1 5310 73 PSYCHOBIOLOGY AND MOLECULAR GENETICS OF RESILIENCE. EVERY INDIVIDUAL EXPERIENCES STRESSFUL LIFE EVENTS. IN SOME CASES ACUTE OR CHRONIC STRESS LEADS TO DEPRESSION AND OTHER PSYCHIATRIC DISORDERS, BUT MOST PEOPLE ARE RESILIENT TO SUCH EFFECTS. RECENT RESEARCH HAS BEGUN TO IDENTIFY THE ENVIRONMENTAL, GENETIC, EPIGENETIC AND NEURAL MECHANISMS THAT UNDERLIE RESILIENCE, AND HAS SHOWN THAT RESILIENCE IS MEDIATED BY ADAPTIVE CHANGES IN SEVERAL NEURAL CIRCUITS INVOLVING NUMEROUS NEUROTRANSMITTER AND MOLECULAR PATHWAYS. THESE CHANGES SHAPE THE FUNCTIONING OF THE NEURAL CIRCUITS THAT REGULATE REWARD, FEAR, EMOTION REACTIVITY AND SOCIAL BEHAVIOUR, WHICH TOGETHER ARE THOUGHT TO MEDIATE SUCCESSFUL COPING WITH STRESS. 2009 2 1884 29 ENDOCANNABINOID-EPIGENETIC CROSS-TALK: A BRIDGE TOWARD STRESS COPING. THERE IS NO ARGUMENT WITH REGARD TO THE PHYSICAL AND PSYCHOLOGICAL STRESS-RELATED NATURE OF NEUROPSYCHIATRIC DISORDERS. YET, THE MECHANISMS THAT FACILITATE DISEASE ONSET STARTING FROM MOLECULAR STRESS RESPONSES ARE ELUSIVE. ENVIRONMENTAL STRESS CHALLENGES INDIVIDUALS' EQUILIBRIUM, ENHANCING HOMEOSTATIC REQUEST IN THE ATTEMPT TO STEER DOWN AROUSAL-INSTRUMENTAL MOLECULAR PATHWAYS THAT UNDERLIE HYPERVIGILANCE AND ANXIETY. A RELEVANT HOMEOSTATIC PATHWAY IS THE ENDOCANNABINOID SYSTEM (ECS). IN THIS REVIEW, WE SUMMARIZE RECENT DISCOVERIES UNAMBIGUOUSLY LISTING ECS AS A STRESS COPING MECHANISM. AS STRESS EVOKES HUGE EXCITATORY RESPONSES IN EMOTIONAL-RELEVANT LIMBIC AREAS, THE ECS LIMITS GLUTAMATE RELEASE VIA 2-ARACHYDONILGLYCEROL (2-AG) STRESS-INDUCED SYNTHESIS AND RETROGRADE CANNABINOID 1 (CB1)-RECEPTOR ACTIVATION AT THE SYNAPSE. HOWEVER, ECS SHOWS INTRINSIC VULNERABILITY AS 2-AG OVERSTIMULATION BY CHRONIC STRESS RAPIDLY LEADS TO CB1-RECEPTOR DESENSITIZATION. IN THIS REVIEW, WE EMPHASIZE THE PROTECTIVE ROLE OF 2-AG IN STRESS-RESPONSE TERMINATION AND STRESS RESILIENCY. INTERESTINGLY, WE DISCUSS ECS REGULATION WITH A FURTHER NUCLEAR HOMEOSTATIC SYSTEM WHOSE NATURE IS EXQUISITELY EPIGENETIC, ORCHESTRATED BY LYSINE SPECIFIC DEMETHYLASE 1. WE HERE EMPHASIZE A REMARKABLE EXAMPLE OF STRESS-COPING NETWORK WHERE TRANSCRIPTIONAL HOMEOSTASIS SUBSERVES SYNAPTIC AND BEHAVIORAL ADAPTATION, AIMING AT REDUCING PSYCHIATRIC EFFECTS OF TRAUMATIC EXPERIENCES. 2020 3 5465 24 RESILIENCE TO STRESS: LESSONS FROM RODENTS ABOUT NATURE VERSUS NURTURE. INDIVIDUAL DIFFERENCES IN HUMAN TEMPERAMENT INFLUENCE HOW WE RESPOND TO STRESS AND CAN CONFER VULNERABILITY (OR RESILIENCE) TO EMOTIONAL DISORDERS. FOR EXAMPLE, HIGH LEVELS OF BEHAVIORAL INHIBITION IN CHILDREN PREDICT INCREASED RISK OF MOOD AND ANXIETY DISORDERS IN LATER LIFE. THE BIOLOGICAL UNDERPINNINGS OF TEMPERAMENT ARE UNKNOWN, ALTHOUGH IMPROVED UNDERSTANDING CAN OFFER INSIGHT INTO THE PATHOGENESIS OF EMOTIONAL DISORDERS. OUR LABORATORY HAS USED A RAT MODEL OF TEMPERAMENTAL DIFFERENCES TO STUDY NEURODEVELOPMENTAL FACTORS THAT LEAD TO A HIGHLY INHIBITED, STRESS VULNERABLE PHENOTYPE. SELECTIVE BREEDING FOR HIGH VERSUS LOW BEHAVIORAL RESPONSE TO NOVELTY CREATED TWO RAT STRAINS