1 2874 118 FUNCTIONAL NUTRITION AS INTEGRATED INTERVENTION FOR IN- AND OUTPATIENT WITH SCHIZOPHRENIA. SCHIZOPHRENIA IS A CHRONIC AND PROGRESSIVE DISORDER CHARACTERIZED BY COGNITIVE, EMOTIONAL,AND BEHAVIORAL ABNORMALITIES ASSOCIATED WITH NEURONAL DEVELOPMENT AND SYNAPTIC PLASTICITY ALTERATIONS. GENETIC AND EPIGENETIC ABNORMALITIES IN CORTICAL PARVALBUMIN-POSITIVE GABAERGIC INTERNEURONS AND CONSEQUENT ALTERATIONS IN GLUTAMATE-MEDIATED EXCITATORY NEUROTRANSMISSION DURING EARLY NEURODEVELOPMENT UNDERLIE SCHIZOPHRENIA MANIFESTATION AND PROGRESSION. ALSO, EPIGENETIC ALTERATIONS DURING PREGNANCY OR EARLY PHASES OF POSTNATAL LIFE ARE ASSOCIATED WITH SCHIZOPHRENIA VULNERABILITY AND IN-FLAMMATORY PROCESSES, WHICH ARE AT THE BASIS OF BRAIN PATHOLOGY AND A HIGHER RISK OF COMORBIDITIES, INCLUDING CARDIOVASCULAR DISEASES AND METABOLIC SYNDROME. IN ADDITION, SCHIZOPHRENIA PATIENTS ADOPT AN UNHEALTHY LIFESTYLE AND POOR NUTRITION, LEADING TO PREMATURE DEATH. HERE, I EXPLORED THE ROLE OF FUNCTIONAL NUTRITION AS AN INTEGRATED INTERVENTION FOR THE LONG-TERM MANAGEMENT OF PATIENTS WITH SCHIZOPHRENIA. SEVERAL NATURAL BIOACTIVE COMPOUNDS IN PLANT-BASED WHOLE FOODS, INCLUDING FLAVONOIDS, PHYTONUTRIENTS, VITAMINS, FATTY ACIDS, AND MINERALS, MODULATE BRAIN FUNCTIONING BY TARGETING NEUROINFLAMMATION AND IMPROVING COGNITIVE DECLINE. ALTHOUGH FURTHER CLINICAL STUDIES ARE NEEDED, A FUNCTIONAL DIET RICH IN NATURAL BIOACTIVE COMPOUNDS MIGHT BE EFFECTIVE IN SYNERGISM WITH STANDARD TREATMENTS TO IMPROVE SCHIZOPHRENIA SYMPTOMS AND REDUCE THE RISK OF COMORBIDITIES. 2023 2 679 22 BRAIN FOODS - THE ROLE OF DIET IN BRAIN PERFORMANCE AND HEALTH. THE PERFORMANCE OF THE HUMAN BRAIN IS BASED ON AN INTERPLAY BETWEEN THE INHERITED GENOTYPE AND EXTERNAL ENVIRONMENTAL FACTORS, INCLUDING DIET. FOOD AND NUTRITION, ESSENTIAL IN MAINTENANCE OF BRAIN PERFORMANCE, ALSO AID IN PREVENTION AND TREATMENT OF MENTAL DISORDERS. BOTH THE OVERALL COMPOSITION OF THE HUMAN DIET AND SPECIFIC DIETARY COMPONENTS HAVE BEEN SHOWN TO HAVE AN IMPACT ON BRAIN FUNCTION IN VARIOUS EXPERIMENTAL MODELS AND EPIDEMIOLOGICAL STUDIES. THIS NARRATIVE REVIEW PROVIDES AN OVERVIEW OF THE ROLE OF DIET IN 5 KEY AREAS OF BRAIN FUNCTION RELATED TO MENTAL HEALTH AND PERFORMANCE, INCLUDING: (1) BRAIN DEVELOPMENT, (2) SIGNALING NETWORKS AND NEUROTRANSMITTERS IN THE BRAIN, (3) COGNITION AND MEMORY, (4) THE BALANCE BETWEEN PROTEIN FORMATION AND DEGRADATION, AND (5) DETERIORATIVE EFFECTS DUE TO CHRONIC INFLAMMATORY PROCESSES. FINALLY, THE ROLE OF DIET IN EPIGENETIC REGULATION OF BRAIN PHYSIOLOGY IS DISCUSSED. 2021 3 1329 36 DEPRESSION ASSOCIATED WITH DIABETES: FROM PATHOPHYSIOLOGY TO TREATMENT. DIABETES IS A CHRONIC AND PROGRESSIVE SYNDROME COMMONLY ASSOCIATED WITH SEVERAL NEUROPSYCHIATRIC COMORBITIES, OF WHICH DEPRESSION IS THE MOST STUDIED. THE PREVALENCE OF DEPRESSION IS ABOUT TWO OR THREE TIMES HIGHER IN DIABETIC PATIENTS COMPARED TO THE GENERAL POPULATION. IT IS BELIEVED THAT THE DIABETES - DEPRESSION RELATION MAY BE BIDIRECTIONAL, I.E., THE DEPRESSION CAN LEAD TO DIABETES AND CONVERSELY DIABETES COULD FACILITATE THE EMERGENCE OF DEPRESSION. DEPRESSION IS ONE OF THE MOST NEGLECTED SYMPTOMS IN DIABETIC PATIENTS AND IS DIRECTLY LINKED WITH LOWERING OF QUALITY OF LIFE. THE TREATMENT OF DEPRESSION IN THESE PATIENTS IS STILL QUITE INEFFECTIVE AND IN MANY CASES TREATMENTREFRACTORY. FURTHERMORE, SOME OF THE FIRST CHOICE DRUGS USED TO TREAT THE DEPRESSION AFFECT THE BLOOD GLUCOSE CONTROL, AGGRAVATING THE HYPERGLYCEMIC STATE. THESE ISSUES UNDERSCORE THE URGENCY IN STUDIES SEARCHING FOR NEW PHARMACOLOGICAL TARGETS FOR THE TREATMENT OF DEPRESSION ASSOCIATED WITH DIABETES. FOR THIS, A BETTER UNDERSTANDING OF THE PATHOPHYSIOLOGY THAT RELATES THIS COMORBIDITY BECOMES CRITICAL. IN THIS RESPECT, THIS REVIEW WILL FOCUS ON SOME HYPOTHESES THAT HAVE BEEN PROPOSED TO EXPLAIN THE MECHANISMS UNDERLYING DEPRESSION ASSOCIATED WITH DIABETES, HIGHLIGHTING THE TREATMENT OPTIONS CURRENTLY AVAILABLE