Postpartum Depression: Heritability and Treatment

Postpartum Depression
Study: Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression

Scientists from the University of North Carolina School of Medicine undertook the largest-ever genomic study of postpartum depression, which revealed genetic links between PPD and other mental illnesses as well as potential evidence of how the sole FDA-approved treatment for PPD works.

CHAPEL HILL, North Carolina – Postpartum depression (PPD), a prevalent subtype of major depressive disorder, is more heritable than other psychiatric diseases, such as anxiety and bipolar disorder, although its genetics are less well understood.

To address this, experts at the UNC School of Medicine led an international team of researchers in the largest-ever meta-analysis of genome-wide association studies (GWAS) to study the genetic architecture of PPD.

Their findings, published in the American Journal of Psychiatry, demonstrate that common genetic variables account for around 14 percent of the diversity reported in PPD patients. PPD is not always the result of external variables, such as past trauma. Instead, PPD susceptibility has a strong hereditary component.

The researchers, led by first author Jerry Guintivano, PhD, assistant professor of psychiatry at the University of North Carolina School of Medicine, also revealed the genetic architecture of PPD, which they report correlates significantly with the genetic architecture of major depression, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, and polycystic ovary syndrome. This suggests that PPD symptoms are most likely caused by the interaction of the same genes that are implicated in these other mental and hormone-related diseases.

“We studied about 1.1 million regions of the human genome,” Guintivano said, “and we can see that PPD has a similar genetic signature to these other psychiatric conditions. The genetic risk factors for PPD appear to be shared by other disorders, such as major depression, bipolar disorder, and anxiety.”

The researchers also discovered that genetic areas affecting GABAergic neurons, notably in the thalamus and hypothalamus, are linked to PPD. The neurotransmitter GABA is controlled by GABAergic neurons.

The only FDA-approved PPD therapy, brexanolone, is known to circulate throughout the body and brain. Earlier this year, UNC researchers discovered that the medication efficiently treated PPD symptoms by acting on GABAergic neurons. However, current research reveals that brexanolone likely operates on GABAergic neurons in two distinct brain regions.

“We view our finding as a refinement of the mechanism by which brexanolone works,” Guintivano said. “We now have preliminary evidence suggesting we should target GABAergic neurons in the thalamus and hypothalamus for future research.”

Despite the fact that the researchers revealed more about the genetics of PPD than ever before, they still had a limited data set. The finest genome-wide association studies collect information from hundreds of thousands of people who have a specific ailment, such as serious depression or schizophrenia.

Guintivano and colleagues employed 18 European ancestry cohorts (17,339 PPD patients and 53,426 controls), one East Asian ancestry cohort (975 cases and 3,780 controls), and one African ancestry cohort (456 cases and 1,255 controls) for their investigation, totaling 18,770 PPD cases and 58,461 controls.

Although this was the largest PPD GWAS to date, Guintivano said there were still too few PPD cases to pinpoint specific locations within the genome that are associated with PPD risk.


Rachel Paul is a Senior Medical Content Specialist. She has a Masters Degree in Pharmacy from Osmania University. She always has a keen interest in medical and health sciences. She expertly communicates and crafts latest informative and engaging medical and healthcare narratives with precision and clarity. She is proficient in researching, writing, editing, and proofreading medical content and blogs.

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