Luteal-Phase Accentuation of Acoustic Startle Response in Women with Premenstrual Dysphoric Disorder

Epperson, C. Neill; Pittman, Brian; Czarkowski, Kathryn A.; Stiklus, Stephanie; Krystal, John H.; Grillon, Christian

doi:10.1038/sj.npp.1301351

Cited by 69 publications

(49 citation statements)

References 60 publications

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“…The major limitation was that the menstrual phase of the women was not assessed. A previous study did not find that the phase of the menstrual cycle affected the affective modulation of startle to emotional pictures in healthy women (Epperson et al, 2007). Whether potentiated startle to shock threats is affected by menstrual cycle is unknown and should be investigated in future studies.…”

Section: Discussionmentioning

confidence: 99%

Greater sustained anxiety but not phasic fear in women compared to men.

Grillon

2008

Emotion

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Startle reflex studies in rodents indicate that female are more reactive than rats in experimental models of sustained anxiety but not in models of phasic fear (Toufexis, 2007). This study examined evidence for a similar effect in humans. Participants were exposed to three conditions, (1) predictable aversive shocks signaled by a cue, (2) unpredictable shocks, and (3) no shocks. Acoustic startle stimuli were delivered regularly across conditions. Phasic startle potential to the threat cue in the predictable condition was not affected by sex. In contrast, and consistent with basic research, the sustained increase in startle in the predictable and unpredictable conditions was greater in women compared to men. Animal studies suggest that such an effect may be mediated by the effects of sexual dimorphism in limbic structures, including the bed nucleus of the stria terminalis. However, psychosocial factors may also contribute to this effect. Keywords fear; anxiety; sex difference; startle; unpredictability The greater prevalence of mood and anxiety disorders among women compared to men (Kessler et al., 1994) points to a potential sex difference in reactivity to threat. Preclinical studies may provide clues as to the nature of this difference. A recent review focusing on animal models, using the startle reflex as an operational measure of aversive states, compared sex differences in two types of aversive responses, anxiety, a sustained state of distress to uncertain threat, and fear, a phasic defensive response to certain danger (Toufexis, 2007). Contrasting phasic and sustained aversive states was motivated by evidence of a neural differentiation between them, the former relying on the central nucleus of the amygdala (CeA) and the latter on the bed nucleus of the stria terminalis (BNST; Davis, 1998), as well as by an indication of strong sexual dimorphism in the BNST (Allen & Gorski, 1990). Toufexis concluded that BNST-mediated sustained potentiated startle (anxiety), but not cued specific fear-potentiated startle (fear), was increased in female rats compared to males.The present study examined evidence for a similar sex difference in humans, also using startle as a measure of aversive states. We have distinguished phasic fear to a predictable threat signaled by a cue from the more sustained contextual anxiety state during administration of predictable (certain) and unpredictable (uncertain) shocks (Grillon et al., 2006; Grillon, Baas, Lissek, Smith, & Milstein, 2004a). Based on Toufexis's review (Toufexis, 2007), we hypothesized that relative to men, women would show enhanced contextual-potentiated startle but not increased fear-potentiated startle to a threat cue.

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Section: Discussionmentioning

confidence: 99%

Greater sustained anxiety but not phasic fear in women compared to men.

Grillon

2008

Emotion

Self Cite

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“…If necessary, varying cycle lengths can be modified statistically to conform to a standardized 28-day cycle. However, the most straightforward way to assess changes in outcomes across the cycle or between phases is to target when a given women is likely to be in the hormonal and/or behavioral state of interest (Epperson et al, 2007;Comasco et al, 2014;Timby et al, 2016). Many women will have several days of spotting before experiencing a full flow.…”

Section: Box 1 How To Examine the Estrous Cycle In Rodentsmentioning

confidence: 99%

Sex as a Biological Variable: Who, What, When, Why, and How

Bale

Epperson

2016

Neuropsychopharmacol

119

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The inclusion of sex as a biological variable in research is absolutely essential for improving our understanding of disease mechanisms contributing to risk and resilience. Studies focusing on examining sex differences have demonstrated across many levels of analyses and stages of brain development and maturation that males and females can differ significantly. This review will discuss examples of animal models and clinical studies to provide guidance and reference for the inclusion of sex as an important biological variable relevant to a Neuropsychopharmacology audience.

