1 4067 126 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 2 6483 32 TOXIC STRESS, EPIGENETICS AND CHILD DEVELOPMENT. OBJECTIVES: TO DESCRIBE THE CONCEPT OF TOXIC STRESS, PRESENT THE BASICS OF EPIGENETICS AND DISCUSS THEIR RELATIONSHIP WITH CHILD DEVELOPMENT. DATA SOURCE: NARRATIVE LITERATURE REVIEW THROUGH A SEARCH IN THE SCIELO, LILACS, MEDLINE DATABASES USING THE TERMS ADVERSE CHILDHOOD EXPERIENCE OR EARLY LIFE STRESS, EPIGENOMIC OR EPIGENETIC, CHILD DEVELOPMENT OR INFANT DEVELOPMENT. DATA SYNTHESIS: CONTINUING STRESS RESPONSE, KNOWN AS TOXIC STRESS, CAN OCCUR WHEN A CHILD EXPERIENCES INTENSE, FREQUENT, AND/OR PROLONGED ADVERSITY-SUCH AS PHYSICAL OR EMOTIONAL ABUSE, CHRONIC NEGLECT, FOR EXAMPLE-WITHOUT ADEQUATE ADULT SUPPORT. THIS TOXIC STRESS CAN HAVE HARMFUL EFFECTS ON LEARNING, BEHAVIOR, AND HEALTH THROUGHOUT LIFE. EPIGENETICS, AN EMERGING SCIENTIFIC RESEARCH AREA?, SHOWS HOW ENVIRONMENTAL INFLUENCES AFFECT GENE EXPRESSIONS AND EXPLAINS HOW EARLY EXPERIENCES CAN IMPACT THROUGHOUT LIFE. CONCLUSIONS: TOXIC STRESS CAUSES CHANGES IN THE HUMAN BODY RESPONSE SYSTEMS THAT CAN BE EXPLAINED IN PART BY EPIGENETIC CHANGES, WHICH CAN BE TEMPORARY OR LONG-LASTING. PEDIATRICIANS MUST BE AWARE OF THESE MECHANISMS AND THEIR CONSEQUENCES, SEEKING TO PREVENT THEM AND THUS PROMOTE THE HEALTH, WELL-BEING, AND QUALITY OF LIFE OF CHILDREN, CONTRIBUTING TO THEIR FULL DEVELOPMENT. 2022 3 1931 32 ENVIRONMENTAL EXPOSURES, THE EPIGENOME, AND AFRICAN AMERICAN WOMEN'S HEALTH. STRESS IS A COMMON FEATURE OF MODERN LIFE, BUT BOTH THE EXTENT OF EXPOSURE TO STRESSORS AND THE DOWNSTREAM EFFECTS OF THESE STRESS EXPOSURES CAN VARY CONSIDERABLY AMONG INDIVIDUALS, COMMUNITIES, AND POPULATIONS. WHEN INDIVIDUALS ARE EXPOSED TO REPEATED OR CHRONIC STRESS, WEAR AND TEAR ON THE BODY CAN ACCUMULATE AND MANIFEST IN MANY WAYS. THE TERM "ALLOSTATIC LOAD" REPRESENTS THE PHYSIOLOGICAL CONSEQUENCES OF REPEATED OR CHRONIC EXPOSURE TO ENVIRONMENTAL STRESSORS AND IS LINKED TO FLUCTUATING AND/OR HEIGHTENED NEURAL OR NEUROENDOCRINE RESPONSES. AFRICAN AMERICAN WOMEN ARE ONE POPULATION SUBGROUP THAT HAS BEEN IDENTIFIED AS POTENTIALLY HAVING BOTH AN ELEVATED ALLOSTATIC LOAD AND AN ENHANCED RESILIENCE TO EXTERNAL FACTORS. ONE MECHANISM BY WHICH ENVIRONMENTAL STRESSORS MAY IMPACT HUMAN HEALTH IS VIA EPIGENETIC REMODELING OF THE GENOME. THIS REVIEW WILL FOCUS ON WHAT IS KNOWN ABOUT HOW DIFFERENT TYPES OF ENVIRONMENTAL STRESSORS MAY AFFECT THE EPIGENOME AND EXPLORE LINKS BETWEEN EPIGENETIC REPROGRAMMING AND ALTERED ALLOSTATIC LOAD AND RESILIENCE AS IT PERTAINS TO AFRICAN AMERICAN WOMEN'S HEALTH. 2019 4 5169 34 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 5 6478 33 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 6 1779 40 EDITORIAL: MATERNAL INFLAMMATION DURING PREGNANCY: A MODIFIABLE PATHWAY TOWARD IMPROVING OFFSPRING SOCIOEMOTIONAL OUTCOMES IN CHILDHOOD AND ADOLESCENCE. CHILDHOOD PSYCHOPATHOLOGY IS A WELL-ESTABLISHED PREDICTOR OF POOR ADULT LIFE-COURSE OUTCOMES INCLUDING LOWER RATES OF EDUCATIONAL ATTAINMENT AND REDUCED FAMILY INCOME, WITH A TOTAL ECONOMIC LOSS OF $2.1 TRILLION IN THE UNITED STATES.