1   704 150 BUILDING RESILIENCE AGAINST THE SEQUELAE OF ADVERSE CHILDHOOD EXPERIENCES: RISE UP, CHANGE YOUR LIFE, AND REFORM HEALTH CARE. A REFORMED APPROACH TO HEALTH CARE TACKLES HEALTH AT ITS ROOTS. ADVERSE CHILDHOOD EXPERIENCES (ACES) IN THOSE EXPOSED TO THEM MAY CONTRIBUTE SIGNIFICANTLY TO THE ROOT CAUSES OF MANY DISEASES OF LIFESTYLE. ACES ARE TRAUMATIC EXPERIENCES, SUCH AS PHYSICAL AND EMOTIONAL ABUSE AND EXPOSURE TO RISKY FAMILY ENVIRONMENTS. IN 1998, A GROUND-BREAKING STUDY FOUND THAT NEARLY 70% OF AMERICANS EXPERIENCE AT LEAST 1 ACE IN THEIR LIFETIME, AND GRADED EXPOSURE IS ASSOCIATED WITH THE PRESENCE OF MENTAL HEALTH DISORDERS, HEART DISEASE, CANCER, AND OTHER CHRONIC DISEASES. OVER THE PAST 20 YEARS, EVIDENCE HAS DEMONSTRATED FURTHER DISEASE RISK, OUTCOMES, AND EPIGENETIC UNDERPINNINGS IN CHILDREN AND ADULTS WITH ACES. BUILDING RESILIENCE-THE CAPACITY TO ADAPT IN HEALTHY WAYS TO TRAUMATIC EXPERIENCES-THROUGH LIFESTYLE MODIFICATION OFFERS POTENTIAL TO COMBAT THE NEGATIVE HEALTH EFFECTS ASSOCIATED WITH ACES. EMERGING RESEARCH DEMONSTRATES RESILIENCE IS CULTIVATED THROUGH INDIVIDUAL SKILLS (EMOTIONAL INTELLIGENCE, COPING, AND FOSTERING HEALTHY LIFESTYLE CHOICES), AND NURTURING SUPPORTIVE RELATIONSHIPS. BEING MINDFUL OF THE IMPACT AND PREVALENCE OF ACES AND DIVERSITY OF INDIVIDUALS' EXPERIENCES IN SOCIETY WILL HELP BUILD RESILIENCE AND COMBAT THE ROOT CAUSE OF CHRONIC DISEASE. THIS REVIEW AIMS TO CULTIVATE THAT AWARENESS AND WILL DISCUSS 3 OBJECTIVES: TO DISCUSS THE EFFECTS AND HYPOTHESIZED PATHOPHYSIOLOGICAL UNDERPINNINGS OF TRAUMATIC EXPERIENCES IN CHILDHOOD ON HEALTH AND WELLBEING THROUGHOUT LIFE, TO PRESENT WAYS WE CAN PROMOTE RESILIENCE IN OUR DAILY LIVES AND PATIENT ENCOUNTERS, AND TO DEMONSTRATE HOW ADVOCACY FOR THE REDUCTION OF ACES AND PROMOTION OF RESILIENT, TRAUMA-INFORMED ENVIRONMENTS ARE FUNDAMENTAL TO HEALTH CARE REFORM.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
2  1221  43 CRITICAL CONNECTIONS AMONG EMBEDDING OF CHILDHOOD ADVERSITY AND ADULT CHRONIC GASTROINTESTINAL AND GENITOURINARY DISORDERS: A REVIEW OF THE LITERATURE. BACKGROUND: A GAP IN THE LITERATURE EXISTS DEMONSTRATING ASSOCIATIONS BETWEEN ADVERSE CHILD EXPERIENCES (ACES) AS POTENTIAL A PRIORI CONTRIBUTING FACTORS AND GASTROINTESTINAL (GI)/GENITOURINARY (GU) DISORDERS. PURPOSE: A NARRATIVE REVIEW OF THE LITERATURE WAS CONDUCTED TO EXPLORE CRITICAL CONNECTIONS BETWEEN ACES AND GI/GU DISORDERS WITH A WORKING HYPOTHESIS OF A DOSE-RESPONSIVE RELATIONSHIP EXISTING AMONG THEM. METHODS: A LITERATURE SEARCH WAS CONDUCTED USING MEDLINE, CUMULATIVE INDEX OF NURSING AND ALLIED HEALTH LITERATURE, PUBMED, AND WEB OF SCIENCE USING SEARCH TERMS ADVERSE CHILDHOOD EXPERIENCES, CHILDHOOD ADVERSITY, OBESITY, GASTROINTESTINAL DISORDERS, AND GENITOURINARY DISORDERS, AND SECONDARY SEARCHES OF OBESITY AND SPECIFIC GI/GU DISORDERS (EG, IRRITABLE BOWEL SYNDROME, PELVIC PAIN). DUPLICATES AND ARTICLES WITH INAPPROPRIATE FOCUS WERE DISCARDED AFTER REVIEW. RESULTS: A TOTAL OF 58 ARTICLES WERE INCLUDED. RESEARCH IDENTIFIED SHOWED THAT ACES DO PLAY A ROLE IN ADULT GI AND GU MORBIDITIES IN A DOSE-RESPONSE MANNER, AND SELECTED FACTORS SUCH AS SOCIOECONOMIC STATUS, RACE, GENDER IDENTITY, AND PHYSIOLOGIC STATE (EG, OBESITY) CONFER HIGHER RISK. RESEARCH ALSO SUGGESTED THAT GENETIC/EPIGENETIC MECHANISMS ARE AT PLAY IN DISEASE OCCURRENCE, AND THE IMPACT OF ACES MAY BE MITIGATED WITH POSITIVE LIFE EXPERIENCES. CONCLUSION: RESEARCH ON THE RELATIONSHIP BETWEEN ACES AND GI/GU DISORDERS IS HETEROGENEOUS, NOTABLY DUE TO WIDE VARIATIONS IN HOW TYPES OF ACES ARE DEFINED AND SCREENING METHODS USED. DESPITE THIS LIMITATION, ASSOCIATIONS ARE DEMONSTRATED. AWARENESS OF A POSSIBLE CORRELATION BETWEEN ACES AND RISK OF GI/GU DISORDERS HAS THE POTENTIAL TO IMPROVE PATIENT CARE, ESPECIALLY THROUGH TRAUMA-INFORMED STRATEGIES.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
