TY - JOUR
T1 - Allopregnanolone in premenstrual dysphoric disorder (PMDD)
T2 - Evidence for dysregulated sensitivity to GABA-A receptor modulating neuroactive steroids across the menstrual cycle
AU - Hantsoo, Liisa
AU - Epperson, C. Neill
N1 - Funding Information:
This work was supported by the National Institutes of Health ( K23 MH107831 , Hantsoo).
Publisher Copyright:
© 2020
PY - 2020/5
Y1 - 2020/5
N2 - Premenstrual dysphoric disorder (PMDD) is a severe mood disorder with core symptoms (affective lability, irritability, depressed mood, anxiety) and increased sensitivity to stress occurring in the luteal phase of the menstrual cycle. PMDD can be conceptualized as a disorder of suboptimal sensitivity to neuroactive steroid hormones (NASs). In this review, we describe the role of the NAS allopregnanolone (ALLO), a positive allosteric modulator of the GABAA receptor (GABAA-R), in PMDD's pathophysiology. We review evidence of impaired interaction between ALLO and GABAA-Rs in terms of affective symptom expression, with evidence from rodent and human studies. We discuss evidence of increased luteal phase stress sensitivity as a result of poor ALLO-GABA control of the HPA axis. Finally, we describe how treatments such as selective serotonin reuptake inhibitors (SSRIs) and new drugs targeting GABAA-Rs provide evidence for impaired ALLO-GABA function in PMDD. In sum, the literature supports the hypothesis that PMDD pathophysiology is rooted in impaired GABAA-R response to dynamic ALLO fluctuations across the menstrual cycle, manifesting in affective symptoms and poor regulation of physiologic stress response.
AB - Premenstrual dysphoric disorder (PMDD) is a severe mood disorder with core symptoms (affective lability, irritability, depressed mood, anxiety) and increased sensitivity to stress occurring in the luteal phase of the menstrual cycle. PMDD can be conceptualized as a disorder of suboptimal sensitivity to neuroactive steroid hormones (NASs). In this review, we describe the role of the NAS allopregnanolone (ALLO), a positive allosteric modulator of the GABAA receptor (GABAA-R), in PMDD's pathophysiology. We review evidence of impaired interaction between ALLO and GABAA-Rs in terms of affective symptom expression, with evidence from rodent and human studies. We discuss evidence of increased luteal phase stress sensitivity as a result of poor ALLO-GABA control of the HPA axis. Finally, we describe how treatments such as selective serotonin reuptake inhibitors (SSRIs) and new drugs targeting GABAA-Rs provide evidence for impaired ALLO-GABA function in PMDD. In sum, the literature supports the hypothesis that PMDD pathophysiology is rooted in impaired GABAA-R response to dynamic ALLO fluctuations across the menstrual cycle, manifesting in affective symptoms and poor regulation of physiologic stress response.
KW - Allopregnanolone
KW - Menstrual cycle
KW - Premenstrual dysphoric disorder
KW - Premenstrual syndrome
KW - Progesterone
KW - Women's health
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U2 - 10.1016/j.ynstr.2020.100213
DO - 10.1016/j.ynstr.2020.100213
M3 - Article
C2 - 32435664
AN - SCOPUS:85079603516
SN - 2352-2895
VL - 12
JO - Neurobiology of Stress
JF - Neurobiology of Stress
M1 - 100213
ER -