Neuroendocrine Unit, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA, USA.
Neuropsychopharmacology. 2018 May;43(6):1436-1444. doi: 10.1038/npp.2017.269. Epub 2017 Nov 1.
3α-5α-Tetrahydroprogesterone, a progesterone metabolite also known as allopregnanolone, and 5α-androstane-3α,17β-diol, a testosterone metabolite also known as 3α-androstanediol, are neuroactive steroids and positive GABA receptor allosteric modulators. Both anorexia nervosa (AN) and obesity are complicated by affective comorbidities and hypothalamic-pituitary-gonadal dysregulation. However, it is not known whether neuroactive steroid levels are abnormal at the extremes of the weight spectrum. We hypothesized that serum allopregnanolone and 3α-androstanediol levels would be decreased in AN compared with healthy controls (HC) and negatively associated with affective symptoms throughout the weight spectrum, independent of body mass index (BMI). Thirty-six women were 1 : 1 age-matched across three groups: AN, HC, and overweight/obese (OW/OB). AN were amenorrheic; HC and OW/OB were studied in the follicular phase. Fasting serum neuroactive steroids were measured by gas chromatography/mass spectrometry. Mean Hamilton depression and anxiety scores were highest in AN (p<0.0001). Mean serum allopregnanolone was lower in AN and OW/OB than HC (AN 95.3±56.4 vs OW/OB 73.8±31.3 vs HC 199.5±167.8 pg/ml, p=0.01), despite comparable mean serum progesterone. Allopregnanolone levels, but not progesterone levels, were negatively associated with depression and anxiety symptom severity, independent of BMI. Serum 3α-androstanediol levels did not differ among groups and were not associated with depression or anxiety scores, despite a significant negative association between free testosterone levels and both anxiety and depression severity. In conclusion, women at both extremes of the weight spectrum have low mean serum allopregnanolone, which is associated with increased depression and anxiety severity, independent of BMI. Neuroactive steroids such as allopregnanolone may be potential therapeutic targets for depression and anxiety in traditionally treatment-resistant groups, including AN.
3α-5α-四氢孕酮，一种孕激素代谢产物，也称为别孕烯醇酮，和 5α-雄烷-3α,17β-二醇，一种睾酮代谢产物，也称为 3α-雄烷二醇，是神经活性甾体和 GABA 受体变构调节剂。神经性厌食症 (AN) 和肥胖都伴有情感共病和下丘脑-垂体-性腺功能失调。然而，目前尚不清楚在体重谱的极端情况下神经活性甾体水平是否异常。我们假设与健康对照组 (HC) 相比，神经性厌食症 (AN) 患者的血清别孕烯醇酮和 3α-雄烷二醇水平降低，并且在整个体重谱范围内与情感症状呈负相关，与体重指数 (BMI) 无关。36 名女性按年龄 1：1 分为三组：AN、HC 和超重/肥胖 (OW/OB)。AN 闭经；HC 和 OW/OB 在卵泡期进行研究。采用气相色谱/质谱法测量空腹血清神经活性甾体。AN 的汉密尔顿抑郁和焦虑评分最高 (p<0.0001)。AN 和 OW/OB 的血清别孕烯醇酮水平均低于 HC (AN 95.3±56.4 比 OW/OB 73.8±31.3 比 HC 199.5±167.8 pg/ml，p=0.01)，尽管血清孕激素水平相当。别孕烯醇酮水平，但不是孕激素水平，与抑郁和焦虑症状严重程度呈负相关，与 BMI 无关。三组之间血清 3α-雄烷二醇水平无差异，与抑郁或焦虑评分无关，尽管游离睾酮水平与焦虑和抑郁严重程度呈显著负相关。总之，体重谱两端的女性血清平均别孕烯醇酮水平较低，与 BMI 无关，与抑郁和焦虑严重程度增加有关。神经活性甾体如别孕烯醇酮可能是传统治疗抵抗性群体（包括神经性厌食症）抑郁和焦虑的潜在治疗靶点。
