Advances in Psychiatry and Women's Health

It has long been known that the immune system undergoes changes during pregnancy to prevent rejection of the fetus while protecting against foreign pathogens. In addition, immune dysregulation has been associated with both physical and mental morbidities of pregnancy, including pre-eclampsia, perinatal depression, and postpartum psychosis – but little has been reported on the link between immunity and perinatal anxiety. NewYork-Presbyterian/Weill Cornell Medicine investigators collaborated with researchers from NewYork-Presbyterian/Columbia and Johns Hopkins University School of Medicine to show that immune functioning in pregnant women with anxiety differs biologically from that in those without anxiety. Their study was published in the November 2022 issue of Brain, Behavior, and Immunity.

It was the first longitudinal study to analyze immune system changes in women with perinatal anxiety in the absence of depression. “Women with anxiety appear to have an immune system that behaves differently from that of healthy women both during pregnancy and after delivery,” explains Lauren M. Osborne, MD, vice chair for clinical research for the Department of Obstetrics and Gynecology at Weill Cornell Medicine and the study’s principal investigator, who conducted the research while on the Johns Hopkins faculty. While more research is required to elucidate the cause-and-effect relationships between anxiety symptoms and immune changes, the data glean insights into the biological underpinnings of perinatal anxiety and could lead to better treatments for anxiety symptoms in pregnant patients.

Lauren M. Osborne, MD

“Anxiety is adaptive during pregnancy and postpartum. A woman has to suddenly be responsible for taking care of this very vulnerable new being. Anxiety and feeling worried and over-vigilant are normal,” Dr. Osborne says. “But in some people it’s taken to an extreme.” As many as one in four women self-report anxiety during pregnancy and 15% during the postpartum period.

“In some people, there is anxiety that is out of proportion to the threat, and such symptoms appear to be related to immune dysregulation,” says Dr. Osborne. As a fellow at NewYork-Presbyterian/Columbia, she treated a cluster of patients with severe anxiety who also had immune dysregulation – an experience that set her on the path to her current research. While there are low-risk medications for anxiety that can be prescribed during pregnancy, many anxious patients refuse to take them because they worry about harm to the fetus. “A patient can hear it intellectually but she can’t feel it emotionally, so she won’t take the medicine,” said Dr. Osborne, who is a reproductive psychiatrist.

“In some people, there is anxiety that is out of proportion to the threat, and such symptoms appear to be related to immune dysregulation.” — Dr. Lauren M. Osborne

Studies have shown that, among pregnant psychiatric patients, those with anxiety have a greater rate of obsessions and postpartum depression and are more likely to take psychiatric medications. Antenatal anxiety has also been reported to raise the risk of pregnancy morbidities, such as preterm birth and lower birthweight, as well as altered immunity, behavioral problems, and cognitive delays in the child. So getting to the heart of anxiety, understanding how it relates to immunity, and treating both anxiety symptoms as well as immune-related inflammation could have benefits for both mother and child.

In this study, Dr. Osborne and her fellow investigators prospectively assessed 107 pregnant women between the ages of 23 and 45 (56 with anxiety and 51 without anxiety) during their second and third trimesters and at six weeks postpartum. They evaluated blood samples for immune activity and conducted psychological evaluations to detect clinical anxiety. Patients with comorbid depression were excluded.

Women in the anxiety group were older, had higher levels of trauma, took more psychiatric medications during pregnancy, and reported poorer sleep quality compared to those without anxiety, and researchers accounted for these differences in their analyses.

“We know that anxiety needs to be treated to ensure healthy outcomes for both mother and child. Knowing there is immune system involvement is a first step toward understanding the biological factors related to anxiety in pregnancy and developing new treatments.” — Dr. Lauren M. Osborne

The researchers found that, in pregnant women with anxiety, levels of cytotoxic T cells were elevated during pregnancy and then declined in the weeks following childbirth. In women without anxiety, the activity of these cells decreased during pregnancy and continued to decline after birth. Moreover, the activity of a cluster of innate immune cytokines was suppressed during pregnancy in women with anxiety and then rose after childbirth, while healthy women exhibited the opposite pattern. The investigators concluded that the immune response throughout the antenatal period differs for women with anxiety symptoms compared to those without, suggestive of a unique immune phenotype of perinatal anxiety.

Digital rendering of T-cells

What remains to be determined in future studies is whether the immune changes precipitate anxiety symptoms or vice versa (or whether the relationship is bidirectional). When the researchers analyzed the patients according to whether they were chronically anxious, healthy at the beginning and then became anxious, or initially anxious and then healthy, they witnessed very different patterns of immunity. Women who were healthy and became anxious experienced an elevation in pro-inflammatory cytokines, suggesting differences between people with acute versus chronic anxiety. However, the subgroups were too small to draw statistically significant conclusions, so these data were not included in the paper. “What is clear is that there is much more work to be done,” asserted Dr. Osborne.

In the meantime, clinicians can counsel their anxious pregnant patients who are reluctant to take anti-anxiety medication about other ways to reduce their symptoms, such mindfulness practices like yoga and meditation, psychotherapy, and getting adequate restorative sleep. “As soon as their anxiety goes down, they may become much more accepting of pharmacologic treatments, if they still need them,” said Dr. Osborne.

“The takeaway is that this is the first clear evidence that immune activity differs for pregnant women depending on their anxiety status,” she continued. “We know that anxiety needs to be treated to ensure healthy outcomes for both mother and child. Knowing there is immune system involvement is a first step toward understanding the biological factors related to anxiety in pregnancy and developing new treatments.”