THAT EXHIBIT DRAMATIC BEHAVIOR DIFFERENCES OVER MULTIPLE DOMAINS RELEVANT TO EMOTIONAL DISORDERS. LOW NOVELTY RESPONDER (BLR) RATS EXHIBIT HIGH LEVELS OF BEHAVIORAL INHIBITION, PASSIVE STRESS COPING, ANHEDONIA, DECREASED SOCIABILITY AND VULNERABILITY TO CHRONIC STRESS COMPARED TO HIGH NOVELTY RESPONDERS (BHRS). ON THE OTHER HAND, BHRS EXHIBIT HIGH LEVELS OF BEHAVIORAL DIS-INHIBITION, ACTIVE COPING, AND AGGRESSION. THIS REVIEW ARTICLE SUMMARIZES OUR WORK WITH THE BHR/BLR MODEL SHOWING THE DEVELOPMENTAL EMERGENCE OF THE BHR/BLR PHENOTYPES, THE ROLE THE ENVIRONMENT PLAYS IN SHAPING IT, AND THE INVOLVEMENT OF EPIGENETIC PROCESSES SUCH AS DNA METHYLATION THAT MEDIATE DIFFERENCES IN EMOTIONALITY AND STRESS REACTIVITY. 2022 4 5466 31 RESILIENCE: SAFETY IN THE AFTERMATH OF TRAUMATIC STRESSOR EXPERIENCES. THE RELATIONSHIP BETWEEN ADVERSE EXPERIENCES AND THE EMERGENCE OF PATHOLOGY HAS OFTEN FOCUSED ON CHARACTERISTICS OF THE STRESSOR OR OF THE INDIVIDUAL (STRESSOR APPRAISALS, COPING STRATEGIES). THESE FEATURES ARE THOUGHT TO INFLUENCE MULTIPLE BIOLOGICAL PROCESSES THAT FAVOR THE DEVELOPMENT OF MENTAL AND PHYSICAL ILLNESSES. LESS OFTEN HAS ATTENTION FOCUSED ON THE AFTERMATH OF TRAUMATIC EXPERIENCES, AND THE IMPORTANCE OF SAFETY AND REASSURANCE THAT IS NECESSARY FOR LONGER-TERM WELL-BEING. IN SOME CASES (E.G., POST-TRAUMATIC STRESS DISORDER) THIS MAY BE REFLECTED BY A FAILURE OF FEAR EXTINCTION, WHEREAS IN OTHER INSTANCES (E.G., HISTORICAL TRAUMA), THE UNCERTAINTY ABOUT THE FUTURE MIGHT FOSTER CONTINUED ANXIETY. IN ESSENCE, THE QUESTION BECOMES ONE OF HOW INDIVIDUALS ATTAIN FEELINGS OF SAFETY WHEN IT IS FULLY UNDERSTOOD THAT THE WORLD IS NOT NECESSARILY A SAFE PLACE, UNCERTAINTIES ABOUND, AND FEELINGS OF AGENCY ARE OFTEN ILLUSORY. WE CONSIDER HOW INDIVIDUALS ACQUIRE RESILIENCE IN THE AFTERMATH OF TRAUMATIC AND CHRONIC STRESSORS. IN THIS RESPECT, WE REVIEW CHARACTERISTICS OF STRESSORS THAT MAY TRIGGER PARTICULAR BIOLOGICAL AND BEHAVIORAL COPING RESPONSES, AS WELL AS FACTORS THAT UNDERMINE THEIR EFFICACY. TO THIS END, WE EXPLORE STRESSOR DYNAMICS AND SOCIAL PROCESSES THAT FOSTER RESILIENCE IN RESPONSE TO SPECIFIC TRAUMATIC, CHRONIC, AND UNCONTROLLABLE STRESSOR CONTEXTS (INTIMATE PARTNER ABUSE; REFUGEE MIGRATION; COLLECTIVE HISTORICAL TRAUMA). WE POINT TO RESILIENCE FACTORS THAT MAY COMPRISE NEUROBIOLOGICAL CHANGES, SUCH AS THOSE RELATED TO VARIOUS STRESSOR-PROVOKED HORMONES, NEUROTROPHINS, INFLAMMATORY IMMUNE, MICROBIAL, AND EPIGENETIC PROCESSES. THESE BEHAVIORAL AND BIOLOGICAL STRESS RESPONSES MAY INFLUENCE, AND BE INFLUENCED BY, FEELINGS OF SAFETY THAT COME ABOUT THROUGH RELATIONSHIPS WITH OTHERS, SPIRITUAL AND PLACE-BASED CONNECTIONS. 