(1) GIVEN THIS HIGH LEVEL OF INDIVIDUAL AND SOCIETAL BURDEN, MUCH EFFORT HAS BEEN DEVOTED TO IDENTIFYING THE MODIFIABLE RISK FACTORS THAT CONFER RISK FOR PSYCHIATRIC DISORDERS DURING EARLY CHILDHOOD. INDEED, NUMEROUS ASPECTS OF EARLY LIFE ADVERSITY, SUCH AS SOCIOECONOMIC DISADVANTAGE, STRESSFUL/TRAUMATIC LIFE EVENTS, AND DISRUPTED PARENT-CHILD RELATIONSHIPS, DEMONSTRATE STRONG ASSOCIATIONS WITH SOCIOEMOTIONAL PROBLEMS AND PSYCHIATRIC DISORDERS INTO ADOLESCENCE.(2) HOWEVER, THE UNDERLYING BIOLOGICAL MECHANISMS THAT ALSO CONTRIBUTE TO THIS RISK TRAJECTORY REMAIN LESS WELL UNDERSTOOD. ONE PROPOSED BIOLOGICAL MECHANISM THAT IS RAPIDLY GAINING MOMENTUM IN THE FIELD OF DEVELOPMENTAL PSYCHOPATHOLOGY CONCERNS EXCESSIVE IMMUNE SYSTEM ACTIVATION AND/OR PROINFLAMMATORY RESPONSES IN THE ORIGINS OF HEALTH AND DISEASE.(3) OF PARTICULAR INTEREST IS THE PRENATAL PERIOD, REPRESENTING A WINDOW OF VULNERABILITY IN WHICH PRENATAL EXPOSURES PREPARE OR PROGRAM THE FETUS FOR THE EXPECTED POSTNATAL ENVIRONMENT.(3-5) MORE SPECIFICALLY, FETAL PROGRAMMING POSITS THAT THE EFFECTS OF MATERNAL ADVERSITY DURING PREGNANCY ARE, AT LEAST IN PART, TRANSMITTED TO THE FETUS VIA MULTIPLE RELATED PATHWAYS INCLUDING CHRONIC MATERNAL INFLAMMATION AND/OR OVERACTIVATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS, RESULTING IN ABERRANT MATERNAL-FETAL IMMUNE/GLUCOCORTICOID SYSTEMS AND DOWNSTREAM EPIGENETIC ALTERATIONS IN THE DEVELOPING FETUS. TOGETHER, THESE FACTORS WORK TO INCREASE THE SUSCEPTIBILITY OF OFFSPRING TO ADVERSITY IN THE POSTNATAL ENVIRONMENT AND, IN TURN, ENHANCE RISK FOR PSYCHIATRIC DISORDERS.(3-6) HOWEVER, MUCH OF THE EXISTING LITERATURE IS BASED ON PRECLINICAL ANIMAL MODELS WITH COMPARATIVELY FEWER CLINICAL STUDIES.(3) AS SUCH, THERE REMAINS A PAUCITY OF LARGE, PROSPECTIVELY DESIGNED CLINICAL STUDIES EXAMINING MATERNAL PROINFLAMMATORY CONDITIONS DURING PREGNANCY IN RELATION TO PSYCHOPATHOLOGY IN OFFSPRING. AS PART OF THE LANDMARK NATIONAL INSTITUTES OF HEALTH-FUNDED ECHO (ENVIRONMENTAL INFLUENCES ON CHILD HEALTH OUTCOMES) CONSORTIUM, THE STUDY BY FRAZIER ET AL.(7) REPRESENTS ONE OF THE LARGEST INVESTIGATIONS LINKING PERINATAL MATERNAL PROINFLAMMATORY CONDITIONS WITH CO-OCCURRING PSYCHIATRIC SYMPTOMS IN CHILDREN AND ADOLESCENTS. 2023 7 5316 30 PSYCHOLOGICAL STRESS IN EARLY LIFE AS A PREDISPOSING FACTOR FOR THE DEVELOPMENT OF CHRONIC PAIN: CLINICAL AND PRECLINICAL EVIDENCE AND NEUROBIOLOGICAL MECHANISMS. A WEALTH OF RESEARCH OVER THE PAST 2 DECADES HAS EXPANDED OUR UNDERSTANDING OF THE IMPACT OF EARLY-LIFE ADVERSITY ON PHYSIOLOGICAL FUNCTION AND, CONSEQUENTLY, HEALTH AND WELLBEING IN LATER LIFE. EARLY-LIFE ADVERSITY INCREASES THE RISK OF DEVELOPING A NUMBER OF DISORDERS, SUCH AS CHRONIC PAIN, FIBROMYALGIA, AND IRRITABLE BOWEL SYNDROME. ALTHOUGH MUCH OF THE RESEARCH HAS EXAMINED THE IMPACT OF PHYSICAL MALTREATMENT, AN INCREASING NUMBER OF STUDIES HAVE BEEN PUBLISHED OVER THE PAST FEW YEARS EXAMINING THE EFFECT OF CHILDHOOD PSYCHOLOGICAL STRESS AND TRAUMA ON THE DEVELOPMENT OF VARIOUS TYPES OF CHRONIC PAIN CONDITIONS. WE REVIEW THE CLINICAL AND PRECLINICAL DATA EXAMINING THE LINK AMONG EARLY-LIFE PSYCHOLOGICAL STRESS, ALTERED