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Both sex hormones and serotonin play a role in peripartum mental health

Presented by
Dr Vibe Frokjaer, Copenhagen University Hospital, Denmark
ECNP 2022
Hormonal transition periods are typically viewed as periods of increased risk for women to develop symptoms of depression. Sex hormone fluctuations and adaptive serotonin changes in late pregnancy both appear to be related to mental health across the peripartum, new findings suggest.

Women have an increased risk of depression compared with men, most prominently during the reproductive years, which suggests a role for hormones in (mal)adaptations. In line with this, it has been found that the use of hormonal contraception, especially among adolescents, is associated with subsequent use of antidepressants and a first diagnosis of depression [1,2]. Recently, it was also shown that healthy women who use oral contraceptives have markedly lower brain 5-HT4 serotonin receptor binding relative to non-users, which constitutes a plausible molecular link between oral contraceptive use and an increased risk of depressive episodes [3]. Dr Vibe Frokjaer (Copenhagen University Hospital, Denmark) presented results from a study that further explored the involvement of serotonin signalling in the emergence of depressive symptoms postpartum and during other sex-hormone transitions [4].

The researchers analysed cerebrospinal fluid of 100 new mothers for central markers of serotonin turn-over (i.e. the metabolite of serotonin, 5-HIAA). They found that higher levels of postpartum mental distress symptoms were positively associated with high antepartum 5-HIAA levels (P=0.06) and negatively associated with a large decrease in oestradiol concentrations (P=0.007). In addition, high antepartum 5-HIAA levels were positively associated with anxiety scores antepartum (P=0.02) [5].

“Adaptive serotonergic changes in late pregnancy appear to be related to mental health across the peripartum and may be important for brain plasticity across the peripartum,” concluded Dr Frokjaer.

  1. Skovlund CW, et al. JAMA Psychiatry. 2016;73:1154–1162.
  2. De Wit AE, et al. JAMA Psychiatry. 2020;77:52–59.
  3. Larsen SV, et al. Acta Psychiatr Scand. 2020;142:294–306.
  4. Frokjaer VG, et al. Imaging serotonergic resilience: from preclinical gonadotropin challenges to oral hormonal contraceptive use and postpartum hormone changes. Abstract S02.02, ECNP Congress 2022, 15–18 October, Vienna, Austria,.
  5. Borgsted C, et al. Acta Psychiatr Scand. 2022;146:357–369.


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