We tested the hypothesis that changes in endogenous neuroactive steroids acting as positive allosteric modulators of gamma-aminobutyric acid (GABA)(A) receptors may be related to the menopause-associated mood alterations. The study sample consisted of twenty five drug-free menopausal women, 1-3 years since the onset of menopause, homogeneous for age and body mass index (BMI) and without personal history of psychiatric, metabolic or endocrine disorders. Depression and anxiety-related symptoms were assessed with the Zung Self-administered Depression Scale (ZSDS) and the Cornell's Dysthymia Rating Scale (CDRS). The cut-off value predicted by the ZSDS index defined two groups of women (asymptomatic [35.5+/-4.6, n=12] and symptomatic [60.8+/-7.9, n=13]), that were also significantly different according to the CDRS scores (10.6+/-3.4 and 31.5+/-12, respectively, P<0.05). Upon evaluation of the scores relative to the anxiety factor of the CDRS (items 11-15) the symptomatic, but not the asymptomatic, group showed a moderate level of anxiety. The plasma concentrations of several neuroactive steroids were measured, after extraction and HPLC purification, by radioimmunoassay with specific antisera. Only dehydroepiandrosterone and its metabolite 5alpha-androstane-3alpha,17betadiol (3alpha-ADIOL), a positive allosteric modulator of GABA(A) receptors, were significantly (P<0.05 and P<0.005) higher (+110% and +64%, respectively) in the asymptomatic group. A highly significant and negative correlation (r=-0.672, P=0.003) was found between the plasma 3alpha-ADIOL concentrations and the scores of the anxiety factor of the CDRS. These data suggest that endogenous 3alpha-ADIOL modulates the central GABAergic tone and that higher 3alpha-ADIOL concentrations could have a role in preventing the expression of anxiety in the asymptomatic women.

Barbaccia, M.L., Lello, S., Sidiropoulou, T., Cocco, T., Sorge, R.P., Cocchiarale, A., et al. (2000). Plasma 5alpha-androstane-3alpha,17betadiol, an endogenous steroid that positively modulates GABA(A) receptor function, and anxiety: a study in menopausal women. PSYCHONEUROENDOCRINOLOGY, 25(7), 659-675.

Plasma 5alpha-androstane-3alpha,17betadiol, an endogenous steroid that positively modulates GABA(A) receptor function, and anxiety: a study in menopausal women

BARBACCIA, MARIA LUISA;SORGE, ROBERTO PIETRO;SABATO, ALESSANDRO FABRIZIO;TRABUCCHI, MARCO MARIO;
2000-10

Abstract

We tested the hypothesis that changes in endogenous neuroactive steroids acting as positive allosteric modulators of gamma-aminobutyric acid (GABA)(A) receptors may be related to the menopause-associated mood alterations. The study sample consisted of twenty five drug-free menopausal women, 1-3 years since the onset of menopause, homogeneous for age and body mass index (BMI) and without personal history of psychiatric, metabolic or endocrine disorders. Depression and anxiety-related symptoms were assessed with the Zung Self-administered Depression Scale (ZSDS) and the Cornell's Dysthymia Rating Scale (CDRS). The cut-off value predicted by the ZSDS index defined two groups of women (asymptomatic [35.5+/-4.6, n=12] and symptomatic [60.8+/-7.9, n=13]), that were also significantly different according to the CDRS scores (10.6+/-3.4 and 31.5+/-12, respectively, P<0.05). Upon evaluation of the scores relative to the anxiety factor of the CDRS (items 11-15) the symptomatic, but not the asymptomatic, group showed a moderate level of anxiety. The plasma concentrations of several neuroactive steroids were measured, after extraction and HPLC purification, by radioimmunoassay with specific antisera. Only dehydroepiandrosterone and its metabolite 5alpha-androstane-3alpha,17betadiol (3alpha-ADIOL), a positive allosteric modulator of GABA(A) receptors, were significantly (P<0.05 and P<0.005) higher (+110% and +64%, respectively) in the asymptomatic group. A highly significant and negative correlation (r=-0.672, P=0.003) was found between the plasma 3alpha-ADIOL concentrations and the scores of the anxiety factor of the CDRS. These data suggest that endogenous 3alpha-ADIOL modulates the central GABAergic tone and that higher 3alpha-ADIOL concentrations could have a role in preventing the expression of anxiety in the asymptomatic women.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/14
English
Con Impact Factor ISI
Personality Inventory; Middle Aged; Anxiety; Climacteric; Female; Depression; Receptors, GABA-A; Etiocholanolone; Humans
Barbaccia, M.L., Lello, S., Sidiropoulou, T., Cocco, T., Sorge, R.P., Cocchiarale, A., et al. (2000). Plasma 5alpha-androstane-3alpha,17betadiol, an endogenous steroid that positively modulates GABA(A) receptor function, and anxiety: a study in menopausal women. PSYCHONEUROENDOCRINOLOGY, 25(7), 659-675.
Barbaccia, Ml; Lello, S; Sidiropoulou, T; Cocco, T; Sorge, Rp; Cocchiarale, A; Piermarini, V; Sabato, Af; Trabucchi, Mm; Romanini, C
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/14897
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