NOCICEPTIVE BEHAVIOR, AND CHRONIC PAIN IN LATER LIFE. EVIDENCE SUPPORTING A ROLE FOR CERTAIN KEY NEUROBIOLOGICAL SUBSTRATES, INCLUDING THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS; MONOAMINERGIC, OPIOIDERGIC, ENDOCANNABINOID AND IMMUNE SYSTEMS; AND EPIGENETIC MECHANISMS IN THE ASSOCIATION BETWEEN EARLY-LIFE PSYCHOLOGICAL STRESS AND CHRONIC PAIN, IS PROVIDED. GREATER UNDERSTANDING OF THE IMPACT OF EARLY-LIFE STRESS MAY INFORM THE DEVELOPMENT OF PERSONALIZED TREATMENTS FOR CHRONIC PAIN IN LATER LIFE AND STRATEGIES TO PREVENT ITS ONSET IN SUSCEPTIBLE INDIVIDUALS. (C) 2016 WILEY PERIODICALS, INC. 2017 8 4985 30 PATHWAYS TO AGING: THE MITOCHONDRION AT THE INTERSECTION OF BIOLOGICAL AND PSYCHOSOCIAL SCIENCES. COMPELLING EVIDENCE SUGGESTS THAT BOTH BIOLOGICAL AND PSYCHOSOCIAL FACTORS IMPACT THE PROCESS OF AGING. HOWEVER, OUR UNDERSTANDING OF THE DYNAMIC INTERPLAY AMONG BIOLOGICAL AND PSYCHOSOCIAL FACTORS ACROSS THE LIFE COURSE IS STILL FRAGMENTARY. FOR EXAMPLE, IT NEEDS TO BE ESTABLISHED HOW THE INTERACTION OF INDIVIDUAL FACTORS (E.G., GENETIC AND EPIGENETIC ENDOWMENT AND PERSONALITY), BEHAVIORAL FACTORS (E.G., PHYSICAL ACTIVITY, DIET, AND STRESS MANAGEMENT), AND PSYCHOSOCIAL EXPERIENCES (E.G., SOCIAL SUPPORT, WELL-BEING, SOCIOECONOMIC STATUS, AND MARRIAGE) IN PERINATAL, CHILDHOOD, AND ADULTHOOD INFLUENCE HEALTH ACROSS THE AGING CONTINUUM. THIS PAPER AIMS TO OUTLINE POTENTIAL INTERSECTION POINTS SERVING AS AN INTERFACE BETWEEN BIOLOGICAL AND PSYCHOSOCIAL FACTORS, WITH AN EMPHASIS ON THE MITOCHONDRION. MITOCHONDRIA ARE CELLULAR ORGANELLES WHICH PLAY A CRITICAL ROLE IN CELLULAR SENESCENCE. BOTH CHRONIC EXPOSURE TO PSYCHOSOCIAL STRESS AND GENETIC-BASED MITOCHONDRIAL DYSFUNCTION HAVE STRIKINGLY SIMILAR BIOLOGICAL CONSEQUENCES; BOTH PREDISPOSE INDIVIDUALS TO ADVERSE AGE-RELATED HEALTH DISORDERS AND EARLY MORTALITY. EXPLORING THE INTERACTIVE NATURE OF THE FACTORS RESULTING IN PATHWAYS TO NORMAL HEALTHY AGING, AS WELL AS THOSE LEADING TO MORBIDITY AND EARLY MORTALITY, WILL CONTINUE TO ENHANCE OUR ABILITY TO TRANSLATE RESEARCH INTO EFFECTIVE PRACTICES THAT CAN BE IMPLEMENTED THROUGHOUT THE LIFE COURSE TO OPTIMISE THE AGING PROCESS. 2011 9 585 26 BEHAVIORAL PERINATOLOGY: BIOBEHAVIORAL PROCESSES IN HUMAN FETAL DEVELOPMENT. BEHAVIORAL PERINATOLOGY IS AS AN INTERDISCIPLINARY AREA OF RESEARCH THAT INVOLVES CONCEPTUALIZATION OF THEORETICAL MODELS AND CONDUCT OF EMPIRICAL STUDIES OF THE DYNAMIC TIME-, PLACE-, AND CONTEXT-DEPENDENT INTERPLAY BETWEEN BIOLOGICAL AND BEHAVIORAL PROCESSES IN FETAL, NEONATAL, AND INFANT LIFE USING AN EPIGENETIC FRAMEWORK OF DEVELOPMENT. THE BIOBEHAVIORAL PROCESSES OF PARTICULAR INTEREST TO OUR RESEARCH GROUP RELATE TO THE EFFECTS OF MATERNAL PRE- AND PERINATAL STRESS AND MATERNAL-PLACENTAL-FETAL STRESS PHYSIOLOGY. WE PROPOSE THAT BEHAVIORAL PERINATOLOGY RESEARCH MAY HAVE IMPORTANT IMPLICATIONS FOR A BETTER UNDERSTANDING OF THE PROCESSES THAT UNDERLIE OR CONTRIBUTE TO THE RISK OF THREE SETS OF OUTCOMES: PREMATURITY, ADVERSE NEURODEVELOPMENT, AND CHRONIC DEGENERATIVE DISEASES IN ADULTHOOD. BASED ON OUR UNDERSTANDING OF THE ONTOGENY OF HUMAN FETAL DEVELOPMENT AND THE