Summary: Researchers explore the genetic basis of postpartum depression (PPD). Their results showed that 14% of PPD variation was due to common genetic factors.
Research also shows that the genetic makeup of PPD is remarkably consistent with other psychiatric and hormonal conditions. GABAergic neurons, particularly in the hippocampus and hypothalamus, have been identified as key areas for future PPD research.
- Approximately 14% of the variation in PPD is due to common genetic components.
- The genetic background of PPD closely mirrors the genetic background of other conditions such as major depression, bipolar disorder, and anxiety.
- GABAergic neurons in the thalamus and hypothalamus are important, revealing possible areas for targeted PPD treatment.
Postpartum depression (PPD), a common subtype of major depressive disorder, is more heritable than other psychiatric conditions, yet the genetics of PPD remain less well studied than other psychiatric conditions. with these other psychiatric conditions, such as anxiety and bipolar disorder.
To fix that, UNC School of Medicine researchers led an international team of researchers to conduct the largest-ever meta-analysis of genome-wide association studies ( GWAS) to investigate the genetic structure of PPD.
Published inAmerican Journal of Psychiatry, their study found that about 14% of the variation seen in PPD cases can be attributed to common genetic factors. A patient’s PPD is often not simply the result of environmental factors, such as past trauma. Instead, susceptibility to PPD 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 makeup of PPD, which they reported was significantly correlated with Genetic structure of major depression, bipolar disorder, anxiety disorders, and post-traumatic stress disorder. stress disorders, insomnia and polycystic ovary syndrome.
This means that PPD symptoms can occur due to interactions between the same genes involved in other psychiatric and hormone-related conditions.
“We studied about 1.1 million regions in the human genome, and we could see that PPD had similar genetic signatures to these other psychiatric conditions,” Guintivano said. Genetic risk factors for PPD appear to be shared by other disorders, such as major depression, bipolar disorder, and anxiety.
Researchers also found that genetic regions associated with GABAergic neurons are associated with PPD, especially in the thalamus and hypothalamus. GABAergic neurons control the release of the neurotransmitter GABA.
Brexanolone, the only FDA-approved treatment for PPD, is known to circulate throughout the body and brain. UNC researchers discovered earlier this year that the drug works through GABAergic neurons to effectively treat PPD symptoms. But now, this new research shows that brexanolone has the ability to act on GABAergic neurons in two specific brain regions.
“We consider our findings to be a refinement of the mechanism of action of brexanolone,” said Guintivano. We now have preliminary evidence that we should target GABAergic neurons in the thalamus and hypothalamus for future research.
Although researchers have revealed much about the genetics of PPD, they still have a limited data set more than ever. The best genome-wide association studies take data from hundreds of thousands of individuals with a specific condition, such as major depression or schizophrenia.
In their study, Guintivano and colleagues used 18 cohorts of European origin (17,339 PPD cases and 53,426 controls), one cohort of East Asian origin (975 cases and 3,780 controls) and a cohort of African origin (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls.
Although this is the largest PPD GWAS to date, Guintivano said there are still too few PPD cases to identify specific locations in the genome that are associated with PPD risk.
Expense: The National Institutes of Health funded this research.
The senior authors of this study are Samantha Meltzer-Brody, MD, MPH, Assad Meymandi Distinguished Professor and Chair of the UNC Department of Psychiatry and director of the UNC Women’s Mood Disorders Center; and Patrick Sullivan, MD, Yeargan Distinguished Professor of Psychiatry and Genetics at the UNC School of Medicine, Director of the UNC Institute for Suicide Prevention, and professor at the Karolinska Institute in Stockholm.
About this PPD and genetic research news
Author: Mark Derewicz
Contact: Mark Derewicz – UNC
Image: Image credited to Neuroscience News
Original research: Closed access.
“Meta-analysis of genome-wide association studies of postpartum depression” by Jerry Guintivano et al. American Journal of Psychiatry
Meta-analysis of genome-wide association studies of postpartum depression
Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable but remains understudied in psychiatric genetics. The authors conducted a meta-analysis of genome-wide association studies (GWAS) to study the genetic architecture of PPD.
Meta-analyses were performed on 18 cohorts of European origin (17,339 PPD cases and 53,426 controls), one cohort of East Asian origin (975 cases and 3,780 controls), and one cohort of African origin (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyzes include 1) single nucleotide polymorphism (SNP)-based heritability (), 2) genetic correlation between PPD and other phenotypes, and 3) enrichment of PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system.
No SNP reached genome-wide significance in the European or trans-ancestry meta-analyses. The of PPD is 0.14 (SE=0.02). Significant genetic correlations have been estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell type enrichment analyzes revealed inhibitory neurons in the thalamus and cholinergic neurons in the septal nucleus of the hypothalamus, a pattern different from MDD.
Although more samples are needed to reach genome-wide significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that although highly correlated with MDD, PPD may have distinctive genetic components. Cell enrichment results show that GABAergic neurons, converging a common mechanism with the only drug approved by the US Food and Drug Administration for PPD (brexanolone).
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