AND THEIR LIMITATIONS. AMONG THESE HYPOTHESES, WE WILL POINT OUT THE HYPERGLYCEMIA AS A PRIMARY METABOLIC CAUSE OF THE DEPRESSION DEVELOPMENT, THE INVOLVEMENT OF THE DYSREGULATION OF HYPOTHALAMIC PITUITARY-ADRENAL (HPA) AXIS AND OF NEUROTRANSMITTER SYSTEMS, SPECIALLY MONOAMINERGIC SYSTEM. BESIDES, THE ROLE OF OXIDATIVE STRESS, NEUROINFLAMMATION AND CELL DEATH, ESPECIALLY IN HIPPOCAMPUS AND PREFRONTAL CORTEX, BRAIN AREAS IMPORTANT FOR THE MEDIATION AND MODULATION OF EMOTIONAL BEHAVIOR WILL ALSO BE DISCUSSED. FINALLY, WE WILL BRING UP THE INFLUENCE OF THE EPIGENETIC REGULATION WITH RESPECT TO NEUROPSYCHIATRIC DISORDERS. 2016 4 6184 33 THE IMPACT OF ENVIRONMENTAL FACTORS IN SEVERE PSYCHIATRIC DISORDERS. DURING THE LAST DECADES, SCHIZOPHRENIA HAS BEEN REGARDED AS A DEVELOPMENTAL DISORDER. THE NEURODEVELOPMENTAL HYPOTHESIS PROPOSES SCHIZOPHRENIA TO BE RELATED TO GENETIC AND ENVIRONMENTAL FACTORS LEADING TO ABNORMAL BRAIN DEVELOPMENT DURING THE PRE- OR POSTNATAL PERIOD. FIRST DISEASE SYMPTOMS APPEAR IN EARLY ADULTHOOD DURING THE SYNAPTIC PRUNING AND MYELINATION PROCESS. META-ANALYSES OF STRUCTURAL MRI STUDIES REVEALING HIPPOCAMPAL VOLUME DEFICITS IN FIRST-EPISODE PATIENTS AND IN THE LONGITUDINAL DISEASE COURSE CONFIRM THIS HYPOTHESIS. APART FROM THE INFLUENCE OF RISK GENES IN SEVERE PSYCHIATRIC DISORDERS, ENVIRONMENTAL FACTORS MAY ALSO IMPACT BRAIN DEVELOPMENT DURING THE PERINATAL PERIOD. SEVERAL ENVIRONMENTAL FACTORS SUCH AS ANTENATAL MATERNAL VIRUS INFECTIONS, OBSTETRIC COMPLICATIONS ENTAILING HYPOXIA AS COMMON FACTOR OR STRESS DURING NEURODEVELOPMENT HAVE BEEN IDENTIFIED TO PLAY A ROLE IN SCHIZOPHRENIA AND BIPOLAR DISORDER, POSSIBLY CONTRIBUTING TO SMALLER HIPPOCAMPAL VOLUMES. IN MAJOR DEPRESSION, PSYCHOSOCIAL STRESS DURING THE PERINATAL PERIOD OR IN ADULTHOOD IS AN IMPORTANT TRIGGER. IN ANIMAL STUDIES, CHRONIC STRESS OR REPEATED ADMINISTRATION OF GLUCOCORTICOIDS HAVE BEEN SHOWN TO INDUCE DEGENERATION OF GLUCOCORTICOID-SENSITIVE HIPPOCAMPAL NEURONS AND MAY CONTRIBUTE TO THE PATHOPHYSIOLOGY OF AFFECTIVE DISORDERS. EPIGENETIC MECHANISMS ALTERING THE CHROMATIN STRUCTURE SUCH AS HISTONE ACETYLATION AND DNA METHYLATION MAY MEDIATE EFFECTS OF ENVIRONMENTAL FACTORS TO TRANSCRIPTIONAL REGULATION OF SPECIFIC GENES AND BE A PROMINENT FACTOR IN GENE-ENVIRONMENTAL INTERACTION. IN ANIMAL MODELS, GENE-ENVIRONMENTAL INTERACTION SHOULD BE INVESTIGATED MORE INTENSELY TO UNRAVEL PATHOPHYSIOLOGICAL MECHANISMS. THESE FINDINGS MAY LEAD TO NEW THERAPEUTIC STRATEGIES INFLUENCING EPIGENETIC TARGETS IN SEVERE PSYCHIATRIC DISORDERS. 2014 5 5829 24 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 6 6034 39 THE CHALLENGE BY MULTIPLE ENVIRONMENTAL AND BIOLOGICAL FACTORS INDUCE INFLAMMATION IN AGING: THEIR ROLE IN THE PROMOTION OF CHRONIC DISEASE. THE AGING PROCESS IS DRIVEN BY MULTIPLE MECHANISMS THAT LEAD TO CHANGES IN ENERGY PRODUCTION, OXIDATIVE STRESS, HOMEOSTATIC DYSREGULATION AND EVENTUALLY TO LOSS OF FUNCTIONALITY AND INCREASED DISEASE SUSCEPTIBILITY. MOST AGED INDIVIDUALS DEVELOP CHRONIC LOW-GRADE INFLAMMATION, WHICH IS AN IMPORTANT RISK FACTOR FOR MORBIDITY, PHYSICAL AND COGNITIVE IMPAIRMENT, FRAILTY, AND DEATH. AT ANY AGE, CHRONIC INFLAMMATORY DISEASES ARE MAJOR CAUSES OF MORBIMORTALITY, AFFECTING UP TO 5-8% OF THE POPULATION OF INDUSTRIALIZED COUNTRIES. SEVERAL ENVIRONMENTAL FACTORS CAN PLAY AN IMPORTANT ROLE FOR MODIFYING THE INFLAMMATORY STATE. GENETICS ACCOUNTS FOR ONLY A SMALL FRACTION OF CHRONIC-INFLAMMATORY DISEASES, WHEREAS ENVIRONMENTAL FACTORS APPEAR TO PARTICIPATE, EITHER WITH A CAUSATIVE OR A PROMOTIONAL ROLE IN 50% TO 75% OF PATIENTS. SEVERAL OF THOSE CHANGES DEPEND ON EPIGENETIC CHANGES THAT WILL FURTHER MODIFY THE INDIVIDUAL RESPONSE TO ADDITIONAL STIMULI. THE INTERACTION BETWEEN INFLAMMATION AND THE ENVIRONMENT OFFERS IMPORTANT INSIGHTS ON AGING AND HEALTH. THESE CONDITIONS, OFTEN DEPENDING ON THE INDIVIDUAL'S SEX, APPEAR TO LEAD TO DECREASED LONGEVITY AND PHYSICAL AND COGNITIVE