3    92  30 A PILOT STUDY INVESTIGATING THE ROLE OF GENDER IN THE INTERGENERATIONAL RELATIONSHIPS BETWEEN GENE EXPRESSION, CHRONIC PAIN, AND ADVERSE CHILDHOOD EXPERIENCES IN A CLINICAL SAMPLE OF YOUTH WITH CHRONIC PAIN. CHRONIC PAIN IS A HIGHLY PREVALENT AND COSTLY ISSUE THAT OFTEN EMERGES DURING CHILDHOOD OR ADOLESCENCE AND PERSISTS INTO ADULTHOOD. ADVERSE CHILDHOOD EXPERIENCES (ACES) INCREASE RISK FOR SEVERAL ADVERSE HEALTH CONDITIONS, INCLUDING CHRONIC PAIN. RECENT EVIDENCE SUGGESTS THAT PARENTAL TRAUMA (ACES, POST-TRAUMATIC STRESS DISORDER (PTSD) SYMPTOMS) CONFERS RISK OF POOR HEALTH OUTCOMES IN THEIR CHILDREN. INTERGENERATIONAL RELATIONSHIPS BETWEEN PARENTAL TRAUMA AND CHILD CHRONIC PAIN MAY BE MEDIATED BY EPIGENETIC MECHANISMS. A CLINICAL SAMPLE OF YOUTH WITH CHRONIC PAIN AND THEIR PARENTS COMPLETED PSYCHOMETRICALLY SOUND QUESTIONNAIRES ASSESSING ACES, PTSD SYMPTOMS, AND CHRONIC PAIN, AND PROVIDED A SALIVA SAMPLE. THESE WERE USED TO INVESTIGATE THE INTERGENERATIONAL RELATIONSHIPS BETWEEN FOUR EPIGENETIC BIOMARKERS (COMT, DRD2, GR, AND SERT), TRAUMA, AND CHRONIC PAIN. THE RESULTS INDICATED THAT THE SIGNIFICANT BIOMARKERS WERE DEPENDENT UPON THE GENDER OF THE CHILD, WHEREIN PARENTAL ACES SIGNIFICANTLY CORRELATED WITH CHANGES IN DRD2 EXPRESSION IN FEMALE CHILDREN AND ALTERED COMT EXPRESSION IN THE PARENTS OF MALE CHILDREN. ADDITIONALLY, THE NATURE OF THE ACE (MALTREATMENT VS. HOUSEHOLD DYSFUNCTION) WAS ASSOCIATED WITH THE SPECIFIC EPIGENETIC CHANGES. THERE MAY BE DIFFERENT PATHWAYS THROUGH WHICH PARENTAL ACES CONFER RISK FOR POOR OUTCOMES FOR MALES AND FEMALES, HIGHLIGHTING THE IMPORTANCE OF CHILD GENDER IN FUTURE INVESTIGATIONS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
4  1151  37 CONNECTIONS AMONG BIOLOGIC EMBEDDING OF CHILDHOOD ADVERSITY, ADULT CHRONIC ILLNESS, AND WOUND CARE: A REVIEW OF THE LITERATURE. ADVERSE CHILDHOOD EXPERIENCES (ACES) BIOLOGICALLY EMBED BY ALTERING BRAIN DEVELOPMENT AND INFLUENCING EPIGENETIC MECHANISMS. THESE EXPERIENCES MAY GENERATE HEALTH RISK FACTORS. PURPOSE: A LITERATURE REVIEW WAS CONDUCTED TO COMPARE ACE-GENERATED HEALTH RISK FACTORS WITH RISK FACTORS FOR WOUND DEVELOPMENT AND ABERRANT HEALING, AS WELL AS TO IDENTIFY A GAP IN LITERATURE REGARDING CRITICAL CONNECTIONS BETWEEN ACES, CHRONIC ILLNESS, AND WOUND DEVELOPMENT/HEALING, WITH ASSOCIATED PRACTICE IMPLICATIONS. METHODOLOGY: A LITERATURE SEARCH OF ENGLISH-LANGUAGE ARTICLES WAS CONDUCTED USING THE CUMULATIVE INDEX OF NURSING AND ALLIED HEALTH LITERATURE, MEDLINE, AND PUBMED USING THE SEARCH TERMS ADVERSE CHILDHOOD EXPERIENCES, ADULTS, WOUNDS, CHRONIC DISEASE OR ILLNESS, AND EPIGENETICS. THE SEARCHES YIELDED 561 PUBLICATIONS REGARDING ACES, CHRONIC ILLNESS OR DISEASE, AND ADULT; 182 FOR ACES; AND 547 FOR EPIGENETICS AND WOUNDS. ABSTRACTS WERE REVIEWED TO REMOVE DUPLICATES AND STUDIES WITH PARTICIPANTS WHO WERE <18 YEARS OLD. PUBLICATIONS WERE REVIEWED FOR SALIENCE; THOSE DISCUSSING THE BIOLOGIC PLAUSIBILITY OF ACES CONTRIBUTING TO ADULT ILLNESSES AND ASSOCIATED WOUND DEVELOPMENT AND HEALING WERE REVIEWED FOR INCLUSION. RESULTS: SIXTY-EIGHT (68) PUBLICATIONS WERE FOUND APPROPRIATE FOR REVIEW AND INCLUDED POPULATION-BASED STUDIES; LITERATURE REVIEWS; EPIDEMIOLOGIC DATA; META-ANALYSES; AND SYSTEMATIC, CROSS-SECTIONAL, OBSERVATIONAL, AND PROSPECTIVE STUDIES AS SINGULAR OR MIXED METHODS DESIGNS. A SUBSTANTIAL OVERLAP WAS FOUND IN TERMS OF RISK FACTORS GENERATED BY ACE EXPOSURE AND RISK FACTORS FOR WOUND DEVELOPMENT/HEALING, AS WAS A GAP IN THE LITERATURE REGARDING THIS RELATIONSHIP. EPIGENETIC MECHANISMS AND ALTERED BRAIN DEVELOPMENT ARE IMPLICATED IN PROCESSES THROUGH WHICH CHILDHOOD ADVERSITY ERODES HUMAN HEALTH. CONCLUSION: ADULT HEALTH RISKS AS A RESULT OF EXPOSURE TO ACES AND CRITICAL CONNECTIONS WITH RISKS FOR WOUND DEVELOPMENT AND DISRUPTED WOUND HEALING VIA EPIGENETIC INFLUENCES ARE RECOGNIZED IN THE LITERATURE. PRACTICE IMPLICATIONS INCLUDE CONSIDERING SCREENING FOR THE RISK FACTOR OF ACES EXPOSURE IN ADULT PATIENTS TO IDENTIFY THIS ADDITIONAL RISK FACTOR AND PRACTICING PATIENT-CENTERED, TRAUMA-INFORMED CARE. FURTHER RESEARCH INTO THE INTEGRATIVE ROLES OF THESE FACTORS IS WARRANTED.	2019	
                                                                                                                                                                                                                                                                                          
