Brambilla Francesca, Biggio Giovanni, Pisu Maria Giuseppina, Bellodi Laura, Perna Giampaolo, Bogdanovich-Djukic Vesna, Purdy Robert H, Serra Mariangela
Dipartimento di Scienze Neuropsichiche, Istituto Scientifico Ospedale S. Raffaele, Universita' Vita e Salute, Milan, Italy.
Psychiatry Res. 2003 May 30;118(2):107-16. doi: 10.1016/s0165-1781(03)00077-5.
Evidence that neurosteroids have anxiolytic effects in animal models of anxiety has suggested that alterations of neurosteroid secretion might be implicated in the pathogenetic mechanisms of anxiety disorders in humans. In 25 female patients with panic disorder (PD) and 11 healthy female controls, we measured plasma concentrations of progesterone (PROG), pregnenolone (PREG), allopregnanolone (3alpha,5alpha-tetrahydroprogesterone=3alpha,5alpha-THPROG), dehydroepiandrosterone (DHEA) and tetrahydrodeoxycorticosterone (3alpha,5alpha-THDOC) during a drug-free month and during the following month of paroxetine therapy. The neurosteroids were measured during the early follicular phase, the mid-luteal phase and the premenstrual phase of both months (days 7, 22 and 27 from the beginning of the cycle). Significantly higher levels in patients than controls were found in PROG during the mid-luteal phase of both months, PREG in the premenstrual phase in the drug-free month, 3alpha,5alpha-THPROG during the follicular phase of the drug-free month and during the premenstrual phase of the therapy month, and 3alpha,5alpha-THDOC during the premenstrual phases of both months. DHEA levels did not differ in patients and controls. These results suggest that neurosteroids in PD are hypersecreted, possibly as an attempt to counteract the anxiogenic underlying hyperactivity of the hypothalamo-pituitary-adrenal axis and to improve a reduced GABA(A) receptor sensitivity.
神经甾体在动物焦虑模型中具有抗焦虑作用的证据表明，神经甾体分泌的改变可能与人类焦虑症的发病机制有关。我们对25名患有惊恐障碍（PD）的女性患者和11名健康女性对照者，在停药的一个月以及随后服用帕罗西汀治疗的一个月期间，测量了血浆中孕酮（PROG）、孕烯醇酮（PREG）、别孕烯醇酮（3α,5α-四氢孕酮=3α,5α-THPROG）、脱氢表雄酮（DHEA）和四氢脱氧皮质酮（3α,5α-THDOC）的浓度。在这两个月的卵泡早期、黄体中期和经前期（月经周期开始后的第7、22和27天）测量神经甾体。在两个月的黄体中期，患者的PROG水平显著高于对照组；在停药月份的经前期，患者的PREG水平显著高于对照组；在停药月份的卵泡期和治疗月份的经前期，患者的3α,5α-THPROG水平显著高于对照组；在两个月的经前期，患者的3α,5α-THDOC水平显著高于对照组。患者和对照组的DHEA水平没有差异。这些结果表明，PD患者的神经甾体分泌过多，可能是为了抵消下丘脑-垂体-肾上腺轴潜在的致焦虑性多动，并改善降低的GABA(A)受体敏感性。
