1  6073 121 THE DRESDEN BURNOUT STUDY: PROTOCOL OF A PROSPECTIVE COHORT STUDY FOR THE BIO-PSYCHOLOGICAL INVESTIGATION OF BURNOUT. OBJECTIVES: THE DRESDEN BURNOUT STUDY (DBS) IS A 12-YEAR LONGITUDINAL COHORT STUDY THAT AIMS TO PROVIDE A DESCRIPTION OF THE BURNOUT SYNDROME ON THE BASIS OF TIME AND SYMPTOM CRITERIA WITH A SPECIAL FOCUS ON THE SEARCH FOR BIOMARKERS. BIOLOGICAL AND PSYCHOSOCIAL APPROACHES ARE APPLIED TO EXAMINE THE LONG-TERM COURSE AND CONSEQUENCES OF BURNOUT WITHIN A POPULATION-BASED GERMAN-SPEAKING SAMPLE AGED 18 TO 68 YEARS. METHODS: DEMOGRAPHICS AND PSYCHOSOCIAL DATA ARE GENERATED BY ONLINE ASSESSMENTS, INCLUDING DEMOGRAPHICS AND QUESTIONNAIRES ON BURNOUT, BURNOUT-RELATED CONSTRUCTS, WORK-ENVIRONMENT, AND HEALTH-RELATED FACTORS. THE LAB-BASED BIOMARKER ASSESSMENT INCLUDES ENDOCRINE, PHYSIOLOGICAL, IMMUNOLOGICAL, AND EPIGENETIC MARKERS OBTAINED FROM BLOOD AND HAIR SAMPLES. IN ADDITION, HEART RATE VARIABILITY IS ALSO MEASURED REPEATEDLY. WITHIN THE FIRST 2 YEARS, THE DBS COLLECTED PSYCHOSOCIAL DATA FROM OVER 7,600 PARTICIPANTS WITH BIOLOGICAL DATA OBTAINED FROM MORE THAN 800 INDIVIDUALS. DURING THE FOLLOWING 10 YEARS, DETAILED ASSESSMENTS OF BIOMARKERS AND PSYCHOSOCIAL FACTORS WILL BE COLLECTED IN ANNUAL STUDY WAVES. RESULTS: RESULTS WILL BE GENERATED DURING THE FOLLOWING DECADE. CONCLUSION: THE FINDINGS OF THE DBS ARE EXPECTED TO PAVE THE ROAD FOR AN IN-DEPTH BIOPSYCHOSOCIAL CHARACTERIZATION OF BURNOUT AND TO GIVE INSIGHT INTO THE LONG-TERM COURSE AND POTENTIAL MENTAL AND PHYSICAL HEALTH CONSEQUENCES OF THE BURNOUT SYNDROME.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
2  4346  26 MIR-10A, MIR-15A, LET-7A, AND LET-7G EXPRESSION AS STRESS-RELEVANT BIOMARKERS TO ASSESS ACUTE OR CHRONIC PSYCHOLOGICAL STRESS AND MENTAL HEALTH IN HUMAN CAPILLARY BLOOD. BACKGROUND: PSYCHOLOGICAL STRESS, AS AN IMPORTANT COFACTOR IN THE DEVELOPMENT OF MANY ACUTE AND CHRONIC DISEASES, IS CRUCIAL FOR GENERAL HEALTH OR WELL-BEING, AND IMPROVED MARKERS ARE NEEDED TO DISTINGUISH SITUATIONS OF PROGRESSIVE PATHOLOGICAL DEVELOPMENT, SUCH AS DEPRESSION, ANXIETY, OR BURNOUT, TO BE RECOGNIZED AT AN EARLY STAGE. EPIGENETIC BIOMARKERS PLAY AN IMPORTANT ROLE IN THE EARLY DETECTION AND TREATMENT OF COMPLEX DISEASES SUCH AS CANCER, AND METABOLIC OR MENTAL DISORDERS. THEREFORE, THIS STUDY AIMED TO IDENTIFY SO-CALLED MIRNAS, WHICH WOULD BE SUITABLE AS STRESS-RELATED BIOMARKERS. METHODS AND RESULTS: IN THIS STUDY, 173 PARTICIPANTS (36.4% MALES, AND 63.6% FEMALES) WERE INTERVIEWED ABOUT STRESS, STRESS-RELATED DISEASES, LIFESTYLE, AND DIET TO ASSESS THEIR ACUTE AND CHRONIC PSYCHOLOGICAL STRESS STATUS. USING QPCR ANALYSIS, 13 DIFFERENT MIRNAS (MIR-10A-5P, MIR-15A-5P, MIR-16-5P, MIR-19B-3P, MIR-26B-5P, MIR-29C-3P, MIR-106B-5P, MIR-126-3P, MIR-142-3P, LET-7A-5P, LET-7G-5P, MIR-21-5P, AND MIR-877-5P) WERE ANALYZED IN DRIED CAPILLARY BLOOD SAMPLES. FOUR MIRNAS WERE IDENTIFIED, MIR-10A-5P, MIR-15A-5P, LET-7A-5P, AND LET-7G-5P (P < 0.05), WHICH COULD BE USED AS POSSIBLE CANDIDATES FOR MEASURING PATHOLOGICAL FORMS OF ACUTE OR CHRONIC STRESS. LET-7A-5P, LET-7G-5P, AND MIR-15A-5P (P < 0.05) WERE ALSO SIGNIFICANTLY HIGHER IN SUBJECTS WITH AT LEAST ONE STRESS-RELATED DISEASE. FURTHER, CORRELATIONS WERE IDENTIFIED BETWEEN LET-7A-5P AND MEAT CONSUMPTION (P < 0.05) AND BETWEEN MIR-15A-5P AND COFFEE CONSUMPTION (P < 0.05). CONCLUSION: THE EXAMINATION OF THESE FOUR MIRNAS AS BIOMARKERS USING A MINIMALLY INVASIVE METHOD OFFERS THE POSSIBILITY OF DETECTING HEALTH PROBLEMS AT AN EARLY STAGE AND COUNTERACTING THEM TO MAINTAIN GENERAL AND MENTAL HEALTH.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