5  1696  31 DYNAMIC DNA METHYLATION CHANGES IN EARLY VERSUS LATE ADULTHOOD SUGGEST NONDETERMINISTIC EFFECTS OF CHILDHOOD ADVERSITY: A META-ANALYSIS. ADVERSE CHILDHOOD EXPERIENCES (ACES) ARE ASSOCIATED WITH A HIGH RISK OF DEVELOPING CHRONIC DISEASES AND DECREASED LIFE EXPECTANCY, BUT NO ACE EPIGENETIC BIOMARKERS HAVE BEEN IDENTIFIED UNTIL NOW. THE LATTER MAY RESULT FROM THE INTERACTION OF MULTIPLE FACTORS SUCH AS AGE, SEX, DEGREE OF ADVERSITY, AND LACK OF TRANSCRIPTIONAL EFFECTS OF DNA METHYLATION CHANGES. WE HYPOTHESIZE THAT DNA METHYLATION CHANGES ARE RELATED TO CHILDHOOD ADVERSITY LEVELS AND CURRENT AGE, AND THESE MARKERS EVOLVE AS AGING PROCEEDS. TWO GENE EXPRESSION OMNIBUS DATASETS, REGARDING ACE, WERE SELECTED (GSE72680 AND GSE70603), CONSIDERING RAW- AND META-DATA AVAILABILITY, INCLUDING VALIDATED ACE INDEX (CHILDHOOD TRAUMA QUESTIONNAIRE (CTQ) SCORE). FOR DNA METHYLATION, ANALYZED PROBES WERE RESTRICTED TO THOSE LAYING WITHIN PROMOTERS AND FIRST EXONS, AND SAMPLES WERE GROUPED BY CTQ SCORES TERCILES, TO COMPARE HIGHLY (ACE) WITH NON-ABUSED (CONTROL) CASES. COMPARISON OF CONTROL AND ACE METHYLOME PROFILE DID NOT RETRIEVE DIFFERENTIALLY METHYLATED CPG SITES (DMCS) AFTER CORRECTING BY FALSE DISCOVERY RATE < 0.05, AND THIS WAS ALSO OBSERVED WHEN SAMPLES WERE SEPARATED BY SEX. IN CONTRAST, GROUPING BY DECADE AGE RANGES (I.E., THE 20S, 30S, 40S, AND 50S) SHOWED A PROGRESSIVE INCREASE IN THE NUMBER OF DMCS AND THE INTENSITY OF CHANGES, MAINLY RELATED WITH HYPOMETHYLATION. COMPARISON WITH TRANSCRIPTOME DATA FOR ACE SUBJECTS IN THE 40S, AND 50S SHOWED A SIMILAR AGE-DEPENDENT EFFECT. THIS STUDY PROVIDES EVIDENCE THAT EPIGENETIC MARKERS OF ACE ARE AGE-DEPENDENT, BUT NOT DEFINED IN THE LONG TERM. THESE DIFFERENCES AMONG EARLY, MIDDLE, AND LATE ADULTHOOD EPIGENOMIC PROFILES SUGGEST A WINDOW FOR INTERVENTIONS AIMED TO PREVENT THE DETRIMENTAL EFFECTS OF ACE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
6  2153  24 EPIGENETIC MECHANISMS ACTIVATED BY CHILDHOOD ADVERSITY. ADVERSE CHILDHOOD EXPERIENCES (ACE) IMPAIR HEALTH AND LIFE EXPECTANCY AND MAY RESULT IN AN EPIGENETIC SIGNATURE THAT DRIVES INCREASED MORBIDITY PRIMED DURING EARLY STAGES OF LIFE. THIS LITERATURE REVIEW FOCUSES ON THE CURRENT EVIDENCE FOR EPIGENETIC-MEDIATED PROGRAMMING OF BRAIN AND IMMUNE FUNCTION RESULTING FROM ACE. TO ADDRESS THIS AIM, A TOTAL OF 88 ARTICLES INDEXED IN PUBMED BEFORE AUGUST 2019 CONCERNING ACE AND EPIGENETICS WERE SURVEYED. CURRENT EVIDENCE PARTIALLY SUPPORTS EPIGENETIC PROGRAMMING OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS, BUT CONVINCINGLY SHOWS THAT ACE IMPAIRS IMMUNE FUNCTION. ADDITIONALLY, THE NEEDS AND CHALLENGES THAT FACE THIS AREA ARE DISCUSSED IN ORDER TO PROVIDE A FRAMEWORK THAT MAY HELP TO CLARIFY THE ROLE OF EPIGENETICS IN THE LONG-LASTING EFFECTS OF ACE.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
7  5160  35 PREADOLESCENT ADVERSITY PROGRAMS A DISRUPTED MATERNAL STRESS REACTIVITY IN HUMANS AND MICE. BACKGROUND: ADVERSE CHILDHOOD EXPERIENCES (ACES) ARE ONE OF THE GREATEST PREDICTORS OF AFFECTIVE DISORDERS FOR WOMEN. PERIODS OF DYNAMIC HORMONAL FLUX, INCLUDING PREGNANCY, EXACERBATE THE RISK FOR AFFECTIVE DISTURBANCE AND PROMOTE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS DYSREGULATION, A KEY FEATURE OF AFFECTIVE DISORDERS. LITTLE IS UNDERSTOOD AS TO HOW STRESS EXPERIENCED IN LATE CHILDHOOD, DEFINED AS PREADOLESCENCE, ALTERS THE PROGRAMMING UNIQUE TO THIS PERIOD OF BRAIN MATURATION AND ITS INTERACTION WITH THE HORMONAL CHANGES OF PREGNANCY AND POSTPARTUM. METHODS: PREADOLESCENT FEMALE MICE WERE EXPOSED TO CHRONIC STRESS AND EXAMINED FOR CHANGES IN THEIR HPA AXIS DURING PREGNANCY AND POSTPARTUM, INCLUDING ASSESSMENT OF MATERNAL-SPECIFIC STRESS RESPONSIVENESS AND TRANSCRIPTOMICS OF THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS. TRANSLATIONALLY, PREGNANT WOMEN WITH LOW OR HIGH ACES WERE EXAMINED FOR THEIR MATERNAL STRESS RESPONSIVENESS. RESULTS: AS PREDICTED, PREADOLESCENT STRESS IN MICE RESULTED IN A SIGNIFICANT BLUNTING OF THE CORTICOSTERONE RESPONSE DURING PREGNANCY. TRANSCRIPTOMIC ANALYSIS OF THE PARAVENTRICULAR NUCLEUS REVEALED WIDESPREAD CHANGES IN EXPRESSION OF IMMEDIATE EARLY GENES AND THEIR TARGETS, SUPPORTING THE LIKELY INVOLVEMENT OF AN UPSTREAM EPIGENETIC MECHANISM. CRITICALLY, IN OUR HUMAN STUDIES, THE HIGH ACE WOMEN SHOWED A SIGNIFICANT BLUNTING OF THE HPA RESPONSE. CONCLUSIONS: THIS UNIQUE MOUSE MODEL RECAPITULATES A CLINICAL OUTCOME OF A HYPORESPONSIVE HPA STRESS AXIS, AN IMPORTANT FEATURE OF AFFECTIVE DISORDERS, DURING A DYNAMIC HORMONAL PERIOD, AND SUGGESTS INVOLVEMENT OF TRANSCRIPTIONAL REGULATION IN THE HYPOTHALAMUS. THESE STUDIES IDENTIFY A NOVEL MOUSE MODEL OF FEMALE ACES THAT CAN BE USED TO EXAMINE HOW ADDITIONAL LIFE ADVERSITY MAY PROVOKE DISEASE RISK OR RESILIENCE.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
