1   993 123 CHRONIC STRESS INDUCES PERSISTENT CHANGES IN GLOBAL DNA METHYLATION AND GENE EXPRESSION IN THE MEDIAL PREFRONTAL CORTEX, ORBITOFRONTAL CORTEX, AND HIPPOCAMPUS. CHRONIC STRESS IS ASSOCIATED WITH A PLETHORA OF COGNITIVE SYMPTOMS SUCH AS EMOTIONAL DYSREGULATION AND IMPAIRED EXECUTIVE FUNCTION THAT HAVE BEEN ATTRIBUTED TO MODIFICATIONS IN NEUROANATOMY IN THE ORBITOFRONTAL CORTEX (OFC), MEDIAL PREFRONTAL CORTEX (MPFC), AND HIPPOCAMPUS (HPC). WHILE MANY STUDIES HAVE EXAMINED STRESS-INDUCED CHANGES IN NEURONAL MORPHOLOGY, SYNAPTIC PLASTICITY, AND CELLULAR FUNCTION, THERE HAS BEEN LITTLE INVESTIGATION INTO PERSISTENT CHANGES IN GENE EXPRESSION THAT MAY BE RESPONSIBLE FOR THE MAINTENANCE OF THESE CHANGES. THIS STUDY EXPOSED ADULT RATS TO A CHRONIC STRESSOR AND THEN EXAMINED CHANGES IN MRNA GENE EXPRESSION IN THE OFC, MPFC AND HPC FOLLOWING A TWO-WEEK WITHDRAWAL PERIOD. MRNA BIO-SEQUENCING RESULTS REVEALED SEX- AND REGION-DEPENDENT CHANGES. SURPRISINGLY THE GREATEST CHANGES IN GENE EXPRESSION WERE FOUND IN THE OFC, AND SIMILAR TO ANATOMICAL STUDIES, ANALYSIS OF GENE CHANGES WITH INGENUITY PATHWAY ANALYSIS SOFTWARE DEMONSTRATED THAT THE MPFC AND OFC EXHIBITED CONTRASTING ACTIVATION OF CANONICAL PATHWAYS AND FUNCTIONAL NETWORKS. THE HPC DEMONSTRATED THE LARGEST DEGREE OF SEX-DEPENDENT CHANGE IN GENE EXPRESSION. IN GENERAL, CHRONIC STRESS INDUCED PERSISTENT CHANGES IN GENE EXPRESSION IN THE THREE BRAIN REGIONS WE EXAMINED AND THESE CHANGES COULD BE ASSOCIATED WITH THE COMMONLY REPORTED COGNITIVE SYMPTOMS. THE CURRENT STUDY HIGHLIGHTS THE REGION- AND SEX-DEPENDENT NATURE OF THE BRAIN'S RESPONSE TO CHRONIC STRESS AND THE DIFFICULTY WE FACE WHEN ATTEMPTING TO DEVELOP TREATMENT OPTIONS.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
2   844  24 CHILDHOOD ALLERGY DISEASE, EARLY DIAGNOSIS, AND THE POTENTIAL OF SALIVARY PROTEIN BIOMARKERS. ALLERGIC DISEASE HAS RISEN TO EPIDEMIC PROPORTIONS SINCE THE LAST DECADE AND IS AMONG THE MOST COMMON NONCOMMUNICABLE, CHRONIC DISEASES IN CHILDREN AND ADOLESCENTS WORLDWIDE. ALLERGIC DISEASE USUALLY OCCURS IN EARLY LIFE; THUS, EARLY BIOMARKERS OF ALLERGIC SUSCEPTIBILITY ARE REQUIRED FOR PREVENTIVE MEASURES TO HIGH-RISK INFANTS WHICH ENABLE EARLY INTERVENTIONS TO DECREASE ALLERGIC SEVERITY. HOWEVER, TO DATE, THERE IS NO RELIABLE GENERAL OR SPECIFIC ALLERGY PHENOTYPE DETECTION METHOD THAT IS EASY AND NONINVASIVE FOR CHILDREN. MOST REPORTED ALLERGIC PHENOTYPE DETECTION METHODS ARE INVASIVE, SUCH AS THE SKIN PRICK TEST (SPT), ORAL FOOD CHALLENGE (OFC), AND BLOOD TEST, AND MANY INVOLVE NOT READILY ACCESSIBLE BIOLOGICAL SAMPLES, SUCH AS CORD BLOOD (CB), MATERNAL BLOOD, OR NEWBORN VERNIX. SALIVA IS A