DECLINE. IN ADDITION TO BIOLOGICAL FACTORS, THE ENVIRONMENT IS ALSO INVOLVED IN THE GENERATION OF PSYCHOLOGICAL AND SOCIAL CONTEXT LEADING TO STRESS. POOR PSYCHOLOGICAL ENVIRONMENTS AND OTHER SOURCES OF STRESS ALSO RESULT IN INCREASED INFLAMMATION. HOWEVER, THE MECHANISMS UNDERLYING THE ROLE OF ENVIRONMENTAL AND PSYCHOSOCIAL FACTORS AND NUTRITION ON THE REGULATION OF INFLAMMATION, AND HOW THE RESPONSE ELICITED FOR THOSE FACTORS INTERACT AMONG THEM, ARE POORLY UNDERSTOOD. WHEREAS CERTAIN DELETERIOUS ENVIRONMENTAL FACTORS RESULT IN THE GENERATION OF OXIDATIVE STRESS DRIVEN BY AN INCREASED PRODUCTION OF REACTIVE OXYGEN AND NITROGEN SPECIES, ENDOPLASMIC RETICULUM STRESS, AND INFLAMMATION, OTHER FACTORS, INCLUDING NUTRITION (POLYUNSATURATED FATTY ACIDS) AND BEHAVIORAL FACTORS (EXERCISE) CONFER PROTECTION AGAINST INFLAMMATION, OXIDATIVE AND ENDOPLASMIC RETICULUM STRESS, AND THUS AMELIORATE THEIR DELETERIOUS EFFECT. HERE, WE DISCUSS PROCESSES AND MECHANISMS OF INFLAMMATION ASSOCIATED WITH ENVIRONMENTAL FACTORS AND BEHAVIOR, THEIR LINKS TO SEX AND GENDER, AND THEIR OVERALL IMPACT ON AGING. 2020 7 1736 31 EARLY DETECTION AND PREVENTION OF SCHIZOPHRENIC PSYCHOSIS-A REVIEW. PSYCHOTIC DISORDERS OFTEN RUN A CHRONIC COURSE AND ARE ASSOCIATED WITH A CONSIDERABLE EMOTIONAL AND SOCIAL IMPACT FOR PATIENTS AND THEIR RELATIVES. THEREFORE, EARLY RECOGNITION, COMBINED WITH THE POSSIBILITY OF PREVENTIVE INTERVENTION, IS URGENTLY WARRANTED SINCE THE DURATION OF UNTREATED PSYCHOSIS (DUP) SIGNIFICANTLY DETERMINES THE FURTHER COURSE OF THE DISEASE. IN ADDITION TO ESTABLISHED DIAGNOSTIC TOOLS, NEUROBIOLOGICAL FACTORS IN THE DEVELOPMENT OF SCHIZOPHRENIC PSYCHOSES ARE INCREASINGLY BEING INVESTIGATED. IT IS SHOWN THAT NUMEROUS MOLECULAR ALTERATIONS ALREADY EXIST BEFORE THE CLINICAL ONSET OF THE DISEASE. AS SCHIZOPHRENIC PSYCHOSES ARE NOT ELICITED BY A SINGLE MUTATION IN THE DEOXYRIBONUCLEIC ACID (DNA) SEQUENCE, EPIGENETICS LIKELY CONSTITUTE THE MISSING LINK BETWEEN ENVIRONMENTAL INFLUENCES AND DISEASE DEVELOPMENT AND COULD POTENTIALLY SERVE AS A BIOMARKER. THE RESULTS FROM TRANSCRIPTOMIC AND PROTEOMIC STUDIES POINT TO A DYSREGULATED IMMUNE SYSTEM, LIKELY EVOKED BY EPIGENETIC ALTERATIONS. DESPITE THE INCREASING KNOWLEDGE OF THE NEUROBIOLOGICAL MECHANISMS INVOLVED IN THE DEVELOPMENT OF PSYCHOTIC DISORDERS, FURTHER RESEARCH EFFORTS WITH LARGE POPULATION-BASED STUDY DESIGNS ARE NEEDED TO IDENTIFY SUITABLE BIOMARKERS. IN CONCLUSION, A COMBINATION OF BLOOD EXAMINATIONS, FUNCTIONAL IMAGING TECHNIQUES, ELECTROENCEPHALOGRAPHY (EEG) INVESTIGATIONS AND POLYGENIC RISK SCORES SHOULD BE CONSIDERED AS THE BASIS FOR PREDICTING HOW SUBJECTS WILL TRANSITION INTO MANIFEST PSYCHOSIS. 2021 8 6260 24 THE MOLECULAR NEUROBIOLOGY OF CHRONIC PAIN-INDUCED DEPRESSION. THE INCREASING NUMBER OF INDIVIDUALS WITH COMORBIDITIES POSES AN URGENT NEED TO IMPROVE THE MANAGEMENT OF PATIENTS WITH MULTIPLE CO-EXISTING DISEASES. AMONG THESE COMORBIDITIES, CHRONIC PAIN AND MOOD DISORDERS, TWO LONG-LASTING DISABLING CONDITIONS THAT SIGNIFICANTLY REDUCE THE QUALITY OF LIFE, COULD BE CITED FIRST. THE RECENT DEVELOPMENT OF ANIMAL MODELS ACCELERATED THE STUDIES FOCUSING ON THE UNDERLYING MECHANISMS OF THE CHRONIC PAIN AND DEPRESSION/ANXIETY COMORBIDITY. THIS REVIEW PROVIDES AN OVERVIEW OF CLINICAL AND PRE-CLINICAL STUDIES PERFORMED OVER THE PAST TWO DECADES ADDRESSING THE MOLECULAR ASPECTS OF THE COMORBID RELATIONSHIP OF CHRONIC PAIN AND DEPRESSION. WE THUS FOCUSED ON THE STUDIES THAT INVESTIGATED THE MOLECULAR CHARACTERISTICS OF THE COMORBID RELATIONSHIP BETWEEN CHRONIC PAIN AND MOOD DISORDERS, ESPECIALLY MAJOR DEPRESSIVE DISORDERS, FROM THE GENETIC AND EPIGENETIC POINT OF VIEW TO KEY NEUROMODULATORS WHICH HAVE BEEN SHOWN TO PLAY AN IMPORTANT ROLE IN THIS COMORBIDITY. 