Chronicity of Depression and Molecular Markers in a Large Sample of Han Chinese Women

Edwards, Alexis C.; Aggen, Steven H.; Cai, Na; Bigdeli, Tim B.; Peterson, Roseann E.; Docherty, Anna R.; Webb, Bradley T.; Bacanu, Silviu‐Alin; Flint, Jonathan; Kendler, Kenneth S.

doi:10.1002/da.22517

Cited by 19 publications

(20 citation statements)

References 36 publications

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“…Bearing in mind we are limited in statistical power by the small sample size of our cohort, and we would not be able to account for effect sizes smaller than beta = 0.29, we found no significant difference in mtDNA copy number or their agerelated dynamic in Holocaust survivors as compared to controls in any generation. This is consistent with findings of no significance difference in telomere length and their agerelated dynamics in Holocaust survivors from the same cohort (Konečná et al, 2019), as mtDNA copy number was previously shown to be negatively correlated with telomere length in chronic stress (Cai et al, 2015b;Edwards et al, 2016).…”

Section: Discussionsupporting

confidence: 91%

“…As such, alterations to mitochondrial function are increasingly investigated as a key mechanism underlying stress-related conditions (Zhang et al, 2006;Manoli et al, 2007;Su et al, 2008). An increase in mtDNA levels obtained from blood samples has been reported in recurrent Major Depressive Disorder (MDD) (Cai et al, 2015b;Edwards et al, 2016) and a decreased in mtDNA levels has been shown in moderately severe post-traumatic stress disorder (PTSD) (Bersani et al, 2016). Other reports showing conflicting results.…”

Section: Introductionmentioning

confidence: 99%

“…The former has been shown to be more pronounced in those experiencing an episode of MDD than those with a history of it, and are reversible upon cessation of the stressful stimuli in animal models (Cai et al, 2015b), demonstrating both disease state-dependence and potential for recovery. Among individuals with a history of severe recurrent MDD, chronicity of disease state was positively associated with mtDNA levels (Edwards et al, 2016), suggesting complete recovery may not be achieved or requires a long time.…”

Section: Introductionmentioning

confidence: 99%

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No Evidence of Persistence or Inheritance of Mitochondrial DNA Copy Number in Holocaust Survivors and Their Descendants

et al. 2020

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Mitochondrial DNA copy number has been previously shown to be elevated with severe and chronic stress, as well as stress-related pathology like Major Depressive Disorder (MDD) and post-traumatic stress disorder (PTSD). While experimental data point to likely recovery of mtDNA copy number changes after the stressful event, time needed for full recovery and whether it can be achieved are still unknown. Further, while it has been shown that stress-related mtDNA elevation affects multiple tissues, its specific consequences for oogenesis and maternal inheritance of mtDNA has never been explored. In this study, we used qPCR to quantify mtDNA copy number in 15 Holocaust survivors and 102 of their second-and third-generation descendants from the Czech Republic, many of whom suffer from PTSD, and compared them to controls in the respective generations. We found no significant difference in mtDNA copy number in the Holocaust survivors compared to controls, whether they have PTSD or not, and no significant elevation in descendants of female Holocaust survivors as compared to descendants of male survivors or controls. Our results showed no evidence of persistence or inheritance of mtDNA changes in Holocaust survivors, though that does not rule out effects in other tissues or mitigating mechanism for such changes.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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No Evidence of Persistence or Inheritance of Mitochondrial DNA Copy Number in Holocaust Survivors and Their Descendants

et al. 2020

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“…The China, Oxford and VCU Experimental Research on Genetic Epidemiology (CONVERGE) group recently detected and replicated the first robustly genome-wide statistically significant association between specific molecular variants and MD. 30 In addition, earlier age at worst episode was significantly associated with telomere shortening in this sample 31 . In the context of this success, it is useful to maximize statistical power and to examine AO as a potentially relevant quantitative phenotype.…”