PHYSIOLOGY OF PREGNANCY AND FETAL DEVELOPMENT, WE HAVE ARTICULATED A NEUROBIOLOGICAL MODEL OF PRE- AND PERINATAL STRESS. OUR MODEL PROPOSES THAT CHRONIC MATERNAL STRESS MAY EXERT A SIGNIFICANT INFLUENCE ON FETAL DEVELOPMENTAL OUTCOMES. MATERNAL STRESS MAY ACT VIA ONE OR MORE OF THREE MAJOR PHYSIOLOGICAL PATHWAYS: NEUROENDOCRINE, IMMUNE/INFLAMMATORY, AND VASCULAR. WE FURTHER SUGGEST THAT PLACENTAL CORTICOTROPIN-RELEASING HORMONE (CRH) MAY PLAY A CENTRAL ROLE IN COORDINATING THE EFFECTS OF ENDOCRINE, IMMUNE/INFLAMMATORY, AND VASCULAR PROCESSES ON FETAL DEVELOPMENTAL OUTCOMES. FINALLY, WE HYPOTHESIZE THAT THE EFFECTS OF MATERNAL STRESS ARE MODULATED BY THE NATURE, DURATION, AND TIMING OF OCCURRENCE OF STRESS DURING GESTATION. IN THIS PAPER, WE ELABORATE ON THE CONCEPTUAL AND EMPIRICAL BASIS FOR THIS MODEL, HIGHLIGHT SOME RELEVANT ISSUES AND QUESTIONS, AND MAKE RECOMMENDATIONS FOR FUTURE RESEARCH IN THIS AREA. 2002 10 4622 20 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 11 6554 25 TRANSGENERATIONAL EFFECTS OF EARLY ENVIRONMENTAL INSULTS ON AGING AND DISEASE INCIDENCE. ADVERSE EARLY LIFE EXPERIENCES ARE MAJOR INFLUENCES ON DEVELOPMENTAL TRAJECTORIES WITH POTENTIALLY LIFE-LONG CONSEQUENCES. PRENATAL OR EARLY POSTNATAL EXPOSURE TO STRESS, UNDERNUTRITION OR ENVIRONMENTAL TOXICANTS MAY REPROGRAM BRAIN DEVELOPMENT AND INCREASE RISK OF BEHAVIOURAL AND NEUROLOGICAL DISORDERS LATER IN LIFE. NOT ONLY EXPERIENCE WITHIN A SINGLE LIFETIME, BUT ALSO ANCESTRAL EXPERIENCE AFFECTS HEALTH TRAJECTORIES AND CHANCES OF SUCCESSFUL AGING. THE CENTRAL MECHANISM IN TRANSGENERATIONAL PROGRAMMING OF A DISEASE MAY BE THE FORMATION OF EPIGENETIC MEMORY. THIS REVIEW EXPLORES TRANSGENERATIONAL EFFECTS OF EARLY ADVERSE EXPERIENCE ON HEALTH AND DISEASE INCIDENCE IN OLDER AGE. FIRST, WE ADDRESS MECHANISMS OF DEVELOPMENTAL AND TRANSGENERATIONAL PROGRAMMING OF DISEASE AND INHERITANCE. SECOND, WE DISCUSS EXPERIMENTAL AND CLINICAL FINDINGS LINKING EARLY ENVIRONMENTAL DETERMINANTS TO ADVERSE AGING TRAJECTORIES IN ASSOCIATION WITH POSSIBLE PARENTAL CONTRIBUTIONS AND SEX-SPECIFIC EFFECTS. THIRD, WE OUTLINE THE MAIN MECHANISMS OF AGE-RELATED FUNCTIONAL DECLINE AND SUGGEST POTENTIAL INTERVENTIONS TO REVERSE NEGATIVE EFFECTS OF TRANSGENERATIONAL PROGRAMMING. THUS, STRATEGIES THAT SUPPORT HEALTHY DEVELOPMENT AND SUCCESSFUL AGING SHOULD TAKE INTO ACCOUNT THE POTENTIAL INFLUENCES OF TRANSGENERATIONAL INHERITANCE. 2020 12 682 38 BRAIN ON STRESS: HOW THE SOCIAL ENVIRONMENT GETS UNDER THE SKIN. STRESS IS A STATE OF THE MIND, INVOLVING BOTH BRAIN AND BODY AS WELL AS THEIR INTERACTIONS; IT DIFFERS AMONG INDIVIDUALS AND REFLECTS NOT ONLY MAJOR LIFE EVENTS BUT ALSO THE CONFLICTS AND PRESSURES OF DAILY LIFE THAT ALTER PHYSIOLOGICAL SYSTEMS TO PRODUCE A CHRONIC STRESS BURDEN THAT, IN TURN, IS A FACTOR IN THE EXPRESSION OF DISEASE. THIS BURDEN REFLECTS THE IMPACT OF NOT ONLY LIFE EXPERIENCES BUT ALSO GENETIC VARIATIONS AND INDIVIDUAL HEALTH BEHAVIORS SUCH AS DIET, PHYSICAL ACTIVITY, SLEEP, AND SUBSTANCE ABUSE; IT ALSO REFLECTS STABLE EPIGENETIC MODIFICATIONS IN DEVELOPMENT THAT SET LIFELONG PATTERNS OF PHYSIOLOGICAL REACTIVITY AND