2019 9 4277 32 MICROGLIA SEQUELAE: BRAIN SIGNATURE OF INNATE IMMUNITY IN SCHIZOPHRENIA. SCHIZOPHRENIA IS A PSYCHIATRIC DISORDER WITH SIGNIFICANT IMPACT ON INDIVIDUALS AND SOCIETY. THE CURRENT PHARMACOLOGIC TREATMENT, WHICH PRINCIPALLY ALLEVIATES PSYCHOSIS, IS FOCUSED ON NEUROTRANSMITTERS MODULATION, RELYING ON DRUGS WITH SEVERE SIDE EFFECTS AND INEFFECTIVENESS IN A SIGNIFICANT PERCENTAGE OF CASES. THEREFORE, AND DUE TO DIFFICULTIES INHERENT TO DIAGNOSIS AND TREATMENT, IT IS VITAL TO REASSESS ALTERNATIVE CELLULAR AND MOLECULAR DRUG TARGETS. DISTINCT RISK FACTORS - GENETIC, DEVELOPMENTAL, EPIGENETIC, AND ENVIRONMENTAL - HAVE BEEN ASSOCIATED WITH DISEASE ONSET AND PROGRESSION, GIVING RISE TO THE PROPOSAL OF DIFFERENT PATHOPHYSIOLOGICAL MECHANISMS AND PUTATIVE PHARMACOLOGICAL TARGETS. IMMUNITY IS INVOLVED AND, PARTICULARLY MICROGLIA - INNATE IMMUNE CELLS OF THE CENTRAL NERVOUS SYSTEM, CRITICALLY INVOLVED IN BRAIN DEVELOPMENT - HAVE CAPTURED ATTENTION AS CELLULAR PLAYERS. MICROGLIA UNDERGO MARKED MORPHOLOGIC AND FUNCTIONAL ALTERATIONS IN THE HUMAN DISEASE, AS WELL AS IN ANIMAL MODELS OF SCHIZOPHRENIA, AS REPORTED IN SEVERAL ORIGINAL PAPERS. WE CLUSTER THE MAIN FINDINGS OF CLINICAL STUDIES BY GROUPS OF PATIENTS: (1) AT ULTRA-HIGH RISK OF PSYCHOSIS, (2) WITH A FIRST EPISODE OF PSYCHOSIS OR RECENT-ONSET SCHIZOPHRENIA, AND (3) WITH CHRONIC SCHIZOPHRENIA; IN TRANSLATIONAL STUDIES, WE HIGHLIGHT THE TIME WINDOW OF APPEARANCE OF PARTICULAR MICROGLIA ALTERATIONS IN THE MOST WELL STUDIED ANIMAL MODEL IN THE FIELD (MATERNAL IMMUNE ACTIVATION). THE ORGANIZATION OF CLINICAL AND TRANSLATIONAL FINDINGS BASED ON SCHIZOPHRENIA-ASSOCIATED MICROGLIA CHANGES IN DIFFERENT PHASES OF THE DISEASE COURSE MAY HELP DEFINING A TEMPORAL PATTERN OF MICROGLIA CHANGES AND MAY DRIVE THE DESIGN OF NOVEL THERAPEUTIC STRATEGIES. 2022 10 1360 34 DEVELOPMENTAL ASPECTS OF A LIFE COURSE APPROACH TO HEALTHY AGEING. WE EXAMINE THE MECHANISTIC BASIS AND WIDER IMPLICATIONS OF ADOPTING A DEVELOPMENTAL PERSPECTIVE ON HUMAN AGEING. PREVIOUS MODELS OF AGEING HAVE CONCENTRATED ON ITS GENETIC BASIS, OR THE DETRIMENTAL EFFECTS OF ACCUMULATED DAMAGE, BUT ALSO HAVE RAISED ISSUES ABOUT WHETHER AGEING CAN BE VIEWED AS ADAPTIVE ITSELF, OR IS A CONSEQUENCE OF OTHER ADAPTIVE PROCESSES, FOR EXAMPLE IF MAINTENANCE AND REPAIR PROCESSES IN THE PERIOD UP TO REPRODUCTION ARE TRADED OFF AGAINST LATER DECLINE IN FUNCTION. A LIFE COURSE MODEL PLACES AGEING IN THE CONTEXT OF THE ATTAINMENT OF PEAK CAPACITY FOR A BODY SYSTEM, STARTING IN EARLY DEVELOPMENT WHEN PLASTICITY PERMITS CHANGES IN STRUCTURE AND FUNCTION INDUCED BY A RANGE OF ENVIRONMENTAL STIMULI, FOLLOWED BY A PERIOD OF DECLINE, THE RATE OF WHICH DEPENDS ON THE PEAK ATTAINED AS WELL AS THE LATER LIFE CONDITIONS. SUCH PATH DEPENDENCY IN THE RATE OF AGEING MAY OFFER NEW INSIGHTS INTO ITS MODIFICATION. FOCUSING ON MUSCULOSKELETAL AND CARDIOVASCULAR FUNCTION, WE DISCUSS THIS MODEL AND THE POSSIBLE UNDERLYING MECHANISMS, INCLUDING ENDOTHELIAL FUNCTION, OXIDATIVE STRESS, STEM CELLS AND NUTRITIONAL FACTORS SUCH AS VITAMIN D STATUS. EPIGENETIC CHANGES INDUCED DURING DEVELOPMENTAL PLASTICITY, AND IMMUNE FUNCTION MAY PROVIDE A COMMON MECHANISTIC PROCESS UNDERLYING A LIFE COURSE MODEL OF AGEING. THE LIFE COURSE TRAJECTORY DIFFERS IN HIGH AND LOW RESOURCE SETTINGS. NEW INSIGHTS INTO THE DEVELOPMENTAL COMPONENTS OF THE LIFE COURSE MODEL OF AGEING MAY LEAD TO THE DESIGN OF BIOMARKERS OF LATER CHRONIC DISEASE RISK AND TO NEW INTERVENTIONS TO PROMOTE HEALTHY AGEING, WITH IMPORTANT IMPLICATIONS FOR PUBLIC HEALTH. 2016 11 5164 33 PRECLINICAL AND CLINICAL EVIDENCE OF DNA METHYLATION CHANGES IN RESPONSE TO TRAUMA AND CHRONIC STRESS. EXPOSURE TO CHRONIC STRESS, EITHER REPEATED SEVERE ACUTE OR MODERATE SUSTAINED STRESS, IS ONE OF THE STRONGEST RISK FACTORS FOR THE DEVELOPMENT OF PSYCHOPATHOLOGIES SUCH AS POST-TRAUMATIC STRESS DISORDER AND DEPRESSION. CHRONIC STRESS IS LINKED WITH SEVERAL LASTING BIOLOGICAL CONSEQUENCES, PARTICULARLY TO THE STRESS ENDOCRINE SYSTEM BUT ALSO AFFECTING INTERMEDIATE PHENOTYPES SUCH AS BRAIN STRUCTURE AND FUNCTION, IMMUNE FUNCTION, AND BEHAVIOR. ALTHOUGH GENETIC PREDISPOSITION CONFERS