8   393  18 AN OVERVIEW OF EPIGENETICS IN NURSING. EPIGENETIC CHANGES TO THE GENOME ARE BIOCHEMICAL ALTERATIONS TO THE DNA THAT DO NOT CHANGE AN INDIVIDUAL'S GENOME BUT DO CHANGE AND INFLUENCE GENE EXPRESSION. THE NURSING PROFESSION IS QUALIFIED TO CONDUCT AND INTEGRATE EPIGENETIC-FOCUSED NURSING RESEARCH INTO PRACTICE. THIS ARTICLE DISCUSSES CURRENT EPIGENETIC NURSING RESEARCH, PROVIDES AN OVERVIEW OF HOW EPIGENETIC RESEARCH RELATES TO NURSING PRACTICE, MAKES RECOMMENDATIONS, AND PROVIDES EPIGENETIC ONLINE RESOURCES FOR NURSING RESEARCH. AN OVERVIEW OF MAJOR EPIGENETIC STUDIES IN NURSING (SPECIFIC TO CHILDBIRTH STUDIES, PREECLAMPSIA, METABOLIC SYNDROME, IMMUNOTHERAPY CANCER, AND PAIN) IS PROVIDED, WITH RECOMMENDATIONS ON NEXT STEPS.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
9  1058  27 CLINICAL MEASURES OF ALLOSTATIC LOAD IN CHILDREN AND ADOLESCENTS WITH FOOD ALLERGY, DEPRESSION, OR ANXIETY. PURPOSE: SUSTAINED HIGH STRESS EXPOSURE RESULTS IN CHRONIC ACTIVATION OF THE STRESS RESPONSE SYSTEM, DYSREGULATED STRESS RESPONSES, HIGH ALLOSTATIC LOAD, AND POOR LATER-LIFE HEALTH. CHILDREN AND ADOLESCENTS WITH CHRONIC HEALTH CONDITIONS FACE STRESSORS RELATED TO THEIR CONDITION IN ADDITION TO THOSE TYPICAL OF CHILDHOOD AND ADOLESCENCE, PLACING THEM AT RISK OF HIGH ALLOSTATIC LOAD. THE PURPOSE OF THIS SECONDARY ANALYSIS WAS TO EXAMINE WHETHER YOUTH WITH CHRONIC HEALTH CONDITIONS DIFFER FROM CONTROLS ON CLINICAL MEASURES OF ALLOSTATIC LOAD. DESIGN AND METHODS: A SECONDARY ANALYSIS OF TWO DATASETS, THE ELECTRONIC HEALTH RECORD OF A TERTIARY CHILDREN'S HOSPITAL AND DATA FROM THE SURVEY OF THE HEALTH OF WISCONSIN, COMPARED YOUTH WITH CHRONIC HEALTH CONDITIONS TO CONTROLS ON CLINICAL MEASURES OF ALLOSTATIC LOAD. ADDITIONAL ANALYSES EXPLORED WHETHER PARENTAL STRESS AND MENTAL HEALTH INFLUENCED THESE RELATIONSHIPS. RESULTS: ANALYSES IDENTIFIED DIFFERENCES IN BMI, BLOOD PRESSURE, AND WAIST CIRCUMFERENCE BETWEEN YOUTH WITH FOOD ALLERGY, ANXIETY, OR DEPRESSION, AND CONTROLS. THESE RELATIONSHIPS DIFFERED FOR MALES AND FEMALES AND FOR THOSE WITH COMORBID MENTAL AND PHYSICAL CONDITIONS, AND WERE INFLUENCED BY PARENT STRESS AND MENTAL HEALTH. CONCLUSIONS: RESULTS SUPPORT FUTURE STUDIES EXPLORING WHETHER HIGH STRESS IN YOUTH WITH CHRONIC HEALTH CONDITIONS LEADS TO INCREASED ALLOSTATIC LOAD. INCORPORATING BIOMARKERS AS WELL AS GENETIC AND EPIGENETIC FACTORS WILL PROVIDE CRITICAL INSIGHTS. PRACTICE IMPLICATIONS: YOUTH WITH MENTAL AND PHYSICAL CHCS MAY BE AT INCREASED RISK OF HIGH ALLOSTATIC LOAD, REFLECTED IN CLINICAL MEASURES OF METABOLISM, AND SHOULD HAVE REGULAR ASSESSMENTS OF THEIR METABOLIC HEALTH.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
10  1746  23 EARLY LIFE ADVERSITY, PUBERTAL TIMING, AND EPIGENETIC AGE ACCELERATION IN ADULTHOOD. BACKGROUND: GIVEN ASSOCIATIONS LINKING EARLY LIFE ADVERSITY, PUBERTAL TIMING, AND BIOLOGICAL AGING, WE EXAMINED THE DIRECT AND INDIRECT EFFECTS OF EARLY LIFE TRAUMA ON ADULT BIOLOGICAL AGING (VIA AGE OF MENARCHE). METHODS: PARTICIPANTS WERE PREMENOPAUSAL WOMEN (N = 183). PATH MODELS EVALUATED WHETHER EARLY LIFE TRAUMA PREDICTED EARLY PUBERTAL TIMING AND THEREBY, ADULT EPIGENETIC AGE ACCELERATION (INDEXED VIA FOUR EPIGENETIC CLOCKS: HORVATH DNAM AGE, HANNUM DNAM AGE, DNAM PHENOAGE, AND DNAM GRIMAGE). SECONDARY ANALYSES EXPLORED THE EFFECTS OF TYPE OF TRAUMA (ABUSE AND NEGLECT) AND ADULT CHRONIC STRESS STATUS (CAREGIVER OF CHILD WITH AUTISM AND NON-CAREGIVER). RESULTS: EARLY LIFE TRAUMA AND EARLIER AGE AT MENARCHE INDEPENDENTLY PREDICTED ACCELERATED AGING BASED ON ONE OF THE FOUR EPIGENETIC CLOCKS, DNAM GRIMAGE, THOUGH EARLY LIFE TRAUMA WAS NOT ASSOCIATED WITH AGE OF MENARCHE. CHILDHOOD ABUSE, BUT NOT NEGLECT, PREDICTED FASTER EPIGENETIC AGING; RESULTS DID NOT DIFFER BY CHRONIC STRESS STATUS. CONCLUSIONS: EARLY TRAUMA AND EARLY MENARCHE APPEAR TO EXERT INDEPENDENT EFFECTS ON DNAM GRIMAGE, WHICH HAS BEEN SHOWN TO BE THE STRONGEST EPIGENETIC PREDICTOR OF MORTALITY RISK. THIS STUDY IDENTIFIES A POTENTIAL CORRELATE OR DETERMINANT OF ACCELERATED EPIGENETIC AGING-MENARCHEAL AGE. FUTURE RESEARCH SHOULD ADDRESS THE LIMITATIONS OF THIS STUDY BY USING RACIALLY DIVERSE SAMPLES.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
