1 5684 187 SHOULD WE EMBRACE THE INCORPORATION OF GENETICALLY GUIDED "DOPAMINE HOMEOSTASIS" IN THE TREATMENT OF REWARD DEFICIENCY SYNDROME (RSD) AS A FRONTLINE THERAPEUTIC MODALITY? IN 2019, THE US CENTER FOR DISEASE CONTROL AND PREVENTION PROVIDED VITAL STATISTICS RELATED TO DRUG OVERDOSES IN THE UNITED STATE1. THEY CONCLUDED THAT IN THE USA THE NUMBER OF DEATHS AT ALMOST 72,000 WAS DUE TO 66.6% OF OPIOID OVERDOSES. IN FACT, THE RATE IS ALARMING AND INCREASING YEARLY. TO MAKE 2021 EVEN MORE SCARY IS THE DAUNTING EFFECT ON INCREASED DRUG USAGE DUE TO COVID 19 AS A PANDEMIC, ALBEIT THE NEW VACCINES. SPECIFICALLY, IN 2020, THE DEATH RATE FROM OPIOID OVERDOSES ROSE TO 13% NATIONALLY AND IN SOME SATES 30%. THE COMMON NEUROMODULATING ASPECTS OF NEUROTRANSMISSION, AND ITS DISRUPTION VIA CHRONIC EXPOSURE OF DRUGS AND BEHAVIORAL ADDICTIONS, REQUIRES FURTHER INTENSE RESEARCH FOCUS ON DEVELOPING NOVEL STRATEGIES TO COMBAT THESE UNWANTED GENETIC AND EPIGENIC INFRACTIONS AS ACCOMPLISHED WITH HEROIN ADDICTION BY OUR GROUP. THE TAKE HOME MESSAGE IS THE PLAUSIBLE ACCEPTANCE OF THE WELL-ESTABLISHED EVIDENCE FOR HYPODOPAMINERGIA, A BLUNTED REWARD PROCESSING SYSTEM, REDUCED RESTING STATE FUNCTIONAL CONNECTIVITY, GENETIC ANTECEDENTS, ANTI- REWARD SYMPTOMATOLOGY, POOR COMPLIANCE WITH MAT, AND GENERALIZED RDS. WITH THIS EVIDENCE IT IS CONCEIVABLE THAT PURSUIT THROUGH INTENSIVE FUTURE RESEARCH SHOULD INVOLVE AN APPROACH THAT INCORPORATES "DOPAMINE HOMEOSTASIS". THIS REQUIRED PARADIGM SHIFT MAY CONSIST OF MANY BENEFICIAL MODALITIES INCLUDING BUT NOT LIMITED TO: EXERCISE, PRO-DOPAMINE REGULATION, NUTRIGENOMICS, COGNITIVE BEHAVIORAL THERAPY, HEDONIC HOT SPOT TARGETS BRAIN, RTMRS, DEEP BRAIN STIMULATION, DIET, GENETIC EDITS, GENETIC GUIDED THERAPEUTICS, EPIGENETIC REPAIR, AMONGST OTHERS. IT IS OUR OPINION THAT NUTRIGENOMICS MAY ASSIST THE MILLIONS OF PEOPLE OF GETTING OUT OF A" HYPODOPAMINERGIC DITCH" WC 250. 2021 2 2518 34 EPIGENETICS AND THE EMBODIMENT OF RACE: DEVELOPMENTAL ORIGINS OF US RACIAL DISPARITIES IN CARDIOVASCULAR HEALTH. THE RELATIVE CONTRIBUTION OF GENETIC AND ENVIRONMENTAL INFLUENCES TO THE US BLACK-WHITE DISPARITY IN CARDIOVASCULAR DISEASE (CVD) IS HOTLY DEBATED WITHIN THE PUBLIC HEALTH, ANTHROPOLOGY, AND MEDICAL COMMUNITIES. IN THIS ARTICLE, WE REVIEW EVIDENCE FOR DEVELOPMENTAL AND EPIGENETIC PATHWAYS LINKING EARLY LIFE ENVIRONMENTS WITH CVD, AND CRITICALLY EVALUATE THEIR POSSIBLE ROLE IN THE ORIGINS OF THESE RACIAL HEALTH DISPARITIES. AFRICAN AMERICANS NOT ONLY SUFFER FROM A DISPROPORTIONATE BURDEN OF CVD RELATIVE TO WHITES, BUT ALSO HAVE HIGHER RATES OF THE PERINATAL HEALTH DISPARITIES NOW KNOWN TO BE THE ANTECEDENTS OF THESE CONDITIONS. THERE IS EXTENSIVE EVIDENCE FOR A SOCIAL ORIGIN TO PREMATURITY AND LOW BIRTH WEIGHT IN AFRICAN AMERICANS, REFLECTING PATHWAYS SUCH AS THE EFFECTS OF DISCRIMINATION ON MATERNAL STRESS PHYSIOLOGY. IN LIGHT OF THE INVERSE RELATIONSHIP BETWEEN BIRTH WEIGHT AND ADULT CVD, THERE IS NOW A STRONG RATIONALE TO CONSIDER DEVELOPMENTAL AND EPIGENETIC MECHANISMS AS LINKS BETWEEN EARLY LIFE ENVIRONMENTAL FACTORS LIKE MATERNAL STRESS DURING PREGNANCY AND ADULT RACE-BASED HEALTH DISPARITIES IN DISEASES LIKE HYPERTENSION, DIABETES, STROKE, AND CORONARY HEART DISEASE. THE MODEL OUTLINED HERE BUILDS UPON SOCIAL CONSTRUCTIVIST PERSPECTIVES TO HIGHLIGHT AN IMPORTANT SET OF MECHANISMS BY WHICH SOCIAL INFLUENCES CAN BECOME EMBODIED, HAVING DURABLE AND EVEN TRANSGENERATIONAL INFLUENCES ON THE MOST PRESSING US HEALTH DISPARITIES. WE CONCLUDE THAT ENVIRONMENTALLY RESPONSIVE PHENOTYPIC PLASTICITY, IN COMBINATION WITH THE BETTER-STUDIED ACUTE AND CHRONIC EFFECTS OF SOCIAL-ENVIRONMENTAL EXPOSURES, PROVIDES A MORE PARSIMONIOUS EXPLANATION THAN GENETICS FOR THE PERSISTENCE OF CVD DISPARITIES BETWEEN MEMBERS OF SOCIALLY IMPOSED RACIAL CATEGORIES. 