A PROPORTION OF THE RISK, THE MOST RELEVANT MOLECULAR MECHANISMS DETERMINING THOSE SUSCEPTIBLE AND RESILIENT TO THE EFFECTS OF STRESS AND TRAUMA MAY BE EPIGENETIC. EPIGENETICS REFERS TO THE MECHANISMS THAT REGULATE GENOMIC INFORMATION BY DYNAMICALLY CHANGING THE PATTERNS OF TRANSCRIPTION AND TRANSLATION OF GENES. MOUNTING EVIDENCE FROM PRECLINICAL RODENT AND CLINICAL POPULATION STUDIES STRONGLY SUPPORT THAT EPIGENETIC MODIFICATIONS CAN OCCUR IN RESPONSE TO TRAUMATIC AND CHRONIC STRESS. HERE, WE DISCUSS THIS LITERATURE EXAMINING STRESS-INDUCED EPIGENETIC CHANGES IN PRECLINICAL MODELS AND CLINICAL COHORTS OF STRESS AND TRAUMA OCCURRING EARLY IN LIFE OR IN ADULTHOOD. WE HIGHLIGHT THAT A COMPLEX RELATIONSHIP BETWEEN THE TIMING OF ENVIRONMENTAL STRESSORS AND GENETIC PREDISPOSITIONS LIKELY MEDIATE THE RESPONSE TO CHRONIC STRESS OVER TIME, AND THAT A BETTER UNDERSTANDING OF EPIGENETIC CHANGES IS NEEDED BY FURTHER INVESTIGATIONS IN LONGITUDINAL AND POSTMORTEM BRAIN CLINICAL COHORTS. 2017 12 2011 33 EPIGENETIC BASIS OF MENTAL ILLNESS. PSYCHIATRIC DISORDERS ARE COMPLEX MULTIFACTORIAL ILLNESSES INVOLVING CHRONIC ALTERATIONS IN NEURAL CIRCUIT STRUCTURE AND FUNCTION AS WELL AS LIKELY ABNORMALITIES IN GLIAL CELLS. WHILE GENETIC FACTORS ARE IMPORTANT IN THE ETIOLOGY OF MOST MENTAL DISORDERS, THE RELATIVELY HIGH RATES OF DISCORDANCE AMONG IDENTICAL TWINS, PARTICULARLY FOR DEPRESSION AND OTHER STRESS-RELATED SYNDROMES, CLEARLY INDICATE THE IMPORTANCE OF ADDITIONAL MECHANISMS. ENVIRONMENTAL FACTORS SUCH AS STRESS ARE KNOWN TO PLAY A ROLE IN THE ONSET OF THESE ILLNESSES. EXPOSURE TO SUCH ENVIRONMENTAL INSULTS INDUCES STABLE CHANGES IN GENE EXPRESSION, NEURAL CIRCUIT FUNCTION, AND ULTIMATELY BEHAVIOR, AND THESE MALADAPTATIONS APPEAR DISTINCT BETWEEN DEVELOPMENTAL VERSUS ADULT EXPOSURES. INCREASING EVIDENCE INDICATES THAT THESE SUSTAINED ABNORMALITIES ARE MAINTAINED BY EPIGENETIC MODIFICATIONS IN SPECIFIC BRAIN REGIONS. INDEED, TRANSCRIPTIONAL DYSREGULATION AND THE ABERRANT EPIGENETIC REGULATION THAT UNDERLIES THIS DYSREGULATION IS A UNIFYING THEME IN PSYCHIATRIC DISORDERS. HERE, WE PROVIDE A PROGRESS REPORT OF EPIGENETIC STUDIES OF THE THREE MAJOR PSYCHIATRIC SYNDROMES, DEPRESSION, SCHIZOPHRENIA, AND BIPOLAR DISORDER. WE REVIEW THE LITERATURE DERIVED FROM ANIMAL MODELS OF THESE DISORDERS AS WELL AS FROM STUDIES OF POSTMORTEM BRAIN TISSUE FROM HUMAN PATIENTS. WHILE EPIGENETIC STUDIES OF MENTAL ILLNESS REMAIN AT EARLY STAGES, UNDERSTANDING HOW ENVIRONMENTAL FACTORS RECRUIT THE EPIGENETIC MACHINERY WITHIN SPECIFIC BRAIN REGIONS TO CAUSE LASTING CHANGES IN DISEASE SUSCEPTIBILITY AND PATHOPHYSIOLOGY IS REVEALING NEW INSIGHT INTO THE ETIOLOGY AND TREATMENT OF THESE CONDITIONS. 2016 13 6133 33 THE EPIGENETIC ROLE OF VITAMIN C IN NEURODEVELOPMENT. THE MATERNAL DIET DURING PREGNANCY IS A KEY DETERMINANT OF OFFSPRING HEALTH. EARLY STUDIES HAVE LINKED POOR MATERNAL NUTRITION DURING GESTATION WITH A PROPENSITY FOR THE DEVELOPMENT OF CHRONIC CONDITIONS IN OFFSPRING. THESE CONDITIONS INCLUDE CARDIOVASCULAR DISEASE, TYPE 2 DIABETES AND EVEN COMPROMISED MENTAL HEALTH. WHILE MULTIPLE FACTORS MAY CONTRIBUTE TO THESE OUTCOMES, DISTURBED EPIGENETIC PROGRAMMING DURING EARLY DEVELOPMENT IS ONE POTENTIAL BIOLOGICAL MECHANISM. THE EPIGENOME IS PROGRAMMED PRIMARILY IN UTERO, AND DURING THIS TIME, THE DEVELOPING FETUS IS HIGHLY SUSCEPTIBLE TO ENVIRONMENTAL FACTORS SUCH AS NUTRITIONAL INSULTS. DURING NEURODEVELOPMENT, EPIGENETIC PROGRAMMING COORDINATES THE FORMATION OF PRIMITIVE CENTRAL NERVOUS SYSTEM STRUCTURES, NEUROGENESIS, AND NEUROPLASTICITY. DYSREGULATED EPIGENETIC PROGRAMMING HAS BEEN IMPLICATED IN THE AETIOLOGY OF SEVERAL NEURODEVELOPMENTAL DISORDERS SUCH AS TATTON-BROWN-RAHMAN SYNDROME. ACCORDINGLY, THERE IS GREAT INTEREST IN DETERMINING HOW MATERNAL NUTRIENT AVAILABILITY IN PREGNANCY MIGHT AFFECT THE EPIGENETIC STATUS OF OFFSPRING, AND HOW SUCH INFLUENCES MAY PRESENT PHENOTYPICALLY. IN RECENT YEARS, A NUMBER OF