Effects of gonadal steroids on peripheral benzodiazepine receptor density in women with PMS and controls

Daly, Robert C.; Schmidt, Peter J.; Davis, Candace L.; Danaceau, Merry A.; Rubinow, David R.

doi:10.1016/s0306-4530(01)00005-1

Cited by 9 publications

(3 citation statements)

References 33 publications

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“…Since there is no evidence that PMDD women differ in the density or affinity of peripheral benzodiazepine receptors, at least as measured on lymphocytes (Daly et al 2001), these results suggest a diminished functional sensitivity of GABA A Rs in PMDD. Moreover, the work of Le Melledo et al (2000) has shown that exposure to flumazenil, a benzodiazepine receptor antagonist, in the luteal phase elicits marked increases in panic symptoms in PMDD women but not in non-PMDD controls.…”

Section: Implications Of Neurosteroid – Hpa-axis Regulation For Humanmentioning

confidence: 77%

Neurosteroid, GABAergic and hypothalamic pituitary adrenal (HPA) axis regulation: what is the current state of knowledge in humans?

Crowley

Girdler

2014

Psychopharmacology

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Rationale A robust epidemiological literature suggests an association between chronic stress and the development of affective disorders. However, the precise biological underpinnings of this relationship remain elusive. Central to the human response and adaptation to stress, activation and inhibition of the hypothalamic pituitary adrenal (HPA) axis involves a multi-level, multi-system, neurobiological stress response which is as comprehensive in its complexity as it is precarious. Dysregulation in this complex system has implications for human stress related illness. Objectives The pioneering research of Robert Purdy and colleagues has laid the groundwork for advancing our understanding of HPA-axis regulation by stress-derived steroid hormones and their neuroactive metabolites (termed neurosteroids), which are potent allosteric modulators of GABAA receptor function in the central nervous system. This review will describe what is known about neurosteroid modulation of the HPA-axis in response to both acute and chronic stress, particularly with respect to the current state of our knowledge of this process in humans. Results Implications of this research to the development of human stress related illness are discussed in the context of two human stress-related psychiatric disorders - major depressive disorder and premenstrual dysphoric disorder. Conclusions Neurosteroid-mediated HPA-axis dysregulation is a potential pathophysiologic mechanism which may cross traditional psychiatric diagnostic classifications. Future research directions are identified.

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Section: Implications Of Neurosteroid – Hpa-axis Regulation For Humanmentioning

confidence: 77%

Neurosteroid, GABAergic and hypothalamic pituitary adrenal (HPA) axis regulation: what is the current state of knowledge in humans?

Crowley

Girdler

2014

Psychopharmacology

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“…The clinical significance of these results comes from their findings that when PMDD women are divided into lower versus higher symptom severity groups, the more severe PMDD symptom groups respond with less of a reduction in SEV (Sundstrom et al, 1997b(Sundstrom et al, , 1998 and with lower sedation ratings (Sundstrom et al, 1998) in response to benzodiazepines. Since there is no evidence that PMDD women differ in the density or affinity of peripheral benzodiazepine receptors, at least as measured on lymphocytes (Daly et al, 2001), the findings of Sundstrom and colleagues indicate diminished functional sensitivity of GABA A receptors in PMDD. This is consistent with studies finding modest or no clinical efficacy with benzodiazepine treatment for PMDD (Schmidt et al, 1993;Freeman et al, 1995;Evans et al, 1998), though exceptions exist (Harrison et al, 1987), and with lack of clinical benefit associated with a progesterone intervention or with progesterone induction of supraphysiologic levels of 5α-and 5β-progesterone metabolites Vanselow et al, 1996;see Wyatt et al, 2001 for review).…”