2009 3 4062 37 MATERNAL AND CHILD HEALTH SERVICES AND AN INTEGRATED, LIFE-CYCLE APPROACH TO THE PREVENTION OF NON-COMMUNICABLE DISEASES. DESCRIBED AS THE 'INVISIBLE EPIDEMIC', NON-COMMUNICABLE DISEASES (NCDS) ARE THE WORLD'S LEADING CAUSE OF DEATH. MOST ARE CAUSED BY PREVENTABLE FACTORS, INCLUDING POOR DIET, TOBACCO USE, HARMFUL USE OF ALCOHOL AND PHYSICAL INACTIVITY. DIABETES, CANCER AND CARDIOVASCULAR AND CHRONIC LUNG DISEASES WERE RESPONSIBLE FOR 38 MILLION (68%) OF GLOBAL DEATHS IN 2012. SINCE 1990, PROPORTIONATE NCD MORTALITY HAS INCREASED SUBSTANTIALLY AS POPULATIONS HAVE AGED AND COMMUNICABLE DISEASES DECLINE. THE MAJORITY OF NCD DEATHS, ESPECIALLY PREMATURE NCD DEATHS (<70 YEARS, 82%), OCCUR IN LOW-INCOME AND MIDDLE-INCOME COUNTRIES, AND AMONG POOR COMMUNITIES WITHIN THEM. ADDRESSING NCDS IS RECOGNISED AS CENTRAL TO THE POST-2015 AGENDA; ACCORDINGLY, NCDS HAVE A SPECIFIC OBJECTIVE AND TARGET IN THE SUSTAINABLE DEVELOPMENT GOALS. WHILE DEATHS FROM NCDS OCCUR MAINLY IN ADULTHOOD, MANY HAVE THEIR ORIGINS IN EARLY LIFE, INCLUDING THROUGH EPIGENETIC MECHANISMS OPERATING BEFORE CONCEPTION. GOOD NUTRITION BEFORE CONCEPTION AND INTERVENTIONS AIMED AT PREVENTING NCDS DURING THE FIRST 1000 DAYS (FROM CONCEPTION TO AGE 2 YEARS), CHILDHOOD AND ADOLESCENCE MAY BE MORE COST-EFFECTIVE THAN MANAGING ESTABLISHED NCDS IN LATER LIFE WITH COSTLY TESTS AND DRUGS. FOLLOWING A LIFE-COURSE APPROACH, MATERNAL AND CHILD HEALTH INTERVENTIONS, BEFORE DELIVERY AND DURING CHILDHOOD AND ADOLESCENCE, CAN PREVENT NCDS AND SHOULD INFLUENCE GLOBAL HEALTH AND SOCIOECONOMIC DEVELOPMENT. THIS PAPER DESCRIBES HOW SUCH AN APPROACH MAY BE PURSUED, INCLUDING THROUGH THE ENGAGEMENT OF NON-HEALTH SECTORS. IT ALSO EMPHASISES EVALUATING AND DOCUMENTING RELATED INITIATIVES TO UNDERWRITE SYSTEMATIC AND EVIDENCE-BASED CROSS-SECTORAL ENGAGEMENT ON NCD PREVENTION IN THE FUTURE. 2017 4 29 37 A BIOPSYCHOSOCIAL OVERVIEW OF THE OPIOID CRISIS: CONSIDERING NUTRITION AND GASTROINTESTINAL HEALTH. THE OPIOID CRISIS HAS REACHED EPIDEMIC PROPORTIONS IN THE UNITED STATES WITH RISING OVERDOSE DEATH RATES. IDENTIFYING THE UNDERLYING FACTORS THAT CONTRIBUTE TO ADDICTION VULNERABILITY MAY LEAD TO MORE EFFECTIVE PREVENTION STRATEGIES. SUPPLY SIDE ENVIRONMENTAL FACTORS ARE A MAJOR CONTRIBUTING COMPONENT. PSYCHOSOCIAL FACTORS SUCH AS STRESS, TRAUMA, AND ADVERSE CHILDHOOD EXPERIENCES HAVE BEEN LINKED TO EMOTIONAL PAIN LEADING TO SELF-MEDICATION. GENETIC AND EPIGENETIC FACTORS ASSOCIATED WITH BRAIN REWARD PATHWAYS AND IMPULSIVITY ARE KNOWN PREDICTORS OF ADDICTION VULNERABILITY. THIS REVIEW ATTEMPTS TO PRESENT A BIOPSYCHOSOCIAL APPROACH THAT CONNECTS VARIOUS SOCIAL AND BIOLOGICAL THEORIES RELATED TO THE ADDICTION CRISIS. THE EMERGING ROLE OF NUTRITION THERAPY WITH AN EMPHASIS ON GASTROINTESTINAL HEALTH IN THE TREATMENT OF OPIOID USE DISORDER IS PRESENTED. THE BIOPSYCHOSOCIAL MODEL INTEGRATES CONCEPTS FROM SEVERAL DISCIPLINES, EMPHASIZING MULTICAUSALITY RATHER THAN A REDUCTIONIST APPROACH. POTENTIAL SOLUTIONS AT MULTIPLE LEVELS ARE PRESENTED, CONSIDERING INDIVIDUAL AS WELL AS POPULATION HEALTH. THIS SINGLE COHESIVE FRAMEWORK IS BASED ON THE INTERDEPENDENCY OF THE ENTIRE SYSTEM, IDENTIFYING RISK AND PROTECTIVE FACTORS THAT MAY INFLUENCE SUBSTANCE-SEEKING BEHAVIOR. NUTRITION SHOULD BE INCLUDED AS ONE FACET OF A MULTIDISCIPLINARY APPROACH TOWARD IMPROVED RECOVERY OUTCOMES. CROSS-DISCIPLINARY COLLABORATIVE EFFORTS, NEW IDEAS, AND FISCAL RESOURCES WILL BE CRITICAL TO ADDRESS THE EPIDEMIC. 2019 5 734 35 CANCER HEALTHCARE DISPARITIES AMONG AFRICAN AMERICANS IN THE UNITED STATES. A NEED EXISTS TO EXAMINE RACIAL DISPARITIES IN THE HEALTHCARE ARENA AND THE IMPACT ON PATIENTS WITH CANCER. DESPITE ONGOING EFFORTS TO INCREASE EQUITY IN PRIMARY HEALTHCARE ACCESS, RACIAL AND SOCIOECONOMIC DISPARITIES PERSIST, THUS CONTRIBUTING TO DISPROPORTIONATE TREATMENT OUTCOMES AND SURVIVORSHIP AMONG MINORITY AND LOW-INCOME PATIENTS. SUCH DISPARITIES HAVE BEEN REVEALED IN TREATMENT COHORTS OF PATIENTS WITH MULTIPLE FORMS OF CANCER, INCLUDING BREAST, CERVICAL, OVARIAN, ENDOMETRIAL, PROSTATE, LUNG, COLORECTAL, GASTROINTESTINAL, AND HEPATOCELLULAR, AND HAVE BEEN ATTRIBUTED TO A RANGE OF CO-OCCURRING BEHAVIORAL, SOCIAL DETERMINANTS OF HEALTH, UNDERLYING GENETIC FACTORS, AS WELL AS ACCESS TO EDUCATIONAL