Metabolites of progesterone in pregnancy: Associations with perinatal anxiety.
Metabolites of progesterone in pregnancy: Associations with perinatal anxiety.
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怀孕期间黄体酮的代谢：与围产期焦虑的关联。
DOI：
10.1016/j.psyneuen.2023.106327
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发表时间：
2023
影响因子：
3.7
通讯作者：
Osborne,LaurenM
中科院分区：
文献类型：
--
作者：
Etyemez,Semra;Miller,KristenN;Voegtline,KristinM;Özdemir,İpek;Standeven,LindsayR;Santovito,LucaSpiro;Pinna,Graziano;Payne,JenniferL;Osborne,LaurenM
背景焦虑是围产期最常见的精神障碍，也是产后抑郁的主要危险因素之一，但对围产期焦虑的生物学病因知之甚少。越来越多的文献指出，神经活性类固醇（NAS）失调与围产期精神疾病有关，但方向性尚未得到明确证明，结果不一致，也没有研究调查NAS在纯焦虑无共病抑郁人群中的作用。我们的目的是增加有限的文献，通过检查焦虑无共病抑郁和NAS在围产期纵向代谢途径之间的关系。方法采用气相色谱-质谱联用技术（GC-MS）对36名焦虑妇女和38名健康对照者在妊娠中期和晚期（T2和T3）和产后第6周（W6）采用心理量表和NAS水平进行测量。通过数据驱动的方法确定焦虑组，并使用横断面和纵向统计方法来检查研究人群与NAS之间的关系。结果焦虑对孕酮与异孕酮之间的关系有显著调节作用，而对孕酮与该通路中的中间体（5α-DHP）或异构体（异孕酮）之间的关系无调节作用，对孕酮转化为孕酮和表孕酮的相应通路无影响。我们还发现，与非焦虑组相比，焦虑组T3和W6之间异孕酮与黄体酮的比值下降幅度较小。对AKR1C2基因单核苷酸多态性的基因型分析表明，异孕酮与中间代谢物5α-DHP的关系因基因型而异。结论我们的探索性发现表明，与没有焦虑的孕妇相比，焦虑孕妇的代谢更积极地向黄体酮到异孕酮代谢途径的终点转移。
BackgroundAnxiety disorders are the most common psychiatric disorder during the perinatal period and one of the major risk factors for postpartum depression, yet we know little about biological factors in the etiology of perinatal anxiety. A growing literature points to neuroactive steroid (NAS) dysregulation in perinatal mental illness, but directionality has not been clearly demonstrated, results are not consistent, and no studies have investigated NAS in a population with pure anxiety without comorbid depression. We aimed to add to the limited literature by examining the association between anxiety without comorbid depression and metabolic pathways of NAS longitudinally across the peripartum.MethodsWe measured anxiety symptoms by psychological scales and NAS levels using Gas Chromatography-Mass Spectrometry (GC-MS) at the second and third trimester (T2 and T3) and week 6 postpartum (W6) in n = 36 women with anxiety and n = 38 healthy controls. The anxiety group was determined by a data-driven approach, and cross-sectional and longitudinal statistical methods were used to examine the relationship between the study population and NAS.ResultsWe found that anxiety had a significant moderating effect on the relationship between progesterone and allopregnanolone, with no such effect for the relationships between progesterone and the intermediate (5α-DHP) or isomeric (isoallopregnanolone) compounds in this pathway, and no effects on the corresponding pathway converting progesterone to pregnanolone and epipregnanolone. We also found a less precipitous decline in the ratio of allopregnanolone to progesterone between T3 and W6 in the anxiety group compared to the non-anxiety group. A genotype analysis of a single-nucleotide polymorphism in the AKR1C2 gene demonstrated that the relationship of allopregnanolone to the intermediate metabolite, 5α-DHP, differed by genotype.ConclusionOur exploratory findings indicate that, for pregnant people with anxiety, metabolism is shunted more aggressively toward the endpoint of the progesterone to allopregnanolone metabolic pathway than it is for those without anxiety.