• DNA methylation
• NR3C1 gene
• early life stress
• psychiatric diagnosis
• resilience

• Humans
• Resilience, Psychological
• Receptors, Glucocorticoid/genetics
• Receptors, Glucocorticoid/metabolism
• DNA Methylation
• Adverse Childhood Experiences
• Stress, Psychological/genetics
• Stress, Psychological/metabolism
• Adult

• BDNF
• Childhood adversity
• Interaction effect
• Longitudinal study
• Posttraumatic stress disorder
• Prediction

• Humans
• Brain-Derived Neurotrophic Factor/blood
• Stress Disorders, Post-Traumatic/blood
• Stress Disorders, Post-Traumatic/diagnosis
• Stress Disorders, Post-Traumatic/psychology
• Female
• Male
• Longitudinal Studies
• Adult
• Adverse Childhood Experiences
• Middle Aged
• Young Adult
• Wounds and Injuries/blood
• Wounds and Injuries/psychology
• Age of Onset

• Adolescents
• Mental health
• Negative life events
• Non-suicidal self-injury
• Sex

• Humans
• Self-Injurious Behavior/psychology
• Self-Injurious Behavior/epidemiology
• Male
• Female
• Young Adult
• Adolescent
• Sex Factors
• Students/psychology
• Adult
• Life Change Events
• Risk Factors
• Mental Health

• 2023 hyx-C33 Anhui Institute of Translational Medicine
• 2023M740022 China Postdoctoral Science Foundation

• Early life stress (ELS)
• Genes-brain-cognition
• Genome-wide polygenic scores (GPS)
• Moderated mediation
• Path modeling

• Anxiety
• epigenetics
• mitochondrial dysfunction
• monoamine oxidase
• oxidative stress.
• papez circuit

• Humans
• Anxiety Disorders/metabolism
• Monoamine Oxidase/metabolism
• Monoamine Oxidase/genetics
• Animals
• Brain/metabolism

• Cannabis
• Childhood trauma
• Hippocampus
• Psychosis onset
• Schizophrenia polygenic risk score

• Humans
• Child
• Cannabis
• Cross-Sectional Studies
• Adverse Childhood Experiences
• Bipolar Disorder/psychology
• Psychotic Disorders/psychology
• Hippocampus/diagnostic imaging

• R21 MH109819 NIMH NIH HHS
• UL1 TR002541 NCATS NIH HHS

• National Natural Science Foundation of China
• Youth Foundation
• Natural Science Foundation of Jiangsu Province
• China Postdoctoral Science Foundation

Genetic and early environmental factors are interwoven in the etiology of Borderline Personality Disorder (BPD). Epigenetic mechanisms offer the molecular machinery to adapt to environmental conditions. There are gaps in the knowledge about how epigenetic mechanisms are involved in the effects of early affective environment, development of BPD, and psychotherapy response. We reviewed the available evidence of the effects of psychotherapy on changes in DNA methylation and conducted a pilot study in a sample of 11 female adolescents diagnosed with BPD, exploring for changes in peripheral DNA methylation of FKBP5 gene, which encodes for a stress response protein, in relation to psychotherapy, on symptomatology and underlying psychological processes. For this purpose, measures of early trauma, borderline and depressive symptoms, psychotherapy outcome, mentalization, and emotional regulation were studied. A reduction in the average FKBP5 methylation levels was observed over time. Additionally, the decrease in FKBP5 methylation observed occurred only in those individuals who had early trauma and responded to psychotherapy. The results suggest an effect of psychotherapy on epigenetic mechanisms associated with the stress response. The finding that epigenetic changes were only observed in patients with early trauma suggests a specific molecular mechanism of recovery. The results should be taken with caution given the small sample size. Also, further research is needed to adjust for confounding factors and include endocrinological markers and therapeutic process variables.

