A meta-analysis of the effects of early life stress on the prefrontal cortex transcriptome suggests long-term effects on myelin.

Background: Early life stress (ELS) refers to exposure to negative childhood experiences, such as neglect, disaster, and physical, mental, or emotional abuse. ELS can permanently alter the brain, leading to cognitive impairment, increased sensitivity to future stressors, and mental health risks. The prefrontal cortex (PFC) is a key brain region implicated in the effects of ELS.

Striatal dopamine gene network moderates the effect of early adversity on the risk for adult psychiatric and cardiometabolic comorbidity.

Cardiometabolic and psychiatric disorders often co-exist and share common early life risk factors, such as low birth weight. However, the biological pathways linking early adversity to adult cardiometabolic/psychiatric comorbidity remain unknown. Dopamine (DA) neurotransmission in the striatum is sensitive to early adversity and influences the development of both cardiometabolic and psychiatric diseases.

Exploring multi-omics and clinical characteristics linked to accelerated biological aging in Asian women of reproductive age: insights from the S-PRESTO study.

Background: Phenotypic age (PhenoAge), a widely used marker of biological aging, has been shown to be a robust predictor of all-cause mortality and morbidity in different populations. Existing studies on biological aging have primarily focused on individual domains, resulting in a lack of a comprehensive understanding of the multi-systemic dysregulation that occurs in aging.

Methods: PhenoAge was evaluated based on a linear combination of chronological age (CA) and 9 clinical biomarkers in 952 multi-ethnic Asian women of reproductive age.

Maternal Depressive Symptoms and Risk for Childhood Depression: Role of Executive Functions.

Objective: Offspring of mothers with depression are at increased risk for executive function (EF) deficits and later depressive symptoms, but limited studies have examined EF as an intermediary pathway. This study examined the role of EF in mediating the association between maternal and child depressive symptoms.

Method: Data were from a longitudinal birth cohort comprising 739 participants followed from the antenatal period for 12 years.

Predictors of Participation in a Perinatal Text Message Screening Protocol for Maternal Depression and Anxiety: Prospective Cohort Study.

Background: Universal screening for depression and anxiety in pregnancy has been recommended by several leading medical organizations, but the implementation of such screening protocols may overburden health care systems lacking relevant resources. Text message screening may provide a low-cost, accessible alternative to in-person screening assessments. However, it is critical to understand who is likely to participate in text message-based screening protocols before such approaches can be implemented at the population level.

Shared and unique transcriptomic signatures of antidepressant and probiotics action in the mammalian brain.

Understanding the shared and divergent mechanisms across antidepressant (AD) classes and probiotics is critical for improving treatment for mood disorders. Here we examine the transcriptomic effects of bupropion (NDRI), desipramine (SNRI), fluoxetine (SSRI) and a probiotic formulation (Lacidofil®) on 10 regions across the mammalian brain. These treatments massively alter gene expression (on average, 2211 differentially expressed genes (DEGs) per region-treatment combination), highlighting the biological complexity of AD and probiotic action.

In vivo whole-cortex marker of excitation-inhibition ratio indexes cortical maturation and cognitive ability in youth.

A balanced excitation-inhibition ratio (E/I ratio) is critical for healthy brain function. Normative development of cortex-wide E/I ratio remains unknown. Here, we noninvasively estimate a putative marker of whole-cortex E/I ratio by fitting a large-scale biophysically plausible circuit model to resting-state functional MRI (fMRI) data.

Faster pace of hippocampal growth mediates the association between perinatal adversity and childhood depression.

Early life adversity has been posited to influence the pace of structural neurodevelopment. Most research, however, has relied on cross-sectional data, which do not reveal whether the pace of neurodevelopmental change is accelerated or slowed following early exposures. In a birth cohort study that included neuroimaging data obtained at 4.

Examining the associations between microglia genetic capacity, early life exposures and white matter development at the level of the individual.

There are inter-individual differences in susceptibility to the influence of early life experiences for which the underlying neurobiological mechanisms are poorly understood. Microglia play a role in environmental surveillance and may influence individual susceptibility to environmental factors. As an index of neurodevelopment, we estimated individual slopes of mean white matter fractional anisotropy (WM-FA) across three time-points (age 4.

Microglial function interacts with the environment to affect sex-specific depression risk.

There is a two-fold higher incidence of depression in females compared to men with recent studies suggesting a role for microglia in conferring this sex-dependent depression risk. In this study we investigated the nature of this relation. Using GWAS enrichment, gene-set enrichment analysis and Mendelian randomization, we found minimal evidence for a direct relation between genes functionally related to microglia and sex-dependent genetic risk for depression.

In-vivo whole-cortex marker of excitation-inhibition ratio indexes cortical maturation and cognitive ability in youth.

A balanced excitation-inhibition ratio (E/I ratio) is critical for healthy brain function. Normative development of cortex-wide E/I ratio remains unknown. Here we non-invasively estimate a putative marker of whole-cortex E/I ratio by fitting a large-scale biophysically-plausible circuit model to resting-state functional MRI (fMRI) data.

Neonatal Nucleus Accumbens Microstructure Modulates Individual Susceptibility to Preconception Maternal Stress in Relation to Externalizing Behaviors.

Objective: Maternal stress influences in utero brain development and is a modifiable risk factor for offspring psychopathologies. Reward circuitry dysfunction underlies various internalizing and externalizing psychopathologies. This study examined (1) the association between maternal stress and microstructural characteristics of the neonatal nucleus accumbens (NAcc), a major node of the reward circuitry, and (2) whether neonatal NAcc microstructure modulates individual susceptibility to maternal stress in relation to childhood behavioral problems.