EPIGENETIC ENZYMES THAT ARE ACTIVE DURING EMBRYONIC DEVELOPMENT HAVE BEEN FOUND TO REQUIRE VITAMIN C AS A COFACTOR. THESE ENZYMES INCLUDE THE TEN-ELEVEN TRANSLOCATION METHYLCYTOSINE DIOXYGENASES (TETS) AND THE JUMONJI C DOMAIN-CONTAINING HISTONE LYSINE DEMETHYLASES THAT CATALYSE THE OXIDATIVE REMOVAL OF METHYL GROUPS ON CYTOSINES AND HISTONE LYSINE RESIDUES, RESPECTIVELY. THESE ENZYMES ARE INTEGRAL TO EPIGENETIC REGULATION AND HAVE FUNDAMENTAL ROLES IN CELLULAR DIFFERENTIATION, THE MAINTENANCE OF PLURIPOTENCY AND DEVELOPMENT. THE DEPENDENCE OF THESE ENZYMES ON VITAMIN C FOR OPTIMAL CATALYTIC ACTIVITY ILLUSTRATES A POTENTIALLY CRITICAL CONTRIBUTION OF THE NUTRIENT DURING MAMMALIAN DEVELOPMENT. THESE INSIGHTS ALSO HIGHLIGHT A POTENTIAL RISK ASSOCIATED WITH VITAMIN C INSUFFICIENCY DURING PREGNANCY. THE LINK BETWEEN VITAMIN C INSUFFICIENCY AND DEVELOPMENT IS PARTICULARLY APPARENT IN THE CONTEXT OF NEURODEVELOPMENT AND HIGH VITAMIN C CONCENTRATIONS IN THE BRAIN ARE INDICATIVE OF IMPORTANT FUNCTIONAL REQUIREMENTS IN THIS ORGAN. ACCORDINGLY, THIS REVIEW CONSIDERS THE EVIDENCE FOR THE POTENTIAL IMPACT OF MATERNAL VITAMIN C STATUS ON NEURODEVELOPMENTAL EPIGENETICS. 2022 14 6375 33 THE ROLE OF NEURO-IMMUNE INTERACTION IN CHRONIC PAIN CONDITIONS; FUNCTIONAL SOMATIC SYNDROME, NEUROGENIC INFLAMMATION, AND PERIPHERAL NEUROPATHY. FUNCTIONAL SOMATIC SYNDROMES ARE INCREASINGLY DIAGNOSED IN CHRONICALLY ILL PATIENTS PRESENTING WITH AN ARRAY OF SYMPTOMS NOT ATTRIBUTED TO PHYSICAL AILMENTS. CONDITIONS SUCH AS CHRONIC FATIGUE SYNDROME, FIBROMYALGIA SYNDROME, OR IRRITABLE BOWEL SYNDROME ARE COMMON DISORDERS THAT BELONG IN THIS BROAD CATEGORY. SUCH SYNDROMES ARE CHARACTERISED BY THE PRESENCE OF ONE OR MULTIPLE CHRONIC SYMPTOMS INCLUDING WIDESPREAD MUSCULOSKELETAL PAIN, FATIGUE, SLEEP DISORDERS, AND ABDOMINAL PAIN, AMONGST OTHER ISSUES. SYMPTOMS ARE BELIEVED TO RELATE TO A COMPLEX INTERACTION OF BIOLOGICAL AND PSYCHOSOCIAL FACTORS, WHERE A DEFINITE AETIOLOGY HAS NOT BEEN ESTABLISHED. THEORIES SUGGEST CAUSATIVE PATHWAYS BETWEEN THE IMMUNE AND NERVOUS SYSTEMS OF AFFECTED INDIVIDUALS WITH SEVERAL RISK FACTORS IDENTIFIED IN PATIENTS PRESENTING WITH ONE OR MORE FUNCTIONAL SYNDROMES. RISK FACTORS INCLUDING STRESS AND CHILDHOOD TRAUMA ARE NOW RECOGNISED AS IMPORTANT CONTRIBUTORS TO CHRONIC PAIN CONDITIONS. EMOTIONAL, PHYSICAL, AND SEXUAL ABUSE DURING CHILDHOOD IS CONSIDERED A SEVERE STRESSOR HAVING A HIGH PREVALENCE IN FUNCTIONAL SOMATIC SYNDROME SUFFERS. SUCH TRAUMA PERMANENTLY ALTERS THE BIOLOGICAL STRESS RESPONSE OF THE SUFFERS LEADING TO NEUROEXCITATORY AND OTHER NERVE ISSUES ASSOCIATED WITH CHRONIC PAIN IN ADULTS. TRAUMATIC AND CHRONIC STRESS RESULTS IN EPIGENETIC CHANGES IN STRESS RESPONSE GENES, WHICH ULTIMATELY LEADS TO DYSREGULATION OF THE HYPOTHALAMIC-PITUITARY AXIS, THE AUTONOMIC NERVOUS SYSTEM, AND THE IMMUNE SYSTEM MANIFESTING IN A BROAD ARRAY OF SYMPTOMS. IMPORTANTLY, THESE SYSTEMS ARE KNOWN TO BE DYSREGULATED IN PATIENTS SUFFERING FROM FUNCTIONAL SOMATIC SYNDROME. FUNCTIONAL SOMATIC SYNDROMES ARE ALSO HIGHLY PREVALENT CO-MORBIDITIES OF PSYCHIATRIC CONDITIONS, MOOD DISORDERS, AND ANXIETY. CONSEQUENTLY, THIS REVIEW AIMS TO PROVIDE INSIGHT INTO THE ROLE OF THE NERVOUS SYSTEM AND IMMUNE SYSTEM IN CHRONIC PAIN DISORDERS ASSOCIATED WITH THE MUSCULOSKELETAL SYSTEM, AND CENTRAL AND PERIPHERAL NERVOUS SYSTEMS. 2022 15 1414 36 DIETARY PHYTOCHEMICALS IN NEUROIMMUNOAGING: A NEW THERAPEUTIC POSSIBILITY FOR HUMANS? ALTHOUGH SEVERAL EFFORTS HAVE BEEN MADE IN THE SEARCH FOR GENETIC AND EPIGENETIC PATTERNS LINKED TO DISEASES, A COMPREHENSIVE EXPLANATION OF THE MECHANISMS UNDERLYING PATHOLOGICAL PHENOTYPIC PLASTICITY IS STILL FAR FROM BEING CLARIFIED. OXIDATIVE STRESS AND INFLAMMATION ARE TWO OF THE MAJOR TRIGGERS OF THE EPIGENETIC ALTERATIONS OCCURRING IN CHRONIC PATHOLOGIES, SUCH AS NEURODEGENERATIVE DISEASES. IN FACT, OVER THE LAST DECADE, REMARKABLE PROGRESS HAS BEEN MADE TO REALIZE THAT CHRONIC, LOW-GRADE INFLAMMATION