• Agencia Nacional de Investigación y Desarrollo
• Fondo Nacional de Desarrollo Cientà­fico, Tecnológico y de Innovación Tecnológica

In this study, we determined the effect(s) of early shearing on Australian Merino ewes (Ovis aries) and their lambs. To test this research question, we used a suite of field and laboratory methods including GPS collars, wool cortisol, and epigenetic change between ewes and lambs identified using Illumina NovaSeq RRBS. Once shorn ewes (n = 24) were kept on their full fleece throughout the entire gestation period, whereas twice (early) shorn ewes (n = 24) had their wool shorn pre-joining. Top-knot wool sample was taken from ewes during pre-joining, day 50 (mid-gestation), and day 90 (late gestation) for laboratory analysis. Ewes were pregnancy scanned at mid-gestation to determine whether they were early or late parturition (this confirmation is provided by the pregnancy scanner based on fetus size). Top-knot wool sample was also taken from the lambs at weaning for hormone and wool quality testing. Ear tissue was taken from ewes at day 50 (mid-gestation) and from lambs at lamb marking for DNA analysis. Results showed that twice or early shorn ewes grazed 10% higher and maintained stronger body condition than once shorn ewes. Wool cortisol levels were also significantly lower in the early shorn ewes between mid- and late gestation. Lambs bred from twice shorn ewes had on average better visual wool quality parameters in terms of micron, spin finesses, and curvature. For the DNA methylation results, when comparing a group of once sheared with twice sheared ewes, we have discovered one locus (Chr20:50404014) that was significantly differentially methylated [False Discovery Rate (FDR) = 0.005]. This locus is upstream of a protein-coding gene (ENSOARG00000002778.1), which shows similarities to the forkhead box C1 (FOXC1) mRNA using BLAST searches. To further our understanding of the potential interaction between pregnancy status and shearing frequency of the ewes, we performed further differential methylation analysis using a combination of shearing treatment and pregnancy scanning status. The comparisons (1) late pregnancy vs. early pregnancy for ewes with one shearing treatment and (2) late pregnancy vs. early pregnancy for sheep with two shearing treatments were carried out to identify associations between loci and pregnancy duration for sheep with either one or two shearing events. We discovered that 36 gene loci were significantly modulated either between different shearing treatments or late vs. early pregnancy status of ewes. This result suggests that maternal pregnancy and nutritional status during gestation influence DNA methylation. We further investigated DNA methylation in lambs and identified 16 annotated gene loci that showed epigenetic modulation as a result of being born from an early or late stage pregnancy. From the genomics data, we pointed out that ewes go through epigenetic modifications during gestation, and there is a degree of intra-individual variation in the reproductive performance of ewes, which could be due to combination of intrinsic (genetic and physiological) and extrinsic (management and climatic) factors. Collectively, this research provides novel dataset combining physiological, molecular epigenetics, and digital tracking indices that advances our understanding of how Merino ewes respond to shearing frequency, and this information could guide further research on Merino sheep breeding and welfare.

Early life stress (ELS) causes long-lasting changes in gene expression through epigenetic mechanisms. However, little is known about the effects of ELS in adulthood, specifically across different age groups. In this study, the epigenetic modifications of p11 expression in adult mice subjected to ELS were investigated in different stages of adulthood. Pups experienced maternal separation (MS) for 3 h daily from postnatal day 1 to 21. At young and middle adulthood, behavioral test, hippocampal p11 expression levels, and levels of histone acetylation and methylation and DNA methylation at the hippocampal p11 promoter were measured. Middle-aged, but not young adult, MS mice exhibited increased immobility time in the forced swimming test. Concurrent with reduced hippocampal p11 levels, mice in both age groups showed a decrease in histone acetylation (AcH3) and permissive histone methylation (H3K4me3) at the p11 promoter, as well as an increase in repressive histone methylation (H3K27me3). Moreover, our results showed that the expression, AcH3 and H3Kme3 levels of p11 gene in response to MS were reduced with age. DNA methylation analysis of the p11 promoter revealed increased CpG methylation in middle-aged MS mice only. The results highlight the age-dependent deleterious effects of ELS on the epigenetic modifications of p11 transcription.

• clinical genetics
• physiology
• human behaviour

Epigenome-wide studies report higher methylation among women than men with decreasing levels with age. Little is known about associations of sex and age with methylation of monoamine oxidase A (MAOA). Methylation of the first exonic and partial first intronic region of MAOA has been shown to strengthen associations of interactions of MAOA-uVNTR genotypes and adversity with aggression and substance misuse. Our study examined associations of sex and age with MAOA first exon and intron methylation levels in 252 women and 157 men aged 14–73 years. Participants included adolescents recruited at a substance misuse clinic, their siblings and parents, and healthy women. Women showed ~ 50% higher levels of exonic, and ~ 15% higher intronic, methylation than men. Methylation levels were similar between younger (M = 22.7 years) and older (M = 46.1 years) participants, and stable across age. Age modified few associations of methylation levels with sex. MAOA genotypes modified few associations of methylation with sex and age. Higher methylation levels among women were not explained by genotype, nor interaction of genotype and sexual abuse. Findings were similar after adjusting for lifetime diagnoses of substance dependence (women = 24.3%; men = 34.2%). Methylation levels were higher among women who experienced sexual abuse than women who did not. Results extend on prior studies by showing that women display higher levels of methylation than men within first intronic/exonic regions of MAOA, which did not decrease with age in either sex. Findings were not conditioned by genotype nor interactions of genotype and trauma, and indicate X-chromosome inactivation.