OPPORTUNITIES THAT LIMIT THE QUALITY OF INFORMED HEALTHCARE. THESE VARIOUS INTERRELATED FACTORS WIDEN CANCER HEALTHCARE DISPARITIES SYNERGISTICALLY THROUGHOUT UNDERSERVED COMMUNITIES, AND THEIR INFLUENCE HAS BEEN AMPLIFIED BY THE CORONAVIRUS DISEASE 2019 (COVID-19) PANDEMIC. FUNDAMENTALLY, A LACK OF BASIC AND CLINICAL RESEARCH EXISTS THAT FAILS TO ADEQUATELY REFLECT DIVERSITY AND MINORITY INVOLVEMENT IN DRUG DEVELOPMENT. ALTHOUGH OVERCOMING THE OBSTACLES RESPONSIBLE FOR CHRONIC TREATMENT DISPARITIES IS A FORMIDABLE TASK, PROMISING MEANS OF ACHIEVING MORE UNIFORM QUALITY HEALTHCARE ARE BECOMING MORE CLEARLY ELUCIDATED. TO REDUCE DISEASE PROGRESSION, INCREASE OVERALL SURVIVAL, AND IMPROVE THE HEALTH OF VULNERABLE POPULATIONS, IT IS NECESSARY TO IDENTIFY AND FULLY DISCLOSE ENVIRONMENTAL, BIOLOGICAL, AND ANCESTRAL FACTORS THAT IMPACT THE RISK FOR CANCER; HEAL HISTORICAL FRACTURES WITHIN COMMUNITIES; AND INCREASE PARTICIPATION OF RACIAL AND ETHNIC MINORITIES IN SCREENING EFFORTS AND RESEARCH STUDIES. THIS REQUIRES DEVELOPING A SYSTEM OF JUSTICE AND TRUST BASED ON SPECIFIC, SOLUTION-ORIENTED GRASSROOTS COMMUNITY EFFORTS WORKING IN TANDEM WITH MEDICAL AND PHARMACEUTICAL LEADERS. BY FULLY EXPLORING AND PINPOINTING THE UNDERLYING CAUSES OF HEALTHCARE DISPARITIES, IT SHOULD BE POSSIBLE TO DEFINE STRATEGIES AND INTERVENTIONS MOST LIKELY TO TRANSFORM CANCER CARE. THE ULTIMATE GOAL IS UNDERSTANDING INDIVIDUAL, CULTURAL, AND BIOLOGICAL VULNERABILITIES, INCLUDING ENVIRONMENTAL AND EPIGENETIC LIABILITIES, TO OPTIMIZE CANCER PREVENTION, DIAGNOSIS, AND TREATMENT. 2022 6 609 43 BEYOND MOR: CAN INDUCTION OF DOPAMINE HOMEOSTASIS ALONG WITH ELECTROTHERAPY ATTENUATE THE OPIOID CRISIS? ONE IMPORTANT AREA FOR CONSIDERATION ESPECIALLY IN TERMS OF COMBATING THE ONGOING NEVER ENDING OPIOID CRISIS, RELATES TO NOVEL NEWER ASSESSMENTS FOR ALL ADDICTIVE BEHAVIORS BOTH SUBSTANCE AND NON-SUBSTANCE BEHAVIORS (RDS). IT IS VERY IMPORTANT TO IDENTIFY EARLY IN ONE'S LIFE THE POSSIBILITY OF, BECAUSE OF KNOWN DNA ANTECEDENTS, THE PRESENCE OF PRE-ADDICTION. THE DEVELOPMENT OF THE GENETIC ADDICTION RISK SEVERITY (GARS) TEST, BLUM'S GROUP BELIEVES THAT THIS TYPE OF TESTING SHOULD BE THE "STANDARD OF CARE" FOLLOWING ADDITIONAL STUDIES. UNDERSTANDABLY THAT WHILE POLYMORPHISMS IN THE MU-OPIOID RECEPTOR (MOR) IS OF REAL CONCERN IN TERMS OF SETTING PEOPLE UP FOR PREDISPOSITION TO OPIOID DEPENDENCE, THE GENETIC AND EPIGENETIC STATUS OF DOPAMINERGIC FUNCTION MUST BE CONSIDERED AS WELL. WHILE THIS SOUNDS BOLD (WHICH IT IS) THE RESULTS SHOULD BE PROTECTED BY THE G.I. N. A. LAW ENACTED IN THE USA IN 2011. ONE AVENUE OF FURTHER INVESTIGATION, INSTEAD OF PROVIDING POWERFUL OPIOIDS FOR OPIOID DEPENDENCE, IS TO SEEK OUT NON-ADDICTIVE ALTERNATIVES. ACCORDINGLY, OTHER NON-ADDICTIVE MODALITIES INCLUDING GENETIC GUIDED KB220 (AMINO-ACID-ENKEPHALINASE-N-ACETYLCYSTEINE-NAD), NON-INVASIVE RTMS FOR PSYCHIATRY AND PAIN, EPIGENETIC REMODELING, GENE EDITS, NON-INVASIVE H-WAVE FOR PAIN MANAGEMENT AND ENHANCED FUNCTIONALITY, BRAIN SPOTTING, COGNITIVE BEHAVIORAL THERAPY AWARENESSS INTEGRATION THERAPY, NUCALM, TRAUMA THERAPY, AWARENESS TOOLS, GENOGRAMS, EXERCISE, SPORTS, FITNESS PROGRAMS (ONE HOUR PER DAY), LIGHT THERAPY AND EVEN LAUGHING THERAPY AS WELL AS ANY OTHER KNOWN MODALITIES THAT CAN INDUCE REWARD SYMMETRY. WHILE THE SHORT TERM USE OF OPIOIDS FOR OPIOID DEPENDENCE TO REDUCE HARM IS CERTAINLY ACCEPTABLE, CLINICIANS SHOULD CONSIDER A BETTER LONG-TERM PLAN. 2023 7 2934 41 GENETIC ADDICTION RISK SCORE (GARS) , A PREDICTOR OF VULNERABILITY TO OPIOID DEPENDENCE. THE INTERACTION OF NEUROTRANSMITTERS AND GENES THAT CONTROL THE RELEASE OF DOPAMINE IS THE BRAIN REWARD CASCADE (BRC). VARIATIONS WITHIN THE BRC, WHETHER GENETIC OR EPIGENETIC, MAY PREDISPOSE INDIVIDUALS TO ADDICTIVE BEHAVIORS AND ALTERED PAIN TOLERANCE. THIS DISCUSSION AUTHORED BY A GROUP OF CONCERNED SCIENTISTS AND CLINICIANS EXAMINES THE GENETIC ADDICTION RISK SCORE (GARS), THE FIRST TEST TO ACCURATELY PREDICT VULNERABILITY TO PAIN, ADDICTION, AND OTHER COMPULSIVE BEHAVIORS, DEFINED