New Study Finds Neurobiological Evidence of Peripartum Depression in Women, Distinguishing It from Major Depressive Disorder

Researchers have identified structural grey matter differences in the brains of women with a history of peripartum depression and those without within a group of major depressive disorder patients. The women who had experienced peripartum depression were also found to be more sensitive to hormone fluctuations during the peripartum period. The novel study opens in new tab/window in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging opens in new tab/window, published by Elsevier, recognizing the biological underpinnings of peripartum depression and disentangling them from major depressive disorder, contributes to improving maternal and child health.

Peripartum depression is a common complication of pregnancy and childbirth and could have potential consequences for the mother’s wellbeing and the infant’s development. Whether peripartum depression should be considered a separate clinical entity from major depressive disorder is currently being debated. In this study a whole brain approach was used for the first time to help determine the answer to this question. Researchers examined 64 female patients with major depressive disorder using voxel-based morphometry analysis, a whole brain approach without a priori hypothesis, to identify potential grey matter structural differences between women who had a history of peripartum depression and those who did not.

Yasmin A. Harrington, PhD candidate at the Vita-Salute San Raffaele University, Milan, Italy, and first author of the study, says, "We found bilateral grey matter clusters within the basal ganglia, an area crucial for motivation, decision-making, and emotional processing, to be larger in women with a history of peripartum depression compared to women who have only experienced depressive episodes outside of this time period."

A biological mechanism often thought to separate major depressive disorder from peripartum depression is the involvement of sex hormones. During pregnancy, hormonal levels, specifically estradiol and progesterone, physiologically soar to high levels and drop sharply shortly before birth. Previous research has hypothesized that women who suffer from peripartum depression have a particular sensitivity to these fluctuations in hormones. Previous studies have shown the significant effects sex hormones have on the brain including altering brain structure and function, providing neuroprotection, and influencing behavioral outcomes.

Lead investigator Francesco Benedetti, MD, Head of the Psychiatry & Clinical Psychobiology Unit at the IRCCS Scientific Institute Ospedale San Raffaele, and Professor of Psychiatry at Vita-Salute San Raffaele University, explains, "We calculated genetic risk scores for estradiol levels and assessed their association with the identified grey matter cluster from the voxel-based morphometry analysis to see if the effect of the genetic scores on the brain was different based on history of peripartum depression. Our findings show that estradiol genetic scores had a positive effect on basal ganglia volumes in women with peripartum depression and a negative effect in women without peripartum depression, suggesting a differential effect of the genetic load from estradiol on brain structure based on history of peripartum depression."

Yasmin A. Harrington says, "We were surprised that the effect of peripartum depression could be seen years after the episode, suggesting that these differences are related to the neurobiology of the disorder rather than to the specific episode. Further corroborating this finding, the genetic load for estradiol showed an impact years after the peripartum episode, suggesting a lifetime neurobiological sensitivity to estradiol in peripartum depression and giving further support for the reproductive hormone theory of the disorder."

Editor-in-Chief of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging Cameron S. Carter, MD, University of California Irvine, comments, "This study not only advances our understanding of major depressive disorder's heterogeneity, but also holds implications for refining clinical strategies to improve outcomes for individuals experiencing depressive episodes both within and beyond the perinatal period."

The researchers of this study hope that their findings can contribute to the destigmatization of peripartum depression.

Dr. Benedetti notes, "Many women still perceive the terrible burden of peripartum depression as their fault, feeling guilty because they cannot meet expectations regarding their role as mothers. We showed that genetic factors that physiologically affect steroid hormones do impact brain structures at a very basic level, possibly predisposing women to develop depressive psychopathology when hormones markedly oscillate, as they do in the peripartum period. We think that refining knowledge on these mechanisms will eventually lead to more precise and personalized strategies for prevention and treatment of this condition."

Notes for editors

The article is "History of Peripartum Depression Moderates the Association Between Estradiol Polygenic Risk Scores and Basal Ganglia Volumes in Major Depressive Disorder," by Yasmin A. Harrington, Marco Paolini, Lidia Fortaner-Uyà, Melania Maccario, Elisa M.T. Melloni, Sara Poletti, Cristina Lorenzi, Raffaella Zanardi, Cristina Colombo, and Francesco Benedetti (https://doi.org/10.1016/j.bpsc.2024.09.011 opens in new tab/window). It appears online in advance of volume 10, issue 1 (January 2025) of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging opens in new tab/window, published by Elsevier opens in new tab/window.

The article is openly available for 30 days at https://www.biologicalpsychiatrycnni.org/article/S2451-9022(24)00279-9/fulltext opens in new tab/window.

Copies of this paper are also available to credentialed journalists upon request; please contact Rhiannon Bugno at [email protected] opens in new tab/window. Journalists wishing to interview the study’s authors should contact the Press Office of IRCCS Ospedale San Raffaele, Milan, Italy, at [email protected] opens in new tab/window.

The authors’ affiliations and disclosures of financial and conflicts of interests are available in the article.

Cameron S. Carter, MD, is Chair of the Department of Psychiatry & Human Behavior at the University of California, Irvine School of Medicine. His disclosures of financial and conflicts of interests are available here opens in new tab/window.

This work was supported by the Italian Ministry of Health, project RF-2019- 12371066.

About Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging opens in new tab/window is an official journal of the Society of Biological Psychiatry opens in new tab/window, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal focuses on studies using the tools and constructs of cognitive neuroscience, including the full range of non-invasive neuroimaging and human extra- and intracranial physiological recording methodologies. It publishes both basic and clinical studies, including those that incorporate genetic data, pharmacological challenges, and computational modeling approaches. The 2023 Journal Impact Factor^TM score, from Clarivate, for Biological Psychiatry: Cognitive Neuroscience and Neuroimaging is 5.7. www.biologicalpsychiatrycnni.org opens in new tab/window

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