Prenatal stress and gestational epigenetic age: No evidence of associations based on a large prospective multi-cohort study.

Psychological stress during pregnancy is known to have a range of long-lasting negative consequences on the development and health of offspring. Here, we tested whether a measure of prenatal early-life stress was associated with a biomarker of physiological development at birth, namely epigenetic gestational age, using foetal cord-blood DNA-methylation data. Longitudinal cohorts from the Netherlands (Generation R Study [Generation R], n = 1,396), the UK (British Avon Longitudinal Study of Parents and Children [ALSPAC], n = 642), and Norway (Mother, Father and Child Cohort Study [MoBa], n1 = 1,212 and n2 = 678) provided data on prenatal maternal stress and genome-wide DNA methylation from cord blood and were meta-analysed (pooled n = 3,928).

The Alpha-Synuclein Gene (SNCA) is a Genomic Target of Methyl-CpG Binding Protein 2 (MeCP2)-Implications for Parkinson's Disease and Rett Syndrome.

Mounting evidence suggests a prominent role for alpha-synuclein (a-syn) in neuronal cell function. Alterations in the levels of cellular a-syn have been hypothesized to play a critical role in the development of Parkinson's disease (PD); however, mechanisms that control expression of the gene for a-syn (SNCA) in cis and trans as well as turnover of a-syn are not well understood. We analyzed whether methyl-CpG binding protein 2 (MeCP2), a protein that specifically binds methylated DNA, thus regulating transcription, binds at predicted binding sites in intron 1 of the SNCA gene and regulates a-syn protein expression.

Increasing the use of functional and multimodal genetic data in social science research.

Genetic studies in the social sciences could be augmented through the additional consideration of functional (transcriptome, methylome, metabolome) and/or multimodal genetic data when attempting to understand the genetics of social phenomena. Understanding the biological pathways linking genetics and the environment will allow scientists to better evaluate the functional importance of polygenic scores.

SKA2 regulated hyperactive secretory autophagy drives neuroinflammation-induced neurodegeneration.

High levels of proinflammatory cytokines induce neurotoxicity and catalyze inflammation-driven neurodegeneration, but the specific release mechanisms from microglia remain elusive. We demonstrate that secretory autophagy (SA), a non-lytic modality of autophagy for secretion of vesicular cargo, regulates neuroinflammation-mediated neurodegeneration via SKA2 and FKBP5 signaling. SKA2 inhibits SA-dependent IL-1β release by counteracting FKBP5 function.

Oxytocin modulates sensitivity to acculturation and discrimination stress in pregnancy.

Background: Latinas in the United States suffer disproportionately high levels of pre- and postnatal depression. However, little is understood regarding the biopsychosocial mechanisms linking socio-environmental factors to this increase in mental health risk. The oxytocinergic system, with its roles in the stress response, social behaviour and mood regulation, may be an important modulator of this sensitivity.

Acculturative stress, telomere length, and postpartum depression in Latinx mothers.

Latinx mothers in the United States are highly vulnerable to psychosocial stressors, including discrimination and acculturative stress, which increase maternal health risks. Previous work in Latinx mothers indicates that prenatal discrimination influences epigenetic immune markers that may increase risk for postpartum depression. Discrimination and acculturative stress have also been linked to cellular aging, including telomere degradation, in Hispanic populations broadly, but not in this particularly vulnerable population.

Superior Frontal Gyrus Locus DNA Methylation in Alzheimer's Disease.

Background: The ɛ4 allele is the strongest known genetic risk factor for sporadic Alzheimer's disease (AD). The neighboring gene has also been implicated in AD due to its close proximity to .

Objective: Here we tested whether methylation of the locus may influence ApoE protein levels and AD pathology.

Intergenerational changes in hippocampal transcription in an animal model of maternal depression.

Chronic stress during early life, such as exposure to social conflict or deficits in parental care, can have persistent adverse behavioural effects. Offspring in a rodent model of maternal depression and early life stress have increased susceptibility to maternal depression themselves, suggesting a pathway by which maternal stress could be intergenerationally inherited. The overall aim of this study was to explore the genetic regulatory pathways underlying how maternal social stress and reduced care mediates stress-related behavioural changes in offspring across generations.

Pregnancy associated epigenetic markers of inflammation predict depression and anxiety symptoms in response to discrimination.

Latina mothers, who have one of the highest fertility rates among ethnic groups in the United States (US), often experience discrimination. Psychosocial influences during pregnancy, such as discrimination stress, promotes inflammation. However, the role of epigenetic markers of inflammation as a mediator between, and predictor of, maternal discrimination stress and neuropsychiatric outcomes has not been extensively studied.

Epigenetic Regulation of BMAL1 with Sleep Disturbances and Alzheimer's Disease.

Background: An early symptom of Alzheimer's disease (AD) is a disturbance of the circadian rhythm that is associated with disrupted sleep/wake cycles.

Objective: To investigate if BMAL1, a key gene that drives the circadian cycle, is epigenetically regulated in brains in relation to longitudinal changes in cognition, sleep quality, and AD neuropathology.

Methods: Frontal cortex tissues were acquired from the Manchester Brain Bank (N = 96).

Regulation of interleukin 6 by a polymorphic CpG within the frontal cortex in Alzheimer's disease.

The cytokine interleukin 6 (IL-6) has been linked to the pathogenesis of Alzheimer's disease (AD). This is the first study to investigate the genetic and epigenetic interactions in the control of IL-6 in human brain and its relation to AD neuropathology in prefrontal cortex tissues from AD and controls genotyped for the SNP -174 C/G rs1800795, a polymorphic CpG in which the G allele creates a CpG site. Within CC homozygotes there were significantly higher brain levels of IL-6 protein compared to G allele carriers.

