Characterizing the role of unpredictability within different dimensions of early life adversity.

Dimensional models of early life adversity highlight the distinct roles of deprivation and threat in shaping neurocognitive development and mental health. However, relatively little is known about the role of unpredictability within each dimension. We estimated both the average levels of, and the temporal unpredictability of deprivation and threat exposure during adolescence in a high-risk, longitudinal sample of 1354 youth (Pathways to Desistance study). We then related these estimates to later life psychological distress, and Antisocial and Borderline personality traits, and tested whether any effects are mediated by future orientation. High average levels of both deprivation and threat exposure were found to be associated with worse mental health on all three outcomes, but only the effects on Antisocial and Borderline personality traits were mediated by decreased future orientation, a pattern consistent with evolutionary models of psychopathology. Unpredictability in deprivation exposure proved to be associated with increased psychological distress and a higher number of Borderline traits, but with increased future orientation. There was some evidence of unpredictability in threat exposure buffering against the detrimental developmental effects of average threat levels. Our results suggest that the effects of unpredictability are distinct within different dimensions of early life adversity.

The extraordinary "ordinary magic" of resilience.

In this essay, I will briefly sample different instances of the utilization of the concept of resilience, attempting to complement a comprehensive representation of the field in the special issue of Development and Psychopathology inspired by the 42nd Minnesota Symposium on Child Psychology, hosted by the Institute of Child Development at the University of Minnesota and held in October of 2022. Having established the general context of the field, I will zoom in on some of its features, which I consider "low-hanging fruit" and which can be harvested in a systematic way to advance the study of resilience in the context of the future of developmental psychopathology.

Impacts of Acute Psychological Stress on the Emotions of Individuals with Early Life Stress.

Objective: The study aimed to evaluate negative and positive emotional responses to acute psychological stress in individuals with early life stress (ELS). Methods: One hundred sixty-one participants from the Birmingham community in Alabama completed the study and were stratified into 2 groups based on measurements of ELS using the Childhood Trauma Questionnaire and a confirmatory clinical interview. Acute psychological stress, that is, the Trier Social Stress Test (TSST), was administered, and emotional responses were measured using the Visual Analogue Scale. Comparisons utilized chi-square for categorical variables and t-test for continuous variables. Analysis of covariance (ANCOVA) was applied to compare the 2 groups after controlling for confounding variables. Stepwise multiple linear regression analysis was used to investigate predictive power of variables for emotional responses to the TSST. Results: Participants with ELS experienced less pleasantness at the baseline (P = .02), and 1 minute (P = .04), but not 90 minutes time points compared to the non-ELS group. Participants in the ELS group also reported higher anxiety at baseline (P = .003), and 90 minutes (P = .04) post-TSST. Data analysis showed the effect of time on emotional responses during the TSST. Different emotional responses, including pleasantness, anxiety, fatigue, and vigor, were able to be predicted by ELS severity. Conclusion: Our data demonstrates that individuals with ELS presented different positive and negative emotional responses when exposed to acute psychological stress. Our findings may be useful for clinicians who work with individuals with ELS. Our findings also highlight the importance of recognizing emotional responses and of building up resilience in response to acute stress.

Pathways From Early Life Adversities to Youth Marginalization: A Longitudinal Study of Youth Not in Education, Employment, or Training.