BEHAVIOR THROUGH BIOLOGICAL EMBEDDING OF EARLY ENVIRONMENTS INTERACTING WITH CUMULATIVE CHANGE FROM EXPERIENCES OVER THE LIFESPAN. HORMONES ASSOCIATED WITH THE CHRONIC STRESS BURDEN PROTECT THE BODY IN THE SHORT RUN AND PROMOTE ADAPTATION (ALLOSTASIS), BUT IN THE LONG RUN, THE BURDEN OF CHRONIC STRESS CAUSES CHANGES IN THE BRAIN AND BODY THAT CAN LEAD TO DISEASE (ALLOSTATIC LOAD AND OVERLOAD). BRAIN CIRCUITS ARE PLASTIC AND REMODELED BY STRESS TO CHANGE THE BALANCE BETWEEN ANXIETY, MOOD CONTROL, MEMORY, AND DECISION MAKING. SUCH CHANGES MAY HAVE ADAPTIVE VALUE IN PARTICULAR CONTEXTS, BUT THEIR PERSISTENCE AND LACK OF REVERSIBILITY CAN BE MALADAPTIVE. HOWEVER, THE CAPACITY OF BRAIN PLASTICITY TO EFFECTS OF STRESSFUL EXPERIENCES IN ADULT LIFE HAS ONLY BEGUN TO BE EXPLORED ALONG WITH THE EFFICACY OF TOP-DOWN STRATEGIES FOR HELPING THE BRAIN CHANGE ITSELF, SOMETIMES AIDED BY PHARMACEUTICAL AGENTS AND OTHER TREATMENTS. 2012 13 1911 27 ENVIRONMENT IN CHILDREN'S HEALTH: A NEW CHALLENGE FOR RISK ASSESSMENT. IN THE LAST FEW YEARS, MANY STUDIES HAVE FOCUSED ON THE EFFECTS OF ENVIRONMENTAL CONTAMINANT EXPOSURE DURING THE PRENATAL PERIOD OR INFANCY AS PREDICTORS OF HEALTH OUTCOMES IN THE FUTURE. IN THESE TIME WINDOWS, DUE TO THEIR RAPID GROWTH, AND PHYSIOLOGIC AND METABOLIC DEVELOPMENT, WE CAN OBSERVE A HIGHER VULNERABILITY TO THE EFFECTS OF ENVIRONMENT, WITH RESPECT TO ADULTHOOD. THE EVIDENCE OF POSSIBLE INFLUENCES, PARTLY MEDIATED BY EPIGENETIC MECHANISMS, INVOLVE NEUROBEHAVIORAL RESPONSES AND IMMUNE, ENDOCRINE, AND RESPIRATORY SYSTEMS, ACTING DIRECTLY ON THE CHILD OR INDIRECTLY WHEN MEDIATED BY PLACENTAL TRANSFER OR BREAST FEEDING. IN PARTICULAR, DUE TO A GREATER INTAKE OF AIR, FOOD, AND FLUIDS RELATIVE TO BODY WEIGHT, CRAWLING BEHAVIORS AND SHORT STATURE, THE RISK OF EXCESSIVE EXPOSURE IS GREATER IN CHILDREN. HOWEVER, DATA ON THE LONG-TERM IMPLICATIONS OF EARLY EXPOSURES ARE SCARCE. ADDITIONALLY, SO THAT PHYSICIANS AND INSTITUTIONS FOR CHILD CARE AND ASSISTANCE OF PREGNANT WOMEN CAN TAKE ACTIONS TO COUNTERACT THE EFFECTS OF CHEMICAL POLLUTION (I.E., BY EDUCATIONAL OPPORTUNITIES), A RISK ASSESSMENT PERSPECTIVE THAT RESPONDS TO THE BIOCOMPLEXITY OF THE HUMAN BEING IS NEEDED. THE PRESENT PAPER PROVIDES AN OVERVIEW OF PHYSIOLOGIC AND BEHAVIORAL CHARACTERISTICS DURING THE PERINATAL PERIOD AND IN CHILDHOOD, SUGGESTING IN A MORE INTEGRATED WAY, THE NEED OF A NEW RISK-ASSESSMENT APPROACH TO MANAGING CHRONIC DISEASE IN PEDIATRIC PATIENTS. 2021 14 1754 26 EARLY LIFE STRESS, THE DEVELOPMENT OF AGGRESSION AND NEUROENDOCRINE AND NEUROBIOLOGICAL CORRELATES: WHAT CAN WE LEARN FROM ANIMAL MODELS? EARLY LIFE STRESS (CHILD AND ADOLESCENT ABUSE, NEGLECT AND TRAUMA) INDUCES ROBUST ALTERATIONS IN EMOTIONAL AND SOCIAL FUNCTIONING RESULTING IN ENHANCED RISK FOR THE DEVELOPMENT OF PSYCHOPATHOLOGIES SUCH AS MOOD AND AGGRESSIVE DISORDERS. HERE, AN OVERVIEW IS GIVEN ON RECENT FINDINGS IN PRIMATE AND RODENT MODELS OF EARLY LIFE STRESS, DEMONSTRATING THAT CHRONIC DEPRIVATION OF EARLY MATERNAL CARE AS WELL AS CHRONIC DEPRIVATION OF EARLY PHYSICAL INTERACTIONS WITH PEERS ARE PROFOUND RISK FACTORS FOR THE DEVELOPMENT OF