2020 5 704 23 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 6 6626 33 UNDERSTANDING RESILIENCE. RESILIENCE IS THE ABILITY TO ADAPT SUCCESSFULLY IN THE FACE OF STRESS AND ADVERSITY. STRESSFUL LIFE EVENTS, TRAUMA, AND CHRONIC ADVERSITY CAN HAVE A SUBSTANTIAL IMPACT ON BRAIN FUNCTION AND STRUCTURE, AND CAN RESULT IN THE DEVELOPMENT OF POSTTRAUMATIC STRESS DISORDER (PTSD), DEPRESSION AND OTHER PSYCHIATRIC DISORDERS. HOWEVER, MOST INDIVIDUALS DO NOT DEVELOP SUCH ILLNESSES AFTER EXPERIENCING STRESSFUL LIFE EVENTS, AND ARE THUS THOUGHT TO BE RESILIENT. RESILIENCE AS SUCCESSFUL ADAPTATION RELIES ON EFFECTIVE RESPONSES TO ENVIRONMENTAL CHALLENGES AND ULTIMATE RESISTANCE TO THE DELETERIOUS EFFECTS OF STRESS, THEREFORE A GREATER UNDERSTANDING OF THE FACTORS THAT PROMOTE SUCH EFFECTS IS OF GREAT RELEVANCE. THIS REVIEW FOCUSES ON RECENT FINDINGS REGARDING GENETIC, EPIGENETIC, DEVELOPMENTAL, PSYCHOSOCIAL, AND NEUROCHEMICAL FACTORS THAT ARE CONSIDERED ESSENTIAL CONTRIBUTORS TO THE DEVELOPMENT OF RESILIENCE. NEURAL CIRCUITS AND PATHWAYS INVOLVED IN MEDIATING RESILIENCE ARE ALSO DISCUSSED. THE GROWING UNDERSTANDING OF RESILIENCE FACTORS WILL HOPEFULLY LEAD TO THE DEVELOPMENT OF NEW PHARMACOLOGICAL AND PSYCHOLOGICAL INTERVENTIONS FOR ENHANCING RESILIENCE AND MITIGATING THE UNTOWARD CONSEQUENCES. 2013 7 6894 22 [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 8 1750 20 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 9 1774 22 EARLY-LIFE STRESS: FROM NEUROENDOCRINE MECHANISMS TO STRESS-RELATED DISORDERS. STRESS EXPOSURE IS HIGHLY PREVALENT IN THE GENERAL POPULATION; HOWEVER, THE EXPERIENCE OF STRESS DURING VULNERABLE PERIODS OF DEVELOPMENT HAS SUBSTANTIAL AND PERMANENT EFFECTS ON BRAIN STRUCTURE AND FUNCTION AND PHYSICAL HEALTH IN ADULTHOOD. STRESS, THE STATE OF THREATENED HOMEOSTASIS, IS GENERALLY ASSOCIATED WITH A TIME-LIMITED ACTIVATION OF THE STRESS SYSTEM, I.E., THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AND THE AROUSAL/SYMPATHETIC NERVOUS SYSTEM, TAILORED TO THE STRESSFUL STIMULUS ALSO KNOWN AS THE STRESSOR. ON THE OTHER HAND, CHRONIC STRESS MAY BE ASSOCIATED WITH LINGERING HYPER- OR HYPOSECRETION OF MEDIATORS OF THE STRESS SYSTEM. THIS CHRONIC CONDITION IS CALLED DYSHOMEOSTASIS, ALLOSTASIS, OR CACOSTASIS AND IS ASSOCIATED WITH INCREASED MENTAL AND PHYSICAL MORBIDITY IN THE LONG TERM. STRESSFUL OR TRAUMATIC EXPERIENCES DURING FETAL LIFE, EARLY CHILDHOOD, AND ADOLESCENCE HAVE BEEN RELATED TO PERSISTENT NEUROENDOCRINE AND EPIGENETIC CHANGES. FURTHER, BRAIN STRUCTURES INVOLVED IN THE STRESS RESPONSE, SUCH AS THOSE OF THE STRESS SYSTEM, THE HIPPOCAMPUS, AND THE AMYGDALA, MAY BE PROGRAMMED EARLY ON FOR A LIFE OF ADVERSITY. 2018 10 2949 23 GENETIC AND EPIGENETIC CONSEQUENCE OF EARLY-LIFE SOCIAL STRESS ON DEPRESSION: ROLE OF SEROTONIN-ASSOCIATED GENES. EARLY-LIFE ADVERSITY CAUSED BY POOR SOCIAL BONDING AND DEPRIVED MATERNAL CARE IS KNOWN TO AFFECT MENTAL WELLBEING AND PHYSICAL HEALTH. IT IS A FORM OF CHRONIC SOCIAL STRESS THAT PERSISTS BECAUSE OF A NEGATIVE ENVIRONMENT, AND THE CONSEQUENCES ARE LONG-LASTING ON MENTAL HEALTH. THE PRESENCE OF SOCIAL STRESS DURING EARLY LIFE CAN HAVE AN EPIGENETIC EFFECT ON THE BODY, POSSIBLY RESULTING IN MANY COMPLEX MENTAL DISORDERS, INCLUDING DEPRESSION IN LATER LIFE. HERE, WE REVIEW THE EVIDENCE FOR EARLY-LIFE SOCIAL STRESS-INDUCED EPIGENETIC CHANGES THAT MODULATE JUVENILE AND ADULT SOCIAL BEHAVIOR (DEPRESSION AND ANXIETY). THIS REVIEW HAS A PARTICULAR EMPHASIS ON THE INTERACTION BETWEEN EARLY-LIFE SOCIAL STRESS AND GENETIC VARIATION OF SEROTONIN ASSOCIATE GENES INCLUDING THE SEROTONIN TRANSPORTER GENE (5-HTT; ALSO KNOWN AS SLC6A4), WHICH ARE KEY MOLECULES INVOLVED IN DEPRESSION. 