Understanding, predicting, and treating depression in pregnancy to improve mothers' and offspring's mental health outcomes: The HappyMums study.

Background: Perinatal depression is common: on average, more than 13% of women suffer from physician-diagnosed disorder and 20% report symptoms bearing clinical relevance. Maternal depression not only significantly impacts women's quality of life but also increases the offspring's risk of negative developmental outcomes, including mental disorders, through a combination of maternal alterations in biology and postnatal rearing factors during the early period of life. The HappyMums project aims to improve our understanding of perinatal depression by identifying the factors that robustly predict risk and resilience in mothers and their offspring, determining underlying neurobiological mechanisms, and, finally, testing the efficacy of potential interventions.

Care Utilization for Acute Respiratory Infections in Children Requiring Invasive Long-Term Mechanical Ventilation.

Introduction: Children who use invasive long-term mechanical ventilation (LTMV) are a rare, clinically heterogenous population with relatively high hospitalization rates, most commonly for acute respiratory infection (ARI). We sought to describe patterns of ARI-related utilization and mortality in pediatric patients with LTMV, evaluating the association of a pre-existing neurologic diagnoses with outcomes.

Methods: We studied a longitudinal retrospective cohort across 40 U.

Lifestyle behaviours do not moderate the association between childhood maltreatment and comorbid depression and cardiometabolic disease in older adults: a meta-analysis.

Background: Comorbidity between depression and cardiometabolic diseases is an emerging health concern, with childhood maltreatment as a major risk factor. These conditions are also linked to unhealthy lifestyle behaviours such as physical inactivity, smoking, and alcohol intake. However, the precise degree to which lifestyle behaviours moderate the risk between childhood maltreatment and comorbid depression and cardiometabolic disease is entirely unknown.

Prenatal stress, epigenetically-assessed glucocorticoid exposure at birth, and child psychiatric symptoms: A prospective, multi-cohort study.

Background: Recent work suggests that DNA methylation can be used as a proxy of fetal glucocorticoid exposure (MPS-GC), showing associations with maternal psychopathology during pregnancy. However, it is unknown whether the MPS-GC may act as a marker for broader prenatal stress and whether it partially mediates associations of prenatal stress with child internalizing and externalizing symptoms.

Methods: Using harmonized data from three prospective birth cohorts (N = 6086), we examined whether a cumulative measure of prenatal stress, and its individual stress domains, associate with the MPS-GC in cord blood at birth.

Biological pathways underlying the relationship between childhood maltreatment and Multimorbidity: A two-step, multivariable Mendelian randomisation study.

Childhood maltreatment has been associated with multimorbidity of depression, coronary artery disease and type 2 diabetes. However, the biological mechanisms underlying this association remain unclear. We employed two-step and multivariable Mendelian randomisation (MR) to understand the role of three potential biological mediating mechanisms - inflammation (92 proteins), metabolic processes (54 markers), and cortisol - in the link between childhood maltreatment liability and multimorbidity.

Smoking and outcomes in candidates for liver transplantation: Analysis of the Pulmonary Vascular Complications of Liver Disease 2 (PVCLD2).

Patients with chronic liver disease commonly have abnormal lung function; however, the impact of smoking on outcomes in these patients is unknown. We hypothesized current or past smoking would be associated with worse survival in patients with advanced liver disease. The Pulmonary Vascular Complications in Liver Disease Study 2 (PVCLD2) was a prospective cohort of patients with advanced liver disease undergoing evaluation for liver transplantation (LT).

Characterising developmental dynamics of adult epigenetic clock sites.

Background: DNA methylation (DNAm), an epigenetic mechanism that regulates gene activity in response to genetic and environmental influences, changes as we age. DNAm at specific sites on the genome can be used to calculate 'epigenetic clocks', which are powerful biomarkers of age, as well as of ageing. However, little is known about how these clock sites 'behave' during development and what factors influence their variability in early life.

Mapping prenatal predictors and neurobehavioral outcomes of an epigenetic marker of neonatal inflammation - A longitudinal population-based study.