AS REWARD DEFICIENCY SYNDROME (RDS). INNOVATIVE STRATEGIES TO COMBAT EPIDEMIC OPIOID, IATROGENIC PRESCRIPTION DRUG ABUSE AND DEATH, BASED ON THE ROLE OF DOPAMINERGIC TONE IN PAIN PATHWAYS, ARE PROPOSED. SENSITIVITY TO PAIN MAY RESIDE IN THE MESOLIMBIC PROJECTION SYSTEM, WHERE GENETIC POLYMORPHISMS ASSOCIATE WITH A PREDISPOSITION TO PAIN VULNERABILITY OR TOLERANCE. THEY PROVIDE UNIQUE THERAPEUTIC TARGETS THAT COULD ASSIST IN THE TREATMENT OF PAIN, AND IDENTIFY RISK FOR SUBSEQUENT ADDICTION. PHARMACOGENOMIC TESTING OF CANDIDATE GENES LIKE CB1, MU RECEPTORS, AND PENK MIGHT RESULT IN PHARMACOGENOMIC, PERSONALIZED SOLUTIONS, AND IMPROVED CLINICAL OUTCOMES. GENETICALLY IDENTIFYING RISK FOR ALL RDS BEHAVIORS, ESPECIALLY IN COMPROMISED POPULATIONS, MAY BE A FRONTLINE TOOL TO ASSIST MUNICIPALITIES TO PROVIDE BETTER RESOURCE ALLOCATION. 2018 8 4080 22 MATERNAL LIFESTYLE INTERVENTIONS: TARGETING PRECONCEPTION HEALTH. ABOUT ONE-THIRD OF WOMEN OF REPRODUCTIVE AGE ARE OBESE, PREDISPOSING BOTH MOTHER AND BABY TO UNFAVOURABLE PREGNANCY OUTCOMES AND INITIATING AN INTERGENERATIONAL CYCLE OF CHRONIC METABOLIC DISORDERS. HERE WE SUMMARISE RECENT RESEARCH ON THE INFLUENCE OF MATERNAL METABOLIC HEALTH ON OFFSPRING SUSCEPTIBILITY TO FUTURE CARDIOMETABOLIC DISEASES. CURRENT PRIMARY LIFESTYLE APPROACHES (I.E., DIET AND EXERCISE INTERVENTIONS) TO HALT THE SUCCESSION OF INHERITED AND EPIGENETIC METABOLIC ABNORMALITIES HAVE MET WITH LIMITED SUCCESS DUE TO LATE IMPLEMENTATION, POOR ADHERENCE, AND/OR GENERIC GUIDELINES. IN OUR OPINION, SUCH INTERVENTIONS MUST COMMENCE PRIOR TO CONCEPTION TO IMPROVE BOTH MATERNAL AND CHILD HEALTH OUTCOMES, WITH NEW APPROACHES URGENTLY NEEDED TO INCREASE ADHERENCE TO PRIMARY LIFESTYLE CHANGES AMONG REPRODUCTIVE-AGE WOMEN. 2020 9 380 29 AN EPIGENETIC PERSPECTIVE ON LIFESTYLE MEDICINE FOR DEPRESSION: IMPLICATIONS FOR PRIMARY CARE PRACTICE. DEPRESSION IS THE MOST COMMON PRESENTING MENTAL HEALTH DISORDER IN PRIMARY CARE. IT IS ALSO A MAJOR CONTRIBUTOR TO SOMATIC COMPLAINTS, WORSENING OF CHRONIC MEDICAL CONDITIONS, POOR QUALITY OF LIFE, AND SUICIDE. CURRENT PHARMACOLOGIC AND PSYCHOTHERAPEUTIC APPROACHES AVERT LESS THAN HALF OF DEPRESSION'S CUMULATIVE BURDEN ON SOCIETY. HOWEVER, THERE IS A GROWING BODY OF RESEARCH DESCRIBING BOTH HOW MALADAPTIVE LIFESTYLE CHOICES CONTRIBUTE TO THE DEVELOPMENT AND WORSENING OF DEPRESSION AND HOW LIFESTYLE-ORIENTED MEDICAL INTERVENTIONS CAN REDUCE THE INCIDENCE AND SEVERITY OF DEPRESSION. THIS RESEARCH, LARGELY DERIVED FROM AN EMERGING FIELD CALLED EPIGENETICS, ELUCIDATES THE INTERACTIONS BETWEEN OUR LIFESTYLE CHOICES AND THOSE EPIGENETIC FACTORS WHICH MEDIATE OUR TENDENCIES TOWARD EITHER HEALTH, OR THE ONSET, IF NOT WORSENING OF DISEASE. THE PRESENT REVIEW HIGHLIGHTS HOW LIFESTYLE CHOICES INVOLVING DIET, PHYSICAL ACTIVITY, SLEEP, SOCIAL RELATIONSHIPS, AND STRESS INFLUENCE EPIGENETIC PROCESSES POSITIVELY OR NEGATIVELY, AND THEREBY PLAY A SIGNIFICANT ROLE IN DETERMINING WHETHER ONE DOES OR DOES NOT SUFFER FROM DEPRESSION. THE AUTHORS PROPOSE THAT MEDICAL TRAINING PROGRAMS CONSIDER AND ADOPT LIFESTYLE MEDICINE ORIENTED INSTRUCTIONAL INITIATIVES THAT WILL ENABLE TOMORROW'S PRIMARY CARE PROVIDERS TO MORE EFFECTIVELY IDENTIFY AND THERAPEUTICALLY INTERVENE IN THE MALADAPTIVE CHOICES CONTRIBUTING TO THEIR PATIENTS' DEPRESSION. 2022 10 2096 32 EPIGENETIC EFFECTS OF CHILDHOOD ADVERSITY IN THE BRAIN AND SUICIDE RISK. WITH PREVALENCE ESTIMATES RANGING BETWEEN 6.4% AND 10.1% [-5], MAJOR DEPRESSION RANKS FIRST AMONG THE MOST SIGNIFICANT CAUSES OF DISABILITY AND PREMATURE DEATH, THUS IMPOSING A CONTINUAL ECONOMIC BURDEN ON SOCIETY. FOR INSTANCE, IN THE UNITED STATES, THE DIRECT AND INDIRECT COSTS ARE ESTIMATED AT U.S.