Dataset Information

Early Life Stress Induced DNA Methylation of Monoamine Oxidases Leads to Depressive-Like Behavior.

ABSTRACT: Major depressive disorder (MDD) is coming to be the regarded as one of the leading causes for human disabilities. Due to its complicated pathological process, the etiology is still unclear and the treatment is still targeting at the monoamine neurotransmitters. Early life stress has been known as a major cause for MDD, but how early life stress affects adult monoaminergic activity is not clear either. Recently, DNA methylation is considered to be the key mechanism of epigenetics and might play a role in early life stress induced mental illness. DNA methylation is an enzymatic covalent modification of DNA, has been one of the main epigenetic mechanisms investigated. The metabolic enzyme for the monoamine neurotransmitters, monoamine oxidases A/B (MAO A/MAO B) are the prime candidates for the investigation into the role of DNA methylation in mental disorders. In this review, we will review recent advances about the structure and physiological function of monoamine oxidases (MAO), brief narrative other factors include stress induced changes, early life stress, perinatal depression (PD) relationship with other epigenetic changes, such as DNA methylation, microRNA (miRNA). This review will shed light on the epigenetic changes involved in MDD, which may provide potential targets for future therapeutics in depression pathogenesis.

SUBMITTER: Xu Q

PROVIDER: S-EPMC7505948 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Early Life Stress Induced DNA Methylation of Monoamine Oxidases Leads to Depressive-Like Behavior.

Xu Qiuyue Q Jiang Mingchen M Gu Simeng S Wang Fushun F Yuan Bin B

Frontiers in cell and developmental biology 20200908

Major depressive disorder (MDD) is coming to be the regarded as one of the leading causes for human disabilities. Due to its complicated pathological process, the etiology is still unclear and the treatment is still targeting at the monoamine neurotransmitters. Early life stress has been known as a major cause for MDD, but how early life stress affects adult monoaminergic activity is not clear either. Recently, DNA methylation is considered to be the key mechanism of epigenetics and might play a ...[more]

PMID: 33015076

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Project description:Early life stress (ELS) is associated with an increased risk of depression and this association may be mediated by epigenetic mechanisms. A previous epigenome-wide DNA methylation (DNAm) study investigating human newborns and two animal models of ELS suggested that the epigenetic regulator MORC1 is differentially methylated following ELS. The ELS-induced DNAm alterations were long-lasting in the animal models. However, whether this finding is also transferable to humans experiencing ELS in childhood was not investigated. Further, MORC1 may provide a link between ELS and adult depression, as MORC1 DNAm and genetic variants were found to be associated with depressive symptoms in humans. In the present study, we investigated the validity of MORC1 DNAm as a biomarker of ELS in humans and its role in linking ELS to depression later in life by studying childhood maltreatment. We analyzed whole blood MORC1 DNAm in an adult cohort (N = 151) that was characterized for both the presence of depressive symptoms and childhood maltreatment. Further, we investigated the association between MORC1 DNAm, depressive symptoms and childhood maltreatment in two additional cohorts (N = 299, N = 310). Overall, our data do not indicate an association of MORC1 DNAm with childhood maltreatment. An association of MORC1 DNAm with depressive symptoms was present in all cohorts, but was inconsistent in the specific CpG sites associated and the direction of effect (Tuebingen cohort: standardized β = 0.16, unstandardized β = 0.01, 95% CI [-0.0004, -0.0179], p = 0.061, PReDICT cohort: standardized β = -0.12, unstandardized β = -0.01, 95% CI [-0.0258, -0.0003], p = 0.045), Grady cohort: standardized β = 0.16, unstandardized β = 0.008, 95% CI [0.0019, 0.0143], p = 0.01). Our study thus suggests that peripheral MORC1 DNAm cannot serve as biomarker of childhood maltreatment in adults, but does provide further indication for the association of MORC1 DNAm with depressive symptoms.

Project description:Early life stress in humans (i.e. maltreatment, violence exposure, loss of a loved one) and in rodents (i.e. disrupted attachment or nesting, electric shock, restraint, predator odor) occurs during critical steps of neural circuit formation. ELS in humans is associated with increased risk for developmental psychopathology, including anxious and depressive phenotypes. The biological mechanisms underlying these potentially persistent maladaptive changes involve long-term epigenetic modifications, which have been suggested to be potentially transmissible to subsequent generations. DNA methylation is an epigenetic mechanism that modifies gene expression patterns in response to environmental challenges and influences mutation rates. It remains to be seen whether a functionally relevant fraction of DNA methylation marks can escape genome-wide erasures that occur in primordial germ cells and after fertilization within the zygote. Early life-stress-triggered changes in epigenetic mediated transmission of acquired behavioral traits among humans have been assessed mainly by targeting genes involved in the hypothalamic-pituitary-adrenal (HPA) axis, such as NR3C1 and FKBP5. Recently, researchers examining epigenetic transmission have begun to apply genome-wide approaches. In humans, reduced representation bisulfite sequencing (RRBS) was performed on peripheral samples that were obtained from individuals who were prenatally exposed to the "Dutch Hunger Winter", resulting in two Differentially Methylated Regions (DMRs) in INSR and CPTIA genes that were functionally, biologically and technically validated, and significantly associated with birth weights and LDL cholesterol levels in offspring. In rodents, non-genomic intergenerational transmission of anxiety which was associated with differentially methylated enhancers that were putatively involved in lipid signaling and synaptic/neurotransmission in hippocampal granule cells, was discovered also using RRBS. Finally, transgenerational transmission of altered behaviors was associated with sperm-derived microRNAs produced by ELS male mice. The field of epigenetic transmission is just beginning to enter the epigenomic era by using genome-wide analyses. Such approaches remain of strong interest to human studies, first in order to help to assess the relevance of the previous targeted studies, and second to discover new important epigenetic modifications of potential clinical importance. New discoveries may help to assess how transmittable the negative impact of stress may be to offspring. The latter may open doors for future treatments and resilience-promoting interventions, as well as new approaches to treat the effects of childhood trauma before the onset of psychiatric disorder.

Dataset Information

Early Life Stress Induced DNA Methylation of Monoamine Oxidases Leads to Depressive-Like Behavior.

Publications

Early Life Stress Induced DNA Methylation of Monoamine Oxidases Leads to Depressive-Like Behavior.

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