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“…Recently, Epperson et al (2007) demonstrated that PMDD patients have an increased baseline startle response during the luteal phase compared to the follicular phase. We had hypothesized that PMDD patients would display increased startle response compared to control subjects only in the luteal phase.…”

Section: Discussionmentioning

confidence: 99%

“…We predicted that subjects with PMDD would have higher ASR than asymptomatic controls in the luteal phase, based on prior studies of ASR in PMDD patients (Epperson et al, 2007), and on a working model of the underlying mechanisms of the etiology of negative mood symptoms. In women with PMDD, symptoms occur in the luteal phase of the menstrual cycle in close correlation to progesterone fluctuations.…”

Section: Introductionmentioning

confidence: 99%

“…The acoustic startle response is increased in an animal model of PMDD , and was recently also shown to be increased in the luteal phase of PMDD patients (Epperson et al, 2007). The acoustic startle reflex (ASR) is a withdrawal reflex to sudden or noxious auditory stimuli, which can be measured as an eyeblink in humans or as a whole body response in laboratory animals (Davis, 1980).…”

Section: Introductionmentioning

confidence: 99%

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Patients with Premenstrual Dysphoric Disorder have Increased Startle Response Across both Cycle Phases and Lower Levels of Prepulse Inhibition During the Late Luteal Phase of the Menstrual Cycle

Kask

Gulinello

Bäckström

et al. 2007

Neuropsychopharmacol

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Patients with premenstrual dysphoric disorder (PMDD) experience their most intense symptoms during the late luteal phase. The aim of the current study was to compare acoustic startle response and prepulse inhibition in PMDD patients and controls during the follicular and late luteal phases of the menstrual cycle. Following two months of prospective daily ratings on the Cyclicity Diagnoser scale, 30 PMDD patients and 30 asymptomatic controls, between the ages of 20 and 46, were included in the study. The eyeblink component of the acoustic startle reflex was assessed using electromyographic measurements of m. orbicularis oculi. Twenty pulse-alone trials (115 dB 40 ms broad-band white noise) and 40 prepulse-pulse trials were presented. The prepulse stimuli consisted of a 115 dB 40 ms noise burst preceded at a 100 ms interval by 20 ms prepulses that were 72, 74, 78, or 86 dB. PMDD patients had a significantly higher startle response than controls during both phases of the menstrual cycle (po0.05). PMDD patients exhibited lower levels of prepulse inhibition with 78 dB and 86 dB prepulses compared to control subjects in the luteal (po0.01) but not in the follicular phase. Whereas control subjects displayed increased PPI during the late luteal phase compared to the follicular phase (po0.01), PPI magnitude remained unchanged in PMDD patients between cycle phases. Relative to controls, PMDD patients displayed increased startle reactivity across both menstrual cycle phases and deficits in prepulse inhibition of acoustic startle during the late luteal phase. These findings are consistent with an altered response to ovarian steroids among PMDD patients.

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Luteal-Phase Accentuation of Acoustic Startle Response in Women with Premenstrual Dysphoric Disorder

Cited by 69 publications

References 60 publications

Greater sustained anxiety but not phasic fear in women compared to men.

Greater sustained anxiety but not phasic fear in women compared to men.

Sex as a Biological Variable: Who, What, When, Why, and How

Patients with Premenstrual Dysphoric Disorder have Increased Startle Response Across both Cycle Phases and Lower Levels of Prepulse Inhibition During the Late Luteal Phase of the Menstrual Cycle

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