BIOLOGICAL SAMPLE THAT HAS GREAT POTENTIAL AS A BIOMARKER MEASUREMENT AS IT CONSISTS OF AN ABUNDANCE OF BIOMARKERS, SUCH AS GENETIC MATERIAL AND PROTEINS. IT IS EASILY ACCESSIBLE, NONINVASIVE, COLLECTED VIA A PAINLESS PROCEDURE, AND AN EASY BEDSIDE SCREENING FOR REAL-TIME MEASUREMENT OF THE ONGOING HUMAN PHYSIOLOGICAL SYSTEM. ALL THESE ADVANTAGES EMPHASISE SALIVA AS A VERY PROMISING DIAGNOSTIC CANDIDATE FOR THE DETECTION AND MONITORING OF DISEASE BIOMARKERS, ESPECIALLY IN CHILDREN. FURTHERMORE, PROTEIN BIOMARKERS HAVE THE ADVANTAGES AS MODIFIABLE INFLUENCING FACTORS RATHER THAN GENETIC AND EPIGENETIC FACTORS THAT ARE MOSTLY NONMODIFIABLE FACTORS FOR ALLERGIC DISEASE SUSCEPTIBILITY IN CHILDHOOD. SALIVA HAS GREAT POTENTIAL TO REPLACE SERUM AS A BIOLOGICAL FLUID BIOMARKER IN DIAGNOSING CLINICAL ALLERGY. HOWEVER, TO DATE, SALIVA IS NOT CONSIDERED AS AN ESTABLISHED MEDICALLY ACCEPTABLE BIOMARKER. THIS REVIEW CONSIDERS WHETHER THE SALIVA COULD BE SUITABLE BIOLOGICAL SAMPLES FOR EARLY DETECTION OF ALLERGIC RISK. SUCH TOOLS MAY BE USED AS JUSTIFICATION FOR TARGETED INTERVENTIONS IN EARLY CHILDHOOD FOR DISEASE PREVENTION AND ASSISTING IN REDUCING MORBIDITY AND MORTALITY CAUSED BY CHILDHOOD ALLERGY.	2021	
                                                                                    
3  4632  23 NEUROIMAGING GENETIC APPROACHES TO POSTTRAUMATIC STRESS DISORDER. NEUROIMAGING GENETIC STUDIES THAT ASSOCIATE GENETIC AND EPIGENETIC VARIATION WITH NEURAL ACTIVITY OR STRUCTURE PROVIDE AN OPPORTUNITY TO LINK GENES TO PSYCHIATRIC DISORDERS, OFTEN BEFORE PSYCHOPATHOLOGY IS DISCERNABLE IN BEHAVIOR. HERE WE REVIEW NEUROIMAGING GENETICS STUDIES WITH PARTICIPANTS WHO HAVE POSTTRAUMATIC STRESS DISORDER (PTSD). RESULTS SHOW THAT GENES RELATED TO THE PHYSIOLOGICAL STRESS RESPONSE (E.G., GLUCOCORTICOID RECEPTOR AND ACTIVITY, NEUROENDOCRINE RELEASE), LEARNING AND MEMORY (E.G., PLASTICITY), MOOD, AND PAIN PERCEPTION ARE TIED TO NEURAL INTERMEDIATE PHENOTYPES ASSOCIATED WITH PTSD. THESE GENES ARE ASSOCIATED WITH AND SOMETIMES PREDICT NEURAL STRUCTURE AND FUNCTION IN AREAS INVOLVED IN ATTENTION, EXECUTIVE FUNCTION, MEMORY, DECISION-MAKING, EMOTION REGULATION, SALIENCE OF POTENTIAL THREATS, AND PAIN PERCEPTION. EVIDENCE SUGGESTS THESE RISK POLYMORPHISMS AND NEURAL INTERMEDIATE PHENOTYPES ARE VULNERABILITIES TOWARD DEVELOPING PTSD IN THE AFTERMATH OF TRAUMA, OR VULNERABILITIES TOWARD PARTICULAR SYMPTOMS ONCE PTSD HAS DEVELOPED. WORK DISTINGUISHING BETWEEN THE RE-EXPERIENCING AND DISSOCIATIVE SUB-TYPES OF PTSD, AND EXAMINING OTHER PTSD SYMPTOM CLUSTERS IN ADDITION TO THE RE-EXPERIENCING AND HYPERAROUSAL SYMPTOMS, WILL FURTHER CLARIFY NEUROBIOLOGICAL MECHANISMS AND INCONSISTENT FINDINGS. FURTHERMORE, AN EXCITING POSSIBILITY IS THAT GENETIC ASSOCIATIONS WITH PTSD MAY EVENTUALLY BE UNDERSTOOD THROUGH DIFFERENTIAL INTERMEDIATE PHENOTYPES OF NEURAL CIRCUIT STRUCTURE AND FUNCTION, POSSIBLY UNDERLYING THE DIFFERENT SYMPTOM CLUSTERS SEEN WITHIN PTSD.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
