Dataset Information

Sex differences in the traumatic stress response: PTSD symptoms in women recapitulated in female rats.

ABSTRACT:

Background

Post-traumatic stress disorder (PTSD) affects men and women differently. Not only are women twice as likely as men to develop PTSD, they experience different symptoms and comorbidities associated with PTSD. Yet the dearth of preclinical research on females leaves a notable gap in understanding the underlying neuropathology of this sex difference.

Methods

Using two standard measures of PTSD-like responses in rats, the acoustic startle response (ASR) and dexamethasone suppression test (DST), we tested the effects of traumatic stress in adult male and female rats using two rodent models of PTSD, single prolonged stress and predator exposure. We then examined the neural correlates underlying these responses with cFos and glucocorticoid receptor immunohistochemistry in brain regions implicated in the traumatic stress response.

Results

We now report that adult male and female rats across two models of PTSD show consistent sex-specific responses that recapitulate fundamental differences of PTSD in men and women. Trauma-exposed males showed the well-established hyper-responsive phenotype of enhanced ASR and exaggerated negative feedback control of the hypothalamic-pituitary-adrenal axis, while the same traumatic event had little effect on these same measures in females. Dramatic sex differences in how trauma affected cFos and glucocorticoid receptor expression in the brain lend further support to the idea that the trauma response of male and female rats is fundamentally different.

Conclusions

Two standard measures, ASR and DST, might suggest that females are resilient to the effects of traumatic stress, but other measures make it clear that females are not resilient, but simply respond differently to trauma. The next important question to answer is why. We conclude that males and females show fundamentally different responses to trauma that do not simply reflect differences in resilience. The divergent effects of trauma in the brains of males and females begin to shed light on the neurobiological underpinnings of these sex differences, paving the way for improved diagnostics and therapeutics that effectively treat both men and women.

SUBMITTER: Pooley AE

PROVIDER: S-EPMC6034295 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Sex differences in the traumatic stress response: PTSD symptoms in women recapitulated in female rats.

Pooley Apryl E AE Benjamin Rebecca C RC Sreedhar Susheela S Eagle Andrew L AL Robison Alfred J AJ Mazei-Robison Michelle S MS Breedlove S Marc SM Jordan Cynthia L CL

Biology of sex differences 20180705 1

<h4>Background</h4>Post-traumatic stress disorder (PTSD) affects men and women differently. Not only are women twice as likely as men to develop PTSD, they experience different symptoms and comorbidities associated with PTSD. Yet the dearth of preclinical research on females leaves a notable gap in understanding the underlying neuropathology of this sex difference.<h4>Methods</h4>Using two standard measures of PTSD-like responses in rats, the acoustic startle response (ASR) and dexamethasone sup ...[more]

PMID: 29976248

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Project description:BackgroundPre-term or full-term childbirth can be experienced as physically or psychologically traumatic. Cumulative and trans-generational effects of traumatic stress on both psychological and physical health indicate the ethical requirement to investigate appropriate preventative treatment for stress symptoms in women following a routine traumatic experience such as childbirth.ObjectiveThe objective of this review was to investigate the effectiveness of early psychological interventions in reducing or preventing post-traumatic stress symptoms and post-traumatic stress disorder in post-partum women within twelve weeks of a traumatic birth.MethodsRandomised controlled trials and pilot studies of psychological interventions preventing or reducing post-traumatic stress symptoms or PTSD, that included women who had experienced a traumatic birth, were identified in a search of Cochrane Central Register of Randomised Controlled Trials, MEDLINE, Embase, Psychinfo, PILOTS, CINAHL and Proquest Dissertations databases. One author performed database searches, verified results with a subject librarian, extracted study details and data. Five authors appraised extracted data and agreed upon risk of bias. Analysis was completed with Rev Man 5 software and quality of findings were rated according to Grading of Recommendation, Assessment, Development, and Evaluation.ResultsEleven studies were identified that evaluated the effectiveness of a range of early psychological interventions. There was firm evidence to suggest that midwifery or clinician led early psychological interventions administered within 72 hours following traumatic childbirth are more effective than usual care in reducing traumatic stress symptoms in women at 4-6 weeks. Further studies of high methodological quality that include longer follow up of 6-12 months are required in order to substantiate the evidence of the effectiveness of specific face to face and online early psychological intervention modalities in preventing the effects of stress symptoms and PTSD in women following a traumatic birth before introduction to routine care and practice.Prospero registrationCRD42020202576, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=202576.

