Low Serum Allopregnanolone Is Associated with Symptoms of Depression in Late Pregnancy

Abstract

Background: Allopregnanolone (3α-hydroxy-5α-pregnan-20-one) is a neurosteroid which has an inhibitory function through interaction with the GABA_A receptor. This progesterone metabolite has strong sedative and anxiolytic properties, and low endogenous levels have been associated with depressed mood. This study aimed to investigate whether the very high serum allopregnanolone levels in late pregnancy covary with concurrent self-rated symptoms of depression and anxiety. Methods: Ninety-six women in pregnancy weeks 37-40 rated symptoms of depression and anxiety with the Montgomery-Åsberg Depression Rating Scale (MADRS-S) and Spielberger State-Trait Anxiety Inventory. Their serum allopregnanolone was analyzed by Celite chromatography and radioimmunoassay. Results: Ten women had elevated depression scores (MADRS-S ≥13), and this group had significantly lower allopregnanolone levels compared to women with MADRS-S scores in the normal range (39.0 ± 17.9 vs. 54.6 ± 18.7 nmol/l, p = 0.014). A significant negative correlation was found between self-rated depression scores and allopregnanolone concentrations (Pearson's correlation coefficient = -0.220, p = 0.031). The linear association between self-rated depression scores and allopregnanolone serum concentrations remained significant when adjusted for gestational length, progesterone levels, and parity. Self-rated anxiety, however, was not associated with allopregnanolone serum concentrations during pregnancy. Conclusion: High allopregnanolone serum concentrations may protect against depressed mood during pregnancy.

Replication of Epigenetic Postpartum Depression Biomarkers and Variation with Hormone Levels

“…Significant research links low levels of allopregnanolone to depressed mood Eser et al, 2006;Le Melledo and Baker, 2004;Padberg et al, 2002;Pinna et al, 2006;Schule et al, 2014;Strohle et al, 1999;Uzunova et al, 2006) and other evidence links mood states or histories thereof with alterations in the ratio of allopregnanolone to its precursors (Girdler et al, 2012;Schiller et al, 2014). In the perinatal period specifically, Deligiannidis et al (2013), in a small sample, found no relationship between pregnancy allopregnanolone and the development of PPD, whereas Hellgren et al (2014) found significantly lower levels of allopregnanolone in depressed pregnant women when compared with healthy controls (Hellgren et al, 2014). In a separate analysis, our group found that low levels of allopregnanolone measured in the second trimester predicted the development of PPD (p = 0.01); this effect was driven by women who were euthymic in the second trimester (Osborne et al, under review).…”

Translocator protein mediates the anxiolytic and antidepressant effects of midazolam

“…Previous studies had been shown that lowered allopregnanolone levels in patients might lead to an imbalance in excitatory neurotransmission that cause anxiety and depressive symptoms (Hellgren et al, 2014). Conversely,…”

Management of perinatal depression with non-drug interventions

“…Allopregnanolone concentrations increase during pregnancy and fall rapidly post partum. Women with higher depression scores in late pregnancy have been found to have lower serum concentrations of allopregnanolone 69. Furthermore, in an exploratory study of 60 pregnant women with a previous diagnosis of mood disorder, higher concentrations of allopregnanolone during the second trimester were associated with a 63% (95% confidence interval 13% to 84%) reduction in the risk of developing postpartum depression (P=0.02) 70.…”