BACKGROUND: Postpartum psychosis (PP) is the most severe psychiatric disorder associated with childbirth, and the risk is particularly high in women with a history of bipolar disorder, schizoaffective disorder or in those who have suffered previous episodes of PP. While studies in patients with psychosis not related to the puerperium have demonstrated that abnormalities in stress response are important risk factors for psychosis, it remains unknown whether this is also the case for PP.

METHODS: This study includes 30 postpartum women, assessed, on average, at postpartum week 14.8 ± 10.1 either with a current episode of PP (n = 14), or at-risk of PP because of a history of bipolar/schizoaffective disorder but who were well (n = 16), and a group of healthy women (n = 26). Details about recent stressful life events were obtained using the List of Threatening Experiences questionnaire, while perceived stress was evaluated using the Perceived Stress Scale. We estimated hypothalamic-pituitary adrenal (HPA) activity by measuring salivary cortisol at awakening; at 15, 30, and 60 min after awakening; at noon; and at 8 pm. An Area Under the Curve analysis was performed to assess the awakening response (AUCi) and cortisol levels during the day (AUCg). Immune markers, including high sensitivity C-Reactive Protein (hs-CRP) and Interleukin (IL)-1a, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, Tumor Necrosis Factor (TNFa), Vascular Endothelial Growth Factor (VEGF), Interferon gamma (INFγ), Monocyte Chemoattractant Protein 1 (MCP-1), and Epidermal Growth Factor (EGF) were evaluated from peripheral blood samples.

RESULTS: Women with current PP reported more frequent recent stressful life events, and higher perceived stress than healthy women. They also showed an activation of the stress and immune response, with higher levels of cortisol AUCg and hs-CRP (but not of other inflammatory markers) than healthy controls. Women at-risk of PP who remained well had values on these measures that were intermediate between those of women with a current episode of PP and those of healthy women. Stress measures and markers of stress and immune response explained 78 % of the variance of in group status between PP and healthy women, and 46 % of variance of in group status between women at-risk and healthy women.

CONCLUSION: These findings suggest that an immune-HPA axis dysregulation, together with current stress may represent an important underlying pathophysiological mechanism in the onset of psychosis after childbirth in vulnerable women.

Original languageEnglish
Article number104558
Early online date19 Dec 2019
Publication statusPublished - 1 Mar 2020


  • Cortisol
  • Immune system
  • Perceived stress
  • Postpartum psychosis
  • Severe mental disorders
  • Stressful life events


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