3  5827  30 STRESS, BURNOUT AND DEPRESSION: A SYSTEMATIC REVIEW ON DNA METHYLATION MECHANISMS. DESPITE THAT BURNOUT PRESENTS A SERIOUS BURDEN FOR MODERN SOCIETY, THERE ARE NO DIAGNOSTIC CRITERIA. ADDITIONAL DIFFICULTY IS THE DIFFERENTIAL DIAGNOSIS WITH DEPRESSION. CONSEQUENTLY, THERE IS A NEED TO DISPOSE OF A BURNOUT BIOMARKER. EPIGENETIC STUDIES SUGGEST THAT DNA METHYLATION IS A POSSIBLE MEDIATOR LINKING INDIVIDUAL RESPONSE TO STRESS AND PSYCHOPATHOLOGY AND COULD BE CONSIDERED AS A POTENTIAL BIOMARKER OF STRESS-RELATED MENTAL DISORDERS. THUS, THE AIM OF THIS REVIEW IS TO PROVIDE AN OVERVIEW OF DNA METHYLATION MECHANISMS IN STRESS, BURNOUT AND DEPRESSION. IN ADDITION TO STATE-OF-THE-ART OVERVIEW, THE GOAL OF THIS REVIEW IS TO PROVIDE A SCIENTIFIC BASE FOR BURNOUT BIOMARKER RESEARCH. WE PERFORMED A SYSTEMATIC LITERATURE SEARCH AND IDENTIFIED 25 PERTINENT ARTICLES. AMONG THESE, 15 FOCUSED ON DEPRESSION, 7 ON CHRONIC STRESS AND ONLY 3 ON WORK STRESS/BURNOUT. THREE EPIGENOME-WIDE STUDIES WERE IDENTIFIED AND THE MAJORITY OF STUDIES USED THE CANDIDATE-GENE APPROACH, ASSESSING 12 DIFFERENT GENES. THE GLUCOCORTICOID RECEPTOR GENE (NR3C1) DISPLAYED DIFFERENT METHYLATION PATTERNS IN CHRONIC STRESS AND DEPRESSION. THE SEROTONIN TRANSPORTER GENE (SLC6A4) METHYLATION WAS SIMILARLY AFFECTED IN STRESS, DEPRESSION AND BURNOUT. WORK-RELATED STRESS AND DEPRESSIVE SYMPTOMS WERE ASSOCIATED WITH DIFFERENT METHYLATION PATTERNS OF THE BRAIN DERIVED NEUROTROPHIC FACTOR GENE (BDNF) IN THE SAME HUMAN SAMPLE. THE TYROSINE HYDROXYLASE (TH) METHYLATION WAS CORRELATED WITH WORK STRESS IN A SINGLE STUDY. ADDITIONAL, THOROUGHLY DESIGNED LONGITUDINAL STUDIES ARE NECESSARY FOR REVEALING THE CAUSE-EFFECT RELATIONSHIP OF WORK STRESS, EPIGENETICS AND BURNOUT, INCLUDING ITS OVERLAP WITH DEPRESSION.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
4  5385  27 REDOX BALANCE SIGNALLING IN OCCUPATIONAL STRESS: MODIFICATION BY NUTRACEUTICAL INTERVENTION. THERE IS INCREASING EVIDENCE THAT PSYCHOSOCIAL STRESS CAN BE VIEWED AS A SYSTEM-WIDE DERANGEMENT OF CELLULAR HOMEOSTASIS, WITH HEIGHTENED OXIDATIVE STRESS AND TRIGGERED PROINFLAMMATORY MECHANISMS. THE AIM OF THIS STUDY IS TWOFOLD: A) TO REPLICATE FINDINGS THAT PSYCHOLOGICAL STRESS INCREASES OXIDATIVE DAMAGE AND B) TO DETERMINE WHETHER A FERMENTED PAPAYA PREPARATION KNOWN TO EXERT SIGNIFICANT PROTECTIVE ANTIOXIDANT PROPERTIES COULD BUFFER SUCH INCREASES IN NUCLEAR DNA DAMAGE WHILE ALSO INDUCING EPIGENETIC PROTECTIVE MECHANISMS. TWENTY-EIGHT SEDENTARY MEN AND WOMEN (AGE RANGE: 28-52), WHO REPORTED LIVING A STRESSFUL LIFESTYLE BUT WITH AN OVERALL POSITIVE ATTITUDE, WERE RECRUITED FOR THIS STUDY. CHRONIC DISEASES AS WELL AS SEVERE BURNOUT AND USE OF DRUGS FOR ANXIETY CONSTITUTED EXCLUSION CRITERIA. SUBJECTS WERE SUPPLEMENTED FOR 1 MONTH WITH 9 G/DAY (4.5 G TWICE A DAY) OF A CERTIFIED FERMENTED PAPAYA PREPARATION. ALL SUBJECTS WERE GIVEN A STRESS AND SLEEP QUALITY QUESTIONNAIRE TOGETHER WITH A DIET AND LIFE STYLE ASSESSMENT. BLOOD WAS COLLECTED AT 2 AND 4 WEEK, ERYTHROCYTE AND LEUKOCYTE WERE SEPARATED TO ASSESS REDOX BALANCE AND HEME OXYGENASE-1 (HO-1) GENE EXPRESSION WHILE BILIRUBIN OXIDIZED METABOLITES (BOMS) WERE TESTED IN THE URINE. STRESSED INDIVIDUALS SHOWED A SIGNIFICANT ABNORMALITY OF REDOX STATUS WITH INCREASED MDA OF ERYTHROCYTE AND INCREASED LEVEL OF 8-0HDG IN LEUKOCYTE AND BOMS EXCRETION (P<0.05). NUTRACEUTICAL SUPPLEMENTATION BROUGHT ABOUT A NORMALIZATION OF SUCH VALUES ALREADY AT THE 2 WEEK OBSERVATION (P<0.05) TOGETHER WITH A SIGNIFICANT UPREGULATION OF HO-1 (P<0.01). TAKEN TOGETHER, THE RESULTS OF THIS STUDY CONFIRM THAT STRESSFUL OCCUPATIONAL LIFE PER SE, WITHOUT ANY OVERT PSYCHIATRIC ILLNESS, MAY BE ASSOCIATED TO INCREASED OXIDATIVE STRESS. SUPPLEMENTATION WITH FUNCTIONAL FOOD AFFECTING REDOX REGULATION MAY BE PART OF THE THERAPEUTIC ARMAMENTARIUM TO BE CONSIDERED IN THIS CLINICAL SETTING.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