$44 BILLION/YEAR [6]. THE GREATEST LOSS TO OUR SOCIETY, HOWEVER, IS THE ASSOCIATED MORTALITY BY SUICIDE RELATED TO MAJOR DEPRESSION. INDEED, IT HAS BEEN ESTIMATED THAT BETWEEN 50% AND 70% OF SUICIDE COMPLETERS WILL DIE DURING AN EPISODE OF MAJOR DEPRESSION [7,8] AND PROSPECTIVE FOLLOW-UP STUDIES OF MAJOR DEPRESSION SUGGEST THAT BETWEEN 7% AND 15% OF THESE PATIENTS WILL DIE BY SUICIDE [-12]. SUICIDE IS A COMPLEX PROBLEM, WHICH IS BELIEVED TO RESULT FROM THE INTERACTION OF SEVERAL DIFFERENT FACTORS [13,14]. INDEED, PSYCHOLOGICAL FACTORS AND PERSONALITY TRAITS SUCH AS IMPULSIVITY AND NEGATIVE AFFECT [14,15], SOCIAL FACTORS [16,17], ENVIRONMENTAL FACTORS SUCH AS EARLY-LIFE ADVERSITY [-20], GENETIC FACTORS [21], AND NEUROBIOLOGICAL FACTORS [22] HAVE BEEN PROPOSED TO INDUCE BEHAVIORAL ALTERATIONS, WHICH IN TURN MAY PREDISPOSE CERTAIN INDIVIDUALS TO DEVELOP DEPRESSIVE AND SUICIDAL BEHAVIORS. HOWEVER, SINCE THESE FACTORS ALONE ARE UNLIKELY TO EXPLAIN SUICIDE AND SUICIDE RISK, IT MAY BE MORE READILY EXPLAINED WHEN CONSIDERING THE INTERACTION BETWEEN THESE DIFFERENT SOURCES OF VARIATION [23,24]. AMONG THESE RISK FACTORS, EARLY-LIFE ADVERSITY, PARTICULARLY CHILDHOOD SEXUAL ABUSE (CSA) AND CHILDHOOD PHYSICAL ABUSE (CPA), IS ONE OF THE STRONGEST PREDICTORS OF MENTAL DISORDERS [25,26] AND SUICIDE [18,19]. FOR EXAMPLE, STUDIES HAVE SHOWN THAT CSA IS ASSOCIATED WITH EARLY ONSET OF DEPRESSION, CHRONIC COURSE, AND MORE SEVERE DEPRESSIVE OUTCOME [-29] BUT, MORE IMPORTANTLY, WITH 12 TIMES HIGHER ODDS OF SUICIDAL BEHAVIORS [26,30]. ALTHOUGH LESS CONSISTENTLY, CPA AND NEGLECT HAVE ALSO BEEN ASSOCIATED WITH SUICIDAL BEHAVIORS [19,31]. CSA AND CPA HAVE BEEN ASSOCIATED WITH HIGHER ODDS OF SELF-HARM [,,-34], SUICIDAL IDEATION [35,36], AND SUICIDE ATTEMPTS [,-39]. MOREOVER, THE PREVALENCE OF SUICIDAL IDEATION AND SUICIDE ATTEMPTS HAS BEEN SHOWN TO INCREASE WITH THE SEVERITY AND INTENSITY OF THE ABUSE [35,36,38]. 2012 11 6620 27 UNDERSTANDING DEVELOPMENT AND PREVENTION OF CHRONIC PHYSICAL AGGRESSION: TOWARDS EXPERIMENTAL EPIGENETIC STUDIES. THE AIM OF THIS PAPER WAS TO HIGHLIGHT HOW DEVELOPMENTAL PSYCHOPATHOLOGY, EPIGENETICS AND PREVENTION EXPERIMENTS ARE STARTING TO BLEND TOGETHER TO EXPLAIN THE DEVELOPMENTAL CAUSES OF CHRONIC PHYSICAL AGGRESSION (CPA) AND, MORE IMPORTANTLY, TO HELP PREVENT CPA AND ITS ASSOCIATED PHYSICAL, MENTAL AND SOCIAL PROBLEMS. AFTER DEFINING THE KEYWORDS (PREVENTION, CHRONIC AND PHYSICAL AGGRESSION), A SELECTED REVIEW OF PUBLISHED STUDIES IS USED TO ANSWER THE FOLLOWING FOUR QUESTIONS: WHEN SHOULD WE ATTEMPT TO PREVENT ONSET OF CPA? WHAT ARE THE RISK FACTORS FOR CPA? HAVE EARLY CHILDHOOD INTERVENTIONS BEEN SHOWN TO PREVENT CPA? CAN EARLY PREVENTIVE INTERVENTIONS BENEFIT FROM EPIGENETIC STUDIES? THE LAST SECTION OF THIS PAPER GIVES TWO EXAMPLES OF EXPERIMENTAL PREVENTION DESIGNS THAT INTEGRATE PRESENT KNOWLEDGE OF CPA DEVELOPMENT, RISK FACTORS, EARLY CHILDHOOD PREVENTIVE INTERVENTIONS AND EPIGENETIC PROGRAMMING OF BRAIN DEVELOPMENT DURING PREGNANCY AND EARLY CHILDHOOD. I CONCLUDE THAT RANDOMIZED CONTROL TRIALS OF PREVENTIVE INTERVENTIONS DURING PREGNANCY AND EARLY CHILDHOOD WITH A SPECIFIC FOCUS ON EPIGENETIC EFFECTS ARE THE RESEARCH DESIGN MOST LIKELY TO ADVANCE OUR UNDERSTANDING OF THE BIOPSYCHOSOCIAL MECHANISMS THAT LEAD TO CPA, AND THE ONLY RESEARCH DESIGN THAT CAN IDENTIFY EFFECTIVE INTERVENTIONS FOR PREVENTING THE DEVELOPMENT OF CPA. 2008 12 5202 25 PRENATAL ORIGINS OF ADULT DISEASE. PURPOSE OF REVIEW: HUMAN EPIDEMIOLOGICAL AND ANIMAL STUDIES SHOW THAT MANY CHRONIC ADULT CONDITIONS HAVE THEIR ANTECEDENTS IN COMPROMISED FETAL AND EARLY POSTNATAL DEVELOPMENT. DEVELOPMENTAL PROGRAMMING IS DEFINED AS THE RESPONSE BY THE DEVELOPING MAMMALIAN ORGANISM TO A SPECIFIC CHALLENGE DURING A CRITICAL TIME WINDOW THAT ALTERS THE TRAJECTORY OF DEVELOPMENT WITH RESULTING PERSISTENT EFFECTS ON PHENOTYPE. MAMMALS PASS MORE BIOLOGICAL MILESTONES BEFORE BIRTH THAN ANY OTHER TIME IN THEIR LIVES. EACH INDIVIDUAL'S PHENOTYPE IS INFLUENCED BY THE DEVELOPMENTAL ENVIRONMENT AS MUCH AS THEIR GENES. A BETTER UNDERSTANDING IS REQUIRED OF GENE-ENVIRONMENT INTERACTIONS LEADING TO ADULT DISEASE. RECENT FINDINGS: DURING DEVELOPMENT, THERE ARE CRITICAL PERIODS OF VULNERABILITY TO SUBOPTIMAL CONDITIONS WHEN PROGRAMMING MAY PERMANENTLY MODIFY DISEASE SUSCEPTIBILITY. PROGRAMMING INVOLVES STRUCTURAL CHANGES IN IMPORTANT ORGANS; ALTERED CELL NUMBER, IMBALANCE