2020 11 678 32 BRAIN DEVELOPMENT UNDER STRESS: HYPOTHESES OF GLUCOCORTICOID ACTIONS REVISITED. ONE OF THE CONUNDRUMS IN TODAY'S STRESS RESEARCH IS WHY SOME INDIVIDUALS FLOURISH AND OTHERS PERISH UNDER SIMILAR STRESSFUL CONDITIONS. IT IS RECOGNIZED THAT THIS INDIVIDUAL VARIABILITY IN ADAPTATION TO STRESS DEPENDS ON THE OUTCOME OF THE INTERACTION OF GENETIC AND COGNITIVE/EMOTIONAL INPUTS IN WHICH GLUCOCORTICOID HORMONES AND RECEPTORS PLAY A CRUCIAL ROLE. HENCE ONE APPROACH TOWARDS UNDERSTANDING INDIVIDUAL VARIATION IN STRESS COPING IS HOW GLUCOCORTICOID ACTIONS CAN CHANGE FROM PROTECTIVE TO HARMFUL. TO ADDRESS THIS QUESTION WE FOCUS ON FOUR HYPOTHESES THAT ARE CONNECTED AND NOT MUTUAL EXCLUSIVE. FIRST, THE CLASSICAL GLUCOCORTICOID CASCADE HYPOTHESIS, IN WHICH THE INABILITY TO COPE WITH CHRONIC STRESS CAUSES A VICIOUS CYCLE OF EXCESS GLUCOCORTICOID AND DOWNREGULATION OF GLUCOCORTICOID RECEPTORS (GR) IN THE HIPPOCAMPUS TRIGGERING A FEED-FORWARD CASCADE OF DEGENERATION AND DISEASE. SECOND, THE BALANCE HYPOTHESIS, WHICH TAKES ALSO THE LIMBIC MINERALOCORTICOID RECEPTORS (MR) INTO ACCOUNT AND PROPOSES THAT AN INTEGRAL LIMBIC MR:GR IMBALANCE IS CAUSAL TO ALTERED PROCESSING OF INFORMATION IN CIRCUITS UNDERLYING FEAR, REWARD, SOCIAL BEHAVIOUR AND RESILIENCE, DYSREGULATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS AND IMPAIRMENT OF BEHAVIOURAL ADAPTATION. THE MR:GR BALANCE IS ALTERED BY GENE VARIANTS OF THESE RECEPTOR COMPLEXES AND EXPERIENCE-RELATED FACTORS, WHICH CAN INDUCE LASTING EPIGENETIC CHANGES IN THE EXPRESSION OF THESE RECEPTORS. A PARTICULAR POTENT EPIGENETIC STIMULUS IS THE MATERNAL ENVIRONMENT WHICH IS FUNDAMENTAL FOR THE MATERNAL MEDIATION HYPOTHESIS. THE OUTCOME OF PERINATAL GENE X ENVIRONMENT INTERACTION, AND THUS OF MR:GR-MEDIATED FUNCTIONS DEPENDS HOWEVER, ON THE DEGREE OF 'MATCHING' WITH ENVIRONMENTAL DEMANDS IN LATER LIFE. THE PREDICTIVE ADAPTATION HYPOTHESIS THEREFORE PRESENTS A CONCEPTUAL FRAMEWORK TO EXAMINE THE ROLE OF GLUCOCORTICOIDS IN UNDERSTANDING INDIVIDUAL PHENOTYPIC DIFFERENCES IN STRESS-RELATED BEHAVIOURS OVER THE LIFESPAN. 2010 12 4067 21 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 13 5873 23 SWEET SUCCESS, BITTER DEFEAT: A TASTE PHENOTYPE PREDICTS SOCIAL STATUS IN SELECTIVELY BRED RATS. FOR SOCIAL OMNIVORES SUCH AS RATS AND HUMANS, TASTE IS FAR MORE THAN A CHEMICAL SENSE ACTIVATED BY FOOD. BY VIRTUE OF EVOLUTIONARY AND EPIGENETIC ELABORATION, TASTE IS ASSOCIATED WITH NEGATIVE AFFECT, STRESS VULNERABILITY, RESPONSES TO PSYCHOACTIVE SUBSTANCES, PAIN, AND SOCIAL JUDGMENT. A CRUCIAL GAP IN THIS LITERATURE, WHICH SPANS BEHAVIOR GENETICS, AFFECTIVE AND SOCIAL NEUROSCIENCE, AND EMBODIED COGNITION, CONCERNS LINKS BETWEEN TASTE AND SOCIAL BEHAVIOR IN RATS. HERE WE SHOW THAT RATS