5  4916  18 PAIN-RELATED INCREASE IN SEROTONIN TRANSPORTER GENE METHYLATION ASSOCIATES WITH EMOTIONAL REGULATION IN 4.5-YEAR-OLD PRETERM-BORN CHILDREN. AIM: THE MAIN GOAL OF THIS STUDY WAS TO ASSESS THE ASSOCIATION BETWEEN PAIN-RELATED INCREASE IN SEROTONIN TRANSPORTER GENE (SLC6A4) METHYLATION AND EMOTIONAL DYSREGULATION IN 4.5-YEAR-OLD PRETERM CHILDREN COMPARED WITH FULL-TERM MATCHED COUNTERPARTS. METHODS: PRETERM (N = 29) AND FULL-TERM (N = 26) CHILDREN RECRUITED FROM TWO ITALIAN HOSPITALS WERE FOLLOWED-UP FROM OCTOBER 2011 TO DECEMBER 2017. SLC6A4 METHYLATION WAS ASSESSED FROM CORD BLOOD AT BIRTH FROM BOTH GROUPS AND PERIPHERAL BLOOD AT DISCHARGE FOR PRETERM ONES. AT 4.5 YEARS, EMOTIONAL REGULATION (IE, ANGER, FEAR AND SADNESS) WAS ASSESSED THROUGH AN OBSERVATIONAL STANDARDISED PROCEDURE. RESULTS: PRETERM CHILDREN (18 FEMALES; MEAN AGE = 4.5, RANGE = 4.3-4.8) SHOWED GREATER ANGER DISPLAY COMPARED WITH FULL-TERM CONTROLS (14 FEMALES; MEAN AGE = 4.5, RANGE = 4.4-4.9) IN RESPONSE TO EMOTIONAL STRESS. CONTROLLING FOR ADVERSE LIFE EVENTS OCCURRENCE FROM DISCHARGE TO 4.5 YEARS AND SLC6A4 METHYLATION AT BIRTH, CPG-SPECIFIC SLC6A4 METHYLATION IN THE NEONATAL PERIOD WAS PREDICTIVE OF GREATER ANGER DISPLAY IN PRETERM CHILDREN BUT NOT IN FULL-TERM ONES. CONCLUSION: THESE FINDINGS CONTRIBUTE TO HIGHLIGHT HOW EPIGENETIC REGULATION OF SEROTONIN TRANSPORTER GENE IN RESPONSE TO NICU PAIN EXPOSURE CONTRIBUTES TO LONG-LASTING PROGRAMMING OF ANGER REGULATION IN PRETERM CHILDREN.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
6  4612  20 NEONATAL PAIN AND COMT VAL158MET GENOTYPE IN RELATION TO SEROTONIN TRANSPORTER (SLC6A4) PROMOTER METHYLATION IN VERY PRETERM CHILDREN AT SCHOOL AGE. CHILDREN BORN VERY PRETERM ARE EXPOSED TO REPEATED NEONATAL PROCEDURES THAT INDUCE PAIN AND STRESS DURING HOSPITALIZATION IN THE NEONATAL INTENSIVE CARE UNIT (NICU). THE COMT VAL158MET GENOTYPE IS INVOLVED WITH PAIN SENSITIVITY, AND EARLY LIFE STRESS IS IMPLICATED IN ALTERED EXPRESSION OF METHYLATION OF THE SEROTONIN TRANSPORTER. WE EXAMINED: (1) WHETHER METHYLATION OF THE SEROTONIN TRANSPORTER GENE (SLC6A4) PROMOTER DIFFERS BETWEEN VERY PRETERM CHILDREN AND FULL-TERM CONTROLS AT SCHOOL AGE, (2) RELATIONSHIPS WITH CHILD BEHAVIOR PROBLEMS, AND (3) WHETHER THE EXTENT OF NEONATAL PAIN EXPOSURE INTERACTS WITH THE COMT VAL158MET GENOTYPE TO PREDICT SLC6A4 METHYLATION AT 7 YEARS IN THE VERY PRETERM CHILDREN. WE EXAMINED THE ASSOCIATIONS BETWEEN THE COMT GENOTYPES, NEONATAL PAIN EXPOSURE (ADJUSTED FOR NEONATAL CLINICAL CONFOUNDERS), SLC6A4 METHYLATION AND BEHAVIOR PROBLEMS. VERY PRETERM CHILDREN HAD SIGNIFICANTLY HIGHER METHYLATION AT 7/10 CPG SITES IN THE SLC6A4 PROMOTER COMPARED TO FULL-TERM CONTROLS AT 7 YEARS. NEONATAL PAIN (ADJUSTED FOR CLINICAL CONFOUNDERS) WAS SIGNIFICANTLY ASSOCIATED WITH TOTAL CHILD BEHAVIOR PROBLEMS ON THE CHILD BEHAVIOR CHECKLIST (CBCL) QUESTIONNAIRE (ADJUSTED FOR CONCURRENT STRESSORS AND 5HTTLPR GENOTYPE) (P = 0.035). CBCL TOTAL PROBLEMS WAS SIGNIFICANTLY ASSOCIATED WITH GREATER SLC6A4 METHYLATION IN VERY PRETERM CHILDREN (P = 0.01). NEONATAL PAIN (ADJUSTED FOR CLINICAL CONFOUNDERS) AND COMT MET/MET GENOTYPE WERE ASSOCIATED WITH SLC6A4 PROMOTER METHYLATION IN VERY PRETERM CHILDREN AT 7 YEARS (P = 0.001). THESE FINDINGS PROVIDE EVIDENCE THAT BOTH GENETIC PREDISPOSITION AND EARLY ENVIRONMENT NEED TO BE CONSIDERED IN UNDERSTANDING SUSCEPTIBILITY FOR DEVELOPING BEHAVIORAL PROBLEMS IN THIS VULNERABLE POPULATION.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
7  5957  26 TELOMERE LENGTH AND EPIGENETIC AGE ACCELERATION IN ADOLESCENTS WITH ANXIETY DISORDERS. EVIDENCE ON THE RELATIONSHIP BETWEEN GENETICS AND MENTAL HEALTH ARE FLOURISHING. HOWEVER, FEW STUDIES ARE EVALUATING EARLY BIOMARKERS THAT MIGHT LINK GENES, ENVIRONMENT, AND PSYCHOPATHOLOGY. WE AIMED TO STUDY TELOMERE LENGTH (TL) AND EPIGENETIC AGE ACCELERATION (AA) IN A COHORT OF ADOLESCENTS WITH AND WITHOUT ANXIETY DISORDERS (N = 234). WE EVALUATED A REPRESENTATIVE SUBSAMPLE OF PARTICIPANTS AT BASELINE AND AFTER 5 YEARS (N = 76) AND CATEGORIZED THEM ACCORDING TO THEIR ANXIETY DISORDER DIAGNOSIS AT BOTH TIME POINTS: (1) CONTROL GROUP (NO ANXIETY DISORDER, N = 18), (2) VARIABLE GROUP (ANXIETY DISORDER IN ONE EVALUATION, N = 38), AND (3) PERSISTENT GROUP (ANXIETY DISORDER AT BOTH TIME POINTS, N = 20). WE ASSESSED RELATIVE MEAN TL BY REAL-TIME QUANTITATIVE PCR AND DNA METHYLATION BY INFINIUM HUMANMETHYLATION450 BEADCHIP. WE CALCULATED AA USING THE HORVATH AGE ESTIMATION ALGORITHM AND ANALYZED DIFFERENCES AMONG GROUPS USING GENERALIZED LINEAR MIXED MODELS. THE PERSISTENT GROUP OF ANXIETY DISORDER DID NOT CHANGE TL OVER TIME (P = 0.495). THE VARIABLE GROUP HAD HIGHER BASELINE TL (P = 0.003) BUT NO ACCELERATED TL EROSION IN COMPARISON TO THE NON-ANXIETY CONTROL GROUP (P = 0.053). FURTHERMORE, THERE WERE NO DIFFERENCES IN AA AMONG GROUPS OVER TIME. OUR FINDINGS SUGGEST THAT ADOLESCENTS WITH CHRONIC ANXIETY DID NOT CHANGE TELOMERE LENGTH OVER TIME, WHICH COULD BE RELATED TO A DELAY IN NEURONAL DEVELOPMENT IN THIS PERIOD OF LIFE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