IN DISTRIBUTION OF DIFFERENT CELL TYPES WITHIN THE ORGAN, AND ALTERED BLOOD SUPPLY OR RECEPTOR NUMBERS. COMPENSATORY EFFORTS BY THE FETUS MAY CARRY A PRICE. EFFECTS OF PROGRAMMING MAY PASS ACROSS GENERATIONS BY MECHANISMS THAT DO NOT NECESSARILY INVOLVE STRUCTURAL GENE CHANGES. PROGRAMMING OFTEN HAS DIFFERENT EFFECTS IN MALES AND FEMALES. SUMMARY: DEVELOPMENTAL PROGRAMMING SHOWS THAT EPIGENETIC FACTORS PLAY MAJOR ROLES IN DEVELOPMENT OF PHENOTYPE AND PREDISPOSITION TO DISEASE IN LATER LIFE. 2008 13 4067 20 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 14 3797 20 INTERNATIONAL BREAST CANCER AND NUTRITION: A MODEL FOR RESEARCH, TRAINING AND POLICY IN DIET, EPIGENETICS, AND CHRONIC DISEASE PREVENTION. THIS ARTICLE SUMMARIZES PRESENTATIONS FROM THE INTERNATIONAL BREAST CANCER AND NUTRITION WORKSHOP HELD DURING THE ASN SCIENTIFIC SESSIONS AND ANNUAL MEETING AT EXPERIMENTAL BIOLOGY 2014 IN SAN DIEGO, CA, ON 28 APRIL 2014. AN INTERNATIONAL COLLABORATION WAS DESCRIBED AMONG TEAMS FROM LOW-, MIDDLE-, AND HIGH-INCOME COUNTRIES ADDRESSING ENVIRONMENTAL FACTORS, ESPECIALLY DIET, AND EPIGENETIC INTERACTIONS THAT AFFECT THE RISK OF CHRONIC DISEASE. SPEAKERS ADDRESSED OPPORTUNITIES AND CHALLENGES INVOLVED IN THIS TYPE OF INTERNATIONAL COLLABORATION, ASSESSING DIET AND NUTRITIONAL STATUS ACROSS A WIDE RANGE OF CULTURES, AND RESEARCH TOOLS AND DISCOVERIES FROM THIS GROUP. 2014 15 4344 26 MINIREVIEW: TRANSLATIONAL ANIMAL MODELS OF HUMAN MENOPAUSE: CHALLENGES AND EMERGING OPPORTUNITIES. INCREASING IMPORTANCE IS PLACED ON THE TRANSLATIONAL VALIDITY OF ANIMAL MODELS OF HUMAN MENOPAUSE TO DISCERN RISK VS. BENEFIT FOR PREDICTION OF OUTCOMES AFTER THERAPEUTIC INTERVENTIONS AND TO DEVELOP NEW THERAPEUTIC STRATEGIES TO PROMOTE HEALTH. BASIC DISCOVERY RESEARCH CONDUCTED OVER MANY DECADES HAS BUILT AN EXTENSIVE BODY OF KNOWLEDGE REGARDING REPRODUCTIVE SENESCENCE ACROSS MAMMALIAN SPECIES UPON WHICH TO ADVANCE ANIMAL MODELS OF HUMAN MENOPAUSE. MODIFICATIONS TO EXISTING ANIMAL MODELS COULD RAPIDLY ADDRESS TRANSLATIONAL GAPS RELEVANT TO CLINICAL ISSUES IN HUMAN MENOPAUSAL HEALTH, WHICH INCLUDE THE IMPACT OF 1) CHRONIC OVARIAN HORMONE DEPRIVATION AND HORMONE THERAPY, 2) CLINICALLY RELEVANT HORMONE THERAPY REGIMENS (CYCLIC VS. CONTINUOUS COMBINED), 3) CLINICALLY RELEVANT HORMONE THERAPY FORMULATIONS, AND 4) WINDOWS OF OPPORTUNITY AND OPTIMAL DURATION OF INTERVENTIONS. MODIFICATIONS IN EXISTING ANIMAL MODELS TO MORE ACCURATELY REPRESENT HUMAN MENOPAUSE AND CLINICAL INTERVENTIONS COULD RAPIDLY PROVIDE PRECLINICAL TRANSLATIONAL DATA TO PREDICT OUTCOMES REGARDING UNRESOLVED CLINICAL ISSUES RELEVANT TO WOMEN'S MENOPAUSAL HEALTH. DEVELOPMENT OF THE NEXT GENERATION OF ANIMAL MODELS OF HUMAN MENOPAUSE COULD LEVERAGE ADVANCES IN IDENTIFYING GENOTYPIC VARIATIONS IN ESTROGEN AND PROGESTERONE RECEPTORS TO DEVELOP PERSONALIZED MENOPAUSAL CARE AND TO PREDICT OUTCOMES OF INTERVENTIONS FOR PROTECTION AGAINST OR VULNERABILITY TO DISEASE. KEY TO THE SUCCESS OF THESE MODELS IS THE CLOSE COUPLING BETWEEN THE TRANSLATIONAL TARGET AND THE RANGE OF PREDICTIVE VALIDITY. PRECLINICAL TRANSLATIONAL ANIMAL MODELS OF HUMAN MENOPAUSE NEED TO KEEP PACE WITH CHANGES IN CLINICAL PRACTICE. WITH FOCUS ON PREDICTIVE VALIDITY AND STRATEGIC USE OF ADVANCES IN GENETIC AND EPIGENETIC SCIENCE, NEW ANIMAL MODELS OF HUMAN MENOPAUSE HAVE THE OPPORTUNITY TO SET NEW DIRECTIONS FOR MENOPAUSAL CLINICAL CARE FOR WOMEN WORLDWIDE. 2012 16 5224 35 PRIORITIZED RESEARCH FOR THE PREVENTION, TREATMENT, AND REVERSAL OF CHRONIC DISEASE: RECOMMENDATIONS FROM THE LIFESTYLE MEDICINE RESEARCH SUMMIT. DECLINING LIFE EXPECTANCY AND INCREASING ALL-CAUSE MORTALITY IN THE UNITED STATES HAVE BEEN ASSOCIATED WITH UNHEALTHY BEHAVIORS, SOCIOECOLOGICAL FACTORS, AND PREVENTABLE DISEASE. A GROWING BODY OF BASIC SCIENCE, CLINICAL RESEARCH, AND POPULATION HEALTH EVIDENCE POINTS TO THE BENEFITS OF HEALTHY BEHAVIORS, ENVIRONMENTS AND POLICIES TO MAINTAIN HEALTH AND PREVENT, TREAT, AND REVERSE THE ROOT CAUSES OF COMMON CHRONIC DISEASES. SIMILARLY, INNOVATIONS IN RESEARCH