INAPPROPRIATE AGGRESSIVE BEHAVIORS. ALTERATIONS IN THE HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL (HPA), VASOPRESSIN AND SEROTONIN SYSTEMS AND THEIR RELEVANCE FOR THE REGULATION OF AGGRESSION ARE DISCUSSED. DATA SUGGEST THAT SOCIAL DEPRIVATION-INDUCED INAPPROPRIATE FORMS OF AGGRESSION ARE ASSOCIATED WITH HIGH OR LOW HPA AXIS (RE)ACTIVITY AND A GENERALLY LOWER FUNCTIONING OF THE SEROTONIN SYSTEM IN ADULTHOOD. MOREOVER, GENETIC AND EPIGENETIC MODIFICATIONS IN HPA AND SEROTONIN SYSTEMS INFLUENCE THE OUTCOME OF EARLY LIFE STRESS AND MAY EVEN MODERATE ADVERSE EFFECTS OF EARLY SOCIAL DEPRIVATION ON AGGRESSION. A MORE COMPREHENSIVE STUDY OF AGGRESSION, NEUROENDOCRINE, NEUROBIOLOGICAL AND (EPI)GENETIC CORRELATES OF EARLY LIFE STRESS USING ANIMAL MODELS IS NECESSARY TO PROVIDE A BETTER UNDERSTANDING OF THE INVASIVE AGGRESSIVE DEFICITS OBSERVED IN HUMANS EXPOSED TO CHILD MALTREATMENT. 2009 15 6822 34 [GENDER MEDICINE. SEX- AND GENDER-SPECIFIC ASPECTS OF CLINICAL MEDICINE]. GENDER MEDICINE STUDIES SEX- AND GENDER-BASED DIFFERENCES IN THE DEVELOPMENT AND PREVENTION OF DISEASES, THE AWARENESS AND PRESENTATION OF SYMPTOMS, AND THE EFFECTIVENESS OF THERAPY. GENDER MEDICINE IS PART OF PERSONALIZED MEDICINE, CONSIDERING DIFFERENCES IN BIOLOGICAL AND PSYCHOSOCIAL FACTORS INDIVIDUALLY. THERE ARE DIFFERENCES IN GENES, CHROMOSOMES, HORMONES, AND METABOLISM AS WELL AS DIFFERENCES IN CULTURE, ENVIRONMENT, AND SOCIETY. LIFELONG INTERACTIONS BETWEEN PHYSICAL AND PSYCHOSOCIAL FACTORS WILL INFLUENCE THE HEALTH AND ILL-HEALTH OF MEN AND WOMEN IN DIFFERENT WAYS. EPIGENETIC MODIFICATIONS PROVIDE EVIDENCE OF THE IMPACT OF ENVIRONMENT AND LIFESTYLE DURING VULNERABLE PHASES ON BIOLOGICAL PROCESSES, EFFECTING FUTURE GENERATIONS. MATERNAL LIFESTYLE AND ENVIRONMENTAL FACTORS DURING PREGNANCY CAN IMPACT THE HEALTH OF OFFSPRING IN LATER LIFE ALREADY IN UTERO IN A SEX-SPECIFIC WAY. PAIN, STRESS, AND COPING STYLES DIFFER BETWEEN MEN AND WOMEN. WOMEN EXPERIENCE MORE DRAMATIC PHYSICAL CHANGES DURING THEIR LIFETIME, WHICH ARE ASSOCIATED WITH SPECIFIC BURDENS AND PSYCHOSOCIAL ALTERATIONS. WOMEN WITH MULTIPLE ROLES AND RESPONSIBILITIES SUFFERING FROM STRESS DEVELOP DEPRESSION MORE FREQUENTLY. HOWEVER, MEN ARE OFTEN NOT DIAGNOSED AND TREATED APPROPRIATELY IN CASES OF DEPRESSION OR OSTEOPOROSIS, DISEASES THAT ARE TYPICALLY CONSIDERED "FEMALE." THERE ARE PROMINENT DIFFERENCES BETWEEN MEN AND WOMEN IN MEDICINE REGARDING THE IMMUNE SYSTEM, INFLAMMATION, AND NONCOMMUNICABLE DISEASES SUCH AS OBESITY, TYPE 2 DIABETES, HYPERTENSION, AND CARDIOVASCULAR DISEASE. WOMEN EXPERIENCE MORE OFTEN AUTOIMMUNE DISEASES AND SUFFER MORE FREQUENTLY FROM (CHRONIC) PAIN, NEURODEGENERATIVE CHANGES, AND FUNCTIONAL DISABILITIES. MEN HAVE SHORTER LIFE EXPECTANCY BUT RELATIVELY MORE HEALTHY YEARS OF LIFE, WHICH IS IN GREATER PART ASCRIBED TO PSYCHOSOCIAL DETERMINANTS. STATE-OF-THE-ART CLINICAL MEDICINE COMPRISES INDIVIDUAL RISK FACTORS BASED ON SEX- AND GENDER-SENSITIVE HEALTH PROGRAMS IN ORDER TO IMPROVE THE HEALTH-RELATED QUALITY OF LIFE FOR MEN AND WOMEN. 