Section: Introductionmentioning

confidence: 72%

Age of onset and family history as indicators of polygenic risk for major depression

et al. 2017

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Background The extent to which earlier age of onset (AO) is a reflection of increased genetic risk for major depression (MD) is still unknown. Previous biometrical research has provided mixed empirical evidence for the genetic overlap of AO with MD. If AO is demonstrated to be relevant to molecular polygenic risk for MD, incorporation of AO as a phenotype could enhance future genetic studies. Methods This research estimated the SNP-based heritability of AO in the China, Oxford and VCU Experimental Research on Genetic Epidemiology (CONVERGE) case-control sample (N = 9854, MD case n = 4,927). Common SNP heritability of MD was also examined across both high and low median-split AO groups, and best linear unbiased predictor (BLUP) scores of polygenic risk, in split-halves, were used to predict AO. Distributions of genetic risk across early and late AO were compared, and presence of self-reported family history of MD was also examined as a predictor of AO. Results AO was not significantly heritable and polygenic risk derived from the aggregated effects of common genetic variants did not significantly predict AO in any analysis. AO was modestly but significantly lower in cases with a first-degree genetic family history of MD. Conclusions Findings indicate that AO is associated with greater self-reported genetic risk for MD in cases, yet not associated with common variant polygenic risk for MD. Future studies of early MD may benefit more from the examination of important moderating variables such as early life events.

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“…Recent reports from smaller samples (n~100) suggest associations of depression and psychosocial stress with mitochondrial changes [ 13 , 14 ]. However, few studies [ 15 , 16 ] have addressed associations of mood or depression with mtDNAcn in larger, community-based samples of mid-life and older men and women, and findings regarding the association are inconclusive.…”

Section: Introductionmentioning

confidence: 99%

Lifestyle and behavioral factors and mitochondrial DNA copy number in a diverse cohort of mid-life and older adults

et al. 2020

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Mitochondrial DNA copy number (mtDNAcn) is a putative biomarker of oxidative stress and biological aging. Modifiable factors, including physical activity (PA), avoidance of heavy alcohol use and smoking, and maintaining good mental health, may reduce oxidative stress and promote healthy aging. Yet, limited data exist regarding how these factors are associated with mtDNAcn or whether age, sex or race/ethnicity moderate associations. In this cross-sectional study, we selected 391 adults (183 non-Hispanic White, 110 Black and 98 Hispanic; mean = 67 years) from the VITAL-DEP (VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention) ancillary to the VITAL trial. We estimated associations between lifestyle and behavioral factors (PA, alcohol consumption, cigarette smoking and depression) and log-transformed mtDNAcn using multivariable linear regression models. MtDNAcn was not correlated with chronological age; women had ~17% higher mtDNAcn compared to men. There were no significant associations between PA measures (frequency, amount or intensity) or alcohol consumption with mtDNAcn. Cigarette smoking (per 5 pack-years) was significantly associated with mtDNAcn (percent difference = -2.9% (95% confidence interval (CI) = -5.4%, -0.4%)); a large contrast was observed among heavy vs. non-smokers (≥30 vs. 0 pack-years): percent difference = -28.5% (95% CI = -44.2%, -8.3%). The estimate of mtDNAcn was suggestively different for past vs. no depression history (percent difference = -15.1% 95% CI = -30.8%, 4.1%), but this difference was not statistically significant. The association between smoking and log-mtDNAcn varied by sex and race/ethnicity; it was stronger in men and Black participants. While chance findings cannot be excluded, results from this study support associations of smoking, but not chronological age, with mtDNAcn and suggest nuanced considerations of mtDNAcn as indicative of varying oxidative stress states vs. biological aging itself.

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Chronicity of Depression and Molecular Markers in a Large Sample of Han Chinese Women

Cited by 19 publications

References 36 publications

No Evidence of Persistence or Inheritance of Mitochondrial DNA Copy Number in Holocaust Survivors and Their Descendants

No Evidence of Persistence or Inheritance of Mitochondrial DNA Copy Number in Holocaust Survivors and Their Descendants

Age of onset and family history as indicators of polygenic risk for major depression

Lifestyle and behavioral factors and mitochondrial DNA copy number in a diverse cohort of mid-life and older adults

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