8   577  31 BDNF PROMOTER METHYLATION AND GENETIC VARIATION IN LATE-LIFE DEPRESSION. THE REGULATION OF THE BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) IS IMPORTANT FOR DEPRESSION PATHOPHYSIOLOGY AND EPIGENETIC REGULATION OF THE BDNF GENE MAY BE INVOLVED. THIS STUDY INVESTIGATED WHETHER BDNF METHYLATION IS A MARKER OF DEPRESSION. ONE THOUSAND AND TWENTY-FOUR PARTICIPANTS WERE RECRUITED AS PART OF A LONGITUDINAL STUDY OF PSYCHIATRIC DISORDERS IN GENERAL POPULATION ELDERLY (AGE ? 65). CLINICAL LEVELS OF DEPRESSION WERE ASSESSED USING THE MINI INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW FOR THE DIAGNOSIS OF MAJOR DEPRESSIVE DISORDER ACCORDING TO THE DIAGNOSTIC AND STATISTICAL MANUAL OF MENTAL DISORDER IV CRITERIA, AND THE CENTRE FOR EPIDEMIOLOGIC STUDIES DEPRESSION SCALE (CES-D) FOR ASSESSMENT OF MODERATE TO SEVERE DEPRESSIVE SYMPTOMS. BUCCAL DNA METHYLATION AT THE TWO MOST WIDELY STUDIED BDNF PROMOTERS, I AND IV, WAS INVESTIGATED USING THE SEQUENOM MASSARRAY PLATFORM THAT ALLOWS HIGH-THROUGHPUT INVESTIGATION OF METHYLATION AT INDIVIDUAL CPG SITES WITHIN DEFINED GENOMIC REGIONS. IN MULTIVARIATE LINEAR REGRESSION ANALYSES ADJUSTED FOR A RANGE OF PARTICIPANT CHARACTERISTICS INCLUDING ANTIDEPRESSANT USE, DEPRESSION AT BASELINE, AS WELL AS CHRONIC LATE-LIFE DEPRESSION OVER THE 12-YEAR FOLLOW-UP, WERE ASSOCIATED WITH OVERALL HIGHER BDNF METHYLATION LEVELS, WITH TWO SITES SHOWING SIGNIFICANT ASSOCIATIONS (PROMOTER I, DELTA MEAN = 0.4%, P = 0.0002; PROMOTER IV, DELTA MEAN = 5.4%, P = 0.021). THREE SINGLE-NUCLEOTIDE POLYMORPHISMS (RS6265, RS7103411 AND RS908867) WERE ALSO FOUND TO MODIFY THE ASSOCIATION BETWEEN DEPRESSION AND PROMOTER I METHYLATION. AS ONE OF THE LARGEST EPIGENETIC STUDIES OF DEPRESSION, AND THE FIRST INVESTIGATING BDNF METHYLATION IN BUCCAL TISSUE, OUR FINDINGS HIGHLIGHT THE POTENTIAL FOR BUCCAL BDNF METHYLATION TO BE A BIOMARKER OF DEPRESSION.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
9  5085  32 PILOT STUDY OF ABSOLUTE TELOMERE LENGTHS IN PRETERM INFANTS. BACKGROUND: ANNUALLY, APPROXIMATELY 15 MILLION BABIES ARE BORN PRETERM (<37 WEEKS GESTATIONAL AGE) GLOBALLY. IN THE NEONATAL INTENSIVE CARE UNIT (NICU) ENVIRONMENT, INFANTS ARE EXPOSED TO REPEATED STRESSFUL OR PAINFUL PROCEDURES AS PART OF ROUTINE LIFESAVING CARE. THESE PROCEDURES HAVE BEEN ASSOCIATED WITH EPIGENETIC ALTERATIONS THAT MAY LEAD TO AN INCREASED RISK OF NEURODEVELOPMENTAL DISORDERS. TELOMERE LENGTH HAS BEEN NEGATIVELY ASSOCIATED WITH ADVERSE LIFE EXPERIENCES IN STUDIES OF ADULTS. OBJECTIVES: THIS PILOT STUDY AIMED TO DESCRIBE TELOMERE LENGTH IN A SAMPLE OF PRETERM INFANTS AT NICU DISCHARGE AND EXAMINE ANY ASSOCIATIONS WITH PAIN, FEEDING METHOD, AND NEURODEVELOPMENT. METHODS: THIS DESCRIPTIVE PILOT STUDY SAMPLE INCLUDES BASELINE ABSOLUTE TELOMERE LENGTH (ATL) OF 36 PRETERM INFANTS IMMEDIATELY PRIOR TO DISCHARGE. QUANTITATIVE POLYMERASE CHAIN REACTION WAS USED TO DETERMINE ATL. INFANT DEMOGRAPHICS, PAIN/STRESS, TYPE OF FEEDING, ANTIBIOTIC USE, NEURODEVELOPMENT, AND BUCCAL SWAB DATA WERE COLLECTED. DESCRIPTIVE DATA ANALYSIS WAS USED TO DESCRIBE THE TELOMERE LENGTH USING GRAPHS. RESULTS: AMONG OUR PRETERM INFANT SAMPLES, THE MEAN ATL WAS FAR GREATER THAN THE AVERAGE ADULT TELOMERE LENGTH. ALTHOUGH NO SIGNIFICANT ASSOCIATIONS WERE FOUND BETWEEN ATL AND PAIN, FEEDING METHOD, AND NEURODEVELOPMENT, A TREND BETWEEN SEX WAS NOTED WHERE MALE TELOMERE LENGTHS WERE SHORTER THAN FEMALES AS THEY AGED. DISCUSSION: THIS IS ONE OF FEW STUDIES TO EVALUATE PRETERM INFANT TELOMERE LENGTH. ALTHOUGH OTHER RESEARCHERS HAVE USED RELATIVE TELOMERE LENGTH, WE USED THE MORE ACCURATE ATL. WE FOUND NONSIGNIFICANT SHORTER TELOMERE LENGTHS AMONG MALES. ADDITIONAL LARGE-SCALE, LONGITUDINAL STUDIES ARE NEEDED TO BETTER IDENTIFY THE PREDICTORS OF TELOMERE LENGTH AT THE TIME OF DISCHARGE FROM NICU.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