• Age
• Child abuse
• Epigenetics
• Gene–environment interaction
• Methylation
• Sex differences

• Childhood
• Corporal punishment
• Cortisol
• DNA methylation
• Epigenetics
• HPA
• Harsh parenting
• NR3C1
• Spanking

• Child
• Child, Preschool
• DNA Methylation/genetics
• Female
• Humans
• Hydrocortisone/metabolism
• Hypothalamo-Hypophyseal System/metabolism
• Male
• Parenting
• Pituitary-Adrenal System/metabolism
• Principal Component Analysis
• Punishment
• Receptors, Glucocorticoid/genetics
• Receptors, Glucocorticoid/metabolism
• Regression Analysis
• Sex Characteristics
• Twins

• Eunice Kennedy Shriver National Institute of Child Health and Human Development

• Canguilhem
• early life adversity
• ecosocial theory
• epigenetics
• milieu
• neuropsychiatry
• risk
• vulnerability

• Epigenetics
• Heritability
• Psychiatric disorders
• Retrotransposons
• ncRNA

Positive experiences in early life may improve the capacity to cope with adulthood stress through epigenetic modification. We investigated whether an enriched environment (EE) in the postnatal period affected epigenetic changes in the p11 gene induced by chronic unpredictable stress (CUS) in adult C57BL/6J mice. EE was introduced for 5 weeks during postnatal days 21–55. After EE, the mice were subjected to CUS for 4 weeks. EE prevented depression-like behavior induced by adult CUS. EE prevented a decrease in p11 mRNA and histone H3 acetylation induced by CUS, with changes in the expression of histone deacetylase 5. Moreover, EE prevented changes in trimethylation of histone H3 lysine 4 (H3K4) and H3K27 induced by CUS. Furthermore, EE had positive effects on behavior and epigenetic alterations in adult mice without CUS. These results suggest that one of the underlying mechanisms of early-life EE may involve epigenetic modification of the hippocampal p11 gene promoter.

• chronic unpredictable stress
• depression
• early enriched environment
• epigenetic mechanism
• p11

• Acetylation
• Animals
• Annexin A2/genetics
• Corticosterone/blood
• Depression/blood
• Depression/prevention & control
• Epigenesis, Genetic
• Gene Expression
• Hippocampus/metabolism
• Histone Deacetylases/metabolism
• Histones/metabolism
• Housing, Animal
• Male
• Mice
• Mice, Inbred C57BL
• Promoter Regions, Genetic/genetics
• RNA, Messenger/genetics
• S100 Proteins/genetics
• Stress, Physiological

• adverse childhood experience
• biopsychosocial
• dopamine
• early life adversity
• eating disorder
• epigenetics
• food addiction
• obesity
• stress
• trauma

• Adolescent
• Adult
• Child
• Diet Therapy
• Dopamine/metabolism
• Epigenomics
• Food Addiction/genetics
• Food Addiction/metabolism
• Food Addiction/psychology
• Glucocorticoids/metabolism
• Humans
• Hypothalamo-Hypophyseal System/metabolism
• Life Change Events
• Obesity/genetics
• Obesity/metabolism
• Obesity/psychology
• Pituitary-Adrenal System/metabolism
• Public Health
• Stress, Psychological/metabolism
• Stress, Psychological/psychology

• Anxiety disorders
• Biomarkers
• Epigenetics
• Gene-environment interactions
• Stress

• Cognition
• Environmental
• Epigenetics
• Heritability
• Suicide

• Aggression
• Humans
• Impulsive Behavior
• Phenotype
• Suicide

Mediation analysis has been a powerful tool to identify factors mediating the association between exposure variables and outcomes. It has been applied to various genomic applications with the hope to gain novel insights into the underlying mechanism of various diseases. Given the high-dimensional nature of epigenetic data, recent effort on epigenetic mediation analysis is to first reduce the data dimension by applying high-dimensional variable selection techniques, then conducting testing in a low dimensional setup. In this paper, we propose to assess the mediation effect by adopting a high-dimensional testing procedure which can produce unbiased estimates of the regression coefficients and can properly handle correlations between variables. When the data dimension is ultra-high, we first reduce the data dimension from ultra-high to high by adopting a sure independence screening (SIS) method. We apply the method to two high-dimensional epigenetic studies: one is to assess how DNA methylations mediate the association between alcohol consumption and epithelial ovarian cancer (EOC) status; the other one is to assess how methylation signatures mediate the association between childhood maltreatment and post-traumatic stress disorder (PTSD) in adulthood. We compare the performance of the method with its counterpart via simulation studies. Our method can be applied to other high-dimensional mediation studies where high-dimensional mediation variables are collected.