PURPOSE: Youth who are Not in Education, Employment, or Training (NEET) are at risk for numerous long-term occupational, social, and mental health-related sequelae. The aim of the present study was to investigate mediated pathways from early life risk factors to NEET status in early adulthood, with a particular focus on the role of the family environment during adolescence. METHODS: Participants were 6,403 respondents from the National Longitudinal Survey of Children and Youth, who were aged 10-11 years in cycles 1 (1994-1995) to 4 (2000-2001). Parents reported on indicators of early life adversity as well as parent-child conflict at age 12-13. Adolescents reported on their mental health and behaviour at age 14-15. NEET status was assessed at age 24 using tax information from the linked T1 Family File. Indirect pathways from childhood exposures, through adolescent factors, to NEET status in young adulthood were assessed via mediation analysis. RESULTS: At age 10/11, living with a single parent, low household income, stressful life events, and having a parent with a chronic condition were associated with greater likelihood of being NEET at age 24; parents' social support was negatively associated with NEET. These associations were mediated through parental depression at age 10/11, parent-child conflict at age 12/13, and adolescent mental health and behaviour at age 14/15. DISCUSSION: Our results add to a large body of literature linking family stressors, parental depression, parent-child interaction, and adolescent behaviour symptoms, suggesting a chain of influence through these factors toward young adult marginalization from the labour market.

Defence-relevant gene expression differences in hatchlings among wild Newfoundland and farmed European and North American Atlantic salmon and their hybrids.

Escape of genetically distinct farmed Atlantic salmon (Salmo salar) raises concerns about their potential interactions with wild populations and the disruption of local adaptation through genetic admixture. It is often unknown whether genetic origin or common domestication effects will have a greater influence on consequences posed by escaped farmed fish. Previous work showed that domestication could have prevalent effects on the behaviour and growth of farmed salmon, independent of their genetic origin. Yet, less is known whether this extends more broadly to gene expression, particularly at critical early life stages. Thus, we compared the expression of 24 transcripts related to the immune response, structural maintenance, stress response and iron metabolism among distinct farmed (North American [NA] and European [EO]), wild (Newfoundland) and F1 hybrid salmon at hatching under controlled conditions using qPCR analyses. A slightly higher number of transcripts were differentially expressed between the wild population relative to EO (i.e. atf3a, atf3b, bnip3, trim37a, ftm, hp and gapdh) than NA-farmed salmon (i.e. epdl2, hba1a, hba1b, hbb4 and ftm). The most differences existed between the two farmed strains themselves (11 of 24 transcripts), with the fewest differentially expressed transcripts found between the F1 hybrids and the domesticated/wild maternal strains (4 of 24 transcripts). Interestingly, despite similarities in the overall extent of gene expression differences among cross types, the expression patterns differed relative to a past study that compared fry from the same cross types at the end of yolk sac absorption. Overall, our findings suggest that interbreeding of escaped farmed salmon with wild Newfoundland populations would alter transcript expression levels and that developmental stage influences these changes.

Iron: Life's primeval transition metal.

Modern life requires many different metal ions, which enable diverse biochemical functions. It is commonly assumed that metal ions' environmental availabilities controlled the evolution of early life. We argue that evolution can only explore the chemistry that life encounters, and fortuitous chemical interactions between metal ions and biological compounds can only be selected for if they first occur sufficiently frequently. We calculated maximal transition metal ion concentrations in the ancient ocean, determining that the amounts of biologically important transition metal ions were orders of magnitude lower than ferrous iron. Under such conditions, primitive bioligands would predominantly interact with Fe(II). While interactions with other metals in certain environments may have provided evolutionary opportunities, the biochemical capacities of Fe(II), Fe-S clusters, or the plentiful magnesium and calcium could have satisfied all functions needed by early life. Primitive organisms could have used Fe(II) exclusively for their transition metal ion requirements.

Early-life ozone exposure and childhood otitis media: Unveiling critical windows of risk.