SELECTIVELY BRED FOR LOW SACCHARIN INTAKE ARE SUBORDINATE TO HIGH-SACCHARIN-CONSUMING RATS WHEN THEY COMPETE IN WEIGHT-MATCHED DYADS FOR FOOD, A TASK USED TO MODEL DEPRESSION. STATISTICAL AND EXPERIMENTAL CONTROLS SUGGEST THAT DIFFERENTIAL RESOURCE UTILIZATION WITHIN DYADS IS NOT AN ARTIFACT OF INDIVIDUAL-LEVEL PROCESSES SUCH AS APPARATUS HABITUATION OR INGESTIVE MOTIVATION. TAIL SKIN TEMPERATURE MEASUREMENTS SHOWED THAT LOS RATS DISPLAY LARGER HYPERTHERMIC RESPONSES TO SOCIAL INTERACTION AFTER STATUS IS ESTABLISHED, EVIDENCE LINKING TASTE, SOCIAL STRESS, AUTONOMIC REACTIVITY, AND DEPRESSION-LIKE SYMPTOMS. BASED ON REGRESSION USING EARLY- AND LATE-COMPETITION PREDICTORS TO PREDICT DYADIC DISPARITY IN FINAL COMPETITION SCORES, WE TENTATIVELY SUGGEST THAT HIS RATS EMERGE AS DOMINANT BOTH BECAUSE OF AN "EARLY SURGE" ON THEIR PART AND BECAUSE LOS ACQUIESCE LATER. THESE FINDINGS SHOULD INVIGORATE THE COMPARATIVE STUDY OF INDIVIDUAL DIFFERENCES IN SOCIAL STATUS AND ITS RELATIONSHIP TO MENTAL AND PHYSICAL HEALTH. 2012 14 6266 20 THE NEUROBIOLOGY OF SUICIDE. THE STRESS-DIATHESIS MODEL POSITS THAT SUICIDE IS THE RESULT OF AN INTERACTION BETWEEN STATE-DEPENDENT (ENVIRONMENTAL) STRESSORS AND A TRAIT-LIKE DIATHESIS OR SUSCEPTIBILITY TO SUICIDAL BEHAVIOUR, INDEPENDENT OF PSYCHIATRIC DISORDERS. FINDINGS FROM POST-MORTEM STUDIES OF THE BRAIN AND FROM GENOMIC AND IN-VIVO NEUROIMAGING STUDIES INDICATE A BIOLOGICAL BASIS FOR THIS DIATHESIS, INDICATING THE IMPORTANCE OF NEUROBIOLOGICAL SCREENING AND INTERVENTIONS, IN ADDITION TO COGNITIVE AND MOOD INTERVENTIONS, IN THE PREVENTION OF SUICIDE. EARLY-LIFE ADVERSITY AND EPIGENETIC MECHANISMS MIGHT EXPLAIN SOME OF THE LINK BETWEEN SUICIDE RISK AND BRAIN CIRCUITRY AND NEUROCHEMISTRY ABNORMALITIES. RESULTS FROM A RANGE OF STUDIES USING DIVERSE DESIGNS AND POST-MORTEM AND IN-VIVO TECHNIQUES SHOW IMPAIRMENTS OF THE SEROTONIN NEUROTRANSMITTER SYSTEM AND THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS STRESS-RESPONSE SYSTEM IN THE DIATHESIS FOR SUICIDAL BEHAVIOUR. THESE IMPAIRMENTS MANIFEST AS IMPAIRED COGNITIVE CONTROL OF MOOD, PESSIMISM, REACTIVE AGGRESSIVE TRAITS, IMPAIRED PROBLEM SOLVING, OVER-REACTIVITY TO NEGATIVE SOCIAL SIGNS, EXCESSIVE EMOTIONAL PAIN, AND SUICIDAL IDEATION, LEADING TO SUICIDAL BEHAVIOUR. BIOMARKERS RELATED TO THE DIATHESIS MIGHT HELP TO INFORM RISK-ASSESSMENT PROCEDURES AND TREATMENT CHOICE IN THE PREVENTION OF SUICIDE. 2014 15 4622 19 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 16 3713 23 INHERITANCE OF ACQUIRED BEHAVIOUR ADAPTATIONS AND BRAIN GENE EXPRESSION IN CHICKENS. BACKGROUND: ENVIRONMENTAL CHALLENGES MAY AFFECT BOTH THE EXPOSED INDIVIDUALS AND THEIR OFFSPRING. WE INVESTIGATED POSSIBLE ADAPTIVE ASPECTS OF SUCH CROSS-GENERATION TRANSMISSIONS, AND HYPOTHESIZED THAT CHRONIC UNPREDICTABLE FOOD ACCESS WOULD CAUSE CHICKENS TO SHOW A MORE CONSERVATIVE FEEDING STRATEGY AND TO BE MORE DOMINANT, AND THAT THESE ADAPTATIONS WOULD BE TRANSMITTED TO THE OFFSPRING. METHODOLOGY/PRINCIPAL FINDINGS: PARENTS WERE RAISED IN AN UNPREDICTABLE (UL) OR IN PREDICTABLE DIURNAL LIGHT RHYTHM (PL, 12:12 H LIGHT:DARK). IN A FORAGING TEST, UL BIRDS PECKED MORE AT FREELY AVAILABLE, RATHER THAN AT HIDDEN AND MORE ATTRACTIVE FOOD, COMPARED TO BIRDS FROM THE PL GROUP. FEMALE OFFSPRING OF UL BIRDS, RAISED IN PREDICTABLE LIGHT CONDITIONS WITHOUT PARENTAL CONTACT, SHOWED A SIMILAR FORAGING BEHAVIOR, DIFFERING FROM OFFSPRING OF PL BIRDS. FURTHERMORE, ADULT OFFSPRING OF UL BIRDS PERFORMED MORE FOOD PECKS IN A DOMINANCE TEST, SHOWED A HIGHER PREFERENCE FOR HIGH ENERGY FOOD, SURVIVED BETTER, AND WERE HEAVIER THAN OFFSPRING OF PL PARENTS. USING CDNA MICROARRAYS, WE FOUND THAT THE DIFFERENTIAL BRAIN GENE EXPRESSION CAUSED BY THE CHALLENGE WAS MIRRORED IN THE OFFSPRING. IN PARTICULAR, SEVERAL IMMUNOGLOBULIN GENES SEEMED TO BE AFFECTED SIMILARLY IN BOTH UL PARENTS AND THEIR OFFSPRING. ESTRADIOL LEVELS WERE SIGNIFICANTLY HIGHER IN EGG YOLK FROM UL BIRDS, SUGGESTING ONE POSSIBLE MECHANISM FOR THESE EFFECTS. CONCLUSIONS/SIGNIFICANCE: OUR FINDINGS SUGGEST THAT UNPREDICTABLE FOOD ACCESS CAUSED SEEMINGLY ADAPTIVE RESPONSES IN FEEDING BEHAVIOR, WHICH MAY HAVE BEEN TRANSMITTED TO THE OFFSPRING BY MEANS OF EPIGENETIC MECHANISMS, INCLUDING REGULATION OF IMMUNE GENES. THIS MAY HAVE PREPARED THE OFFSPRING FOR COPING WITH AN UNPREDICTABLE ENVIRONMENT. 2009 17 235 21 ADDING FUEL TO THE FIRE: THE IMPACT OF STRESS ON THE AGEING BRAIN. BOTH AGEING AND CHRONIC STRESS ARE ASSOCIATED WITH ALTERED BRAIN PLASTICITY, DYSREGULATION OF THE IMMUNE SYSTEM, AND AN INCREASED RISK OF DEVELOPING BRAIN DISORDERS; ALL OF WHICH HAVE CONSEQUENCES FOR COGNITIVE AND EMOTIONAL PROCESSING. HERE WE EXAMINE THE SIMILARITIES BETWEEN BEHAVIOURAL CHANGES DURING AGEING AND STRESS ALTERED BEHAVIOURS (ANXIETY, DEPRESSIVE-LIKE BEHAVIOUR, COGNITION, AND SOCIABILITY) IN RODENTS AND HUMANS. THE MOLECULAR MECHANISMS HYPOTHESISED TO MEDIATE AGE-RELATED CHANGES IN BRAIN FUNCTION INCLUDING DYSFUNCTION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS, DYSREGULATION OF NEUROTRANSMISSION AND NEUROTROPHIC FACTOR SIGNALLING, INCREASED INFLAMMATORY STATE, GENETIC AND EPIGENETIC CHANGES, OXIDATIVE STRESS, METABOLIC CHANGES, AND CHANGES IN THE MICROBIOTA-GUT-BRAIN AXIS ARE DISCUSSED. FINALLY, WE EXPLORE HOW THE ALREADY STRESSED AGED BRAIN PSYCHOLOGICALLY AND PHYSIOLOGICALLY RESPONDS TO EXTERNAL STRESSORS. 2015 18 248 31 ADVANCE IN STRESS FOR DEPRESSIVE DISORDER. STRESS IS AN ADAPTIVE RESPONSE TO ENVIRONMENT AVERSIVE STIMULI AND A COMMON LIFE EXPERIENCE OF ONE'S DAILY LIFE. CHRONIC OR EXCESSIVE STRESS ESPECIALLY THAT HAPPENED IN EARLY LIFE IS FOUND TO BE DELETERIOUS TO INDIVIDUAL'S PHYSICAL AND MENTAL HEALTH, WHICH IS HIGHLY RELATED TO DEPRESSIVE DISORDERS ONSET. STRESSFUL LIFE EVENTS ARE CONSISTENTLY CONSIDERED TO BE THE HIGH-RISK FACTORS OF ENVIRONMENT FOR PREDISPOSING DEPRESSIVE DISORDERS. IN LINKING STRESSFUL LIFE EVENTS WITH DEPRESSIVE DISORDER ONSET, DYSREGULATED HPA AXIS ACTIVITY IS SUPPOSED TO PLAY AN IMPORTANT ROLE IN MEDIATING AVERSIVE IMPACTS OF LIFE STRESS ON BRAIN STRUCTURE AND FUNCTION. INCREASING