In a recent study, a team of researchers led by Johns Hopkins Medicine discovered that female mice who experience social stress during adolescence have higher levels of the hormone cortisol after they give birth. The researchers found that this is similar to the hormonal changes seen in postpartum women who had adverse early life experiences, suggesting that early life stress may contribute to the worsening of postpartum depression.
The research team’s discoveries were initially released on Apr. 11, 2024, in Nature Mental Health. The findings also propose that existing medications for PPD in individuals may not always effectively address the relevant chemical imbalances in the brain, and that alternative approaches could be more advantageous.
Previous studies indicate that about one-third of mental health conditions do not respond to current treatments, and study senior author Akira Sawa, M.D., Ph.D., director of the Johns Hopkins Schizophrenia Center and professor of psychiatry, neuroscience, biom, emphasized that “PPD is difficult to treat.”Medical engineering, genetic medicine and pharmacology at the Johns Hopkins University School of Medicine. “The latest findings from the study contribute to the growing body of evidence that not all patients with PPD are the same, and that a more personalized approach to diagnosis and treatment is necessary, known as precision medicine.”
According to the federal government’s Office on Women’s Health, PPD is believed to affect 7% to 20% of women, with the majority experiencing symptoms within six weeks of giving birth. These symptoms can include feelings of sadness, anxiety, and fatigue, which can make it challenging to perform basic self-care activities and care for the new baby.
The current primary treatment for PPD is use of a certain group of antidepressant medications known as selective serotonin reuptake inhibitors (SSRIs) can be effective for about half of patients. SSRIs work by increasing the effects of the natural brain chemical serotonin, which helps regulate mood. In some cases, patients may also receive intravenous infusions of a different type of medication that targets GABAA, a brain chemical associated with nerve hyperactivity.
However, these calming infusions can be expensive (costing over $30,000 for a single course of treatment) and often require hospitalization. They are usually only used for the most severe and difficult-to-treat cases.f PPD.
A recent Johns Hopkins-led study aimed to expand on the evidence that adverse life events can impact the likelihood and severity of PPD. Previous research has indicated that PPD is more common among teenagers and urban populations.
Using mice, the researchers established four test groups: unstressed virgins, stressed virgins, unstressed mothers, and stressed mothers. The stressed mice experienced social isolation during their adolescence, and all groups were tested for stress. At seven days postpartum, the stressed mothers exhibited reduced mobility and a decrease insugar preference, and depression markers. This lasted for a minimum of three weeks after giving birth.
The researchers then measured the plasma levels of various hormones and discovered that cortisol levels were elevated in mothers, regardless of their early life experiences. However, in unstressed mothers, cortisol levels returned to normal after delivery. In contrast, mothers with adverse early life experiences had high cortisol levels for one to three weeks after giving birth. This indicates a connection between prolonged post-delivery cortisol elevation and depression.A study on postpartum mice who were isolated in their adolescence showed that they exhibited behavioral changes. The results of this study could potentially apply to humans, indicating that a different type of antidepressant called a glucocorticoid receptor (GR) antagonist, which can block the effects of high cortisol levels, may be a new approach to treating postpartum depression (PPD). Mifepristone is one such potential drug for this treatment.
Dr. Sawa, a researcher, expressed concern about the impact of PPD on both mothers and babies, stating that almost everyone knows someone affected by it. He also mentioned that the findings from the study on mice align with their own observations and suggest an alternative approach to treating PPD.A new study in humans could potentially allow mothers to receive treatment for postpartum depression (PPD) at home, avoiding separation from their babies. This could also target a different mechanism for depression that is specific to PPD.
According to Sawa, plans are in progress to gather accurate data on cortisol levels in people with PPD to determine if GR antagonists would be more effective than current treatments for some individuals. Additionally, the team aims to conduct clinical trials with alternatives to SSRIs in the future.
The study team from Johns Hopkins Medicine includes Sawa, Sedona Lockhart, Jennifer Payne, Gary Wand, Daniel Wood, and Kun Yang. Team members from the University of Alabama at Birmingham are also involved.The lead author of the study conducted at the Johns Hopkins University School of Medicine is Minae Niwa, along with Adeel Ahmed, Shin-ichi Kano, Kyohei Kin, and Jose Francis-Oliveira.
Funding for this research was provided by National Institutes of Health grants MH-092443, MH-094268, K99MH-094408, MH-105660, MH-107730, DA-040127, and MH-116869; the Brain and Behavior Research Foundation (formerly the National Alliance for Research on Schizophrenia and Depression); and other sources.
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