BACKGROUND: Despite increasing evidence of a strong correlation between air pollution and otitis media (OM), the impact of early-life ozone (O3) exposure on the development of OM in children remains uncertain. OBJECTIVES: To explore the connection between early-life O3 exposure and OM, and to identify the critical time period(s) during which O3 exposure significantly influences the development of OM in children. METHODS: We conducted a study involving 8689 children living in Changsha, China. Information regarding personal factors, health conditions, and the indoor environment was gathered using questionnaires. Personal exposure to outdoor O3 and other major pollutants at the place of residence during the periods before conception, prenatal periods, and after birth was calculated by applying the inverse distance weighted (IDW) method with data gathered from ten air quality monitoring stations. Multiple logistic regression analyses were employed to investigate the associations between O3 exposure and children's OM. RESULTS: After controlling for covariates and ambient temperature, exposure to O3 during the year preceding pregnancy was correlated with childhood lifetime OM, showing ORs (95 % CI) of 1.28 (1.01-1.64). O3 exposures in the 10th-12th, 7th-9th, and 4th-6th months before pregnancy were all linked to children's lifetime OM. Within the multi-window model, we detected that O3 exposure in the 10th to 12th month prior to pregnancy was significantly related to lifetime OM, showing ORs (95 % CI) of 1.28 (1.05-1.55). A significant link was discovered between childhood OM and O3 exposure after controlling for six other pollutants (SO2, PM2.5, NO2, PM2.5-10, CO, and PM10) during the 10th to 12th month prior to conception. Exposure to O3 during the 36th gestational week significantly raised the likelihood of childhood lifetime OM. There is a significant interaction between O3 and temperature exposure during the first trimester of pregnancy and one year before pregnancy on childhood lifetime OM. CONCLUSIONS: Preconceptional O3 exposure and its interaction with low temperature played critical roles in children's OM development, backing the hypothesis of "(pre) fetal origins of childhood OM".

Alzheimer's Disease Has Its Origins in Early Life via a Perturbed Microbiome.

Alzheimer's disease (AD) is a neurodegenerative disorder with limited therapeutic options. Accordingly, new approaches for prevention and treatment are needed. One focus is the human microbiome, the consortium of microorganisms that live in and on us, which contributes to human immune, metabolic, and cognitive development and that may have mechanistic roles in neurodegeneration. AD and Alzheimer's disease-related dementias (ADRD) are recognized as spectrum disorders with complex pathobiology. AD/ADRD onset begins before overt clinical signs, but initiation triggers remain undefined. We posit that disruption of the normal gut microbiome in early life leads to a pathological cascade within septohippocampal and cortical brain circuits. We propose investigation to understand how early-life microbiota changes may lead to hallmark AD pathology in established AD/ADRD models. Specifically, we hypothesize that antibiotic exposure in early life leads to exacerbated AD-like disease endophenotypes that may be amenable to specific microbiological interventions. We propose suitable models for testing these hypotheses.

From womb to wellness: early environmental exposures, cord blood DNA methylation and disease origins.

Fetal exposures can induce epigenetic modifications, particularly DNA methylation, potentially predisposing individuals to later health issues. Cord blood (CB) DNA methylation provides a unique window into the fetal epigenome, reflecting the intrauterine environment's impact. Maternal factors, including nutrition, smoking and toxin exposure, can alter CB DNA methylation patterns, associated with conditions from obesity to neurodevelopmental disorders. These epigenetic changes underscore prenatal exposures' enduring effects on health trajectories. Technical challenges include tissue specificity issues, limited coverage of current methylation arrays and confounding factors like cell composition variability. Emerging technologies, such as single-cell sequencing, promise to overcome some of these limitations. Longitudinal studies are crucial to elucidate exposure-epigenome interactions and develop prevention strategies. Future research should address these challenges, advance public health initiatives to reduce teratogen exposure and consider ethical implications of epigenetic profiling. Progress in CB epigenetics research promises personalized medicine approaches, potentially transforming our understanding of developmental programming and offering novel interventions to promote lifelong health from the earliest stages of life.

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Nicotine addiction and the influence of life adversity and acute stress on PYY: Prediction of early smoking relapse.

