2026 ECNP Congress

PS01-1096

Effects of short-term estrogen intervention on cognitive function in women at high risk of postpartum depression

Sif Camilla Olsen — S. Høgh, V.G. Frokjaer, V.H. Dam · Copenhagen University Hospital- Rigshospitalet, Neurobiology Research Unit, Copenhagen, Denmark

2026 ECNP Congress

Introduction

Postpartum depression (PPD) is a debilitating condition for which the risk mechanisms remain poorly understood, limiting the development of effective prevention and treatment strategies. In individuals who are particular sensitive to hormonal shifts, the sharp decline in sex steroid hormones, e.g. estradiol, following childbirth appears to contribute to triggering PPD [1]. Moreover, cognitive impairments, including memory deficits, executive dysfunction and psychomotor slowing, are common in both PPD and Major Depressive Disorder [2, 3], and may persist past remission. Estradiol influences brain regions and functional domains implicated in depression [4], however its effects on cognition in individuals at high risk for PPD remain unclear.

Aims

Using preliminary data from the Maternal Mental Health (MAMA) trial, we aim to examine the role of estradiol in cognitive functioning, specifically verbal memory, working memory and reaction time, during the postpartum phase among women at high risk for PPD. We hypothesize that short-term estradiol treatment may promote better cognitive functioning relative to placebo, possibly in a manner dependent on depressive symptom severity.

Methods

In a double-blinded placebo-controlled randomized clinical trial, 187 women who were singleton pregnant with a prior history of PPD, were randomized to receive either transdermal estradiol patches (200 µg/day) or placebo patches for three weeks starting 0-2 days after birth. Cognitive testing took place in late pregnancy (n=182) and 8-10 weeks postpartum (n=164); Verbal memory was assessed with the Verbal Affective Memory Task 24 (VAMT-24), working memory with the Letter Number Sequence (LNS), and reaction time with the Simple Reaction Task (SRT). Using linear mixed effect models, we assessed the effects of the intervention on the three cognitive tasks over time, with age as a covariate. To determine the role of depression severity on the cognitive outcomes we repeated the analyses adjusting for depressive symptoms at the time of the cognitive testing, as measured on the Edinburgh Postnatal Depression Scale (EPDS).

Preliminary results:We found no statistically significant group differences in any of the cognitive domains: verbal memory (β=0.62, CI95% [-0.21,1.45], p=0.15), working memory (β=0.29, CI95% [-0.37,0.97], p=0.86) or reaction time (β=-2.14, CI95% [-12.47,8.19], p=0.69). Correcting for depressive symptoms (EPDS scores) did not significantly influence our findings for either verbal memory (p=0.20), working memory (p=0.54) or reaction time (p=0.60). Results are preliminary pending unblinding of the data.

Conclusions

We found no evidence that estradiol intervention affects cognitive performance across the perinatal transition in women at high risk for PDD. These findings suggest that short-term cognitive trajectories in the perinatal period are relatively robust to hormonal manipulations. It is possible that endogenous hormonal fluctuations overshadow exogenous estradiol effects, or that hormone/cognition relationships are context-dependent. Additionally, the external circumstances during the perinatal and postpartum period, e.g. changed sleep patterns, cortisol levels, immunological conditions etc., could potentially obscure any small effects of estradiol intervention. We cannot exclude that other cognitive domains such as emotion processing or social cognition may be differently affected; however further studies are needed to clarify these associations.

References

1.Lokuge, S., et al., Depression in women: windows of vulnerability and new insights into the link between estrogen and serotonin. Journal of Clinical Psychiatry, 2011. 72(11): p. 1563-9. 2.de Almeida, L.S.P., et al., Working and short-term memories are impaired in postpartum depression. Journal of Affective Disorders, 2012. 136(3): p. 1238-1242. 3.McIntyre, R.S., et al., Cognitive deficits and functional outcomes in major depressive disorder: determinants, substrates, and treatment interventions. Depress Anxiety, 2013. 30(6): p. 515-27. 4.Comasco, E., V.G. Frokjaer, and I. Sundstrøm-Poromaa, Functional and molecular neuroimaging of menopause and hormone replacement therapy. Frontiers in Neuroscience, 2014. 8.