IS ONE OF THE MAJOR RISK FACTOR UNDERLYING BRAIN AGING. ACCUMULATED DATA STRONGLY SUGGEST THAT PHYTOCHEMICALS FROM FRUITS, VEGETABLES, HERBS, AND SPICES MAY EXERT RELEVANT IMMUNOMODULATORY AND/OR ANTI-INFLAMMATORY ACTIVITIES IN THE CONTEXT OF BRAIN AGING. STARTING BY THE EVIDENCE THAT A COMMON DENOMINATOR OF AGING AND CHRONIC DEGENERATIVE DISEASES IS REPRESENTED BY INFLAMMATION, AND THAT SEVERAL DIETARY PHYTOCHEMICALS ARE ABLE TO POTENTIALLY INTERFERE WITH AND REGULATE THE NORMAL FUNCTION OF CELLS, IN PARTICULAR NEURONAL COMPONENTS, AIM OF THIS REVIEW IS TO SUMMARIZE RECENT STUDIES ON NEUROINFLAMMAGING PROCESSES AND PROOFS INDICATING THAT SPECIFIC PHYTOCHEMICALS MAY ACT AS POSITIVE MODULATORS OF NEUROINFLAMMATORY EVENTS. IN ADDITION, CRITICAL PATHWAYS INVOLVED IN MEDIATING PHYTOCHEMICALS EFFECTS ON NEUROINFLAMMAGING WERE DISCUSSED, EXPLORING THE REAL IMPACT OF THESE COMPOUNDS IN PRESERVING BRAIN HEALTH BEFORE THE ONSET OF SYMPTOMS LEADING TO INFLAMMATORY NEURODEGENERATION AND COGNITIVE DECLINE. 2016 16 2226 37 EPIGENETIC MODIFICATIONS INDUCED BY NUTRIENTS IN EARLY LIFE PHASES: GENDER DIFFERENCES IN METABOLIC ALTERATION IN ADULTHOOD. METABOLIC CHRONIC DISEASES, ALSO NAMED NONCOMMUNICABLE DISEASES (NCDS), ARE CONSIDERED MULTIFACTORIAL PATHOLOGIES, WHICH ARE DRAMATICALLY INCREASED DURING THE LAST DECADES. NONCOMMUNICABLE DISEASES SUCH AS CARDIOVASCULAR DISEASES, OBESITY, DIABETES MELLITUS, CANCERS, AND CHRONIC RESPIRATORY DISEASES MARKEDLY INCREASE MORBIDITY, MORTALITY, AND SOCIOECONOMIC COSTS. MOREOVER, NCDS INDUCE SEVERAL AND COMPLEX CLINICAL MANIFESTATIONS THAT LEAD TO A GRADUAL DETERIORATION OF HEALTH STATUS AND QUALITY OF LIFE OF AFFECTED INDIVIDUALS. MULTIPLE FACTORS ARE INVOLVED IN THE DEVELOPMENT AND PROGRESSION OF THESE DISEASES SUCH AS SEDENTARY BEHAVIOR, SMOKING, POLLUTION, AND UNHEALTHY DIET. INDEED, NUTRITION HAS A PIVOTAL ROLE IN MAINTAINING HEALTH, AND DIETARY IMBALANCES REPRESENT MAJOR DETERMINANTS FAVORING CHRONIC DISEASES THROUGH METABOLIC HOMEOSTASIS ALTERATIONS. IN PARTICULAR, IT APPEARS THAT SPECIFIC NUTRIENTS AND ADEQUATE NUTRITION ARE IMPORTANT IN ALL PERIODS OF LIFE, BUT THEY ARE ESSENTIAL DURING SPECIFIC TIMES IN EARLY LIFE SUCH AS PRENATAL AND POSTNATAL PHASES. INDEED, EPIDEMIOLOGIC AND EXPERIMENTAL STUDIES REPORT THE DELETERIOUS EFFECTS OF AN INCORRECT NUTRITION ON HEALTH STATUS SEVERAL DECADES LATER IN LIFE. DURING THE LAST DECADE, A GROWING INTEREST ON THE POSSIBLE ROLE OF EPIGENETIC MECHANISMS AS LINK BETWEEN NUTRITIONAL IMBALANCES AND NCDS DEVELOPMENT HAS BEEN OBSERVED. FINALLY, BECAUSE OF THE PIVOTAL ROLE OF THE HORMONES IN FAT, CARBOHYDRATE, AND PROTEIN METABOLISM REGULATION THROUGHOUT LIFE, IT IS EXPECTED THAT ANY HORMONAL MODIFICATION OF THESE PROCESSES CAN IMBALANCE METABOLISM AND FAT STORAGE. THEREFORE, A PARTICULAR INTEREST TO SEVERAL CHEMICALS ABLE TO ACT AS ENDOCRINE DISRUPTORS HAS BEEN RECENTLY DEVELOPED. IN THIS REVIEW, WE WILL PROVIDE AN OVERVIEW AND DISCUSS THE EPIGENETIC ROLE OF SOME SPECIFIC NUTRIENTS AND CHEMICALS IN THE MODULATION OF PHYSIOLOGICAL AND PATHOLOGICAL MECHANISMS. 2019 17 2157 31 EPIGENETIC MECHANISMS ELICITED BY NUTRITION IN EARLY LIFE. A GROWING NUMBER OF STUDIES FOCUSING ON THE DEVELOPMENTAL ORIGIN OF HEALTH AND DISEASE HYPOTHESIS HAVE IDENTIFIED LINKS AMONG EARLY NUTRITION, EPIGENETIC PROCESSES AND DISEASES ALSO IN LATER LIFE. DIFFERENT EPIGENETIC MECHANISMS ARE ELICITED BY DIETARY FACTORS IN EARLY CRITICAL DEVELOPMENTAL AGES THAT ARE ABLE TO AFFECT THE SUSCEPTIBILITY TO SEVERAL DISEASES IN ADULTHOOD. THE STUDIES HERE REVIEWED SUGGEST THAT MATERNAL AND NEONATAL DIET MAY HAVE LONG-LASTING EFFECTS IN THE DEVELOPMENT OF NON-COMMUNICABLE CHRONIC ADULTHOOD DISEASES, IN PARTICULAR THE COMPONENTS OF THE SO-CALLED METABOLIC SYNDROME, SUCH AS INSULIN RESISTANCE, TYPE 2 DIABETES, OBESITY, DYSLIPIDAEMIA, HYPERTENSION, AND CVD. BOTH MATERNAL UNDER- AND OVER-NUTRITION MAY REGULATE THE EXPRESSION OF GENES INVOLVED IN LIPID AND CARBOHYDRATE