10  3179  37 HAIR CORTISOL AS A HYPOTHALAMIC-PITUITARY-ADRENAL AXIS BIOMARKER IN PREGNANT WOMEN WITH ASTHMA: A RETROSPECTIVE OBSERVATIONAL STUDY. BACKGROUND: CORTISOL IS A HORMONE INVOLVED IN MANY PHYSIOLOGICAL FUNCTIONS INCLUDING FETAL MATURATION AND EPIGENETIC PROGRAMMING DURING PREGNANCY. THIS STUDY AIMED TO USE HAIR CORTISOL AS A BIOMARKER OF CHRONIC INHALED CORTICOSTEROID (ICS) EXPOSURE AND ASSESS THE POTENTIAL EFFECTS OF ASTHMA ON THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS IN PREGNANT WOMEN. WE HYPOTHESIZED THAT PREGNANT WOMEN WITH ASTHMA TREATED WITH ICS WOULD EXHIBIT LOWER HAIR CORTISOL CONCENTRATIONS, INDICATIVE OF ADRENAL SUPPRESSION, COMPARED TO WOMEN WITH ASTHMA NOT USING ICS AND WOMEN WHO DO NOT HAVE ASTHMA. METHODS: WE PERFORMED AN OBSERVATIONAL RETROSPECTIVE COHORT STUDY. HAIR SAMPLES WERE ANALYZED FROM PREGNANT WOMEN WITH ASTHMA, WITH (N = 56) AND WITHOUT (N = 31) ICS TREATMENT, AND PREGNANT WOMEN WITHOUT ASTHMA (N = 31). HAIR SAMPLES WERE SEGMENTED BASED ON THE GROWTH RATE OF 1 CM/MONTH AND ANALYZED BY ENZYME IMMUNOASSAY TO PROVIDE CORTISOL CONCENTRATIONS CORRESPONDING TO PRECONCEPTION, TRIMESTERS 1-3, AND POSTPARTUM. HAIR CORTISOL CONCENTRATIONS WERE COMPARED WITHIN AND AMONG THE GROUPS USING NON-PARAMETRIC STATISTICAL TESTS. RESULTS: HAIR CORTISOL CONCENTRATIONS INCREASED ACROSS TRIMESTERS FOR ALL THREE GROUPS, BUT THIS INCREASE WAS DAMPENED IN WOMEN WITH ASTHMA (P = 0.03 FOR CONTROLS VS. ICS TREATED AND CONTROLS VS. NO ICS). ICS TREATED WOMEN TAKING MORE THAN FIVE DOSES PER WEEK HAD HAIR CORTISOL CONCENTRATIONS 47 % LOWER IN THIRD TRIMESTER THAN CONTROLS. LINEAR REGRESSION OF THE THIRD TRIMESTER HAIR CORTISOL RESULTS IDENTIFIED ASTHMA AS A SIGNIFICANT FACTOR WHEN COMPARING CONSISTENT ICS USE OR ASTHMA AS THE PREDICTOR (F(1, 25) = 9.7, P = 0.005, R(2) ADJ = 0.257). CONCLUSIONS: HAIR CORTISOL SUCCESSFULLY SHOWED THE EXPECTED CHANGE IN CORTISOL OVER THE COURSE OF PREGNANCY AND MAY BE A USEFUL BIOMARKER OF HPA AXIS FUNCTION IN PREGNANT WOMEN WITH ASTHMA. THE POTENTIAL IMPACT OF DECREASED MATERNAL CORTISOL IN WOMEN WITH ASTHMA ON PERINATAL OUTCOMES REMAINS TO BE DETERMINED.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
11  1058  29 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
12  2646  27 EPIGENOMIC LINKS BETWEEN SOCIAL DETERMINANTS OF HEALTH AND SYMPTOMS: A SCOPING REVIEW. SOCIAL DETERMINANTS OF HEALTH (SDOH) IMPACT HEALTH AND WELLNESS. THE LINK BETWEEN SDOH AND ADVERSE HEALTH OUTCOMES, INCLUDING SYMPTOM OCCURRENCE AND SEVERITY, MAY BE EXPLAINED BY AN INDIVIDUAL'S PHYSIOLOGIC RESPONSE TO ONE OR MORE SDOH. ONE POTENTIAL MECHANISM UNDERLYING THIS PHYSIOLOGIC RESPONSE LINKING SDOH AND SYMPTOMS IS THE DYNAMIC EPIGENOME. THE PURPOSE OF THIS SCOPING REVIEW OF THE LITERATURE WAS TO EXAMINE DIFFERENTIAL SUSCEPTIBILITY FOR SYMPTOMS BY IDENTIFYING AND SUMMARIZING RESEARCH LINKING SDOH AND SYMPTOMS THROUGH EPIGENOMIC MECHANISMS. PUBMED WAS SEARCHED TO IDENTIFY EMPIRICAL RESEARCH WHERE AT LEAST ONE SDOH WAS AN INDEPENDENT OR DEPENDENT VARIABLE, AT LEAST ONE SYMPTOM WAS INVESTIGATED, AND THE INVESTIGATION INCLUDED AN EPIGENOMIC MEASURE. OF THE 484 ARTICLES INITIALLY RETRIEVED, AFTER THOROUGH VETTING, 41 ARTICLES MET ELIGIBILITY. THE MOST STUDIED SYMPTOM WAS DEPRESSIVE SYMPTOMS FOLLOWED BY ANXIETY, COGNITIVE FUNCTION, SLEEP DYSFUNCTION, AND PAIN. THE MOST FREQUENTLY STUDIED SDOH WERE: 1) STRESS, PARTICULARLY EARLY LIFE STRESS AND ACCULTURATIVE STRESS; AND 2) TRAUMA, PREDOMINANTLY CHILDHOOD TRAUMA. DNA METHYLATION AND TELOMERE LENGTH WERE THE MOST STUDIED EPIGENOMIC MEASURES. FOUR GENES (SLC6A4, BDNF, NR3C1, OXTR) HAD EVIDENCE FROM MULTIPLE STUDIES AND ACROSS METHODOLOGICAL APPROACHES LINKING SDOH TO SYMPTOMS. THIS REVIEW SUPPORTS THE INCLUSION OF EPIGENOMIC APPROACHES TO BETTER UNDERSTAND THE LINK BETWEEN SDOH AND SYMPTOMS AND PROVIDES EVIDENCE THAT SDOH IMPACT TELOMERE LENGTH AND THE METHYLATION OF GENES INVOLVED IN NEUROTRANSMITTER SIGNALING, NEURONAL SURVIVAL, BEHAVIOR, INFLAMMATION AND STRESS RESPONSE.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