EVIDENCE HAVE INDICATED THE STRONG ASSOCIATION OF STRESS, ESPECIALLY THE CHRONIC STRESS AND EARLY LIFE STRESS, WITH DEPRESSIVE DISORDERS DEVELOPMENT, WHILE THE ASSOCIATION OF STRESS WITH DEPRESSION IS MODERATED BY GENETIC RISK FACTORS, INCLUDING POLYMORPHISM OF SERT, BDNF, GR, FKBP5, MR, AND CRHR1. MEANWHILE, STRESSFUL LIFE EXPERIENCE PARTICULARLY EARLY LIFE STRESS WILL EXERT EPIGENETIC MODIFICATION IN THESE RISK GENES VIA DNA METHYLATION AND MIRNA REGULATION TO GENERATE LONG-LASTING EFFECTS ON THESE GENES EXPRESSION, WHICH IN TURN CAUSE BRAIN STRUCTURAL AND FUNCTIONAL ALTERATION, AND FINALLY INCREASE THE VULNERABILITY TO DEPRESSIVE DISORDERS. THEREFORE, THE INTERACTION OF ENVIRONMENT WITH GENE, IN WHICH STRESSFUL LIFE EXPOSURE INTERPLAY WITH GENETIC RISK FACTORS AND EPIGENETIC MODIFICATION, IS ESSENTIAL IN PREDICTING DEPRESSIVE DISORDERS DEVELOPMENT. AS THE MEDIATOR OF ENVIRONMENTAL RISK FACTORS, STRESS WILL FUNCTION TOGETHER WITH GENETIC AND EPIGENETIC MECHANISM TO INFLUENCE BRAIN STRUCTURE AND FUNCTION, PHYSIOLOGY AND PSYCHOLOGY, AND FINALLY THE VULNERABILITY TO DEPRESSIVE DISORDERS. 2019 19 1548 29 DNA METHYLATION IN THE DEVELOPING HIPPOCAMPUS AND AMYGDALA OF ANXIETY-PRONE VERSUS RISK-TAKING RATS. ALL ORGANISMS EXHIBIT A WIDE RANGE OF EMOTIONAL BEHAVIORS AND INTERACT WITH THE ENVIRONMENT IN DIFFERENT WAYS. SOME INDIVIDUALS MAY BE MORE QUIET AND SHY WHEREAS OTHERS ARE MORE OUTGOING AND ADVENTUROUS. THESE TEMPERAMENTAL AND PERSONALITY DIFFERENCES CAN PREDISPOSE INDIVIDUALS TO CERTAIN PSYCHOPATHOLOGIES WHICH MAY BE INFLUENCED BY GENETIC VULNERABILITY AND/OR EARLY LIFE EXPERIENCES. RODENT MODELS CAN BE USED TO RECAPITULATE EMOTIONAL REACTIVITY DIFFERENCES, AND THESE MODELS CAN, IN TURN, BE USED TO EXAMINE POTENTIAL NEUROBIOLOGICAL UNDERPINNINGS OF THESE TRAITS. THE PRESENT STUDY UTILIZES TWO STRAINS OF RATS THAT WERE SELECTIVELY BRED FOR DIFFERENCES IN NOVELTY SEEKING. HIGH NOVELTY-RESPONDING (BHR) RATS ARE VERY ACTIVE IN RESPONSE TO NOVELTY, EXHIBIT EXAGGERATED RISK-TAKING, AGGRESSION, IMPULSIVITY, AND SHOW INCREASED BEHAVIORAL RESPONSE TO COCAINE. LOW NOVELTY-RESPONDING (BLR) RATS SHOW INCREASED ANXIETY, DEPRESSIVE BEHAVIOR AND VULNERABILITY TO CHRONIC STRESS. ONE WAY IN WHICH THE BHR VERSUS BLR BEHAVIORAL PHENOTYPES MAY DIFFER IS THROUGH EPIGENETIC MODIFICATION OF DNA. DNA CAN BE MODIFIED THROUGH PROCESSES SUCH AS ACETYLATION OR METHYLATION TO EITHER ENHANCE OR SUBDUE GENE EXPRESSION. THIS STUDY EXAMINES PUTATIVE DIFFERENCES IN METHYLATION LEVELS IN THE HIPPOCAMPUS AND AMYGDALA OF DEVELOPING BHR-BLR RATS. PREVIOUS RESEARCH OBSERVED WIDESPREAD GENE EXPRESSION DIFFERENCES IN THE BLR DEVELOPING HIPPOCAMPUS, AND THE CURRENT STUDY AIMS TO BEGIN TO EXAMINE POTENTIAL EPIGENETIC FACTORS THAT MAY CONTRIBUTE TO THOSE GENE DIFFERENCES. THE AMYGDALA WAS CHOSEN BECAUSE IT IS INVOLVED IN EMOTIONAL PROCESSES, IN PART THROUGH ITS CONNECTIONS WITH THE HIPPOCAMPUS. THEREFORE, THE PRESENT STUDY USED IN SITU HYBRIDIZATION TO ASSESS THE EXPRESSION OF DNA METHYLTRANSFERASE-1 (DNMT1) MRNA IN THE