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- Guintivano, Jerry, et al.
(författare)
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Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression
- 2023
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 180:12, s. 884-895
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: 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.METHOD: 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 ([Formula: see text]), 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.RESULTS: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The [Formula: see text] 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.CONCLUSIONS: 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).
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| 2. |
- Daníelsdóttir, Hilda Björk, et al.
(författare)
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Adverse childhood experiences and resilience among adult women : A population-based study
- 2022
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adverse childhood experiences (ACEs) have consistently been associated with elevated risk of multiple adverse health outcomes, yet their contribution to coping ability and psychiatric resilience in adulthood is unclear.Methods: Cross-sectional data were derived from the ongoing Stress-And-Gene-Analysis cohort, representing 30% of the Icelandic nationwide female population, 18-69 years. Participants in the current study were 26,198 women with data on 13 ACEs measured with the ACE-International Questionnaire. Self-reported coping ability was measured with the Connor-Davidson Resilience Scale and psychiatric resilience was operationalized as absence of psychiatric morbidity. Generalized linear regression assuming normal or Poisson distribution were used to assess the associations of ACEs with coping ability and psychiatric resilience controlling for multiple confounders.Results: Number of ACEs was inversely associated with adult resilience in a dose-dependent manner; every 1SD unit increase in ACE scores was associated with both lower levels of coping ability (β = -0.14; 95% CI-0.15,-0.13) and lower psychiatric resilience (β = -0.28; 95% CI-0.29,-0.27) in adulthood. Compared to women with 0 ACEs, women with ≥5 ACEs had 36% lower prevalence of high coping ability (PR = 0.64, 95% CI 0.59,0.70) and 58% lower prevalence of high psychiatric resilience (PR = 0.42; 95% CI 0.39,0.45). Specific ACEs including emotional neglect, bullying, sexual abuse and mental illness of household member were consistently associated with reduced adult resilience. We observed only slightly attenuated associations after controlling for adult socioeconomic factors and social support in adulthood.Conclusions: Cumulative ACE exposure is associated with lower adult resilience among women, independent of adult socioeconomic factors and social support, indicating that adult resilience may be largely determined in childhood.
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