Early life adversity (ELA) is associated with earlier initiation and maintenance of tobacco smoking and with a greater risk of subsequent relapse. There is growing evidence that appetite hormones, including peptide YY (PYY), which modulates craving and satiety responses, play a role in stress and addiction processes. This study employed a quasi-experimental design to examine the association between ELA and circulating PYY stress responses in smokers and nonsmokers (N = 152, ages 19-73 years) to examine the effects of nicotine addiction. Smokers initiated a quit attempt as part of the study and were classified as either abstinent smokers or relapsed smokers based on their nicotine use during the follow-up period. PYY levels were measured at five timepoints during three lab sessions and compared between nonsmokers and the two smoking groups (abstainers, relapsers): while smokers were using nicotine ad libitum, 24 h after smokers initiated a quit attempt, and 4 weeks after smokers initiated a quit attempt. Multivariate analyses showed the main effects of time on PYY, which decreased over time within each session. The main effects of ELA during the first (ad libitum smoking) and second (24-h post-cessation for smokers) sessions indicated that experiencing ELA was associated with lower PYY. No systematic effect of nicotine addiction or relapse was observed in this study. These findings suggest that adults with higher ELA may experience lower PYY. Additional research is needed to further explore the role of PYY in stress and addiction processes.

Selective human milk oligosaccharide utilization by members of the Bifidobacterium pseudocatenulatum taxon.

Human milk oligosaccharides (HMOs) are essentially unaffected by the digestive enzymes of the nursling and are known for their ability to enrich certain microbial species in the infant gut microbiota, in particular bifidobacteria. HMO metabolism has been studied in various bifidobacterial species such as B. breve, B. bifidum, and B. longum subsp. infantis. In the current study, we describe differential growth abilities elicited by twenty-three newly isolated Bifidobacterium pseudocatenulatum strains on particular HMOs, such as 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lacto-N-tetraose (LNT), and lacto-N-neotetraose (LNnT). Through gene-trait matching and comparative genome analysis, we identified genes involved in the degradation of fucosylated HMOs in this strain set, while we employed a transcriptomic approach to facilitate the identification and characterization of genes and associated enzymes involved in LNT metabolism by strain B. pseudocatenulatum MM0196. A total of 252 publicly available genomes of the B. pseudocatenulatum taxon were screened for homologs of the glycosyl hydrolases (GHs) identified here as being required for selected HMO metabolism. From this analysis, it is clear that all members of this species possess homologs of the genes involved in LNT degradation, while genes required for degradation of fucosylated HMOs are variably present.IMPORTANCEOur findings allow a better understanding of the complex interaction between Bifidobacterium and its host and provide a roadmap toward future applications of B. pseudocatenulatum as a probiotic with a focus on infant health. Furthermore, our investigations have generated information on the role of HMOs in shaping the infant gut microbiota, thus also facilitating applications of HMOs in infant nutrition, with potential extension into the mature or adult gut microbiota. Supplementation of HMOs is known to result in the modulation of bacterial communities toward a higher relative abundance of bifidobacteria, which in turn enforces their ability to modulate particular immune functions and strengthen the intestinal barrier. This work may therefore inspire future studies to improve the formulation of neonatal nutritional products, aimed at facilitating the development of a healthy digestive and immune system and reducing the differences in gut microbiota composition observed between breastfed and formula-fed babies or full-term and preterm infants.

Role of stress and early-life stress in the pathogeny of inflammatory bowel disease.

Numerous preclinical and clinical studies have shown that stress is one of the main environmental factor playing a significant role in the pathogeny and life-course of bowel diseases. However, stressful events that occur early in life, even during the fetal life, leave different traces within the central nervous system, in area involved in stress response and autonomic network but also in emotion, cognition and memory regulation. Early-life stress can disrupt the prefrontal-amygdala circuit thus favoring an imbalance of the autonomic nervous system and the hypothalamic-pituitary adrenal axis, resulting in anxiety-like behaviors. The down regulation of vagus nerve and cholinergic anti-inflammatory pathway favors pro-inflammatory conditions. Recent data suggest that emotional abuse at early life are aggravating risk factors in inflammatory bowel disease. This review aims to unravel the mechanisms that explain the consequences of early life events and stress in the pathophysiology of inflammatory bowel disease and their mental co-morbidities. A review of therapeutic potential will also be covered.