METHODOLOGIES, STANDARDS OF EVIDENCE, EMERGENCE OF UNIQUE STUDY COHORTS, AND BREAKTHROUGHS IN DATA ANALYTICS AND MODELING CREATE NEW POSSIBILITIES FOR PRODUCING BIOMEDICAL KNOWLEDGE AND CLINICAL TRANSLATION. TO UNDERSTAND THESE ADVANCES AND INFORM FUTURE DIRECTIONS RESEARCH, THE LIFESTYLE MEDICINE RESEARCH SUMMIT WAS CONVENED AT THE UNIVERSITY OF PITTSBURGH ON DECEMBER 4-5, 2019. THE SUMMIT'S GOAL WAS TO REVIEW CURRENT STATUS AND DEFINE RESEARCH PRIORITIES IN THE SIX CORE AREAS OF LIFESTYLE MEDICINE: PLANT-PREDOMINANT NUTRITION, PHYSICAL ACTIVITY, SLEEP, STRESS, ADDICTIVE BEHAVIORS, AND POSITIVE PSYCHOLOGY/SOCIAL CONNECTION. FORTY INVITED SUBJECT MATTER EXPERTS (1) REVIEWED EXISTING KNOWLEDGE AND GAPS RELATING LIFESTYLE BEHAVIORS TO COMMON CHRONIC DISEASES, SUCH AS CARDIOVASCULAR DISEASE, DIABETES, MANY CANCERS, INFLAMMATORY- AND IMMUNE-RELATED DISORDERS AND OTHER CONDITIONS; AND (2) DISCUSSED THE POTENTIAL FOR APPLYING CUTTING-EDGE MOLECULAR, CELLULAR, EPIGENETIC AND EMERGING SCIENCE KNOWLEDGE AND COMPUTATIONAL METHODOLOGIES, RESEARCH DESIGNS, AND STUDY COHORTS TO ACCELERATE CLINICAL APPLICATIONS ACROSS ALL SIX DOMAINS OF LIFESTYLE MEDICINE. NOTABLY, FEDERAL HEALTH AGENCIES, SUCH AS THE DEPARTMENT OF DEFENSE AND VETERANS ADMINISTRATION HAVE BEGUN TO ADOPT "WHOLE-PERSON HEALTH AND PERFORMANCE" MODELS THAT ADDRESS THESE LIFESTYLE AND ENVIRONMENTAL ROOT CAUSES OF CHRONIC DISEASE AND ASSOCIATED MORBIDITY, MORTALITY, AND COST. RECOMMENDATIONS STRONGLY SUPPORT LEVERAGING EMERGING RESEARCH METHODOLOGIES, SYSTEMS BIOLOGY, AND COMPUTATIONAL MODELING IN ORDER TO ACCELERATE EFFECTIVE CLINICAL AND POPULATION SOLUTIONS TO IMPROVE HEALTH AND REDUCE SOCIETAL COSTS. NEW AND ALTERNATIVE HIERARCHIES OF EVIDENCE ARE ALSO BE NEEDED IN ORDER TO ASSESS THE QUALITY OF EVIDENCE AND DEVELOP EVIDENCE-BASED GUIDELINES ON LIFESTYLE MEDICINE. CHILDREN AND UNDERSERVED POPULATIONS WERE IDENTIFIED AS PRIORITIZED GROUPS TO STUDY. THE COVID-19 PANDEMIC, WHICH DISPROPORTIONATELY IMPACTS PEOPLE WITH CHRONIC DISEASES THAT ARE AMENABLE TO EFFECTIVE LIFESTYLE MEDICINE INTERVENTIONS, MAKES THE SUMMIT'S FINDINGS AND RECOMMENDATIONS FOR FUTURE RESEARCH PARTICULARLY TIMELY AND RELEVANT. 2020 17 3910 33 LIFE COURSE OF ASTHMA. ASTHMA IS A HETEROGENEOUS CHRONIC AIRWAY DISEASE THAT CAN VARY OVER A LIFETIME. ALTHOUGH BROAD CATEGORIES OF ASTHMA BY SEVERITY AND TYPE HAVE BEEN CONSTRUCTED, THERE REMAINS A TREMENDOUS OPPORTUNITY TO DISCOVER AN APPROACH TO MANAGING ASTHMA WITH ADDITIONAL FACTORS IN MIND. MANY IN THE FIELD HAVE SUGGESTED AND ARE PURSUING A NOVEL PARADIGM SHIFT IN HOW ASTHMA MIGHT BE BETTER MANAGED, CONSIDERING THE LIFE COURSE OF EXPOSURES, MANAGEMENT PRIORITIES, AND PREDICTED TRAJECTORY OF LUNG FUNCTION GROWTH. THIS APPROACH WILL REQUIRE A MORE HOLISTIC VIEW OF PRENATAL, POSTNATAL, ADOLESCENCE, HORMONAL AND GENDER ASPECTS, AND THE AGING PROCESS. IN ADDITION, THE ENVIRONMENT, EXTERNALLY AND INTERNALLY, INCLUDING IN ONE'S GENETIC CODE AND EPIGENETIC CHANGES, ARE FACTORS THAT AFFECT HOW ASTHMA PROGRESSES OR BECOMES MORE STABLE IN INDIVIDUALS. THIS CHAPTER FOCUSES ON THE VARIOUS INFLUENCES THAT MAY, TO DIFFERING DEGREES, AFFECT PEOPLE WITH ASTHMA, WHICH CAN DEVELOP AT ANY TIME IN THEIR LIVES. SHIFTING THE PARADIGM OF THOUGHT AND STRATEGIES FOR CARE AND ADVOCATING FOR PUBLIC POLICIES AND HEALTH DELIVERY THAT FOCUS ON THIS PHILOSOPHY IS PARAMOUNT TO ADVANCE ASTHMA CARE FOR ALL. 2023 18 3035 34 GENETICS/GENOMICS IN CHRONIC KIDNEY DISEASE--TOWARDS PERSONALIZED MEDICINE? THE PROGRESSION RATE OF CHRONIC KIDNEY DISEASE (CKD) TO ITS TERMINAL STAGE, END-STAGE RENAL DISEASE (ESRD), AND THE DEVELOPMENT AND SEVERITY OF VARIOUS COMPLICATIONS, ARE AT LEAST INDIRECTLY INFLUENCED BY GENETIC--AND EPIGENETIC--FACTORS. FOR YEARS, SCIENTISTS HAVE HELD OUT HOPE THAT THE RAPIDLY EVOLVING FIELD OF GENETICS COULD TRANSFORM MEDICAL DIAGNOSIS AND TREATMENT, MOVING BEYOND A TRIAL-AND-ERROR APPROACH TOWARDS "PERSONALIZED MEDICINE." INDEED, THERE ARE NOW SIGNS THAT THE ROLE OF GENETICS AND THE PURSUIT OF "PERSONALIZED MEDICINE" IN MEDICAL CARE WILL