• DNA methylation
• de-sparsify
• high-dimensional mediation
• high-dimensional testing
• mediation analysis

• childhood maltreatment
• physiological processes
• psychopathology

• Biomarkers
• Depression
• Epigenetics
• Gene-environment interactions
• Stress

Epigenetic mechanisms are potential mediators of the physiological response to abuse by altering the genetic predisposition of the cellular response to the environment, leading to changes in the regulation of multiple organ systems. This study was established to review the epigenetic mechanisms associated with childhood abuse as well as the long-term determinants that these epigenetic changes may have on future illness. We retrospectively analysed the effect of exposure to adverse childhood experiences (ACEs, specifically those relating to childhood maltreatment) between the ages of 0 and 16 years on the human epigenome, as well as possible clinical associations. After meeting inclusion and exclusion criteria, 36 articles were included in this systematic review. Eight of these studies did not find a relationship between childhood maltreatment and DNA methylation. Of the remaining 28 studies, nine were genome-wide association studies, whereas the rest were candidate gene studies, mainly studying effects on neuroendocrine, serotoninergic and immunoregulatory systems. Meta-analysis of correlation coefficients from candidate gene studies estimated an association of childhood adversity and DNA methylation variation at r = 0.291 (P < 0.0001), and meta-analysis of two epigenome-wide association studies (EWASs) identified 44 differentially methylated CpG sites. In conclusion, childhood maltreatment may mediate epigenetic mechanisms through DNA methylation, thereby affecting physiological responses and conferring a predisposition to an increased risk for psychopathology and forensic repercussions. Similar evidence for somatic illnesses is not yet available.

• DNA methylation
• Forensic sciences
• HPA axis
• child abuse
• epigenetics
• forensic genetics
• mental illness
• meta-analysis

• neuroscience
• epigenetics and behaviour

• Animals
• Animals, Newborn
• Behavior, Animal
• Brain-Derived Neurotrophic Factor/genetics
• Cytidine/analogs & derivatives
• Cytidine/pharmacology
• DNA Methylation/drug effects
• Female
• Gene Expression Regulation/drug effects
• Male
• Maternal Behavior/drug effects
• Maternal Behavior/physiology
• Maternal Behavior/psychology
• Preoptic Area/drug effects
• Rats, Long-Evans
• Sex Ratio

• P20 GM103446 NIGMS NIH HHS
• R01 HD087509 NICHD NIH HHS
• U.S. Department of Health &amp; Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

• Gut microbiota
• Intestinal permeability
• Prebiotics
• Probiotics

• environment
• epigenetics
• narrative
• review

• Wellcome Trust
• 108574 Wellcome Trust

While biological alterations associated with childhood maltreatment (CM) have been found in affected individuals, it remains unknown to what degree these alterations are biologically transmitted to the next generation. We investigated intergenerational effects of maternal CM on DNA methylation and gene expression in N = 113 mother-infant dyads shortly after parturition, additionally accounting for the role of the FKBP5 rs1360780 genotype. Using mass array spectrometry, we assessed the DNA methylation of selected stress-response-associated genes (FK506 binding protein 51 [FKBP5], glucocorticoid receptor [NR3C1], corticotropin-releasing hormone receptor 1 [CRHR1]) in isolated immune cells from maternal blood and neonatal umbilical cord blood. In mothers, CM was associated with decreased levels of DNA methylation of FKBP5 and CRHR1 and increased NR3C1 methylation, but not with changes in gene expression profiles. Rs1360780 moderated the FKBP5 epigenetic CM-associated regulation profiles in a gene × environment interaction. In newborns, we found no evidence for any intergenerational transmission of CM-related methylation profiles for any of the investigated epigenetic sites. These findings support the hypothesis of a long-lasting impact of CM on the biological epigenetic regulation of stress-response mediators and suggest for the first time that these specific epigenetic patterns might not be directly transmitted to the next generation.