11  6478  34 TOPICAL REVIEW: THE EMERGING FIELD OF EPIGENETICS: INFORMING MODELS OF PEDIATRIC TRAUMA AND PHYSICAL HEALTH. OBJECTIVE: TRAUMA EXPERIENCED DURING CHILDHOOD AND ADOLESCENCE HAS BEEN LINKED TO A NUMBER OF CHRONIC MEDICAL CONCERNS. WE HIGHLIGHT MAJOR FINDINGS FROM THE PEDIATRIC TRAUMA LITERATURE TO PROVIDE A MODEL FOR UNDERSTANDING THIS ASSOCIATION. METHODS: STUDIES EXAMINING THE EFFECTS OF TRAUMA WERE SYSTEMATICALLY REVIEWED AND SYNTHESIZED INTO A MODEL PROPOSING A CENTRAL ROLE FOR EPIGENETICS IN THE WAYS THAT CHILDHOOD EXPERIENCES CAN AFFECT HEALTH. RESULTS: EARLY HYPOTHALAMIC PITUITARY ADRENAL (HPA) AXIS RESPONSE MAY IMPACT INITIAL TRAUMA EXPERIENCE, WITH DOWNSTREAM EFFECTS ON POSTTRAUMA ADJUSTMENT REFLECTED IN POSTTRAUMA NEUROBIOLOGY, PSYCHOLOGICAL HEALTH, AND PHYSICAL HEALTH. CONCLUSIONS: PROSPECTIVE RESEARCH WITH CHILDREN AND ADOLESCENTS EXPOSED TO TRAUMA IS NEEDED TO BETTER CHARACTERIZE THE GENETIC AND EPIGENETIC INFLUENCES ON THE COURSE OF HPA AND IMMUNE PROCESSES AS RELATED TO POSTTRAUMA PSYCHOLOGICAL AND PHYSICAL HEALTH OUTCOMES.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
12  5169  33 PRECONCEPTIONAL STRESS AND RACIAL DISPARITIES IN PRETERM BIRTH: AN OVERVIEW. OBJECTIVE: WE REVIEWED THE EVIDENCE FOR THREE THEORIES OF HOW PRECONCEPTIONAL PSYCHOSOCIAL STRESS COULD ACT AS A CONTRIBUTING DETERMINANT OF EXCESS PRETERM BIRTH RISK AMONG AFRICAN AMERICAN WOMEN: EARLY LIFE DEVELOPMENTAL PLASTICITY AND EPIGENETIC PROGRAMMING OF ADULT NEUROENDOCRINE SYSTEMS; BLUNTING, WEATHERING, OR DYSFUNCTION OF NEUROENDOCRINE AND IMMUNE FUNCTION IN RESPONSE TO CHRONIC STRESS ACTIVATION THROUGH THE LIFE COURSE; INDIVIDUALS' ADOPTION OF RISKY BEHAVIORS SUCH AS SMOKING AS A RESPONSE TO STRESSFUL STIMULI. METHODS: BASIC SCIENCE, CLINICAL, AND EPIDEMIOLOGIC STUDIES INDEXED IN MEDLINE AND WEB OF SCIENCE DATABASES ON PRECONCEPTIONAL PSYCHOSOCIAL STRESS, PRETERM BIRTH AND RACE WERE REVIEWED. RESULTS: MIXED EVIDENCE LEANS TOWARDS MODEST ASSOCIATIONS BETWEEN PRECONCEPTIONAL CHRONIC STRESS AND PRETERM BIRTH (FOR EXAMPLE COMMON ODDS RATIOS OF 1.2-1.4), PARTICULARLY IN AFRICAN AMERICAN WOMEN, BUT IT IS UNCLEAR WHETHER THIS ASSOCIATION IS CAUSAL OR EXPLAINS A SUBSTANTIAL PORTION OF THE BLACK-WHITE RACIAL DISPARITY IN PRETERM BIRTH. THE STRESS-PRETERM BIRTH ASSOCIATION MAY BE MEDIATED BY HYPOTHALAMIC-PITUITARY-ADRENAL AXIS DYSFUNCTION AND SUSCEPTIBILITY TO BACTERIAL VAGINOSIS, ALTHOUGH THESE MECHANISMS ARE INCOMPLETELY UNDERSTOOD. EVIDENCE FOR THE ROLE OF EPIGENETIC OR EARLY LIFE PROGRAMMING AS A DETERMINANT OF RACIAL DISPARITIES IN PRETERM BIRTH RISK IS MORE CIRCUMSTANTIAL. CONCLUSIONS: PRECONCEPTIONAL STRESS, DIRECTLY OR IN INTERACTION WITH HOST GENETIC SUSCEPTIBILITY OR INFECTION, REMAINS AN IMPORTANT HYPOTHESIZED RISK FACTOR FOR UNDERSTANDING AND REDUCING RACIAL DISPARITIES IN PRETERM BIRTH. FUTURE STUDIES THAT INTEGRATE ADEQUATELY SIZED EPIDEMIOLOGIC SAMPLES WITH MEASURES OF STRESS, INFECTION, AND GENE EXPRESSION, WILL ADVANCE OUR KNOWLEDGE AND ALLOW DEVELOPMENT OF TARGETED INTERVENTIONS.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
13  1971  35 EPIGENETIC ALTERATIONS ASSOCIATED WITH CHILDHOOD TRAUMA AND ADULT MENTAL HEALTH OUTCOMES: A SYSTEMATIC REVIEW. OBJECTIVES: MULTIPLE, CHRONIC AND REPEATED TRAUMA EXPOSURE IN CHILDHOOD IS ASSOCIATED WITH ADVERSE MENTAL HEALTH OUTCOMES IN ADULTHOOD. IN THIS PAPER WE SYNTHESISE THE LITERATURE ON EPIGENETIC MODIFICATIONS IN CHILDHOOD TRAUMA (CT) AND THE MEDIATING EFFECTS OF DIFFERENTIAL EPIGENETIC MECHANISMS ON THE ASSOCIATION BETWEEN CT AND THE LATER ONSET OF PSYCHIATRIC DISORDERS.METHODS: WE REVIEWED THE LITERATURE UP TO MARCH 2018 IN FOUR DATABASES: PUBMED, WEB OF SCIENCE, EBSCOHOST AND SCOPUS. NON-HUMAN STUDIES WERE EXCLUDED. ALL STUDIES INVESTIGATING CT EXPOSURE BOTH IN HEALTHY ADULTS (18 YEARS AND OLDER) AND ADULTS WITH PSYCHIATRIC DISORDERS