For new mothers, the joy of welcoming a baby into the world can be overshadowed by a debilitating condition known as postpartum depression (PPD). This mental health disorder, which affects an estimated 7 percent to 20 percent of all women, can lead to feelings of sadness, anxiety, and fatigue, making it difficult for mothers to care for themselves and their newborns. While PPD is a well-known condition, its underlying causes have remained a mystery — until now.
In a seminal study published in Nature Mental Health, a research team led by Johns Hopkins Medicine has uncovered a potential link between early life stress and the development of PPD later in life. The findings suggest that adverse experiences during adolescence may alter the way the body responds to hormonal changes after giving birth, leading to prolonged elevation of the stress hormone cortisol.
To investigate this connection, researchers conducted experiments using mice. They created four test groups: unstressed virgins, stressed virgins, unstressed mothers, and stressed mothers. The stressed mice were subjected to social isolation during their adolescence, a form of early life stress. After giving birth, the stressed mothers displayed decreased mobility and a reduced preference for sugar, both of which are considered markers for depression in mice. These symptoms persisted for at least three weeks after delivery.
The most crucial finding came when Johns Hopkins researchers tested the plasma levels of various hormones in the mice. They discovered that cortisol levels were elevated in all mothers, regardless of whether they had experienced early life stress. However, there was a striking difference between the two groups. In unstressed mothers, cortisol levels returned to normal shortly after delivery. In contrast, mothers who had undergone social isolation during adolescence maintained high cortisol levels for one to three weeks after giving birth.
“PPD is difficult to treat,” says study senior author Dr. Akira Sawa, director of the Johns Hopkins Schizophrenia Center and professor of psychiatry, neuroscience, biomedical engineering, genetic medicine and pharmacology at the Johns Hopkins University School of Medicine, in a media release. “The new study results add to evidence that patients with PPD are not all the same, and more individualized diagnosis and treatment — a precision medicine approach — is needed.”
Currently, the first-line treatment for PPD is the use of selective serotonin reuptake inhibitors (SSRIs), a class of antidepressant medications that boost the effects of the brain chemical serotonin. SSRIs are only effective in approximately half of all patients, though. In severe and resistant cases, IV infusions of drugs targeting GABAA, a brain chemical linked to nerve hyperactivity, may be used. But these infusions are expensive and often require hospitalization.
The new study suggests that a different type of antidepressant, known as a glucocorticoid receptor (GR) antagonist, could be a novel treatment option for PPD. GR antagonists work by blocking the effects of elevated cortisol, which may be the underlying cause of PPD in some women who have experienced early life stress. One such drug, mifepristone, has shown promise in this regard.
“Unfortunately, everyone knows someone who has suffered or currently suffers from PPD, and it has such a huge impact on both mother and baby,” explains Dr. Sawa. “The alternative line of treatment suggested by the mouse study — where the findings are consistent with those from our observational study in humans — might enable mothers to be treated at home and avoid separation from their babies, and target a different mechanism for depression that may be specific to PPD.”
Researchers plan to collect precise data on cortisol levels in people with PPD to determine if GR antagonists would be more beneficial than current treatments for some patients. If the results are promising, clinical trials with alternatives to SSRIs could be on the horizon.
This revolutionary study is shedding new light on the complex interplay between early life experiences and the development of PPD. By identifying a potential mechanism underlying the condition, researchers have opened the door to more targeted and effective treatments. While much work remains to be done, the findings offer hope for the millions of women who struggle with PPD each year, and for the babies who depend on them for love and care.