HIPPOCAMPUS, AMYGDALA AND SEVERAL OTHER BRAIN AREAS OF BHR AND BLR PUPS AT THREE DEVELOPMENTAL TIME POINTS: POSTNATAL DAYS (P) 7, 14, AND 21. WE FOCUSED ON THE FIRST 3 POSTNATAL WEEKS, IN PART TO PARALLEL OUR EARLY MICROARRAY GENE EXPRESSION WORK, AND BECAUSE THIS REPRESENTS A CRITICAL PERIOD OF BRAIN DEVELOPMENT, WHICH SHAPES INDIVIDUALS' LIFELONG EMOTIONAL AND STRESS REACTIVITY. WE FOUND SIGNIFICANT DIFFERENCES IN DENTATE GYRUS AND CA3 REGIONS OF THE HIPPOCAMPUS AT P7 WITH NO DIFFERENCES SEEN AT P14 OR P21. INTERESTINGLY, WE ALSO FOUND SIGNIFICANT BHR-BLR DNMT1 DIFFERENCES AT P7 WITHIN THE LATERAL, BASOLATERAL AND MEDIAL NUCLEI OF THE AMYGDALA, WITH NO DIFFERENCE AT P14 AND P21, SUGGESTING THAT THE FIRST POSTNATAL WEEK IS A CRITICAL PERIOD FOR DNA METHYLATION DURING BRAIN DEVELOPMENT. 2012 20 6627 49 UNDERSTANDING RESILIENCE: NEW APPROACHES FOR PREVENTING AND TREATING PTSD. ALL INDIVIDUALS EXPERIENCE STRESSFUL LIFE EVENTS, AND UP TO 84% OF THE GENERAL POPULATION WILL EXPERIENCE AT LEAST ONE POTENTIALLY TRAUMATIC EVENT. IN SOME CASES, ACUTE OR CHRONIC STRESSORS LEAD TO THE DEVELOPMENT OF POSTTRAUMATIC STRESS DISORDER (PTSD) OR OTHER PSYCHOPATHOLOGY; HOWEVER, THE MAJORITY OF PEOPLE ARE RESILIENT TO SUCH EFFECTS. RESILIENCE IS THE ABILITY TO ADAPT SUCCESSFULLY IN THE FACE OF STRESS AND ADVERSITY. A WEALTH OF RESEARCH HAS BEGUN TO IDENTIFY THE GENETIC, EPIGENETIC, NEURAL, AND ENVIRONMENTAL UNDERPINNINGS OF RESILIENCE, AND HAS INDICATED THAT RESILIENCE IS MEDIATED BY ADAPTIVE CHANGES ENCOMPASSING SEVERAL ENVIRONMENTAL FACTORS, NEURAL CIRCUITS, NUMEROUS NEUROTRANSMITTERS, AND MOLECULAR PATHWAYS. THE FIRST PART OF THIS REVIEW FOCUSES ON RECENT FINDINGS REGARDING THE GENETIC, EPIGENETIC, DEVELOPMENTAL, PSYCHOSOCIAL, AND NEUROCHEMICAL FACTORS AS WELL AS NEURAL CIRCUITS AND MOLECULAR PATHWAYS THAT UNDERLIE THE DEVELOPMENT OF RESILIENCE. EMERGING AND EXCITING AREAS OF RESEARCH AND NOVEL METHODOLOGICAL APPROACHES, INCLUDING GENOME-WIDE GENE EXPRESSION STUDIES, IMMUNE, ENDOCANNABINOID, OXYTOCIN, AND GLUTAMATERGIC SYSTEMS, ARE EXPLORED TO HELP DELINEATE INNOVATIVE MECHANISMS THAT MAY CONTRIBUTE TO RESILIENCE. THE SECOND PART REVIEWS SEVERAL INTERVENTIONS AND PREVENTATIVE APPROACHES DESIGNED TO ENHANCE RESILIENCE IN BOTH DEVELOPMENTAL AND ADULT POPULATIONS. SPECIFICALLY, THE REVIEW WILL DELINEATE APPROACHES AIMED TO BOLSTER RESILIENCE IN INDIVIDUALS WITH PTSD. FURTHERMORE, WE DISCUSS NOVEL PHARMACOLOGIC APPROACHES, INCLUDING THE N-METHYL-D-ASPARTATE (NMDA) RECEPTOR KETAMINE AND NEUROPEPTIDE Y (NPY), AS EXCITING NEW PROSPECTS FOR NOT ONLY THE TREATMENT OF PTSD BUT AS NEW TARGETS TO ENHANCE RESILIENCE. OUR GROWING UNDERSTANDING OF RESILIENCE AND INTERVENTIONS WILL HOPEFULLY LEAD TO THE DEVELOPMENT OF NEW STRATEGIES FOR NOT JUST TREATING PTSD BUT ALSO SCREENING AND EARLY IDENTIFICATION OF AT-RISK YOUTH AND ADULTS. TAKEN TOGETHER, EFFORTS AIMED AT DISSEMINATION AND IMPLEMENTATION OF NOVEL INTERVENTIONS TO ENHANCE RESILIENCE WILL HAVE TO KEEP PACE WITH THE GROWTH OF NEW PREVENTIVE AND TREATMENT STRATEGIES. 2016