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.

Shared and distinct alterations in brain structure of youth with internalizing or externalizing disorders: Findings from the ENIGMA Antisocial Behavior, ADHD, MDD, and Anxiety Working Groups.

Background: Externalizing and internalizing disorders are common in youth but are often studied separately, preventing researchers from identifying shared (i.e., transdiagnostic) alterations in brain structure.

Associations between epigenetic age and brain age in young people.

Recent research suggests biological age, based on epigenetic or neuroimaging measures, may predict health traits in adulthood more accurately than chronological age. However, it is unclear if these findings apply earlier in life. We aimed to characterise the performance and interdependence between measures of biological age in young people, leveraging a longitudinal subsample from the population-based ALSPAC cohort (n = 386).

Type and developmental timing of childhood adversity predicts psychopathology symptoms in a South African birth cohort.

Background: Childhood adversity is widespread globally and is one of the strongest predictors of later psychopathology. However, the differential effects of type and timing of childhood adversities on childhood psychopathology remain unclear, highlighting the need to explore which life-course hypotheses (sensitive periods, accumulation of exposure, and/or recency of exposure) best explain these associations. Of particular importance, there is a lack of research in low- and middle-income countries (LMIC), where children experience higher rates of adversity relative to children in high-income countries (HIC).

The association between epigenetic ageing from childhood to early adulthood and psychotic-like experiences in early adulthood.

Background: Psychotic-like experiences (PLEs) are associated with cognitive impairment and premature mortality, which may be indicative of accelerated biological ageing. Epigenetic clocks provide a measure of biological age based on DNA methylation, yet the long-term relationship between epigenetic ageing and PLEs remains largely unclear. We tested the relationship between epigenetic ageing and PLEs using a 17-year longitudinal approach.

Orbitofrontal Thickness and Network Associations as Transdiagnostic Signature of Amotivation Along the Bipolar-Schizophrenia Spectrum.

Background And Hypothesis: Negative symptoms of schizophrenia (SCZ), particularly amotivation, are prominent across both SCZ and bipolar disorder (BD). While orbitofrontal cortex (OFC) alterations have been implicated in the development of negative symptoms, their contributions across disorders remain to be established. Here, we examined how OFC thickness and network associations relate to amotivation compared to diminished expression across the BD-SCZ spectrum.

Testing the ecophenotype hypothesis: Differences in white matter microstructure in youth with conduct disorder with versus without a history of childhood abuse.

Childhood maltreatment is a key risk factor for conduct disorder (CD), and the "ecophenotype hypothesis" suggests that maltreatment-related versus non-maltreatment-related CD are neurobiologically distinct. This may explain inconsistent findings in previous structural connectivity studies of CD. We tested this hypothesis by comparing youth with CD with (CD/+) versus without (CD/-) childhood physical or sexual abuse in white-matter microstructure.

Strengthening Rigor and Reproducibility in Epigenome-Wide Association Studies of Social Exposures and Brain-Based Health Outcomes.

Purpose Of Review: Studies examining the effects of social factors on the epigenome have proliferated over the last two decades. Social epigenetics research to date has broadly demonstrated that social factors spanning childhood adversity, to neighborhood disadvantage, educational attainment, and economic instability are associated with alterations to DNA methylation that may have a functional impact on health. These relationships are particularly relevant to brain-based health outcomes such as psychiatric disorders, which are strongly influenced by social exposures and are also the leading cause of disability worldwide.

Epigenetic timing effects on child developmental outcomes: a longitudinal meta-regression of findings from the Pregnancy And Childhood Epigenetics Consortium.

Background: DNA methylation (DNAm) is a developmentally dynamic epigenetic process; yet, most epigenome-wide association studies (EWAS) have examined DNAm at only one timepoint or without systematic comparisons between timepoints. Thus, it is unclear whether DNAm alterations during certain developmental periods are more informative than others for health outcomes, how persistent epigenetic signals are across time, and whether epigenetic timing effects differ by outcome.

Methods: We applied longitudinal meta-regression models to published meta-analyses from the PACE consortium that examined DNAm at two timepoints-prospectively at birth and cross-sectionally in childhood-in relation to the same child outcome (ADHD symptoms, general psychopathology, sleep duration, BMI, asthma).

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.

The importance of using an optimal cutoff value for the 10-item Autism-Spectrum Quotient (AQ10).

The 10-item Autism-Spectrum Quotient (AQ10) is frequently used to screen adults for high autistic traits in clinical practice and research. For the past decade, however, the National Institute for Health and Care Excellence has recommended the use of a suboptimal ≥ 7 cutoff value, instead of the optimal ≥ 6 value specified during the AQ10's development. A comprehensive review into the use and reporting of the AQ10 cutoff suggests that this discrepancy has proliferated across the literature, with over 58% of reports citing a suboptimal (27.

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.

Stress reactivity moderates the association between stressful life events and depressive symptoms in adolescents: Results from a population-based study.

Background: A large body of evidence links stressful life events with depression. However, little is understood about the role of perceived impact in this association.

Methods: We performed regression analysis to investigate whether self-reported stress reactivity (derived by regressing the impact-weighted life event score on the unweighted score) moderated the association between stressful life events and depressive symptoms in adolescents from the Avon Longitudinal Study of Parents and Children cohort (n = 4791), controlling for age at outcome, sex, ethnicity, and maternal education.

Maximizing insights from longitudinal epigenetic age data: simulations, applications, and practical guidance.

Background: Epigenetic age (EA) is an age estimate, developed using DNA methylation (DNAm) states of selected CpG sites across the genome. Although EA and chronological age are highly correlated, EA may not increase uniformly with time. Departures, known as epigenetic age acceleration (EAA), are common and have been linked to various traits and future disease risk.

Transient patterns of advanced brain ageing in female adolescents with anorexia nervosa.

Background: Anorexia nervosa is a psychiatric disorder characterised by undernutrition, significantly low body weight and large, although possibly transient, reductions in brain structure. Advanced brain ageing tracks accelerated age-related changes in brain morphology that have been linked to psychopathology and adverse clinical outcomes.

Aim: The aim of the current case-control study was to characterise cross-sectional and longitudinal patterns of advanced brain age in acute anorexia nervosa and during the recovery process.

Exploring associations between psychotic experiences and structural brain age: a population-based study in late adolescence.

Neuroimaging studies show advanced structural "brain age" in schizophrenia and related psychotic disorders, potentially reflecting aberrant brain ageing or maturation. The extent to which altered brain age is associated with subthreshold psychotic experiences (PE) in youth remains unclear. We investigated the association between PE and brain-predicted age difference (brain-PAD) in late adolescence using a population-based sample of 117 participants with PE and 115 without PE (aged 19-21 years) from the Avon Longitudinal Study of Parents and Children.

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.

Maximizing Insights from Longitudinal Epigenetic Age Data: Simulations, Applications, and Practical Guidance.

Background: Epigenetic Age (EA) is an age estimate, developed using DNA methylation (DNAm) states of selected CpG sites across the genome. Although EA and chronological age are highly correlated, EA may not increase uniformly with time. Departures, known as epigenetic age acceleration (EAA), are common and have been linked to various traits and future disease risk.

The role of loneliness and social isolation in mediating the relationship between childhood maltreatment and schizophrenia: A genetically informed approach.

Observational studies have found loneliness and social isolation to mediate the relationship between childhood maltreatment and schizophrenia. Limitations with observational studies (e.g.

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).

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).