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Neuroactive Steroids in Brain and Relevance to Mood

  • Torbjörn Bückström
  • Lotta Andréen
  • Marie Bixo
  • Inger Björn
  • Guillén Fernández
  • Inga-Maj Johansson
  • Per Lundgren
  • Magnus Löfgren
  • Sigrid Nyberg
  • Gianna Ragagnin
  • Inger Sundström-Poromaa
  • Jessica Strömberg
  • Frank van Broekhoven
  • Guido van Wingen
  • Ming-De Wang

Depression and anxiety often affect women in relation to reproductive events like menarche, premenstrual periods, post-partum and perimenopause. A prominent example of the interaction between mood, neuroactive-steroids and the GABA system is premenstrual dysphoric disorder (PMDD). Severe premenstrual negative mood symptoms occur in 3–8% of women. Sex and stress hormones are metabolized to neuroactive steroids with effects on brain function as positive modulators of the GABAA receptor (called GABA-steroids) similar to benzodiazepines, barbiturates and alcohol. One example of a neuroactive sex steroid is allopregnanolone, and other GABA-steroids, are produced within the brain, by the adrenals at stress and from the ovary during the menstrual cycle. Animal and human studies show that benzodiazepines, barbiturates, alcohol and allopregnanolone have a bimodal effect on behavior. In high dosages or concentrations the positive GABAA receptor modulators are CNS depressants, anesthetic, and anxiolytic, whereas in certain sensitive individuals low concentrations instead of being anxiolytic cause severe anxiety, irritability, aggressiveness and depressive mood in 3–6% of individuals, and moderate symptoms in up to 30%. Low concentrations of GABA-steroids are found endogenously during the luteal phase and induce adverse emotional reactions. In women with PMDD/ PMS this paradoxical effect of neuroactive steroids seems to provoke negative mood symptoms as tension, irritability and depression. The mechanism behind the effect is called disinhibition that acts together with tolerance development by GABAA receptor active substances. Effective treatments are inhibition of ovarian steroid production or changing the CNS response to neuroactive steroids.

Keywords

GABAA receptor premenstrual dysphoric disorder negative mood menstrual cycle allopregnanolone progesterone paradoxical effect gaba-steroids 

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Copyright information

© Springer Science + Business Media, B.V 2008

Authors and Affiliations

  • Torbjörn Bückström
    • 1
  • Lotta Andréen
    • 1
  • Marie Bixo
    • 1
  • Inger Björn
    • 1
  • Guillén Fernández
    • 2
  • Inga-Maj Johansson
    • 1
  • Per Lundgren
    • 1
  • Magnus Löfgren
    • 1
  • Sigrid Nyberg
    • 1
  • Gianna Ragagnin
    • 1
  • Inger Sundström-Poromaa
    • 1
  • Jessica Strömberg
    • 1
  • Frank van Broekhoven
    • 3
  • Guido van Wingen
    • 2
    • 3
  • Ming-De Wang
    • 1
  1. 1.Department of Clinical SciencesNorrlands University HospitalSweden
  2. 2.F.C. Donders Centre for Cognitive NeuroimagingRadboud University NijmegenNetherlands
  3. 3.Department of PsychiatryRadboud University Nijmegen Medical CenterNetherlands

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