Technical variability across the 450K, EPICv1, and EPICv2 DNA methylation arrays: lessons learned for clinical and longitudinal studies.

DNA methylation (DNAm) is the most commonly measured epigenetic mechanism in human populations, with most studies using Illumina arrays to assess DNAm levels. In 2023, Illumina updated their DNAm arrays to the EPIC version 2 (EPICv2), building on prior iterations, namely the EPIC version 1 (EPICv1) and 450K arrays. Whether DNAm measurements are stable across these three generations of arrays has yet not been investigated, limiting the ability of researchers-especially those with longitudinal data-to compare and replicate results across arrays.

Consortium Profile: The Methylation, Imaging and NeuroDevelopment (MIND) Consortium.

Epigenetic processes, such as DNA methylation, show potential as biological markers and mechanisms underlying gene-environment interplay in the prediction of mental health and other brain-based phenotypes. However, little is known about how peripheral epigenetic patterns relate to individual differences in the brain itself. An increasingly popular approach to address this is by combining epigenetic and neuroimaging data; yet, research in this area is almost entirely comprised of cross-sectional studies in adults.

DNA methylation as a possible mechanism linking childhood adversity and health: results from a 2-sample mendelian randomization study.

Childhood adversity is an important risk factor for adverse health across the life course. Epigenetic modifications, such as DNA methylation (DNAm), are a hypothesized mechanism linking adversity to disease susceptibility. Yet, few studies have determined whether adversity-related DNAm alterations are causally related to future health outcomes or if their developmental timing plays a role in these relationships.

Depressive Symptoms and Plasma Markers of Alzheimer's Disease and Neurodegeneration: A Coordinated Meta-Analysis of 8 Cohort Studies.

Background: Depressive symptoms are associated with an increased risk of Alzheimer's disease (AD). There has been a recent emergence in plasma biomarkers for AD pathophysiology, such as amyloid-beta (Aβ) and phosphorylated tau (p-tau), as well as for axonal damage (neurofilament light, NfL) and astrocytic activation (glial fibrillary acidic protein, GFAP). Hypothesizing that depressive symptoms may occur along the AD process, we investigated associations between plasma biomarkers of AD with depressive symptoms in individuals without dementia.

Early-life stress and the gut microbiome: A comprehensive population-based investigation.

Early-life stress (ELS) has been robustly associated with a range of poor mental and physical health outcomes. Recent studies implicate the gut microbiome in stress-related mental, cardio-metabolic and immune health problems, but research on humans is scarce and thus far often based on small, selected samples, often using retrospective reports of ELS. We examined associations between ELS and the human gut microbiome in a large, population-based study of children.

The bidirectional effects between cognitive ability and brain morphology: A life course Mendelian randomization analysis.

Introduction: Little is understood about the dynamic interplay between brain morphology and cognitive ability across the life course. Additionally, most existing research has focused on global morphology measures such as estimated total intracranial volume, mean thickness, and total surface area.

Methods: Mendelian randomization was used to estimate the bidirectional effects between cognitive ability, global and regional measures of cortical thickness and surface area, estimated total intracranial volume, total white matter, and the volume of subcortical structures (N=37,864).

Plasma neurofilament light chain in association to late-life depression in the general population.

Aim: Investigating what is underlying late-life depression is becoming increasingly important with the rapidly growing elderly population. Yet, the associations between plasma biomarkers of neuroaxonal damage and late-life depression remain largely unclear. Therefore, we determined cross-sectional and longitudinal associations of neurofilament light chain (NfL) with depression in middle-aged and elderly individuals, and total tau, β-amyloid 40 and 42 for comparison.

On Navigating Analytical Choices in Research on Early Life Adversity: A Commentary on Sisitsky et al. (2023).

Early life adversities (ELA), including exposure to childhood maltreatment, deprivation or community violence, rarely occur in isolation. This co-occurrence poses several conceptual and methodological challenges for researchers, who must decide how best to model ELA and its association with outcomes. In this commentary, we discuss how different analytical choices come with their own - often complementary - sets of assumptions, strengths and limitations, which should be carefully considered when designing research on ELA.

A Longitudinal Study of Stress During Pregnancy, Children's Sleep and Polygenic Risk for Poor Sleep in the General Pediatric Population.

Early life stress is robustly associated with poor sleep across life. Preliminary studies suggest that these associations may begin already in utero. Here, we study the longitudinal associations of prenatal psychosocial stress with sleep across childhood, and assess whether prenatal stress interacts with genetic liability for poor sleep.

Life stress and adiposity in mothers: A 14-year follow-up in the general population.

Exposure to specific stressors has been found to associate with higher adiposity in adulthood. However, the potential overlapping effects of stress domains have been overlooked, as well as the role of parenting-related stressors that mothers are widely exposed to in mid-adulthood. Therefore, we assessed the association of overlapping effects of stress domains, including parenting-related stress, with subsequent adiposity in mothers.

The Association of Life Stress with Subsequent Brain and Cognitive Reserve in Middle-Aged Women.

Background: Cognitive and brain reserve refer to individual differences that allow some people to better withstand brain pathology than others. Although early life stress has been recognized as a risk factor for low reserve in late life, no research yet has studied this across midlife.

Objective: To examine the associations of life stress with brain and cognitive reserve in midlife.

10-Year trajectories of depressive symptoms and subsequent brain health in middle-aged adults.

Depressive symptoms differ in severity and stability over time. Trajectories depicting these changes, particularly those with high late-life depressive symptoms, have been associated with poor brain health at old age. To better understand these associations across the lifespan, we examined depressive symptoms trajectories in relation to brain health in middle age.

The gut microbiome and child mental health: A population-based study.

The link between the gut microbiome and the brain has gained increasing scientific and public interest for its potential to explain psychiatric risk. While differences in gut microbiome composition have been associated with several mental health problems, evidence to date has been largely based on animal models and human studies with modest sample sizes. In this cross-sectional study in 1,784 ten-year-old children from the multi-ethnic, population-based Generation R Study, we aimed to characterize associations of the gut microbiome with child mental health problems.

The association of early life stress with IQ-achievement discrepancy in children: A population-based study.

Early life stress (ELS) is associated with lower IQ and academic achievement; however, it remains unclear whether it additionally explains their discrepancy. In 2,401 children (54% girls, 30.2% migration background) from the population-based study Generation R Study, latent factors of prenatal and postnatal (age 0-10) ELS were estimated, and IQ-achievement discrepancy (age 12) was quantified as variance in academic achievement not explained by IQ.

Child mental health problems as a risk factor for academic underachievement: A multi-informant, population-based study.

Objective: To investigate whether child mental health problems prospectively associate with IQ-achievement discrepancy (i.e., academic under- and over-achievement) in emerging adolescence.

Cognitive performance in children and adolescents with psychopathology traits: A cross-sectional multicohort study in the general population.

Psychopathology and cognitive development are closely related. Assessing the relationship between multiple domains of psychopathology and cognitive performance can elucidate which cognitive tasks are related to specific domains of psychopathology. This can help build theory and improve clinical decision-making in the future.

Early life stress and behavior problems in early childhood: Investigating the contributions of child temperament and executive functions to resilience.

This preregistered study examined whether child temperament and executive functions moderated the longitudinal association between early life stress (ELS) and behavior problems. In a Dutch population-based cohort (n = 2803), parents reported on multiple stressors (age 0-6 years), child temperament (age 5), and executive functions (age 4), and teachers rated child internalizing and externalizing problems (age 7). Results showed that greater ELS was related to higher levels of internalizing and externalizing problems, with betas reflecting small effects.