External morphology and growth patterns of larvae and juveniles of Bryconops gracilis (Characiformes, Iguanodectidae) from Amazon basin.

During early development, fishes undergo significant changes that influence external morphology and the functioning of internal organs and systems. This often results in gradual variation of the morphological traits of individuals across developmental stages. The investigation of larval and juvenile fish development and growth patterns has pertinent implications for the systematic and ecological elucidation of species. Bryconops gracilis is a medium-sized fish, omnivorous that inhabits lotic and lentic environments with acidic and transparent waters in the Amazon basin. In this study, the early development of B. gracilis is described, until recently a practically unknown species. In terms of development, we used morphological, meristic, and morphometric data to characterize the larvae and juveniles. The individuals were collected in the Curuá-Una River, Amazon basin, Brazil. Fifty-four specimens were examined. Samples include individuals with 3.39-21.79 mm SL. Yolk-sac larvae have two attachment organs on the dorsal surface of head and body. The larvae of B. gracilis are considered altricial, with a fusiform body, and the intestine reaches the median region of the body. Initially, the mouth is subterminal and becomes isognathic from the postflexion stage on. During the postflexion stage, the most relevant morphological changes occur (e.g., presence of all fins, mouth position similar to adults, increased body pigmentation), making individuals more specialized to explore new habitats and diets and maximize their chances of survival. Furthermore, vertebrae and myomeres are compared and assist with differentiating some Bryconops species at early life stages that occur in sympatry in the Amazon basin. Our results contribute to knowledge about the external morphology of neotropical freshwater fishes, enabling the identification of larvae and juveniles through traditional taxonomy and broadening the perspective on the ontogenetic study of the adipose fin in Characoidei.

Complications and long-term impact of early life pneumonia.

Pneumonia is an infection affecting the lower airway, where the air sacs are filled with mucus and pus; and typically presents with cough, fever, and fast breathing. Pneumonia is estimated to be the leading cause of mortality in children under five worldwide with 120 million episodes result in 1 million deaths globally. The Low-Income and Middle-Income Countries (LMICs) are more affected. In a study in southeast Nigeria, bronchopneumonia accounted for 41.9%, of the cases admitted in the tertiary hospitals and in another hospital based study among children, pneumonia had the highest respiratory admission rates at 34.0%. Pneumonia can be caused by various organisms: Bacterial (Streptococcus, staphylococcus etc), Viral (RSV) and recently COVID 19 pneumonia. RSV has been noted globally to be a major cause of childhood lower respiratory tract infection, with morbidity/mortality occurring in 99% of (LMICs). Some of the long term sequalae are discussed.

Early-Life Gut Microbiota: A Possible Link Between Maternal Exposure to Non-Nutritive Sweeteners and Metabolic Syndrome in Offspring.

Metabolic syndrome (MetS) is recognized as a group of metabolic abnormalities, characterized by clustered interconnected traits that elevate the risks of obesity, cardiovascular and atherosclerotic diseases, hyperlipidemia, and type 2 diabetes mellitus. Non-nutritive sweeteners (NNS) are commonly consumed by those with imbalanced calorie intake, especially in the perinatal period. In the past, accumulating evidence showed the transgenerational and mediated roles of human microbiota in the development of early-life MetS. Maternal exposure to NNS has been recognized as a risk factor for filial metabolic disturbance through various mechanisms, among which gut microbiota and derived metabolites function as nodes linking NNS and MetS in early life. Despite the widespread consumption of NNS, there remain growing concerns about their transgenerational impact on metabolic health. There is growing evidence of NNS being implicated in the development of metabolic abnormalities. Intricate complexities exist and a comprehensive understanding of how the gut microbiota interacts with mechanisms related to maternal NNS intake and disrupts metabolic homeostasis of offspring is critical to realize its full potential in preventing early-life MetS. This review aims to elucidate the effects of early-life gut microbiota and links to maternal NNS exposure and imbalanced offspring metabolic homeostasis and discusses potential perspectives and challenges, which may provide enlightenment and understanding into optimal perinatal nutritional management.