• Adversity
• Built environment
• DNA methylation
• Enriched environment
• Epigenetics
• Histone modifications
• Interpersonal
• Learning
• Pain
• Parenting
• Social environment
• Stress

• DNA Methylation
• Epigenesis, Genetic
• Epigenomics
• Humans
• Memory
• Pain
• Social Environment

• Adverse Childhood Experience (ACE)
• Bisulfite sequencing
• DNA methylation
• Illumina methylation BeadChip array
• Methyl-binding pull-down
• Pediatric trauma
• Saliva cell composition

• KL2 TR000131 NCATS NIH HHS
• R01 MH096093 NIMH NIH HHS
• UL1 TR000041 NCATS NIH HHS
• UL1 TR001855 NCATS NIH HHS
• P50 GM085273 NIGMS NIH HHS

• Child abuse
• DNA hydroxymethylation
• DNA methylation
• Kappa opioid receptor
• Postmortem
• Reporter assay

• Adult
• Child
• Child Abuse
• CpG Islands
• DNA Methylation
• Epigenesis, Genetic
• Humans
• Machine Learning
• Male
• Spermatozoa/metabolism
• Young Adult

• R01 HD057368 NICHD NIH HHS
• UM1 CA176726 NCI NIH HHS
• P30 ES009089 NIEHS NIH HHS
• Robert Wood Johnson Foundation (RWJF)
• U.S. Department of Health & Human Services | NIH | Center for Information Technology (CIT)

Early-life adversity (ELA) represents a major risk factor for the development of behavioral dysfunctions and mental disorders later in life. On the other hand, dependent on type, time point, and duration, ELA exposure can also induce adaptations, which result in better stress coping and resilience later in life. Guided by the hypothesis that chronic exposure to ELA results in dysfunctional brain and behavior, whereas short exposure to ELA may result in resilience, the behavioral and neurobiological consequences of long-term separation stress (LTSS) and short-term separation stress (STSS) were compared in a mouse model for ELA. In line with our hypothesis, we found that LTSS induced depressive-like behavior, whereas STSS reduced depressive-like behavioral symptoms. We then tested the hypothesis that the opposite behavioral outcomes of the two stress paradigms may be mediated by functional, epigenetically regulated changes of dopaminergic modulation in the hippocampal formation. We found that STSS exposure elevated dopamine receptor D1 (DRD1) gene expression and decreased gene expression of its downstream modulator DARPP-32 (32-kDa dopamine- and cAMP-regulated phosphoprotein), which was paralleled by decreased H3 acetylation at its gene promoter region. In contrast, LTSS elevated DARPP-32 gene expression, which was not paralleled by changes in histone acetylation and DRD1 gene expression. These findings indicate that short- and long-term neonatal exposure to ELA induces changes in dopaminergic molecular pathways, some of which are epigenetically regulated and which either alleviate or aggravate depressive-like symptoms later in life.

• DARPP-32
• Depression
• Dopamine receptor 1
• Histone modification
• Resilience

Recent research in psychiatric genetics has led to a move away from simple diathesis-stress models to more complex models of psychopathology incorporating a focus on gene–environment interactions and epigenetics. Our increased understanding of the way biology encodes the impact of life events on organisms has also generated more sophisticated theoretical models concerning the molecular processes at the interface between “nature” and “nurture.” There is also increasing consensus that psychotherapy entails a specific type of learning in the context of an emotional relationship (i.e., the therapeutic relationship) that may also lead to epigenetic modifications across different therapeutic treatment modalities. This paper provides a systematic review of this emerging body of research. It is concluded that, although the evidence is still limited at this stage, extant research does indeed suggest that psychotherapy may be associated with epigenetic changes. Furthermore, it is argued that epigenetic studies may play a key role in the identification of biomarkers implicated in vulnerability for psychopathology, and thus may improve diagnosis and open up future research opportunities regarding the mechanism of action of psychotropic drugs as well as psychotherapy. We review evidence suggesting there may be important individual differences in susceptibility to environmental input, including psychotherapy. In addition, given that there is increasing evidence for the transgenerational transmission of epigenetic modifications in animals and humans exposed to trauma and adversity, epigenetic changes produced by psychotherapy may also potentially be passed on to the next generation, which opens up new perspective for prevention science. We conclude this paper stressing the limitations of current research and by proposing a set of recommendations for future research in this area.