WERE INCLUDED.RESULTS: THIRTY-SIX PUBLICATIONS WERE INCLUDED. FOR MOOD DISORDERS, METHYLATION OF THE GLUCOCORTICOID RECEPTOR NR3C1 GENE, SPECIFICALLY AT THE NGFI-A BINDING SITE IN EXON 1F, AND CORRELATION WITH CT WAS A ROBUST FINDING. SEVERAL STUDIES DOCUMENTED DIFFERENTIAL METHYLATION OF SLC6A4, BDNF, OXTR AND FKBP5 IN ASSOCIATION WITH CT. COMMON PATHWAYS IDENTIFIED INCLUDE NEURONAL FUNCTIONING AND MAINTENANCE, IMMUNE AND INFLAMMATORY PROCESSES, CHROMATIN AND HISTONE MODIFICATION, AND TRANSCRIPTION FACTOR BINDING.CONCLUSIONS: A VARIETY OF EPIGENETIC MEDIATORS THAT LIE ON A COMMON PATHWAY BETWEEN CT AND PSYCHIATRIC DISORDERS HAVE BEEN IDENTIFIED, ALTHOUGH LONGITUDINAL STUDIES AND CONSISTENCY IN METHODOLOGICAL APPROACH ARE NEEDED TO DISENTANGLE CAUSE AND EFFECT ASSOCIATIONS.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
14  2725  35 EXPERIENCES OF TRAUMA AND DNA METHYLATION PROFILES AMONG AFRICAN AMERICAN MOTHERS AND CHILDREN. POTENTIALLY TRAUMATIC EXPERIENCES HAVE BEEN ASSOCIATED WITH CHRONIC DISEASES. EPIGENETIC MECHANISMS, INCLUDING DNA METHYLATION (DNAM), HAVE BEEN PROPOSED AS AN EXPLANATION FOR THIS ASSOCIATION. WE EXAMINED THE ASSOCIATION OF EXPERIENCES OF TRAUMA WITH EPIGENOME-WIDE DNAM AMONG AFRICAN AMERICAN MOTHERS (N = 236) AND THEIR CHILDREN AGED 3-5 YEARS (N = 232; N = 500), USING THE LIFE EVENTS CHECKLIST-5 (LEC) AND TRAUMATIC EVENTS SCREENING INVENTORY-PARENT REPORT REVISED (TESI-PRR). WE IDENTIFIED NO DNAM SITES SIGNIFICANTLY ASSOCIATED WITH POTENTIALLY TRAUMATIC EXPERIENCE SCORES IN MOTHERS. ONE CPG SITE ON THE ENOX1 GENE WAS METHYLOME-WIDE-SIGNIFICANT IN CHILDREN (FDR-CORRECTED Q-VALUE = 0.05) FROM THE TESI-PRR. THIS PROTEIN-CODING GENE IS ASSOCIATED WITH MENTAL ILLNESS, INCLUDING UNIPOLAR DEPRESSION, BIPOLAR, AND SCHIZOPHRENIA. FUTURE RESEARCH SHOULD FURTHER EXAMINE THE ASSOCIATIONS BETWEEN CHILDHOOD TRAUMA, DNAM, AND HEALTH OUTCOMES AMONG THIS UNDERSTUDIED AND HIGH-RISK GROUP. FINDINGS FROM SUCH LONGITUDINAL RESEARCH MAY INFORM CLINICAL AND TRANSLATIONAL APPROACHES TO PREVENT ADVERSE HEALTH OUTCOMES ASSOCIATED WITH EPIGENETIC CHANGES.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
15  6315  32 THE RELATIONSHIP OF MATERNAL AND CHILD METHYLATION OF THE GLUCOCORTICOID RECEPTOR NR3C1 DURING EARLY CHILDHOOD AND SUBSEQUENT CHILD PSYCHOPATHOLOGY AT SCHOOL-AGE IN THE CONTEXT OF MATERNAL INTERPERSONAL VIOLENCE-RELATED POST-TRAUMATIC STRESS DISORDER. INTRODUCTION: INTERPERSONAL VIOLENT (IPV) EXPERIENCES WHEN THEY BEGIN IN CHILDHOOD AND CONTINUE IN VARIOUS FORMS DURING ADULTHOOD OFTEN LEAD TO CHRONIC POST-TRAUMATIC STRESS DISORDER (PTSD) THAT IS ASSOCIATED IN MULTIPLE STUDIES WITH HYPOCORTISOLISM AND LOWER PERCENTAGE OF METHYLATION OF THE PROMOTER REGION OF THE GENE CODING FOR THE GLUCOCORTICOID RECEPTOR (NR3C1). THIS PROSPECTIVE, LONGITUDINAL STUDY EXAMINED THE RELATIONSHIP OF NR3C1 METHYLATION AMONG MOTHERS WITH IPV-RELATED PTSD AND THEIR TODDLERS AND THEN LOOKED AT THE RELATIONSHIP OF MATERNAL NR3C1 METHYLATION AND CHILD PSYCHOPATHOLOGY AT SCHOOL AGE. METHODS: FORTY-EIGHT MOTHERS WERE EVALUATED FOR LIFE-EVENTS HISTORY AND POST-TRAUMATIC STRESS DISORDER VIA STRUCTURED CLINICAL INTERVIEW WHEN THEIR CHILDREN WERE AGES 12-42 MONTHS (MEAN AGE 26.7 MONTHS, SD 8.8). THEIR CHILDREN'S PSYCHOPATHOLOGY IN TERMS OF INTERNALIZING SYMPTOMS AND EXTERNALIZING BEHAVIORS WAS EVALUATED USING THE CHILD BEHAVIOR CHECKLIST AT AGES 5-9 YEARS (MEAN AGE 7 YEARS, SD 1.1). PERCENTAGE OF METHYLATION FOR THE NR3C1 GENE PROMOTER REGION WAS ASSESSED FROM DNA EXTRACTED FROM MATERNAL AND CHILD SALIVA USING BISULFITE PYROSEQUENCING. DATA ANALYSIS INVOLVED PARAMETRIC AND NON-PARAMETRIC CORRELATIONS AND MULTIPLE LINEAR AND LOGISTIC REGRESSION MODELING. RESULTS: LOGISTIC REGRESSION MODELS USING CHILD NR3C1 METHYLATION AS THE DEPENDENT VARIABLE AND MATERNAL NR3C1 METHYLATION AND PTSD GROUP STATUS AS PREDICTORS, AS WELL AS THE INTERACTION INDICATED THAT ALL THREE OF THESE SIGNIFICANTLY PREDICTED CHILD NR3C1 METHYLATION. THESE FINDINGS REMAINED SIGNIFICANT WHEN CONTROLLING FOR CHILD AGE, SEX AND MATERNAL CHILD ABUSE HISTORY. OVERALL, MATERNAL NR3C1 METHYLATION WHEN CHILDREN WERE TODDLERS WAS NEGATIVELY AND SIGNIFICANTLY ASSOCIATED WITH CHILD EXTERNALIZING BEHAVIOR SEVERITY AT SCHOOL AGE. DISCUSSION: WE FOUND THAT CORRELATIONS BETWEEN MOTHERS AND THEIR CHILDREN OF NR3C1 METHYLATION LEVELS OVERALL AND AT ALL INDIVIDUAL CPG SITES OF INTEREST WERE SIGNIFICANT ONLY IN THE IPV-PTSD GROUP. THE LATTER FINDINGS SUPPORT THAT NR3C1 METHYLATION IN MOTHERS POSITIVELY AND STATISTICALLY SIGNIFICANTLY CORRELATES WITH NR3C1 METHYLATION IN THEIR CHILDREN ONLY IN PRESENCE OF IPV-PTSD IN THE MOTHERS. THIS MATERNAL EPIGENETIC SIGNATURE WITH RESPECT TO THIS GLUCOCORTICOID RECEPTOR IS SIGNIFICANTLY ASSOCIATED WITH CHILD BEHAVIOR THAT MAY WELL POSE A RISK FOR INTERGENERATIONAL TRANSMISSION OF VIOLENCE AND RELATED PSYCHOPATHOLOGY.	2022	