Project description:BackgroundTraumatic sexual experiences can negatively affect sexual functioning and increase pelvic floor activity in women, especially when post-traumatic stress disorder (PTSD) is developed. However, little is known about the effect of other types of interpersonal and non-interpersonal, traumatic experiences on sexual function and pelvic floor overactivity.ObjectiveThe aim of this study was to examine the effects of lifetime traumatic experiences and subsequent PTSD symptoms on sexual function and pelvic floor activity and to investigate whether the effects differ for interpersonal and non-interpersonal trauma.MethodsWomen (N=82) with obesity and a history of infertility, participating in a follow-up study of an RCT investigating a lifestyle intervention programme, completed questionnaires on lifetime exposure to traumatic events (LEC-5), PTSD symptoms (PC-PTSD-5), sexual function (MFSQ) and pelvic floor activity (AOPFS-SV).ResultsA large majority of women (85%) reported exposure to at least one traumatic event during their lifetime. Sexual function and pelvic floor activity did not differ between women who experienced non-interpersonal or interpersonal (including sexual) trauma and those who did not experience traumatic events during their lifetime. Women who had developed PTSD symptoms, however, did have higher pelvic floor activity, but sexual function was not affected. Women with a positive screen for PTSD had the highest pelvic floor activity score, and individual PTSD symptoms nightmares and hypervigilance were associated with significantly higher pelvic floor activity scores.ConclusionTrauma exposure is associated with pelvic floor overactivity in women with a positive screen for PTSD, such that pelvic floor overactivity is more severe with greater PTSD severity. These findings suggest that the development of PTSD after interpersonal trauma is pivotal in this association. Sexual function was unrelated to trauma exposure and pelvic floor function, perhaps related to the fact that the interpersonal trauma events reported in this study were mainly non-sexual.

Project description:BackgroundOur previous study revealed that adult female rats respond differently to trauma than adult males, recapitulating sex differences in symptoms of post-traumatic stress disorder (PTSD) exhibited by women and men. Here, we asked two questions: does the female phenotype depend on (1) social housing condition and/or (2) circulating gonadal hormones?MethodsFor the first study, the effects of single prolonged stress (SPS) were compared for females singly or pair-housed. For the second study, adult male and female rats were gonadectomized or sham-gonadectomized 2 weeks prior to exposure to SPS, with half the gonadectomized rats given testosterone. In addition to the typical measures of the trauma response in rats, acoustic startle response (ASR), and the dexamethasone suppression test (DST), we also used two other measures typically used to assess depressive-like responses, social interaction and sucrose preference. Glucocorticoid receptor (GR) expression in the hypothalamus was also examined.ResultsWe now report that the distinct trauma response of female rats is not influenced by social housing condition. Moreover, sex differences in the response to SPS based on ASR and DST, replicated in the current study, are independent of adult gonadal hormones. Regardless of hormonal status, traumatized males show a hyper-responsive phenotype whereas traumatized females do not. Moreover, testosterone treatment in adulthood did not masculinize the response to trauma in females. Notably, both sucrose preference and social interaction tests revealed an effect of trauma in females but not in males, with the effects of SPS on sucrose preference dependent on ovarian hormones. Effects of SPS on GR expression in the hypothalamus also depended on gonadal hormones in females.ConclusionsWe propose that the trauma response for female rats is depressive in nature, recapitulating the female bias in PTSD for internalizing symptoms and major depression in contrast to the externalizing symptoms of males. Presumed core markers of PTSD (enhanced ASR and negative feedback control of corticosterone) are apparently relevant only to males and are independent of adult gonadal hormones. Such sex differences in trauma responding are likely determined earlier in life. We conclude that males and females show fundamentally different responses to trauma that do not simply reflect differences in resilience.

Dataset Information

Sex differences in the traumatic stress response: PTSD symptoms in women recapitulated in female rats.

Background

Methods

Results

Conclusions

Publications

Sex differences in the traumatic stress response: PTSD symptoms in women recapitulated in female rats.

Similar Datasets

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