BE A PRIORITY FOR GOVERNMENTS DURING YEARS TO COME. BUT THE VISION OF INDIVIDUALIZED TREATMENT BASED ON A PATIENT'S GENETIC MAKEUP AND OTHER BIOLOGICAL MARKERS HAS YET TO MATERIALIZE IN THE FIELD OF CKD AND ESRD. AS THE TOXIC UREMIC ENVIRONMENT MAY RENDER CKD PATIENTS MORE SENSITIVE TO THE EFFECTS OF GENETIC VARIANTS, IT IS LIKELY THAT GENETIC FACTORS COULD BE OF SPECIAL IMPORTANCE IN THIS HIGH-RISK POPULATION. THEREFORE, OUTCOME IN THE CKD POPULATION MAY BE IMPROVED BY ESTABLISHING INDIVIDUAL GENETIC/EPIGENETIC PROFILES, THUS ENABLING PHYSICIANS TO DESIGN AN INDIVIDUALIZED THERAPEUTIC STRATEGY. PERSONALIZED MEDICINE BASED ON A MORE INDIVIDUALIZED THERAPY COULD BE APPLIED IN, FOR EXAMPLE, PHARMACOTHERAPY (CYP GENES), DIALYSIS THERAPY, AND NUTRITIONAL AND LIFESTYLE MODIFICATIONS. 2009 19 3606 34 IMPROVING TREATMENT OF NEURODEVELOPMENTAL DISORDERS: RECOMMENDATIONS BASED ON PRECLINICAL STUDIES. INTRODUCTION: NEURODEVELOPMENTAL DISORDERS (NDDS) ARE COMMON AND SEVERELY DEBILITATING. THEIR CHRONIC NATURE AND RELIANCE ON BOTH GENETIC AND ENVIRONMENTAL FACTORS MAKES STUDYING NDDS AND THEIR TREATMENT A CHALLENGING TASK. AREAS COVERED: HEREIN, THE AUTHORS DISCUSS THE NEUROBIOLOGICAL MECHANISMS OF NDDS, AND PRESENT RECOMMENDATIONS ON THEIR TRANSLATIONAL RESEARCH AND THERAPY, OUTLINED BY THE INTERNATIONAL STRESS AND BEHAVIOR SOCIETY. VARIOUS DRUGS CURRENTLY PRESCRIBED TO TREAT NDDS ALSO REPRESENT A HIGHLY DIVERSE GROUP. ACTING ON VARIOUS NEUROTRANSMITTER AND PHYSIOLOGICAL SYSTEMS, THESE DRUGS OFTEN LACK SPECIFICITY OF ACTION, AND ARE COMMONLY USED TO TREAT MULTIPLE OTHER PSYCHIATRIC CONDITIONS. THERE HAS ALSO BEEN RELATIVELY LITTLE PROGRESS IN THE DEVELOPMENT OF NOVEL MEDICATIONS TO TREAT NDDS. BASED ON CLINICAL, PRECLINICAL AND TRANSLATIONAL MODELS OF NDDS, OUR RECOMMENDATIONS COVER A WIDE RANGE OF METHODOLOGICAL APPROACHES AND CONCEPTUAL STRATEGIES. EXPERT OPINION: TO IMPROVE PHARMACOTHERAPY AND DRUG DISCOVERY FOR NDDS, WE NEED A STRONGER EMPHASIS ON TARGETING MULTIPLE ENDOPHENOTYPES, A BETTER DISSECTION OF GENETIC/EPIGENETIC FACTORS OR "HIDDEN HERITABILITY," AND A CAREFUL CONSIDERATION OF POTENTIAL DEVELOPMENTAL/TROPHIC ROLES OF BRAIN NEUROTRANSMITTERS. THE VALIDITY OF ANIMAL NDD MODELS CAN BE IMPROVED THROUGH DISCOVERY OF NOVEL (BEHAVIORAL, PHYSIOLOGICAL AND NEUROIMAGING) BIOMARKERS, APPLYING PROPER ENVIRONMENTAL ENRICHMENT, WIDENING THE SPECTRUM OF MODEL ORGANISMS, TARGETING DEVELOPMENTAL TRAJECTORIES OF NDD-RELATED BEHAVIORS AND COMORBID CONDITIONS BEYOND TRADITIONAL NDDS. WHILE THESE RECOMMENDATIONS CANNOT BE ADDRESSED ALL IN ONCE, OUR INCREASED UNDERSTANDING OF NDD PATHOBIOLOGY MAY TRIGGER INNOVATIVE CROSS-DISCIPLINARY RESEARCH EXPANDING BEYOND TRADITIONAL METHODS AND CONCEPTS. 2016 20 4797 25 NUTRITIONAL INTERVENTIONS TO IMPROVE BRAIN OUTCOMES IN PRETERM INFANTS. THE LAST 20 YEARS HAVE SEEN DRAMATIC IMPROVEMENTS IN SURVIVAL FOR PRETERM INFANTS IN BOTH HIGH- AND LOW-INCOME SETTINGS. SURVIVAL RATES OF OVER 50% IN INFANTS BORN 16 WEEKS EARLY (24 WEEKS' GESTATION) ARE NOW COMMONPLACE IN WELL-RESOURCED NEONATAL INTENSIVE CARE UNITS. HOWEVER, ENSURING ADEQUATE NUTRIENT INTAKES ESPECIALLY IN THE FIRST FEW DAYS AND WEEKS IS CHALLENGING, AND MANY INFANTS SHOW POOR GROWTH AND NUTRITIONAL STATUS. GOOD NUTRITIONAL MANAGEMENT SHOULD BE SEEN AS THE CORNERSTONE OF GOOD NEONATAL CARE AND IS KEY TO IMPROVING A RANGE OF IMPORTANT OUTCOMES INCLUDING REDUCED RATES OF RETINOPATHY OF PREMATURITY, CHRONIC LUNG DISEASE, NECROTIZING ENTEROCOLITIS (NEC), AND SEPSIS. EQUALLY IMPORTANTLY, IS THAT GOOD NUTRITIONAL STATUS IS ESSENTIAL TO OPTIMIZE BRAIN GROWTH AND DIFFERENTIATION. THERE ARE MULTIPLE POTENTIAL MECHANISMS THAT LINK NUTRITION TO BRAIN OUTCOMES IN PRETERM INFANTS INCLUDING NEEDS FOR TISSUE ACCRETION, ENERGY SUPPLY, SIGNALING ROLES, FUNCTIONAL COMPONENTS IN HUMAN MILK, EPIGENETIC REGULATION, PREVENTION OF NEC AND DISEASE, AND IMPACTS ON THE GUT BRAIN AXES. THIS ARTICLE WILL REVIEW DATA IN SUPPORT OF DIFFERENT MECHANISTIC LINKS FOR THE IMPACT OF NUTRITION ON BRAIN OUTCOMES IN PRETERM INFANTS. 2021