2014 16 6119 23 THE EPIGENETIC IMPACTS OF SOCIAL STRESS: HOW DOES SOCIAL ADVERSITY BECOME BIOLOGICALLY EMBEDDED? EPIGENETIC MECHANISMS ARE IMPLICATED IN THE PROCESSES THROUGH WHICH SOCIAL STRESSORS ERODE HEALTH IN HUMANS AND OTHER ANIMALS. HERE I REVIEW PROGRESS IN ELUCIDATING THE BIOLOGICAL PATHWAYS UNDERLYING THE SOCIAL GRADIENT IN HEALTH, WITH PARTICULAR EMPHASIS ON HOW BEHAVIORAL STRESSES INFLUENCE EPIGENOMIC VARIATION LINKED TO HEALTH. THE EVIDENCE THAT EPIGENETIC CHANGES ARE INVOLVED IN EMBEDDING OF SOCIAL STATUS-LINKED CHRONIC STRESS IS REVIEWED IN THE CONTEXT OF CURRENT KNOWLEDGE ABOUT BEHAVIOR WITHIN ANIMAL DOMINANCE HIERARCHIES AND THE IMPACTS OF SOCIAL POSITION ON BEHAVIORS THAT AFFECT HEALTH. THE ROLES OF EPIGENETIC MECHANISMS IN RESPONSES TO TRAUMA AND THE EVIDENCE FOR THEIR INVOLVEMENT IN INTERGENERATIONAL TRANSMISSION OF THE BIOLOGICAL IMPACTS OF TRAUMATIC STRESS ARE ALSO CONSIDERED. TAKEN TOGETHER, THE EMERGING INSIGHTS HAVE IMPORTANT IMPLICATIONS FOR DEVELOPMENT OF STRATEGIES TO IMPROVE SOCIETAL HEALTH AND WELL-BEING. 2016 17 6894 20 [SOCIAL INEQUALITY AND MENTAL HEALTH]. SOCIAL INEQUALITY REFERS TO THE INEQUITABLE DISTRIBUTION OF SOCIAL PROSPERITY INCLUDING THE RESOURCE OF HEALTH. THE RELATIONSHIP BETWEEN SOCIAL INEQUALITY AND MENTAL HEALTH CAN BE ESTABLISHED BY MEANS OF INDICATORS OF SOCIAL INEQUALITY THROUGHOUT ALL AGE GROUPS IN GERMANY. THERE ARE SOCIAL GRADIENTS OF MENTAL HEALTH ON THE POPULATION LEVEL, I.E. THE LINEAR RELATIONSHIP BETWEEN SOCIAL CLASSES OR STATUS AND STATE OF HEALTH. FUNDAMENTAL DETERMINANTS OF HEALTH DISPARITY ARE CULTURAL, SOCIAL, POLITICAL, AND GEOGRAPHICAL CONDITIONS, WHICH INTERACT WITH THE GENETIC MAKE-UP AND EPIGENETIC PROCESSES. THESE DETERMINANTS ALSO INFLUENCE THE MANAGEMENT OF DEVELOPMENTAL TASKS DURING THE LIFE COURSE AND ARE OF UTMOST IMPORTANCE FOR THE DEVELOPMENT OF MENTAL DISORDERS. THE MALADAPTATION TO CHRONIC STRESS IS AT THE CORE OF HEALTH DISPARITY. INTERVENTIONS AT THE INDIVIDUAL BEHAVIORAL LEVEL SHOULD COMPRISE THE DEVELOPMENT OF STRESS MANAGEMENT AND COPING STRATEGIES. 2019 18 5829 26 STRESS, PSYCHIATRIC DISORDERS, MOLECULAR TARGETS, AND MORE. MENTAL HEALTH IS CENTRAL TO NORMAL HEALTH OUTCOMES. A WIDELY ACCEPTED THEORY IS THAT CHRONIC PERSISTENT STRESS DURING ADULTHOOD AS WELL AS DURING EARLY LIFE TRIGGERS ONSET OF NEUROPSYCHIATRIC AILMENTS. HOWEVER, QUESTIONS RELATED TO HOW THAT OCCURS, AND WHY ARE SOME INDIVIDUALS RESISTANT TO STRESS WHILE OTHERS ARE NOT, REMAIN UNANSWERED. AN INTEGRATED, MULTISYSTEMIC STRESS RESPONSE INVOLVING NEUROINFLAMMATORY, NEUROENDOCRINE, EPIGENETIC AND METABOLIC CASCADES HAVE BEEN SUGGESTED TO HAVE CAUSATIVE LINKS. SEVERAL THEORIES HAVE BEEN PROPOSED OVER THE YEARS TO CONCEPTUALIZE THIS LINK INCLUDING THE CYTOKINE HYPOTHESIS, THE ENDOCRINE HYPOTHESIS, THE OXIDATIVE STRESS HYPOTHESIS AND THE OXIDO-NEUROINFLAMMATION HYPOTHESIS. THE DATA DISCUSSED IN THIS REVIEW DESCRIBES POTENTIAL BIOCHEMICAL BASIS OF THE LINK BETWEEN STRESS, AND STRESS-INDUCED NEURONAL, BEHAVIORAL AND EMOTIONAL DEFICITS, PROVIDING INSIGHTS INTO POTENTIALLY NOVEL DRUG TARGETS. 