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. Credit: Neuroscience News
Summary: Researchers explore the genetic underpinnings of postpartum depression (PPD). Their results reveal that 14% of PPD variability is due to common genetic factors.
The study also found that PPD’s genetic architecture significantly aligns with other psychiatric and hormonal conditions. GABAergic neurons, specifically in the thalamus and hypothalamus, were identified as key areas for future PPD research.
About 14% of PPD’s variation is attributed to shared genetic components.
The genetic foundation of PPD closely mirrors that of other conditions such as major depression, bipolar disorder, and anxiety.
GABAergic neurons in the thalamus and hypothalamus are significant, revealing possible areas for focused PPD treatment.
Postpartum depression (PPD), a common subtype of major depressive disorder, is more heritable than other psychiatric conditions, yet the genetics of PPD are understudied compared to these other psychiatric conditions., such as anxiety and bipolar disorder.
To remedy that, UNC School of Medicine researchers led an international team of researchers to conduct the largest-ever meta-analyses of genome-wide association studies (GWAS) to investigate the genetic architecture of PPD.
Published in the American Journal of Psychiatry, their research shows that approximately 14 percent of the variation seen in PPD cases can be attributed to common genetic factors. A patient’s PPD is often not merely the result of environmental factors, such as past trauma. Instead PPD susceptibility carries a significant genetic component.
The researchers, led by first author Jerry Guintivano, PhD, assistant professor of psychiatry at the UNC School of Medicine, also revealed the genetic architecture of PPD, which they report significantly correlates with the genetic architecture of major depression, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, and polycystic ovary syndrome.
This means PPD symptoms likely occur as a result of the interplay between the same genes involved in these other psychiatric and hormone-related conditions.
“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 regions involving GABAergic neurons is associated with PPD, particularly in the thalamus and hypothalamus. GABAergic neurons control the release of the neurotransmitter GABA.
Brexanolone, the only FDA-approved PPD treatment, is known to circulate throughout the body and brain. UNC researchers had discovered earlier this year that the drug worked through GABAergic neurons to treat PPD symptoms so effectively. But now, this new research suggests brexanolone likely acts on GABAergic neurons in two particular 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.”
Although the researchers revealed much about the genetics of PPD, more than ever before, they still had a limited data set. The best genome-wide association studies pull data from hundreds of thousands of individuals with a particular condition, such as major depression or schizophrenia.
For their study, Guintivano and colleagues used 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), 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.
Funding: The National Institutes of Health funded this research.
Senior authors of this study were Samantha Meltzer-Brody, MD, MPH, the Assad Meymandi Distinguished Professor and Chair of the UNC Department of Psychiatry and director of the UNC Center for Women’s Mood Disorders; and Patrick Sullivan, MD, the Yeargan Distinguished Professor of Psychiatry and Genetics at the UNC School of Medicine, Director of the UNC Suicide Prevention Institute, and professor at the Karolinska Institutet in Stockholm.
About this PPD and genetics research news
Author: Mark Derewicz Source: UNC Contact: Mark Derewicz – UNC Image: The image is credited to Neuroscience News
Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression
Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD.
Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)–based heritability (), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system.
No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD.
While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone).