Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons

@article{Bckstrm2011ParadoxicalEO,
  title={Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons},
  author={Torbj{\"o}rn B{\"a}ckstr{\"o}m and David Haage and Magnus L{\"o}fgren and Inga-Maj Johansson and Jessica Str{\"o}mberg and Sigrid Nyberg and Lotta Andr{\'e}en and Lindsey Ossewaarde and Guido A. van Wingen and S. Turkmen and Sara K. S. Bengtsson},
  journal={Neuroscience},
  year={2011},
  volume={191},
  pages={46-54}
}

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References

SHOWING 1-10 OF 129 REFERENCES

The Role of Hormones and Hormonal Treatments in Premenstrual Syndrome

TLDR
SSRIs and substances inhibiting ovulation, such as gonadotrophin-releasing hormone (GnRH) agonists, have proven to be effective treatments and add-back hormone replacement therapy is recommended to avoid adverse effects when high dosages of GnRH agonists are sed.

GABA(A) receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid.

TLDR
This model reports a progesterone-withdrawal paradigm, designed to mimic PMS and post-partum syndrome in a rat model, and finds that increased susceptibility to seizure after progesferone withdrawal is due to a sixfold decrease in the decay time for GABA currents and consequent decreased inhibitory function.

Progesterone selectively increases amygdala reactivity in women

TLDR
Investigating whether a single progesterone administration to healthy young women in their follicular phase modulates the amygdala response to salient, biologically relevant stimuli reveals a neural mechanism by which progester one may mediate adverse effects on anxiety and mood.

Increase of estrogen dose deteriorates mood during progestin phase in sequential hormonal therapy.

TLDR
The conclusion is that an increase of the estrogen dose accentuates negative mood and physical symptoms during the progestin phase of sequential hormonal therapy.

Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor.

TLDR
Two metabolites of the steroid hormones progesterone and deoxycorticosterone are potent barbiturate-like ligands of the gamma-aminobutyric acid (GABA) receptor-chloride ion channel complex and potentiated the inhibitory actions of GABA in cultured rat hippocampal and spinal cord neurons, which may explain the ability of certain steroid hormones to rapidly alter neuronal excitability.

Reversal of neurosteroid effects at alpha4beta2delta GABAA receptors triggers anxiety at puberty.

TLDR
It is shown that THP (allopregnanolone), a steroid that is released as a result of stress, increases anxiety in pubertal female mice, in contrast to its anxiety-reducing effect in adults.

Reversal of neurosteroid effects at α4β2δ GABAA receptors triggers anxiety at puberty

TLDR
It is shown that THP (allopregnanolone), a steroid that is released as a result of stress, increases anxiety in pubertal female mice, in contrast to its anxiety-reducing effect in adults.

Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome.

TLDR
In women with premenstrual syndrome, the occurrence of symptoms represents an abnormal response to normal hormonal changes.

Allopregnanolone concentration and mood—a bimodal association in postmenopausal women treated with oral progesterone

TLDR
Mood effects during progesterone treatment seem to be related to allopregnanolone concentration, and a bimodal association between allopreginolone and adverse mood is evident.

Persistence of Premenstrual Syndrome During Low-Dose Administration of the Progesterone Antagonist RU 486

TLDR
Luteal-phase administration of low-dose RU 486 does not significantly reduce the physical or behavioral manifestations of PMS.
...