2019 19 4790 34 NUTRITIONAL ADVERSITY, SEX AND REPRODUCTION: 30 YEARS OF DOHAD AND WHAT HAVE WE LEARNED? IT IS WELL ESTABLISHED THAT EARLY LIFE ENVIRONMENTAL SIGNALS, INCLUDING NUTRITION, SET THE STAGE FOR LONG-TERM HEALTH AND DISEASE RISK - EFFECTS THAT SPAN MULTIPLE GENERATIONS. THIS RELATIONSHIP BEGINS EARLY, IN THE PERICONCEPTIONAL PERIOD AND EXTENDS INTO EMBRYONIC, FETAL AND EARLY INFANT PHASES OF LIFE. NOW KNOWN AS THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD), THIS CONCEPT DESCRIBES THE ADAPTATIONS THAT A DEVELOPING ORGANISM MAKES IN RESPONSE TO EARLY LIFE CUES, RESULTING IN ADJUSTMENTS IN HOMEOSTATIC SYSTEMS THAT MAY PROVE MALADAPTIVE IN POSTNATAL LIFE, LEADING TO AN INCREASED RISK OF CHRONIC DISEASE AND/OR THE INHERITANCE OF RISK FACTORS ACROSS GENERATIONS. REPRODUCTIVE MATURATION AND FUNCTION IS SIMILARLY INFLUENCED BY EARLY LIFE EVENTS. THIS SHOULD NOT BE SURPRISING, SINCE PRIMORDIAL GERM CELLS ARE ESTABLISHED EARLY IN LIFE AND THUS VULNERABLE TO EARLY LIFE ADVERSITY. A MULTITUDE OF 'MODIFYING' CUES INDUCING DEVELOPMENTAL ADAPTATIONS HAVE BEEN IDENTIFIED THAT RESULT IN CHANGES IN REPRODUCTIVE DEVELOPMENT AND IMPAIRMENTS IN REPRODUCTIVE FUNCTION. MANY TYPES OF NUTRITIONAL CHALLENGES INCLUDING CALORIC RESTRICTION, MACRONUTRIENT EXCESS AND MICRONUTRIENT INSUFFICIENCIES HAVE BEEN SHOWN TO INDUCE EARLY LIFE ADAPTATIONS THAT PRODUCE LONG-TERM REPRODUCTIVE DYSFUNCTION. MANY PATHWAYS HAVE BEEN SUGGESTED TO UNDERPIN THESE ASSOCIATIONS, INCLUDING EPIGENETIC REPROGRAMMING OF GERM CELLS. WHILE THE MECHANISMS STILL REMAIN TO BE FULLY INVESTIGATED, IT IS CLEAR THAT A LIFECOURSE APPROACH TO UNDERSTANDING LIFETIME REPRODUCTIVE FUNCTION IS NECESSARY. FURTHERMORE, INVESTIGATIONS OF THE IMPACTS OF EARLY LIFE ADVERSITY MUST BE EXTENDED TO INCLUDE THE PATERNAL ENVIRONMENT, ESPECIALLY IN EPIDEMIOLOGICAL AND CLINICAL STUDIES OF OFFSPRING REPRODUCTIVE FUNCTION. 2019 20 5136 29 POTENTIAL MECHANISMS LINKING PSYCHOLOGICAL STRESS TO BONE HEALTH. CHRONIC PSYCHOLOGICAL STRESS AFFECTS MANY BODY SYSTEMS, INCLUDING THE SKELETON, THROUGH VARIOUS MECHANISMS. THIS REVIEW AIMS TO PROVIDE AN OVERVIEW OF THE FACTORS MEDIATING THE RELATIONSHIP BETWEEN PSYCHOLOGICAL STRESS AND BONE HEALTH. THESE FACTORS CAN BE DIVIDED INTO PHYSIOLOGICAL AND BEHAVIOURAL CHANGES INDUCED BY PSYCHOLOGICAL STRESS. THE PHYSIOLOGICAL FACTORS INVOLVE ENDOCRINOLOGICAL CHANGES, SUCH AS INCREASED GLUCOCORTICOIDS, PROLACTIN, LEPTIN AND PARATHYROID HORMONE LEVELS AND REDUCED GONADAL HORMONES. LOW-GRADE INFLAMMATION AND HYPERACTIVATION OF THE SYMPATHETIC NERVOUS SYSTEM DURING PSYCHOLOGICAL STRESS ARE ALSO PHYSIOLOGICAL CHANGES DETRIMENTAL TO BONE HEALTH. THE BEHAVIOURAL CHANGES DURING MENTAL STRESS, SUCH AS ALTERED DIETARY PATTERN, CIGARETTE SMOKING, ALCOHOLISM AND PHYSICAL INACTIVITY, ALSO THREATEN THE SKELETAL SYSTEM. PSYCHOLOGICAL STRESS MAY BE PARTLY RESPONSIBLE FOR EPIGENETIC REGULATION OF SKELETAL DEVELOPMENT. IT MAY ALSO MEDIATE THE RELATIONSHIP BETWEEN SOCIOECONOMIC STATUS AND BONE HEALTH. HOWEVER, MORE DIRECT EVIDENCE IS REQUIRED TO PROVE THESE HYPOTHESES. IN CONCLUSION, CHRONIC PSYCHOLOGICAL STRESS SHOULD BE RECOGNISED AS A RISK FACTOR OF OSTEOPOROSIS AND STRESS-COPING METHODS SHOULD BE INCORPORATED AS PART OF THE COMPREHENSIVE OSTEOPOROSIS-PREVENTING STRATEGY. 2021