13  4917  21 PAIN-RELATED STRESS DURING THE NEONATAL INTENSIVE CARE UNIT STAY AND SLC6A4 METHYLATION IN VERY PRETERM INFANTS. VERY PRETERM (VPT) INFANTS NEED LONG-LASTING HOSPITALIZATION IN THE NEONATAL INTENSIVE CARE UNIT (NICU) DURING WHICH THEY ARE DAILY EXPOSED TO PAIN-RELATED STRESS. ALTERATIONS OF DNA METHYLATION AT THE PROMOTER REGION OF THE SLC6A4 HAVE BEEN ASSOCIATED WITH EARLY ADVERSE EXPERIENCES IN INFANTS. THE MAIN AIM OF THE PRESENT WORK WAS TO INVESTIGATE THE ASSOCIATION BETWEEN LEVEL OF EXPOSURE TO PAIN-RELATED STRESS DURING HOSPITALIZATION AND CHANGES IN SLC6A4 DNA METHYLATION AT NICU DISCHARGE IN VPT INFANTS. IN ORDER TO EXCLUDE THE POTENTIAL EFFECT OF BIRTH STATUS (I.E., PRETERM VS. FULL-TERM BIRTH) ON SLC6A4 METHYLATION, WE PRELIMINARILY ASSESSED SLC6A4 EPIGENETIC DIFFERENCES BETWEEN VPT AND FULL-TERM (FT) INFANTS AT BIRTH. FIFTY-SIX VPT AND THIRTY-TWO FT INFANTS PARTICIPATED IN THE STUDY. THE LEVEL OF EXPOSURE TO PAIN-RELATED STRESS WAS QUANTIFIED ON THE BASIS OF THE AMOUNT OF SKIN-BREAKING PROCEDURES TO WHICH THEY WERE EXPOSED. VPT INFANTS WERE DIVIDED IN TWO SUB-GROUPS: LOW-PAIN EXPOSURE (LPE, N = 25) AND HIGH-PAIN EXPOSURE (HPE, N = 31). DNA METHYLATION WAS EVALUATED AT BIRTH FOR BOTH VPT AND FT INFANTS, ASSESSING 20 CPG SITES WITHIN THE SLC6A4 PROMOTER REGION. THE SAME CPG SITES WERE RE-EVALUATED FOR VARIATIONS IN DNA METHYLATION AT NICU DISCHARGE IN LPE AND HPE VPT INFANTS. NO DIFFERENCES IN SLC6A4 CPG SITES' METHYLATION EMERGED BETWEEN FT AND VPT INFANTS AT BIRTH. METHYLATION AT CPG SITES 5 AND 6 SIGNIFICANTLY INCREASED FROM BIRTH TO NICU DISCHARGE ONLY FOR HPE VPT INFANTS. FINDINGS SHOW THAT PRETERM BIRTH PER SE IS NOT ASSOCIATED WITH EPIGENETIC ALTERATIONS OF THE SLC6A4, WHEREAS HIGHER LEVELS OF PAIN-RELATED STRESS EXPOSURE DURING NICU STAY MIGHT ALTER THE TRANSCRIPTIONAL FUNCTIONALITY OF THE SEROTONIN TRANSPORTER GENE.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
14  5395  26 REDUCED EPIGENETIC AGE IN OLDER ADULTS WITH HIGH SENSE OF PURPOSE IN LIFE. PSYCHOSOCIAL RISK FACTORS HAVE BEEN LINKED WITH ACCELERATED EPIGENETIC AGING, BUT LITTLE IS KNOWN ABOUT WHETHER PSYCHOSOCIAL RESILIENCE FACTORS (EG, SENSE OF PURPOSE IN LIFE) MIGHT REDUCE EPIGENETIC AGE ACCELERATION. IN THIS STUDY, WE TESTED IF OLDER ADULTS WHO EXPERIENCE HIGH LEVELS OF PURPOSE MIGHT SHOW REDUCED EPIGENETIC AGE ACCELERATION. WE EVALUATED THE RELATIONSHIP BETWEEN PURPOSE AND EPIGENETIC AGE ACCELERATION AS MEASURED BY 13 DNA METHYLATION (DNAM) "EPIGENETIC CLOCKS" ASSESSED IN 1 572 OLDER ADULTS FROM THE HEALTH AND RETIREMENT STUDY (MEAN AGE 70 YEARS). WE QUANTIFIED THE TOTAL ASSOCIATION BETWEEN PURPOSE AND DNAM AGE ACCELERATION AS WELL AS THE EXTENT TO WHICH THAT TOTAL ASSOCIATION MIGHT BE ATTRIBUTABLE TO DEMOGRAPHIC FACTORS, CHRONIC DISEASE, OTHER PSYCHOSOCIAL VARIABLES (EG, POSITIVE AFFECT), AND HEALTH-RELATED BEHAVIORS (HEAVY DRINKING, SMOKING, PHYSICAL ACTIVITY, AND BODY MASS INDEX [BMI]). PURPOSE IN LIFE WAS ASSOCIATED WITH REDUCED EPIGENETIC AGE ACCELERATION ACROSS 4 "SECOND-GENERATION" DNAM CLOCKS OPTIMIZED FOR PREDICTING HEALTH AND LONGEVITY (FALSE DISCOVERY RATE [FDR] Q < 0.0001: PHENOAGE, GRIMAGE, ZHANG EPIGENETIC MORTALITY INDEX; FDR Q < 0.05: DUNEDINPOAM). THESE ASSOCIATIONS WERE INDEPENDENT OF DEMOGRAPHIC AND PSYCHOSOCIAL FACTORS, BUT SUBSTANTIALLY ATTENUATED AFTER ADJUSTING FOR HEALTH-RELATED BEHAVIORS (DRINKING, SMOKING, PHYSICAL ACTIVITY, AND BMI). PURPOSE SHOWED NO SIGNIFICANT ASSOCIATION WITH 9 "FIRST-GENERATION" DNAM EPIGENETIC CLOCKS TRAINED ON CHRONOLOGICAL AGE. OLDER ADULTS WITH GREATER PURPOSE IN LIFE SHOW "YOUNGER" DNAM EPIGENETIC AGE ACCELERATION. THESE RESULTS MAY BE DUE IN PART TO ASSOCIATED DIFFERENCES IN HEALTH-RELATED BEHAVIORS. RESULTS SUGGEST NEW OPPORTUNITIES TO REDUCE BIOLOGICAL AGE ACCELERATION BY ENHANCING PURPOSE AND ITS BEHAVIORAL SEQUELAE IN LATE ADULTHOOD.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