METABOLISM. EARLY POSTNATAL NUTRITION MAY ALSO REPRESENT A VITAL DETERMINANT OF ADULT HEALTH BY MAKING AN IMPACT ON THE DEVELOPMENT AND FUNCTION OF GUT MICROBIOTA. AN INADEQUATE GUT MICROBIOTA COMPOSITION AND FUNCTION IN EARLY LIFE SEEMS TO ACCOUNT FOR THE DEVIANT PROGRAMMING OF LATER IMMUNITY AND OVERALL HEALTH STATUS. IN THIS REGARD PROBIOTICS, WHICH HAVE THE POTENTIAL TO RESTORE THE INTESTINAL MICROBIOTA BALANCE, MAY BE EFFECTIVE IN PREVENTING THE DEVELOPMENT OF CHRONIC IMMUNE-MEDIATED DISEASES. MORE RECENTLY, THE EPIGENETIC MECHANISMS ELICITED BY PROBIOTICS THROUGH THE PRODUCTION OF SCFA ARE HYPOTHESISED TO BE THE KEY TO UNDERSTAND HOW THEY MEDIATE THEIR NUMEROUS HEALTH-PROMOTING EFFECTS FROM THE GUT TO THE PERIPHERAL TISSUES. 2011 18 4914 25 PAIN VULNERABILITY: A NEUROBIOLOGICAL PERSPECTIVE. THERE ARE MANY KNOWN RISK FACTORS FOR CHRONIC PAIN CONDITIONS, YET THE BIOLOGICAL UNDERPINNINGS THAT LINK THESE FACTORS TO ABNORMAL PROCESSING OF PAINFUL SIGNALS ARE ONLY JUST BEGINNING TO BE EXPLORED. THIS REVIEW WILL DISCUSS THE POTENTIAL MECHANISMS THAT HAVE BEEN PROPOSED TO UNDERLIE VULNERABILITY AND RESILIENCE TOWARD DEVELOPING CHRONIC PAIN. PARTICULAR FOCUS WILL BE GIVEN TO GENETIC AND EPIGENETIC PROCESSES, PRIMING EFFECTS ON A CELLULAR LEVEL, AND ALTERATIONS IN BRAIN NETWORKS CONCERNED WITH REWARD, MOTIVATION/LEARNING AND DESCENDING MODULATORY CONTROL. ALTHOUGH RESEARCH IN THIS AREA IS STILL IN ITS INFANCY, A BETTER UNDERSTANDING OF HOW PAIN VULNERABILITY EMERGES HAS THE POTENTIAL TO HELP IDENTIFY INDIVIDUALS AT RISK AND MAY OPEN UP NEW THERAPEUTIC AVENUES. 2014 19 5069 23 PHYSICAL ACTIVITY IN THE PREVENTION OF HUMAN DISEASES: ROLE OF EPIGENETIC MODIFICATIONS. EPIGENETIC MODIFICATION REFERS TO HERITABLE CHANGES IN GENE FUNCTION THAT CANNOT BE EXPLAINED BY ALTERATIONS IN THE DNA SEQUENCE. THE CURRENT LITERATURE CLEARLY DEMONSTRATES THAT THE EPIGENETIC RESPONSE IS HIGHLY DYNAMIC AND INFLUENCED BY DIFFERENT BIOLOGICAL AND ENVIRONMENTAL FACTORS SUCH AS AGING, NUTRIENT AVAILABILITY AND PHYSICAL EXERCISE. AS SUCH, IT IS WELL ACCEPTED THAT PHYSICAL ACTIVITY AND EXERCISE CAN MODULATE GENE EXPRESSION THROUGH EPIGENETIC ALTERNATIONS ALTHOUGH THE TYPE AND DURATION OF EXERCISE ELICITING SPECIFIC EPIGENETIC EFFECTS THAT CAN RESULT IN HEALTH BENEFITS AND PREVENT CHRONIC DISEASES REMAINS TO BE DETERMINED. THIS REVIEW HIGHLIGHTS THE MOST SIGNIFICANT FINDINGS FROM EPIGENETIC STUDIES INVOLVING PHYSICAL ACTIVITY/EXERCISE INTERVENTIONS KNOWN TO BENEFIT CHRONIC DISEASES SUCH AS METABOLIC SYNDROME, DIABETES, CANCER, CARDIOVASCULAR AND NEURODEGENERATIVE DISEASES. 2017 20 38 19 A COMMON ROLE FOR PSYCHOTROPIC MEDICATIONS: MEMORY IMPAIRMENT. THE PSYCHOPATHOLOGIC PROFILE OF MENTAL DISORDERS IS VERY DIVERSE AND PSYCHOTROPIC MEDICATIONS USED TO TREAT THEM DIFFER IN THEIR CHEMICAL STRUCTURE. NEVERTHELESS, THESE DRUGS SHARE THESE FOUR CHARACTERISTICS: DELAYED ONSET OF CLINICAL RESPONSE, NOT ONE OF THEM CAN BE SAID TO CURE, THERE IS A HIGH NUMBER OF NON-RESPONDERS, AND THE MECHANISM RESPONSIBLE FOR THEIR THERAPEUTIC ACTION IS NOT KNOWN. IT IS HYPOTHESIZED THAT THE ACTION OF PSYCHOTROPIC MEDICATIONS IS MEMORY IMPAIRMENT, UNDERSTANDING MEMORY AS THE TRACE LEFT IN THE NERVOUS SYSTEM NOT ONLY BY INDIVIDUAL EXPERIENCES BUT ALSO BY GENETIC AND EPIGENETIC PHENOMENA. IT IS SUGGESTED THAT IT WOULD BE BENEFICIAL TO TRANSLATE SOME RESEARCH STRATEGIES FROM THE NEUROBIOLOGY OF LEARNING AND MEMORY TO THE STUDY OF THE EFFECTS OF PSYCHOTROPIC MEDICATIONS. THE HYPOTHESIS IS BRIEFLY ASSESSED ACCORDING TO THE FOLLOWING THREE CRITERIA: (A). THE COMPARISON BETWEEN THE MOLECULAR EFFECTS OF PSYCHOTROPIC MEDICATIONS AND THE SO-CALLED MOLECULAR BIOLOGY OF LEARNING AND MEMORY, (B). THE EFFECTS OF THESE DRUGS, PREFERENTIALLY AFTER CHRONIC USE, ON MEMORY TESTS, AND (C). THE EFFECTS OF DRUGS THAT IMPAIR MEMORY ON TESTS USED FOR SCREENING PSYCHOTROPIC MEDICATIONS. FINALLY, SOME GENERAL SUGGESTIONS FOR FUTURE RESEARCH ARE POINTED OUT. 2003