Section: Hpa Axis and Gaba A Receptor Function In Pmddmentioning

confidence: 98%

Neurosteroids in the context of stress: Implications for depressive disorders

Girdler

Klatzkin

2007

Pharmacology & Therapeutics

129

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Animal models indicate that the neuroactive steroids 3α,5α-THP (allopregnanolone) and 3α,5α-THDOC (allotetrahydroDOC) are stress responsive, serving as homeostatic mechanisms in restoring normal GABAergic and hypothalamic-pituitary-adrenal (HPA) function following stress. While neurosteroid increases to stress are adaptive in the short term, animal models of chronic stress and depression find lower brain and plasma neurosteroid concentrations and alterations in neurosteroid responses to acute stressors. It has been suggested that disruption in this homeostatic mechanism may play a pathogenic role in some psychiatric disorders related to stress. In humans, neurosteroid depletion is consistently documented in patients with current depression and may reflect their greater chronic stress. Women with the depressive disorder, premenstrual dysphoric disorder (PMDD), have greater daily stress and a greater rate of traumatic stress. While results on baseline concentrations of neuroactive steroids in PMDD are mixed, PMDD women have diminished functional sensitivity of GABA A receptors and our laboratory has found blunted allopregnanolone responses to mental stress relative to non-PMDD controls. Similarly, euthymic women with histories of clinical depression, which may represent a large proportion of PMDD women, show more severe dysphoric mood symptoms and blunted allopregnanolone responses to stress versus never-depressed women. It is suggested that failure to mount an appropriate allopregnanolone response to stress may reflect the price of repeated biological adaptations to the increased life stress that is well documented in depressive disorders and altered allopregnanolone stress responsivity may also contribute to the dysregulation seen in HPA axis function in depression.

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“…At the beginning of the first session the participants were informed about the general procedure, and then data on handedness and menstrual cycle were collected. Additionally, their current mood was assessed by using the State-Trait-Cheerfulness-Inventory (STCI-S18; Ruch et al, 1997) to register and control potential premenstrual changes (PMS) caused by gonadal hormones (e.g., Daly et al, 2001;Man et al, 1999;Reilly & Kremer, 2002) that might influence cognitive performance (e.g., Boyle, 2002; Erez & Isen, *A reanalysis of these data (unpublished) for sex differences (7 men and 9 women) revealed a marginally significant interaction between sex and visual half field [F(1,14) 5 4.028, P 5 .065]. Multiple post-hoc comparisons resulted in a significant difference (P , .05) between males and females regarding the AB in the LVF, with males showing a less pronounced AB than women.…”

Section: Acquisition Of Cycle Phase/moodmentioning

confidence: 99%

Sex hormonal modulation of hemispheric asymmetries in the attentional blink

Holländer

Hausmann

Hamm

et al. 2005

J Int Neuropsychol Soc

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The present study examines differences in functional cerebral asymmetries modulated by gonadal steroid hormones during the menstrual cycle in women. Twenty-one right-handed women with regular menstrual cycles performed a double-stream rapid serial visual presentation (RSVP) task, with one stream in each visual field, during the low steroid menses and the high steroid midluteal phase. They were required to detect a target item, and then a probe item, each of which could appear in either stream. If the probe item appeared 200 ms after the target, detection of the probe was impaired-a phenomenon known as the "attentional blink." This occurred in both streams in the midluteal phase, but only in the right visual field during menses. Thus low steroid levels appeared to restrict the attentional blink to the left hemisphere, while high levels of estradiol and progesterone in the midluteal phase appeared to reduce functional asymmetries by selectively increasing the attentional blink in the right hemisphere. This effect appears to be mediated by estradiol rather than progesterone, and it is compatible with the assumption of a hormone-related suppression of right hemisphere functions during the midluteal phase.

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Effects of gonadal steroids on peripheral benzodiazepine receptor density in women with PMS and controls

Cited by 9 publications

References 33 publications

Neurosteroid, GABAergic and hypothalamic pituitary adrenal (HPA) axis regulation: what is the current state of knowledge in humans?

Neurosteroid, GABAergic and hypothalamic pituitary adrenal (HPA) axis regulation: what is the current state of knowledge in humans?

Neurosteroids in the context of stress: Implications for depressive disorders

Sex hormonal modulation of hemispheric asymmetries in the attentional blink

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