16  5200  22 PRENATAL MATERNAL STRESS PREDICTS METHYLATION OF GENES REGULATING THE HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL SYSTEM IN MOTHERS AND NEWBORNS IN THE DEMOCRATIC REPUBLIC OF CONGO. EXPOSURE TO STRESS EARLY IN LIFE PERMANENTLY SHAPES ACTIVITY OF THE HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL (HPA) AXIS AND THE BRAIN. PRENATALLY, GLUCOCORTICOIDS PASS THROUGH THE PLACENTA TO THE FETUS WITH POSTNATAL IMPACTS ON BRAIN DEVELOPMENT, BIRTH WEIGHT (BW), AND HPA AXIS FUNCTIONING. LITTLE IS KNOWN ABOUT THE BIOLOGICAL MECHANISMS BY WHICH PRENATAL STRESS AFFECTS POSTNATAL FUNCTIONING. THIS STUDY ADDRESSES THIS GAP BY EXAMINING THE EFFECT OF CHRONIC STRESS AND TRAUMATIC WAR-RELATED STRESS ON EPIGENETIC CHANGES IN FOUR KEY GENES REGULATING THE HPA AXIS IN NEONATAL CORD BLOOD, PLACENTA, AND MATERNAL BLOOD: CRH, CRHBP, NR3C1, AND FKBP5. PARTICIPANTS WERE 24 MOTHER-NEWBORN DYADS IN THE CONFLICT-RIDDEN REGION OF THE EASTERN DEMOCRATIC REPUBLIC OF CONGO. BW DATA WERE COLLECTED AT DELIVERY AND MATERNAL INTERVIEWS WERE CONDUCTED TO ASSESS CULTURALLY RELEVANT CHRONIC AND WAR-RELATED STRESSORS. CHRONIC STRESS AND WAR TRAUMA HAD WIDESPREAD EFFECTS ON HPA AXIS GENE METHYLATION, WITH SIGNIFICANT EFFECTS OBSERVED AT TRANSCRIPTION FACTOR BINDING (TFB) SITES IN ALL TARGET GENES TESTED. SOME CHANGES IN METHYLATION WERE UNIQUE TO CHRONIC OR WAR STRESS, WHEREAS OTHERS WERE OBSERVED ACROSS BOTH STRESSOR TYPES. MOREOVER, STRESS EXPOSURES IMPACTED MATERNAL AND FETAL TISSUES DIFFERENTLY, SUPPORTING THEORETICAL MODELS THAT STRESS IMPACTS VARY ACCORDING TO LIFE PHASE. METHYLATION IN SEVERAL NR3C1 AND CRH CPG SITES, ALL LOCATED AT TFB SITES, WAS ASSOCIATED WITH BW. THESE FINDINGS SUGGEST THAT PRENATAL STRESS EXPOSURE IMPACTS DEVELOPMENT VIA EPIGENETIC CHANGES IN HPA AXIS GENES.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
17  4394  39 MODIFICATION OF EPIGENETIC PATTERNS IN LOW BIRTH WEIGHT CHILDREN: IMPORTANCE OF HYPOMETHYLATION OF THE ACE GENE PROMOTER. THERE IS A GROWING BODY OF EVIDENCE THAT EPIGENETIC ALTERATIONS ARE INVOLVED IN THE PATHOLOGICAL MECHANISMS OF MANY CHRONIC DISORDERS LINKED TO FETAL PROGRAMMING. ANGIOTENSIN-CONVERTING ENZYME (ACE) APPEARS AS ONE CANDIDATE GENE THAT BRINGS NEW INSIGHTS INTO THE EPIGENETIC CONTROL AND LATER DEVELOPMENT OF DISEASES. IN THIS VIEW, WE HAVE POSTULATED THAT EPIGENETIC MODIFICATIONS IN THE ACE GENE MIGHT SHOW DIFFERENT INTERACTIONS BETWEEN BIRTH WEIGHT (BW), BLOOD PRESSURE LEVELS, PLASMA ACE ACTIVITY AND ACE I/D POLYMORPHISM. TO EXPLORE THIS HYPOTHESIS, WE PERFORMED A CROSS-SECTIONAL STUDY TO EVALUATE THE DNA METHYLATION OF 3 CPG SITES USING PYROSEQUENCING WITHIN THE ACE GENE PROMOTER OF PERIPHERAL BLOOD LEUKOCYTES FROM 45 LBW CHILDREN COMPARED WITH 70 NBW CHILDREN. OUR RESULTS HAVE REVEALED THAT LBW CHILDREN HAVE LOWER METHYLATION LEVELS (P<0.001) IN PARALLEL WITH A HIGHER ACE ACTIVITY (P = 0.001). ADJUSTING FOR PREMATURITY, GENDER, AGE, BODY MASS INDEX, AND FAMILY HISTORY OF CARDIOVASCULAR DISEASE DID NOT ALTER THESE FINDINGS. WE HAVE ALSO PERFORMED ANALYSES OF INDIVIDUAL CPG SITES. THE FREQUENCY OF DNA METHYLATION WAS SIGNIFICANTLY DIFFERENT AT TWO CPG SITES (SITE 1: NUCLEOTIDE POSITION +555; AND SITE 3: NUCLEOTIDE POSITION +563). IN ADDITION, WE HAVE FOUND A SIGNIFICANT INVERSE CORRELATION BETWEEN DEGREE OF DNA METHYLATION AND BOTH ACE ACTIVITY (P<0.001) AND SYSTOLIC BLOOD PRESSURE LEVELS (P<0.001). WE ALSO OBSERVED THAT THE METHYLATION LEVEL WAS SIGNIFICANTLY LOWER IN LBW CHILDREN WHO ARE CARRIERS OF THE DD GENOTYPE COMPARED TO NBW CHILDREN WITH DD GENOTYPE (P<0.024). IN CONCLUSION, WE ARE ABLE TO DEMONSTRATE THAT THE HYPOMETHYLATION IN THE 3 CPG SITES OF ACE GENE PROMOTER IS ASSOCIATED WITH LBW IN 6 TO 12 YEAR-OLD CHILDREN. THE MAGNITUDE OF THESE EPIGENETIC CHANGES APPEARS TO BE CLINICALLY IMPORTANT, WHICH IS SUPPORTED BY THE OBSERVATION THAT DISCRETE CHANGES IN DNA METHYLATION CAN AFFECT SYSTOLIC BLOOD PRESSURE AND ACE PROTEIN ACTIVITY LEVELS.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