15   524  32 ASSOCIATIONS OF BDNF GENOTYPE AND PROMOTER METHYLATION WITH ACUTE AND LONG-TERM STROKE OUTCOMES IN AN EAST ASIAN COHORT. BACKGROUND: BRAIN DERIVED NEUROTROPHIC FACTOR (BDNF) HAS BEEN SHOWN TO PLAY AN IMPORTANT ROLE IN POSTSTROKE RECOVERY. BDNF SECRETION IS INFLUENCED BY GENETIC AND EPIGENETIC PROFILES. THIS STUDY AIMED TO INVESTIGATE WHETHER BDNF VAL66MET POLYMORPHISM AND PROMOTER METHYLATION STATUS WERE ASSOCIATED WITH OUTCOMES AT TWO WEEKS AND ONE YEAR AFTER STROKE. METHODS AND FINDINGS: A TOTAL OF 286 PATIENTS WERE EVALUATED AT THE TIME OF ADMISSION AND TWO WEEKS AFTER STROKE, AND 222 (78%) WERE FOLLOWED ONE YEAR LATER IN ORDER TO EVALUATE CONSEQUENCES OF STROKE AT BOTH ACUTE AND CHRONIC STAGES. STROKE OUTCOMES WERE DICHOTOMISED INTO GOOD AND POOR BY THE MODIFIED RANKIN SCALE. STROKE SEVERITY (NATIONAL INSTITUTES OF HEALTH STROKE SCALE), PHYSICAL DISABILITY (BARTHEL INDEX), AND COGNITIVE FUNCTION (MINI-MENTAL STATE EXAMINATION) WERE MEASURED. ASSOCIATIONS OF BDNF GENOTYPE AND METHYLATION STATUS ON STROKE OUTCOMES AND ASSESSMENT SCALE SCORES WERE INVESTIGATED USING LOGISTIC REGRESSION, REPEATED MEASURES ANOVA AND PARTIAL CORRELATION TESTS. BDNF VAL66MET POLYMORPHISM WAS INDEPENDENTLY ASSOCIATED WITH POOR OUTCOME AT 2 WEEKS AND AT 1 YEAR, AND WITH WORSENING PHYSICAL DISABILITY AND COGNITIVE FUNCTION OVER THAT PERIOD. HIGHER BDNF PROMOTER METHYLATION STATUS WAS INDEPENDENTLY ASSOCIATED WITH WORSE OUTCOMES AT 1 YEAR, AND WITH THE WORSENING OF PHYSICAL DISABILITY AND COGNITIVE FUNCTION. NO SIGNIFICANT GENOTYPE-METHYLATION INTERACTIONS WERE FOUND. CONCLUSIONS: A ROLE FOR BDNF IN POSTSTROKE RECOVERY WAS SUPPORTED, AND CLINICAL UTILITY OF BDNF GENETIC AND EPIGENETIC PROFILE AS PROGNOSTIC BIOMARKERS AND A TARGET FOR DRUG DEVELOPMENT WAS SUGGESTED.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
16  1746  19 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
17  2734  29 EXPLORING THE RELATIONSHIP BETWEEN DNA METHYLATION AGE MEASURES AND PSYCHONEUROLOGICAL SYMPTOMS IN WOMEN WITH EARLY-STAGE BREAST CANCER. PURPOSE: THE EPIGENETIC CLOCK HAS BEEN ACKNOWLEDGED AS AN INDICATOR FOR MOLECULAR AGING, BUT FEW STUDIES HAVE EXAMINED POSSIBLE ASSOCIATIONS OF DNA METHYLATION (DNAM) AGE OR AGE ACCELERATION (AA) WITH SYMPTOM BURDEN IN INDIVIDUALS WHO ARE TREATED FOR CANCER. THIS STUDY EXPLORED THE ASSOCIATION OF DNAM AGE OR AA WITH PSYCHONEUROLOGICAL (PN) SYMPTOMS, INCLUDING COGNITIVE IMPAIRMENT, FATIGUE, SLEEP DISTURBANCES, PAIN, AND DEPRESSIVE SYMPTOMS, IN BREAST CANCER SURVIVORS OVER A 2-YEAR PERIOD. METHODS: WE MEASURED PN SYMPTOMS USING RELIABLE INSTRUMENTS AND DNAM LEVELS BY INFINIUM HUMANMETHYLATION450K BEADCHIP (N = 72). DNAM AGE WAS CALCULATED BY THE HORVATH, GRIM, AND HANNUM-BASED INTRINSIC AND EXTRINSIC AGE ESTIMATIONS. AA WAS DEFINED BY THE RESIDUAL REGRESSING ESTIMATED EPIGENETIC AGE ON CHRONOLOGICAL AGE. MIXED REGRESSION MODELS WERE FITTED FOR AA AND CHANGES IN AA TO STUDY THE ASSOCIATION OVER TIME. SEPARATE LINEAR REGRESSION MODELS AND A MIXED-EFFECTS MODEL WERE FITTED FOR AA AT EACH TIME POINT. RESULTS: HORVATH-AA, GRIM-AA, AND EXTRINSIC EPIGENETIC AA WERE SIGNIFICANTLY CHANGED OVER TIME, WHILE INTRINSIC EPIGENETIC AA DID NOT EXHIBIT ANY TEMPORAL CHANGES. INCREASED AA WAS ASSOCIATED WITH GREATER ANXIETY AND FATIGUE, AS WELL AS WORSE COGNITIVE MEMORY, ADJUSTING FOR RACE, BMI, INCOME, CHEMOTHERAPY, RADIATION THERAPY, AND CHRONOLOGICAL AGE. INCREASED DNAM AGE WAS ASSOCIATED WITH GREATER ANXIETY OVER 2 YEARS. CONCLUSION: OUR FINDINGS SUGGEST DNAM AGE AND AA MAY BE ASSOCIATED WITH PN SYMPTOMS OVER THE COURSE OF CANCER TREATMENT AND SURVIVORSHIP. SOME PN SYMPTOMS MAY BE AMENABLE TO PREVENTIVE INTERVENTIONS TARGETED TO EPIGENETIC CLOCKS THAT INFLUENCE AGING-ASSOCIATED PROCESSES.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