Background: DNA methylation levels at specific sites can be used to proxy C-reactive protein (CRP) levels, providing a potentially more stable and accurate indicator of sustained inflammation and associated health risk. However, its use has been primarily limited to adults or preterm infants, and little is known about determinants for - or offspring outcomes of - elevated levels of this epigenetic proxy in cord blood. The aim of this study was to comprehensively map prenatal predictors and long-term neurobehavioral outcomes of neonatal inflammation, as assessed with an epigenetic proxy of inflammation in cord blood, in the general pediatric population.

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).

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.

Inflammatory markers in pregnancy - surprisingly stable. Mapping trajectories and drivers in four large cohorts.

Adaptations of the immune system throughout gestation have been proposed as important mechanisms regulating successful pregnancy. Dysregulation of the maternal immune system has been associated with adverse maternal and fetal outcomes. To translate findings from mechanistic preclinical studies to human pregnancies, studies of serum immune markers are the mainstay.

Examining longitudinal associations between prenatal exposure to infections and child brain morphology.

Background: Maternal infection during pregnancy has been identified as a prenatal risk factor for the later development of psychopathology in exposed offspring. Neuroimaging data collected during childhood has suggested a link between prenatal exposure to maternal infection and child brain structure and function, potentially offering a neurobiological explanation for the emergence of psychopathology. Additionally, preclinical studies utilizing repeated measures of neuroimaging data suggest that effects of prenatal maternal infection on the offspring's brain may normalize over time (i.

Genetics impact risk of Alzheimer's disease through mechanisms modulating structural brain morphology in late life.

Background: Alzheimer's disease (AD)-related neuropathological changes can occur decades before clinical symptoms. We aimed to investigate whether neurodevelopment and/or neurodegeneration affects the risk of AD, through reducing structural brain reserve and/or increasing brain atrophy, respectively.

Methods: We used bidirectional two-sample Mendelian randomisation to estimate the effects between genetic liability to AD and global and regional cortical thickness, estimated total intracranial volume, volume of subcortical structures and total white matter in 37 680 participants aged 8-81 years across 5 independent cohorts (Adolescent Brain Cognitive Development, Generation R, IMAGEN, Avon Longitudinal Study of Parents and Children and UK Biobank).

Running in the FAMILY: understanding and predicting the intergenerational transmission of mental illness.

Over 50% of children with a parent with severe mental illness will develop mental illness by early adulthood. However, intergenerational transmission of risk for mental illness in one's children is insufficiently considered in clinical practice, nor is it sufficiently utilised into diagnostics and care for children of ill parents. This leads to delays in diagnosing young offspring and missed opportunities for protective actions and resilience strengthening.

Fairness and bias correction in machine learning for depression prediction across four study populations.

A significant level of stigma and inequality exists in mental healthcare, especially in under-served populations. Inequalities are reflected in the data collected for scientific purposes. When not properly accounted for, machine learning (ML) models learned from data can reinforce these structural inequalities or biases.

Gestational epigenetic age and ADHD symptoms in childhood: a prospective, multi-cohort study.

Epigenetic age acceleration (EAA), defined as the difference between chronological age and epigenetically predicted age, was calculated from multiple gestational epigenetic clocks (Bohlin, EPIC overlap, and Knight) using DNA methylation levels from cord blood in three large population-based birth cohorts: the Generation R Study (The Netherlands), the Avon Longitudinal Study of Parents and Children (United Kingdom), and the Norwegian Mother, Father and Child Cohort Study (Norway). We hypothesized that a lower EAA associates prospectively with increased ADHD symptoms. We tested our hypotheses in these three cohorts and meta-analyzed the results (n = 3383).

What makes clocks tick? Characterizing developmental dynamics of adult epigenetic clock sites.

DNA methylation (DNAm) at specific sites can be used to calculate 'epigenetic clocks', which in adulthood are used as indicators of age(). However, little is known about how these clock sites 'behave' during development and what factors influence their variability in early life. This knowledge could be used to optimize healthy aging well before the onset of age-related conditions.