The effects of acute social ostracism on subsequent snacking behavior and future body mass index in children.

Background/objectives: Ostracism may lead to increased food intake, yet it is unclear whether greater reactivity to ostracism contributes to higher body mass index (BMI). We investigated whether children who exhibited greater stress to social exclusion subsequently consume more energy and whether this predicts BMI 6- and 18-months later.

Subjects/methods: Children (8.

Screen time, brain network development and socio-emotional competence in childhood: moderation of associations by parent-child reading.

Background: Screen time in infancy is linked to changes in social-emotional development but the pathway underlying this association remains unknown. We aim to provide mechanistic insights into this association using brain network topology and to examine the potential role of parent-child reading in mitigating the effects of screen time.

Methods: We examined the association of screen time on brain network topology using linear regression analysis and tested if the network topology mediated the association between screen time and later socio-emotional competence.

Exploring the validity of the ASQ-SE for socio-emotional competency screening of a low-risk Asian cohort at 2 years of age.

Aims: To assess the Ages & Stages Questionnaire: Social-Emotional (ASQ-SE)'s concurrent validity in a low-risk Singapore cohort and study its association with maternal mental health status.

Methods: Concurrent validity of the parent-filled ASQ-SE with Child Behavior Checklist (CBCL1.5-5) was evaluated in 341 children at age 24 months.

Associations between Social Adversity and Biomarkers of Inflammation, Stress, and Aging in Children.

Background: Prior work has found relationships between childhood social adversity and biomarkers of stress, but knowledge gaps remain. To help address these gaps, we explored associations between social adversity and biomarkers of inflammation (interleukin-1β [IL-1β], IL-6, IL-8, tumor necrosis factor-alpha [TNF-α], and salivary cytokine hierarchical "clusters" based on the three interleukins), neuroendocrine function (cortisol, cortisone, dehydroepiandrosterone, testosterone, and progesterone), neuromodulation (N-arachidonoylethanolamine, stearoylethanolamine, oleoylethanolamide, and palmitoylethanolamide), and epigenetic aging (Pediatric-Buccal-Epigenetic clock).

Methods: We collected biomarker samples of children ages 0-17 recruited from an acute care pediatrics clinic and examined their associations with caregiver-endorsed education, income, social risk factors, and cumulative adversity.

Parental and child genetic burden of glycaemic dysregulation and early-life cognitive development: an Asian and European prospective cohort study.

Insulin resistance and glucose metabolism have been associated with neurodevelopmental disorders. However, in the metabolically more susceptible Asian populations, it is not clear whether the genetic burden of glycaemic dysregulation influences early-life neurodevelopment. In a multi-ethnic Asian prospective cohort study in Singapore (Growing Up in Singapore Towards healthy Outcomes (GUSTO)), we constructed child and parental polygenic risk scores (PRS) for glycaemic dysregulation based on the largest genome-wide association studies of type 2 diabetes and fasting glucose among Asians.

Accumbal μ-opioid receptors and salt taste-elicited hedonic responses in a rodent model of prenatal adversity, and their correlates using human functional genomics.

Prenatal adversity is associated with behavioral obesogenic features such as preference for palatable foods. Salt appetite may play a role in the development of adiposity and its consequences in individuals exposed to prenatal adversity, and sodium consumption involves individual differences in accumbal µ-opioid receptors function. We investigated the hedonic responses to salt and the levels of µ-opioid receptors and tyrosine hydroxylase in the nucleus accumbens (Nacc) of pups from an animal model of prenatal dietary restriction.

A global multicohort study to map subcortical brain development and cognition in infancy and early childhood.

The human brain grows quickly during infancy and early childhood, but factors influencing brain maturation in this period remain poorly understood. To address this gap, we harmonized data from eight diverse cohorts, creating one of the largest pediatric neuroimaging datasets to date focused on birth to 6 years of age. We mapped the developmental trajectory of intracranial and subcortical volumes in ∼2,000 children and studied how sociodemographic factors and adverse birth outcomes influence brain structure and cognition.

Independent Prediction of Child Psychiatric Symptoms by Maternal Mental Health and Child Polygenic Risk Scores.

Objective: Prenatal maternal symptoms of depression and anxiety are associated with an increased risk for child socioemotional and behavioral difficulties, supporting the fetal origins of mental health hypothesis. However, to date, studies have not considered specific genomic risk as a possible confound.

Method: The Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (n = 5,546) was used to test if child polygenic risk score for attention-deficit/hyperactivity disorder (ADHD), schizophrenia, or depression confounds or modifies the impact of prenatal maternal depression and anxiety on child internalizing, externalizing, and total emotional/behavioral symptoms from age 4 to 16 years.

Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes.

Pathological placental inflammation increases the risk for several adult disorders, but these mediators are also expressed under homeostatic conditions, where their contribution to adult health outcomes is unknown. Here we define an inflammation-related expression signature, primarily expressed in Hofbauer cells of the term placenta and use expression quantitative trait loci to create a polygenic score (PGS) predictive of its expression. Using this PGS in the UK Biobank we conduct a phenome-wide association study, followed by Mendelian randomization and identify protective, sex-dependent effects of the placental module on cardiovascular and depressive outcomes.

Preparation and processing of dried blood spots for microRNA sequencing.

Dried blood spots (DBS) are biological samples commonly collected from newborns and in geographic areas distanced from laboratory settings for the purposes of disease testing and identification. MicroRNAs (miRNAs)-small non-coding RNAs that regulate gene activity at the post-transcriptional level-are emerging as critical markers and mediators of disease, including cancer, infectious diseases, and mental disorders. This protocol describes optimized procedural steps for utilizing DBS as a reliable source of biological material for obtaining peripheral miRNA expression profiles.