CRISPR disruption and UK Biobank analysis of a highly conserved polymorphic enhancer suggests a role in male anxiety and ethanol intake.

Excessive alcohol intake is associated with 5.9% of global deaths. However, this figure is especially acute in men such that 7.

A meta-analysis of peripheral tocopherol levels in age-related cognitive decline and Alzheimer's disease.

Findings from observational studies and clinical trials on the associations between vitamin E and dementia remain controversial. Here we conducted a meta-analysis to determine the difference in blood tocopherols levels between patients with Alzheimer's disease (AD) or age-related poor cognitive function and healthy controls. Standardised mean difference (SMD) and 95% confidence intervals (CIs) were calculated and entered into a random effects model.

Mismatched Prenatal and Postnatal Maternal Depressive Symptoms and Child Behaviours: A Sex-Dependent Role for DNA Methylation in the Wirral Child Health and Development Study.

Evolutionary hypotheses predict that male fetuses are more vulnerable to poor maternal conditions (Sex-biased Maternal Investment), but female fetuses are at greater risk of glucocorticoid-mediated disorders where there is a mismatch between fetal and postnatal environments (Predictive Adaptive Response). Self-reported prenatal and postnatal depression and maternal report of child anxious-depressed symptoms at 2.5, 3.

Dysregulation of BDNF in Prefrontal Cortex in Alzheimer's Disease.

Background: Brain-derived neurotrophic factor (BDNF) is essential for neurogenesis and has been implicated in Alzheimer's disease (AD). However, few studies have investigated together the epigenetic, transcriptional, and translational regulation of this peptide in the brain in relation to AD.

Objective: To investigate mechanisms underlying how BDNF is possibly dysregulated in the brain in relation to aging and AD neuropathology.

An anti-inflammatory diet as a potential intervention for depressive disorders: A systematic review and meta-analysis.

Background & Aims: There is a large body of evidence which supports the role of inflammation in the pathophysiology of mental health disorders, including depression. Dietary patterns have been shown to modulate the inflammatory state, thus highlighting their potential as a therapeutic tool in disorders with an inflammatory basis. Here we conduct a systematic review and meta-analysis of current literature addressing whether there is a link between the inflammatory potential of a diet and risk of depression or depressive symptoms.

Epigenetic Programming by Early-Life Stress.

Studies show that adverse conditions during early life can increase risks of developing mood disorders later in life. It is currently hypothesized that levels of environmental adversity in this early developmental period are able to shape the experience-dependent maturation of stress-regulating pathways leading to long-lasting alterations in stress responsivity during adulthood; a phenomenon often referred to as "early-life programming." Research is addressing the molecular mechanisms underlying this programming by which gene-environment interactions can predispose individuals toward psychopathology.

Investigating the Glycating Effects of Glucose, Glyoxal and Methylglyoxal on Human Sperm.

Glycation is the non-enzymatic reaction between reducing sugars, such as glucose, and proteins, lipids or nucleic acids, producing Advanced Glycation End (AGE) products. AGEs, produced during natural senescence as well as through lifestyle factors such as diet and smoking, are key pathogenic compounds in the initiation and progression of diabetes. Importantly, many of these factors and conditions also have influence on male fertility, affecting sperm count and semen quality, contributing to the decreasing trend in male fertility.

The Regulation of Monoamine Oxidase A Gene Expression by Distinct Variable Number Tandem Repeats.

The monoamine oxidase A (MAOA) uVNTR (upstream variable number tandem repeat) is one of the most often cited examples of a gene by environment interaction (GxE) in relation to behavioral traits. However, MAOA possesses a second VNTR, 500 bp upstream of the uVNTR, which is termed d- or distal VNTR. Furthermore, genomic analysis indicates that there are a minimum of two transcriptional start sites (TSSs) for MAOA, one of which encompasses the uVNTR within the 5' untranslated region of one of the isoforms.

Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance.

Chronic low-grade inflammation during aging (inflammaging) is associated with cognitive decline and neurodegeneration; however, the mechanisms underlying inflammaging are unclear. We studied a population (n = 361) of healthy young and old adults from the MyoAge cohort. Peripheral levels of C-X-C motif chemokine ligand 10 (CXCL10) was found to be higher in older adults, compared with young, and negatively associated with working memory performance.

Sex differences in the effects of 12 weeks sprint interval training on body fat mass and the rates of fatty acid oxidation and VOmax during exercise.

Background: The purpose of this study was to examine whether very short duration, very high intensity sprint interval training (SIT) leads to loss of body fat mass in association with improvements to VOmax and fatty acid oxidation, and to assess the extent of sex dimorphism in these physiological responses.

Methods: A total of 24 men and 17 women (mean (SEM) age: 39 (±2) years; body mass index 24.6 (0.

Association between osteocalcin and cognitive performance in healthy older adults.

Introduction: cognitive deterioration and reductions of bone health coincide with increasing age. We examine the relationship between bone composition and plasma markers of bone remodelling with measures of cognitive performance in healthy adults.

Methods: this cross-sectional study included 225 old (52% women, mean age: 74.

Epigenetic alterations following early postnatal stress: a review on novel aetiological mechanisms of common psychiatric disorders.

Stressor exposure during early life has the potential to increase an individual's susceptibility to a number of neuropsychiatric conditions such as mood and anxiety disorders and schizophrenia in adulthood. This occurs in part due to the dysfunctional stress axis that persists following early adversity impairing stress responsivity across life. The mechanisms underlying the prolonged nature of this vulnerability remain to be established.