18  1750  32 EARLY LIFE STRESS AND PEDIATRIC POSTTRAUMATIC STRESS DISORDER. TRAUMATIC STRESS EXPOSURE DURING CRITICAL PERIODS OF DEVELOPMENT MAY HAVE ESSENTIAL AND LONG-LASTING EFFECTS ON THE PHYSICAL AND MENTAL HEALTH OF INDIVIDUALS. TWO THIRDS OF YOUTH ARE EXPOSED TO POTENTIALLY TRAUMATIC EXPERIENCES BY THE AGE OF 17, AND APPROXIMATELY 5% OF ADOLESCENTS MEET LIFETIME CRITERIA FOR POSTTRAUMATIC STRESS DISORDER (PTSD). THE ROLE OF THE STRESS SYSTEM IS THE MAINTENANCE OF HOMEOSTASIS IN THE PRESENCE OF REAL/PERCEIVED AND ACUTE/CHRONIC STRESSORS. EARLY-LIFE STRESS (ELS) HAS AN IMPACT ON NEURONAL BRAIN NETWORKS INVOLVED IN STRESS REACTIONS, AND COULD EXERT A PROGRAMMING EFFECT ON GLUCOCORTICOID SIGNALING. STUDIES ON PEDIATRIC PTSD REVEAL DIVERSE NEUROENDOCRINE RESPONSES TO ADVERSE EVENTS AND RELATED LONG-TERM NEUROENDOCRINE AND EPIGENETIC ALTERATIONS. NEUROENDOCRINE, NEUROIMAGING, AND GENETIC STUDIES IN CHILDREN WITH PTSD AND ELS EXPERIENCES ARE CRUCIAL IN UNDERSTANDING RISK AND RESILIENCE FACTORS, AND ALSO THE NATURAL HISTORY OF PTSD.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
19  4067  32 MATERNAL AND PEDIATRIC HEALTH AND DISEASE: INTEGRATING BIOPSYCHOSOCIAL MODELS AND EPIGENETICS. THE CONCEPTS OF ALLOSTASIS (STABILITY THROUGH ADAPTATION) AND ACCUMULATED LIFE STRESS (MCEWEN'S ALLOSTATIC LOAD) AIM TO UNDERSTAND CHILDHOOD AND ADULT OUTCOMES. CHRONIC MALNUTRITION, CHANGES IN SOCIAL CONDITION, AND ADVERSE EARLY-LIFE EXPERIENCES MAY PROGRAM PHENOTYPES AND CONTRIBUTE TO LONG-LASTING DISEASE RISK. HOWEVER, INTEGRATION OF LIFE COURSE APPROACHES, SOCIAL AND ECONOMIC CONTEXTS, AND COMPARISON AMONG DIFFERENT BIOPSYCHOSOCIAL MODELS HAS NOT GENERALLY BEEN EXPLORED. THIS REVIEW CRITICALLY EXAMINES THE LITERATURE AND EVALUATES RECENT INSIGHTS INTO HOW ENVIRONMENTAL STRESS CAN ALTER LIFELONG HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AND IMMUNE SYSTEM RESPONSIVENESS AND INDUCE METABOLIC AND NEURODEVELOPMENTAL MALADAPTATION. MODELS OF BIOPSYCHOSOCIAL STRESS OVERLAP BUT MAY CONSIDER DIFFERENT CONDITIONS. CONCEPTS INCLUDE ALLOSTASIS, WHICH INCORPORATES HORMONAL RESPONSES TO PREDICTABLE ENVIRONMENTAL CHANGES, AND GERONIMUS'S "WEATHERING," WHICH AIMS TO EXPLAIN HOW SOCIALLY STRUCTURED, REPEATED STRESS CAN ACCUMULATE AND INCREASE DISEASE VULNERABILITY. WEATHERING EMPHASIZES ROLES OF INTERNALIZED/INTERPERSONAL RACISM IN OUTCOMES DISPARITIES. FOR MEXICAN IMMIGRANTS AND MEXICAN AMERICANS, THE "ACCULTURATION" FRAMEWORK HAS PROVEN ESPECIALLY USEFUL TO EXPLORE DISPARITIES, INCLUDING PRETERM BIRTH AND NEUROPSYCHIATRIC RISKS IN CHILDHOOD. COMPLEXITIES OF STRESS ASSESSMENTS AND RECENT RESEARCH INTO EPIGENETIC MECHANISMS MEDIATING EFFECTS OF PHYSICAL, NUTRITIONAL, PSYCHOLOGICAL, AND SOCIAL STRESS ARE REVIEWED.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
20  4622  24 NEUROBIOLOGICAL DEVELOPMENT IN THE CONTEXT OF CHILDHOOD TRAUMA. NEUROBIOLOGICAL SYSTEMS MAY BE PARTICULARLY SUSCEPTIBLE TO DELETERIOUS IMPACT OF CHILDHOOD TRAUMA, AND THE IMPACT OF CHILDHOOD TRAUMA ON DEVELOPMENT AND SUBSEQUENT FUNCTIONAL OUTCOMES ACROSS THE LIFESPAN HAS BEEN WELL-DOCUMENTED. THE CURRENT REVIEW ADDRESSES THE NEUROBIOLOGICAL IMPACT OF EXPOSURE TO INTERPERSONAL TRAUMA IN CHILDHOOD IN THE CONTEXT OF EXECUTIVE FUNCTION, EMOTION REGULATION, AND DISSOCIATION/INTEROCEPTIVE AWARENESS. SUBSEQUENT RISK FOR PTSD AND DEPRESSION IS ALSO DISCUSSED. THE PATHWAY OF RISK FROM CHILDHOOD TRAUMA TO THESE COGNITIVE, EMOTIONAL, AND PSYCHIATRIC OUTCOMES IS ADDRESSED IN TERMS OF POTENTIAL STRUCTURAL AND FUNCTIONAL ALTERATIONS WITHIN THE HIPPOCAMPUS, PREFRONTAL CORTEX, AND AMYGDALA RESULTING FROM CHRONIC OR REPEATED ACTIVATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS AND ITS INTERACTION WITH AND INFLUENCE ON GENETIC AND EPIGENETIC PROCESSES DURING SENSITIVE PERIODS OF DEVELOPMENT. IMPLICATIONS FOR PRACTICE ARE DISCUSSED.	2017