• epigenetic modifications
• gene–environment interactions
• psychopathology
• psychotherapeutic change
• subjective experience

Exposure to adversity early in development alters brain and behavioral trajectories. Data continue to accumulate that epigenetic mechanisms are a mediating factor between early-life adversity and adult behavioral phenotypes. Previous work from our laboratory has shown that female Long-Evans rats exposed to maltreatment during infancy display both aberrant forced swim behavior and patterns of brain DNA methylation in adulthood. Therefore, we examined the possibility of rescuing the aberrant forced swim behavior in maltreated-adult females by administering an epigenome-modifying drug (zebularine) at a dose previously shown to normalize DNA methylation. We found that zebularine normalized behavior in the forced swim test in maltreated females such that they performed at the levels of controls (females that had been exposed to only nurturing care during infancy). These data help link DNA methylation to an adult phenotype in our maltreatment model, and more broadly provide additional evidence that non-targeted epigenetic manipulations can change behavior associated with early-life adversity.

• DNA methylation
• DNMT
• behavioral outcomes
• development
• early-life stress
• epigenetics
• females
• maltreatment

This review argues for a central role of the lateral hypothalamus in those deviant forms of aggression, which result from chronic glucocorticoid deficiency. Currently, this nucleus is considered a key region of the mechanisms that control predatory aggression. However, recent findings demonstrate that it is strongly activated by aggression in subjects with a chronically downregulated hypothalamus-pituitary-adrenocortical (HPA) axis; moreover, this activation is causally involved in the emergence of violent aggression. The review has two parts. In the first part, we review human findings demonstrating that under certain conditions, strong stressors downregulate the HPA-axis on the long run, and that the resulting glucocorticoid deficiency is associated with violent aggression including aggressive delinquency and aggression-related psychopathologies. The second part addresses neural mechanisms in animals. We show that the experimental downregulation of HPA-axis function elicits violent aggression in rodents, and the activation of the brain circuitry that originally subserves predatory aggression accompanies this change. The lateral hypothalamus is not only an integral part of this circuitry, but can elicit deviant and violent forms of aggression. Finally, we formulate a hypothesis on the pathway that connects unfavorable social conditions to violent aggression via the neural circuitry that includes the lateral hypothalamus.

• aggression
• humans
• hypothalamus
• rodents
• violence

• dna methylation
• genome-wide
• alspac
• conduct problems
• risk exposure

• Adolescent
• Age of Onset
• Child
• Child, Preschool
• Conduct Disorder/genetics
• DNA Methylation/genetics
• Epigenesis, Genetic/genetics
• Female
• Fetal Blood/metabolism
• Genome-Wide Association Study
• Humans
• Infant, Newborn
• Longitudinal Studies
• Male

• MC_UU_00011/4 Medical Research Council
• MC_UU_12013/2 Medical Research Council
• 102215 Wellcome Trust
• MC_PC_15018 Medical Research Council
• R01 HD068437 NICHD NIH HHS
• MC_UU_12013/8 Medical Research Council
• G9815508 Medical Research Council
• Wellcome Trust
• 102215/2/13/2 Wellcome Trust

• Catecholamine-O-methyl transferase
• Depression
• Epigenetics
• Methylation
• Prefrontal cortex

• DNA methylation
• adolescence
• childhood
• developmental psychopathology
• environmental risk
• epigenetics
• externalising problems
• internalising problems

• developmental plasticity
• early life effects
• gene-environment interaction
• epigenetics
• evolution of plasticity
• developmental origins of health and disease

• P01 AG031719 NIA NIH HHS
• P2C HD065563 NICHD NIH HHS
• P30 AG034424 NIA NIH HHS
• R01 AG053330 NIA NIH HHS

• Adolescent
• Brain-derived neurotrophic factor (BDNF)
• Cognitive inflexibility
• Epigenetic mechanism
• Social stress

• Cardiometabolic disease
• Childhood adversity
• DNA methylation

• Adolescent
• Adult
• Adverse Childhood Experiences
• Anxiety/genetics
• Child
• CpG Islands
• DNA Methylation
• Epigenesis, Genetic
• Female
• Genetic Association Studies
• Genetic Predisposition to Disease
• Humans
• Introns
• Longitudinal Studies
• Male
• Prospective Studies
• Receptors, Oxytocin/genetics
• Sequence Analysis, DNA
• Sex Factors
• Stress, Psychological/genetics
• Young Adult

• CIHR

• BDNF
• Bipolar disorder
• Childhood trauma
• Serotonin promoter