrogenic influence of HDAC4 regulation and expression that may contribute to PTSD in women.

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Section: Introductionmentioning

confidence: 53%

Estrogen-dependent association of HDAC4 with fear in female mice and women with PTSD

et al. 2017

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“…Forty‐seven women with histories of trauma exposure participated in the current study as part of a larger investigation of menstrual cycle effects on the psychophysiology and neurobiology of PTSD (Nillni et al, ; Pineles et al, ). Participants were recruited from a Veterans Affairs (VA) hospital and the surrounding community.…”

Section: Methodsmentioning

confidence: 99%

“…This is notable because there are several studies demonstrating impaired PPI in the luteal phase of the menstrual cycle (Jovanovic et al, ; Kumari et al, ; Swerdlow, Hartman, & Auerbach, ). Participants included in the current study completed several other psychophysiological tasks and self‐report measures as part of a larger investigation; menstrual phase effects were observed for mood and anxiety symptoms (Nillni et al, ), as well as retention of extinction learning (Pineles et al, ). Although nicotine withdrawal has been found to impair PPI and smoking to satisfaction has been found to enhance PPI in smokers (Della Casa, Hofer, Weiner, & Feldon, ; Kumari, Checkley, & Gray, ), only one study of PPI in PTSD assessed tobacco use (Vrana et al, ).…”

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confidence: 99%

Prepulse inhibition deficits in women with PTSD

et al. 2016

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Prepulse inhibition (PPI) is an automatic and preattentive process, whereby a weak stimulus attenuates responding to a sudden and intense startle stimulus. PPI is a measure of sensorimotor filtering, which is conceptualized as a mechanism that facilitates processing of an initial stimulus and is protective from interruption by a later response. Impaired PPI has been found in (a) healthy women during the luteal phase of the menstrual cycle, and (b) individuals with types of psychopathology characterized by difficulty suppressing and filtering sensory, motor, or cognitive information. In the current study, 47 trauma-exposed women with or without posttraumatic stress disorder (PTSD) completed a PPI session during two different phases of the menstrual cycle: the early follicular phase, when estradiol and progesterone are both low, and the midluteal phase, when estradiol and progesterone are both high. Startle stimuli were 100 dB white noise bursts presented for 50 ms, and prepulses were 70 dB white noise bursts presented for 20 ms that preceded the startle stimuli by 120 ms. Women with PTSD showed deficits in PPI relative to the healthy trauma-exposed participants. Menstrual phase had no effect on PPI. These results provide empirical support for individuals with PTSD having difficulty with sensorimotor filtering. The potential utility of PPI as a Research Domain Criteria (RDoC) phenotype is discussed.

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“…A series of studies on a sample of trauma-exposed females have provided data on progesterone levels during specific menstrual phases and its associations with various aspects of fear learning (Nillni et al, 2015;Pineles et al, 2016aPineles et al, , 2016bPineles et al, , 2018. Using a PPI paradigm, one study found that greater progesterone levels (assayed from plasma) were significantly associated with increased PPI among trauma-exposed females in the early follicular phase (Pineles et al, 2016a).…”

Section: Human Research On Progesterone In Fear and Ptsdmentioning

confidence: 99%

Translational studies of estradiol and progesterone in fear and PTSD

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Hurly

Mellen

et al. 2020

European Journal of Psychotraumatology

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Translational models of fear have greatly informed our understanding of PTSD and its underlying fear circuitry. One of the most replicated findings in the field is the two-fold higher PTSD incidence in females compared to males. While sociocultural factors play a role, the most robust biological influencers to date are gonadal hormones, such as estradiol and progesterone, which fluctuate across the menstrual cycle. Among studies that account for these hormones, most do so in isolation or collect both and only report one. Variation in study findings suggests that the ratio between these two hormones (the P/E ratio) may be an important and missing variable to further understand gonadal hormone influences on fear. Here we review cross-species examinations of fear and PTSD, within the contexts of estradiol and progesterone as well as P/E ratios that were calculated based on extant literature. We then provide recommendations for best practices in assay methods and reporting to improve research on the P/E ratio in fear and PTSD. Ultimately, greater understanding of this important variable will advance efforts to characterize gonadal hormone influences on fear learning processes in humans and animals.

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Menstrual Cycle Effects on Psychological Symptoms in Women With PTSD

Cited by 75 publications

References 24 publications

Estrogen-dependent association of HDAC4 with fear in female mice and women with PTSD

Estrogen-dependent association of HDAC4 with fear in female mice and women with PTSD

Prepulse inhibition deficits in women with PTSD

Translational studies of estradiol and progesterone in fear and PTSD

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