Exposure and potential risks of thirteen endocrine- disrupting chemicals in pharmaceuticals and personal care products for breastfed infants in China.

Ingestion of breast milk represents the primary exposure pathway for endocrine-disrupting chemicals (EDCs) in newborns. To elucidate the associated risks, it is essential to quantify EDC levels in both breast milk and infant urine. This study measured the concentrations of 13 EDCs, including parabens (methyl paraben (MP), ethyl paraben (EP), propyl paraben (PP), iso-propyl paraben, butyl paraben, and iso-butyl paraben), bisphenols (bisphenol A (BPA), bisphenol F, bisphenol S, bisphenol AF, and bisphenol Z), triclosan (TCS), and triclocarban, in breast milk and infant urine to assess their potential health effects and endocrine disruption risks. In total, 1 014 breast milk samples were collected from 20 cities across China, along with 144 breast milk samples and 134 urine samples from a mother-infant cohort in Hangzhou. The EDCs were detected using ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry. Endocrine-disrupting potency was evaluated using a predictive method based on EDC affinity for 15 hormone receptor proteins. The toxicological priority index (ToxPi), incorporating population exposure data, was employed to assess health risks associated with exposure to multiple EDCs. Among the 13 EDCs, MP, EP, PP, BPA, and TCS were detected in over 50 % of breast milk samples, with the highest median concentrations observed for MP (0.37 ng/mL), EP (0.29 ng/mL), and BPA (0.17 ng/mL). Across the 20 cities, 0 %-40 % of infants had a hazard index (HI) exceeding 1. Based on affinity prediction analysis and estimated exposure, cumulative endocrine disruption risk intensity was ranked as MP > TCS > BPA > EP > PP. This research highlights the extensive exposure of Chinese infants to EDCs, offering a detailed analysis of their varying endocrine disruption potencies and underscoring the significant health risks associated with EDCs in breast milk.

The impact of early-life conditions on visual discrimination abilities in free-ranging laying hens.

Conditions during incubation and rearing can greatly affect the developmental trajectory of chickens, in a positive and negative way. In this study, the effect of early-life conditions on the visual discrimination abilities of adult, free-ranging laying hens was examined. These early-life treatments entailed incubation in a 12/12h green light/dark cycle and rearing with Black soldier fly larvae (BSFL) as foraging enrichment. Through a modified pebble-floor test, 171 hens of 41 to 42 wk old, housed in mobile stables with outdoor access, were tested for their ability to discriminate between food and nonfood items (mealworms and decoy mealworms). Each hen was allowed 60 pecks during the trial, from which the overall success rate, as well as within-trial learning was investigated. The latter was accomplished by dividing the 60 pecks into 3 blocks of 20 pecks and comparing the success rate between these blocks. Due to another ongoing experiment on range use, roughly half the hens received range enrichment (mealworms) at the time of testing, so this was included as a covariate in the analysis. Incubation with green light did not have an effect on the visual discrimination abilities of adult laying hens. Rearing with BSFL did have a limited beneficial effect on the visual discrimination abilities, as evidenced by a higher success rate during the first block of the visual discrimination trial. These enhanced visual discrimination abilities might be useful in a more complex free-range setting, where the animals have more foraging opportunities. Hens that received range enrichment at the time of testing, also had a higher success rate during the visual discrimination test, though they had a lower degree of test completion, likely due to habituation to the mealworms as an enrichment. The positive effects of BSFL during rearing and mealworms during the laying period stress the importance of enrichment throughout the life of the hens.

NR2F2 Reactivation in Early-life Adipocyte Stem-like Cells Rescues Adipocyte Mitochondrial Oxidation.

