Identifying genetic differences between bipolar disorder and major depression through multiple genome-wide association analyses.

Background: Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

Aims: We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Prenatal exposures and cell type proportions are main drivers of DNA methylation in maltreated and non-maltreated children.

DNA methylation in peripheral tissues may be a relevant biomarker of risk for developing mental disorders after exposure to early life adversity. Genes involved in HPA axis regulation, such as , might play a key role. In this study, we aimed to identify the main drivers of salivary methylation in a cohort of 162 maltreated and non-maltreated children aged 3-5 years at two measurement timepoints.

Epigenetic signature of very low birth weight in young adult life.

Background: Globally, one in ten babies is born preterm (<37 weeks), and 1-2% preterm at very low birth weight (VLBW, <1500 g). As adults, they are at increased risk for a plethora of health conditions, e.g.

Genetic predisposition for negative affect predicts mental health burden during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic was accompanied by an increase in mental health challenges including depression, stress, loneliness, and anxiety. Common genetic variants can contribute to the risk for psychiatric disorders and may present a risk factor in times of crises. However, it is unclear to what extent polygenic risk played a role in the mental health response to the COVID-19 pandemic.

Serial Diurnal Salivary Cortisol Profiles in 667 Pregnant Women-Association With Cardiometabolic Complications.

Context: Maternal obesity, hypertensive pregnancy disorders, and gestational diabetes (GDM) are linked to an increased risk of negative offspring health outcomes. This association may be mediated by maternal hypothalamic-pituitary-adrenal axis (HPA axis) activity, resulting in elevated maternal cortisol levels and fetal exposure, but evidence remains scarce.

Objective: We (1) examined maternal diurnal cortisol profiles longitudinally across gestation, and (2) explored associations with maternal cardiometabolic complications.

Cohort profile: BioMD-Y (biopsychosocial factors of major depression in youth) - a biobank study on the molecular genetics and environmental factors of depression in children and adolescents in Munich.

Purpose: BioMD-Y is a comprehensive biobank study of children and adolescents with major depression (MD) and their healthy peers in Germany, collecting a host of both biological and psychosocial information from the participants and their parents with the aim of exploring genetic and environmental risk and protective factors for MD in children and adolescents.

Participants: Children and adolescents aged 8-18 years are recruited to either the clinical case group (MD, diagnosis of MD disorder) or the typically developing control group (absence of any psychiatric condition).

Findings To Date: To date, four publications on both genetic and environmental risk and resilience factors (including , glucocorticoid receptor activation, polygenic risk scores, psychosocial and sociodemographic risk and resilience factors) have been published based on the BioMD-Y sample.

Human cortical neurogenesis is altered via glucocorticoid-mediated regulation of ZBTB16 expression.

Glucocorticoids are important for proper organ maturation, and their levels are tightly regulated during development. Here, we use human cerebral organoids and mice to study the cell-type-specific effects of glucocorticoids on neurogenesis. We show that glucocorticoids increase a specific type of basal progenitors (co-expressing PAX6 and EOMES) that has been shown to contribute to cortical expansion in gyrified species.

DNA methylation patterns of FKBP5 regulatory regions in brain and blood of humanized mice and humans.

Humanized mouse models can be used to explore human gene regulatory elements (REs), which frequently lie in non-coding and less conserved genomic regions. Epigenetic modifications of gene REs, also in the context of gene x environment interactions, have not yet been explored in humanized mouse models. We applied high-accuracy measurement of DNA methylation (DNAm) via targeted bisulfite sequencing (HAM-TBS) to investigate DNAm in three tissues/brain regions (blood, prefrontal cortex and hippocampus) of mice carrying the human FK506-binding protein 5 (FKBP5) gene, an important candidate gene associated with stress-related psychiatric disorders.

Epigenetics of prenatal stress in humans: the current research landscape.

Fetal exposure to prenatal stress can have significant consequences on short- and long-term health. Epigenetic mechanisms, especially DNA methylation (DNAm), are a possible process how these adverse environmental events could be biologically embedded. We evaluated candidate gene as well as epigenome-wide association studies associating prenatal stress and DNAm changes in peripheral tissues; however, most of these findings lack robust replication.

A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation.

Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium.

High-throughput screening of glucocorticoid-induced enhancer activity reveals mechanisms of stress-related psychiatric disorders.

Exposure to stressful life events increases the risk for psychiatric disorders. Mechanistic insight into the genetic factors moderating the impact of stress can increase our understanding of disease processes. Here, we test 3,662 single nucleotide polymorphisms (SNPs) from preselected expression quantitative trait loci in massively parallel reporter assays to identify genetic variants that modulate the activity of regulatory elements sensitive to glucocorticoids, important mediators of the stress response.

Transdiagnostic evaluation of epigenetic age acceleration and burden of psychiatric disorders.

Different psychiatric disorders as well as exposure to adverse life events have individually been associated with multiple age-related diseases and mortality. Age acceleration in different epigenetic clocks can serve as biomarker for such risk and could help to disentangle the interplay of psychiatric comorbidity and early adversity on age-related diseases and mortality. We evaluated five epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge and DunedinPoAm) in a transdiagnostic psychiatric sample using epigenome-wide DNA methylation data from peripheral blood of 429 subjects from two studies at the Max Planck Institute of Psychiatry.

Epigenome-wide meta-analysis of prenatal maternal stressful life events and newborn DNA methylation.

Prenatal maternal stressful life events are associated with adverse neurodevelopmental outcomes in offspring. Biological mechanisms underlying these associations are largely unknown, but DNA methylation likely plays a role. This meta-analysis included twelve non-overlapping cohorts from ten independent longitudinal studies (N = 5,496) within the international Pregnancy and Childhood Epigenetics consortium to examine maternal stressful life events during pregnancy and DNA methylation in cord blood.

Associations of psychiatric disease and ageing with FKBP5 expression converge on superficial layer neurons of the neocortex.

Identification and characterisation of novel targets for treatment is a priority in the field of psychiatry. FKBP5 is a gene with decades of evidence suggesting its pathogenic role in a subset of psychiatric patients, with potential to be leveraged as a therapeutic target for these individuals. While it is widely reported that FKBP5/FKBP51 mRNA/protein (FKBP5/1) expression is impacted by psychiatric disease state, risk genotype and age, it is not known in which cell types and sub-anatomical areas of the human brain this occurs.