18  5658  16 SEX-DIMORPHIC PATHWAYS IN THE ASSOCIATIONS BETWEEN MATERNAL TRAIT ANXIETY, INFANT BDNF METHYLATION, AND NEGATIVE EMOTIONALITY. MATERNAL ANTENATAL ANXIETY IS AN EMERGING RISK FACTOR FOR CHILD EMOTIONAL DEVELOPMENT. BOTH SEX AND EPIGENETIC MECHANISMS, SUCH AS DNA METHYLATION, MAY CONTRIBUTE TO THE EMBEDDING OF MATERNAL DISTRESS INTO EMOTIONAL OUTCOMES. HERE, WE INVESTIGATED SEX-DEPENDENT PATTERNS IN THE ASSOCIATION BETWEEN ANTENATAL MATERNAL TRAIT ANXIETY, METHYLATION OF THE BRAIN-DERIVED NEUROTROPHIC FACTOR GENE (BDNF DNAM), AND INFANT NEGATIVE EMOTIONALITY (NE). MOTHER-INFANT DYADS (N = 276) WERE RECRUITED AT DELIVERY. MATERNAL TRAIT ANXIETY, AS A MARKER OF ANTENATAL CHRONIC STRESS EXPOSURE, WAS ASSESSED SOON AFTER DELIVERY USING THE STAIT-TRAIT ANXIETY INVENTORY (STAI-Y). INFANTS' BDNF DNAM AT BIRTH WAS ASSESSED IN 11 CPG SITES IN BUCCAL CELLS WHEREAS INFANTS' NE WAS ASSESSED AT 3 (N = 225) AND 6 MONTHS (N = 189) USING THE INFANT BEHAVIOR QUESTIONNAIRE-REVISED (IBQ-R). HIERARCHICAL LINEAR ANALYSES SHOWED THAT HIGHER MATERNAL ANTENATAL ANXIETY WAS ASSOCIATED WITH GREATER 6-MONTH-OLDS' NE. FURTHERMORE, MATERNAL ANTENATAL ANXIETY PREDICTED GREATER INFANTS' BDNF DNAM IN FIVE CPG SITES IN MALES BUT NOT IN FEMALES. HIGHER METHYLATION AT THESE SITES WAS ASSOCIATED WITH GREATER 3-TO-6-MONTH NE INCREASE, INDEPENDENTLY OF INFANTS' SEX. MATERNAL ANTENATAL ANXIETY EMERGED AS A RISK FACTOR FOR INFANT'S NE. BDNF DNAM MIGHT MEDIATE THIS EFFECT IN MALES. THESE RESULTS MAY INFORM THE DEVELOPMENT OF STRATEGIES TO PROMOTE MOTHERS AND INFANTS' EMOTIONAL WELL-BEING.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
19   325  25 ALLELE-SPECIFIC DNA METHYLATION LEVEL OF FKBP5 IS ASSOCIATED WITH POST-TRAUMATIC STRESS DISORDER. BACKGROUND: FK506-BINDING PROTEIN 5 (FKBP5) BINDS TO GLUCOCORTICOID RECEPTORS AND MODULATES GLUCOCORTICOID SENSITIVITY. THE FKBP5 GENE HAS BEEN IMPLICATED IN THE DYSREGULATION OF HUMAN STRESS RESPONSES, CONTRIBUTING TO THE RISK AND TREATMENT RESPONSE OF STRESS-RELATED DISORDERS. THE PRESENT STUDY EXAMINED WHETHER EPIGENETIC CHANGES IN FKBP5 ARE ASSOCIATED WITH CHRONIC POST-TRAUMATIC STRESS DISORDER (PTSD) STATUS IN THE CONTEXT OF FKBP5 GENETIC VARIATION (RS1360780 POLYMORPHISM) AMONG MALE VETERANS EXPOSED TO COMBAT TRAUMA. METHODS: KOREAN MALE VETERANS WHO SERVED ON ACTIVE DUTY DURING THE VIETNAM WAR WERE CATEGORIZED INTO 2 GROUPS: WITH PTSD (N = 123) AND WITHOUT PTSD (N = 116). THE GENOTYPE OF FKBP5 RS1360780 AND DNA METHYLATION LEVELS OF TWO CPG SITES AT THE FKBP5 INTRON 7 REGION WERE ASSESSED IN PERIPHERAL BLOOD. ANALYSIS OF COVARIANCE WAS PERFORMED TO EXAMINE MAIN AND INTERACTION EFFECTS OF PTSD STATUS AND FKBP5 GENOTYPE ON FKBP5 DNA METHYLATION LEVEL, WITH AGE, TRAUMA LEVELS, AND ALCOHOL USE AS COVARIATES. RESULTS: A SIGNIFICANT MAIN EFFECT OF FKBP5 RS1360780 AND PTSD AND AN INTERACTION EFFECT BETWEEN GENOTYPE AND PTSD STATUS WERE FOUND ON MEAN FKBP5 DNA METHYLATION LEVEL. THE T ALLELE OF RS1360780 WAS ASSOCIATED WITH LOWER FKBP5 METHYLATION LEVEL. IN ADDITION, THE PTSD GROUP SHOWED SIGNIFICANTLY HIGHER METHYLATION THAN DID THE NON-PTSD GROUP AMONG VETERANS CARRYING THE RISK T ALLELE (N = 96), WHILE NO GROUP DIFFERENCE WAS OBSERVED ON METHYLATION LEVELS AMONG VETERANS WITH THE CC GENOTYPE (N = 143). AMONG VETERANS CARRYING THE T ALLELE, FKBP5 METHYLATION LEVELS WERE POSITIVELY CORRELATED WITH THE SEVERITY OF PTSD SYMPTOMS. CONCLUSIONS: THE PRESENT STUDY DEMONSTRATED DIFFERENT FKBP5 METHYLATION LEVELS IN PTSD DEPENDING ON FKBP5 GENETIC VARIATION AMONG VETERANS EXPOSED TO COMBAT TRAUMA. THE PRESENT FINDING SUGGESTS THAT THE GENETIC AND EPIGENETIC MODULATION OF FKBP5 IS INVOLVED IN THE PATHOPHYSIOLOGY OF PTSD. FURTHER LONGITUDINAL RESEARCH INVOLVING PEOPLE EXPOSED TO TRAUMA IS REQUIRED TO UNDERSTAND CAUSAL RELATIONSHIPS OF FKBP5 IN THE DEVELOPMENT AND RECOVERY OF PTSD.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
20  6315  22 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