In humans, perinatal exposure to an elevated omega-6 (n6) relative to omega-3 (n3) Fatty Acid (FA) ratio is associated with the likelihood of childhood obesity. In mice, we show perinatal exposure to excessive n6-FA programs neonatal Adipocyte Stem-like cells (ASCs) to differentiate into adipocytes with lower mitochondrial nutrient oxidation and a propensity for nutrient storage. Omega-6 FA exposure reduced fatty acid oxidation (FAO) capacity, coinciding with impaired induction of beige adipocyte regulatory factors PPARγ, PGC1α, PRDM16, and UCP1. ASCs from n6-FA exposed pups formed adipocytes with increased lipogenic genes in vitro, consistent with an in vivo accelerated adipocyte hypertrophy, greater triacylglyceride accumulation, and increased % body fat. Conversely, n6-FA exposed pups had impaired whole animal 13C-palmitate oxidation. The metabolic nuclear receptor, NR2F2, was suppressed in ASCs by excess n6-FA intake preceding adipogenesis. ASC deletion of NR2F2, prior to adipogenesis, mimicked the reduced FAO capacity observed in ASCs from n6-FA exposed pups, suggesting that NR2F2 is required in ASCs for robust beige regulator expression and downstream nutrient oxidation in adipocytes. Transiently re-activating NR2F2 with ligand prior to differentiation in ASCs from n6-FA exposed pups, restored their FAO capacity as adipocytes by increasing the PPARγ-PGC1α axis, mitochondrial FA transporter CPT1A, ATP5 family synthases, and NDUF family Complex I proteins. Our findings suggest that excessive n6-FA exposure early in life dampens an NR2F2-mediated induction of beige adipocyte regulators, resulting in metabolic programming that is shifted towards nutrient storage.

Early-life adversity severity, timing, and context type are associated with SLC6A4 methylation in emerging adults: Results from a prospective cohort study.

BACKGROUND: Epigenetic modifications, including DNA methylation (DNAm), can play a role in the biological embedding of early-life adversity (ELA) through serotonergic mechanisms. The current study examines methylation of the CpG island in the promoter region of the stress-responsive serotonin transporter gene (SLC6A4) and is the first to jointly assess how it is influenced by ELA severity, timing, and type-specifically, deprivation and threat. METHODS: We use data from 627 Youth Emotion Project study participants, recruited from two US high schools. Using adjusted linear regressions, we analyze DNA collected in early adulthood from 410 participants and ELA based on interviewer-rated responses from concurrent Childhood Trauma Interviews, adjusting for survey-measured covariates. RESULTS: ELA robustly predicted mean CpG island SLC6A4 DNAm percent across 71 CpG sites. Each additional major-severity ELA event was associated with a 0.121-percentage-point increase (p<0.001), equating to a 0.177 standard deviation (sd) higher DNAm level (95 % CI: 0.080, 0.274) with each 1-sd higher adversity score. When modeled separately, both childhood and adolescent ELA predicted SLC6A4 DNAm. When modeled jointly, adolescent ELA was most strongly predictive, and child adversity remained significantly associated with DNAm through indirect associations via adolescent adversity. Additionally, the ELA-SLC6A4 DNAm association may vary by adversity type. Across separate models for childhood and adolescent exposures, deprivation coefficients are positive and statistically significant. Meanwhile, threat coefficients are positive and not significantly significant but do not statistically differ from deprivation coefficients. In models including all ELA dimensions, one major adolescent deprivation event is associated with a 0.222-percentage-point increased SLC6A4 DNAm (p<0.05), or a 1-sd higher deprivation score with a 0.157-sd increased DNAm. CONCLUSION: Results further implicate epigenetic modification on serotonergic neurotransmission via DNAm in the downstream sequelae of ELA-particularly adolescent deprivation-and support preventive interventions in adolescence to mitigate biological embedding.