Prospects for epigenetic research within cohort studies of psychological disorder: A pilot investigation of a peripheral cell marker of epigenetic risk for depression

Olsson, Craig A.; Foley, Debra L.; Parkinson-Bates, Mandy; Byrnes, Graham; McKenzie, Maria; Patton, George C.; Morley, Ruth; Anney, Richard; Craig, Jeffrey M; Saffery, Richard

doi:10.1016/j.biopsycho.2009.12.003

Cited by 125 publications

(107 citation statements)

References 21 publications

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“…These results suggest that methylation of the remaining CpG sites in the promoter is unrelated to gene function. Notably, in this example, there was no association observed between the four gene expression-relevant CpG sites and depression [12], emphasizing the complexity of pinpointing gene-expression relevant epigenetic signatures that are also relevant to complex mental illness.…”

Section: Discussionmentioning

confidence: 79%

“…More specifically, within any single gene, methylation of some CpG sites may be unimportant to gene function and thus lack relevance to the phenotype under investigation. For example, in the focused study of SLC6A4 methylation differences associated with depressive symptoms discussed in the introduction, in vitro expression analyses showed that partial methylation of just four targeted sites within the promoter region of this gene was adequate to reduce gene expression to levels obtained through complete methylation of the entire promoter region [12]. These results suggest that methylation of the remaining CpG sites in the promoter is unrelated to gene function.…”

Section: Discussionmentioning

confidence: 99%

“…For example, numerous studies investigating variation in the serotonin transporter promoter (5HTTLPR) locus have demonstrated that carriers of the short allele are more susceptible to depression following exposure to stressful life experiences (reviewed in [11]). The s allele, in turn, has recently been associated with increased depressive symptoms in adolescents, but only among individuals who also showed relatively high methylation levels at this locus [12]. More broadly, in the case of PTSD, epigenetic effects offer a plausible way in which an environmental exposure (i.e.…”

Section: Introductionmentioning

confidence: 99%

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Gene Expression and Methylation Signatures ofMAN2C1are Associated with PTSD

et al. 2011

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Abstract. As potential regulators of DNA accessibility and activity, epigenetic modifications offer a mechanism by which the environment can moderate the effects of genes. To date, however, there have been relatively few studies assessing epigenetic modifications associated with post-traumatic stress disorder (PTSD). Here we investigate PTSD-associated methylation differences in 33 genes previously shown to differ in whole blood-derived gene expression levels between those with vs. without the disorder. Drawing on DNA samples similarly obtained from whole blood in 100 individuals, 23 with and 77 without lifetime PTSD, we used methylation microarray data to assess whether these 33 candidate genes showed epigenetic signatures indicative of increased risk for, or resilience to, PTSD. Logistic regression analyses were performed to assess the main and interacting effects of candidate genes' methylation values and number of potentially traumatic events (PTEs), adjusting for age and other covariates. Results revealed that only one candidate gene -MAN2C1 -showed a significant methylation x PTE interaction, such that those with both higher MAN2C1 methylation and greater exposure to PTEs showed a marked increase in risk of lifetime PTSD (OR 4.35, 95% CI: 1.07, 17.77, p = 0.04). These results indicate that MAN2C1 methylation levels modify cumulative traumatic burden on risk of PTSD, and suggest that both gene expression and epigenetic changes at specific loci are associated with this disorder.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Gene Expression and Methylation Signatures ofMAN2C1are Associated with PTSD

et al. 2011

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“…Indeed, methylation at CpG islands make a gene less accessible to the molecular transcriptional apparatus that decodes the DNA sequence into mRNA and hence the production of specific proteins is reduced. An early study found a trend of association between history of MDD and increased SLC6A4 methylation (Philibert et al 2008), and a subsquent study reported that depressive symptoms were more common among adolescents with elevated SLC6A4 methylation who carried the 5-HTTLPR S allele (Olsson et al 2010). Higher SLC6A4 promoter methylation in subjects with a history of childhood adversities was demonstrated (Kang et al 2013b;Booij et al 2015) and associated with family history of depression and more severe depressive psychopathology (Kang et al 2013b).…”

Section: Gene Methylationmentioning

confidence: 99%

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Fabbri

Hosák

Mößner

et al. 2016

The World Journal of Biological Psychiatry

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Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under-or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels. Polymorphisms in genes involved in anti-depressant metabolism (cytochrome P450 isoenzymes), antidepressant transport (ABCB1), glucocorticoid signalling (FKBP5) and serotonin neurotransmission (SLC6A4 and HTR2A) were among those included in the first pharmacogenetic assays that have been tested for clinical applicability. The results of these investigations were encouraging when examining patient-outcome improvement. Furthermore, a nine-serum biomarker panel (including BDNF, cortisol and soluble TNF-a receptor type II) showed good sensitivity and specificity in differentiating between MDD and healthy controls. These first diagnostic and response-predictive tests for MDD provided a source of optimism for future clinical applications. However, such findings should be considered very carefully because their benefit/cost ratio and clinical indications were not clearly demonstrated. Future tests may include combinations of different types of biomarkers and be specific for MDD subtypes or pathological dimensions.

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“…Increased 5-HTT gene methylation has been associated with lower 5-HTT expression as well as depression. [49][50][51]. Thus, short allele carriers that also exhibit 5-HTT gene methylation may be at greater risk of experiencing negative outcomes associated with lower 5-HTT expression.…”

Section: -Htt Gene Methylationmentioning

confidence: 99%

A relationship between early life stress and depression: the role of the serotonin transporter gene polymorphism (5-HTTLPR)

Valderrama¹,

Pato²,

Pato³

2017

IJCNMH

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Early life stress has been associated with many different negative outcomes including adulthood depression. Studies have suggested a role of the serotonin transporter gene polymorphism (5-HTTLPR) in explaining this relationship. However, consistent replication of this gene-environment interaction have proven difficult. This paper will review contrasting evidence assessing this interaction. Previous research has revealed a complex interplay of factors that might explain how certain 5-HTTLPR genotypes interact with early life stress to produce sensitivity to stress and adulthood depression. Maladaptive cognitive and behavioral patterns will be reviewed in light of 5-HTTLPR's impact on brain regions associated with mood regulation. Future research directions and clinical interventions will also be discussed.

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Prospects for epigenetic research within cohort studies of psychological disorder: A pilot investigation of a peripheral cell marker of epigenetic risk for depression

Cited by 125 publications

References 21 publications

Gene Expression and Methylation Signatures ofMAN2C1are Associated with PTSD

Gene Expression and Methylation Signatures ofMAN2C1are Associated with PTSD

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

A relationship between early life stress and depression: the role of the serotonin transporter gene polymorphism (5-HTTLPR)

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