4  4622  24 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
5  4062  23 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	
                                                                                                                                                                                                                                                                                                                                                    
6  6478  25 TOPICAL REVIEW: THE EMERGING FIELD OF EPIGENETICS: INFORMING MODELS OF PEDIATRIC TRAUMA AND PHYSICAL HEALTH. OBJECTIVE: TRAUMA EXPERIENCED DURING CHILDHOOD AND ADOLESCENCE HAS BEEN LINKED TO A NUMBER OF CHRONIC MEDICAL CONCERNS. WE HIGHLIGHT MAJOR FINDINGS FROM THE PEDIATRIC TRAUMA LITERATURE TO PROVIDE A MODEL FOR UNDERSTANDING THIS ASSOCIATION. METHODS: STUDIES EXAMINING THE EFFECTS OF TRAUMA WERE SYSTEMATICALLY REVIEWED AND SYNTHESIZED INTO A MODEL PROPOSING A CENTRAL ROLE FOR EPIGENETICS IN THE WAYS THAT CHILDHOOD EXPERIENCES CAN AFFECT HEALTH. RESULTS: EARLY HYPOTHALAMIC PITUITARY ADRENAL (HPA) AXIS RESPONSE MAY IMPACT INITIAL TRAUMA EXPERIENCE, WITH DOWNSTREAM EFFECTS ON POSTTRAUMA ADJUSTMENT REFLECTED IN POSTTRAUMA NEUROBIOLOGY, PSYCHOLOGICAL HEALTH, AND PHYSICAL HEALTH. CONCLUSIONS: PROSPECTIVE RESEARCH WITH CHILDREN AND ADOLESCENTS EXPOSED TO TRAUMA IS NEEDED TO BETTER CHARACTERIZE THE GENETIC AND EPIGENETIC INFLUENCES ON THE COURSE OF HPA AND IMMUNE PROCESSES AS RELATED TO POSTTRAUMA PSYCHOLOGICAL AND PHYSICAL HEALTH OUTCOMES.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
7  6266  21 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
8  3926  29 LITERATURE REVIEW AND METHODOLOGICAL CONSIDERATIONS FOR UNDERSTANDING CIRCULATING RISK BIOMARKERS FOLLOWING TRAUMA EXPOSURE. EXPOSURE TO TRAUMATIC EVENTS IS COMMON. WHILE MANY INDIVIDUALS RECOVER FOLLOWING TRAUMA EXPOSURE, A SUBSTANTIAL SUBSET DEVELOP ADVERSE POSTTRAUMATIC NEUROPSYCHIATRIC SEQUELAE (APNS) SUCH AS POSTTRAUMATIC STRESS, MAJOR DEPRESSION, AND REGIONAL OR WIDESPREAD CHRONIC MUSCULOSKELETAL PAIN. APNS CAUSE SUBSTANTIAL BURDEN TO THE INDIVIDUAL AND TO SOCIETY, CAUSING FUNCTIONAL IMPAIRMENT AND PHYSICAL DISABILITY, RISK FOR SUICIDE, LOST WORKDAYS, AND INCREASED HEALTH CARE COSTS. CONTEMPORARY TREATMENT IS LIMITED BY AN INABILITY TO IDENTIFY INDIVIDUALS AT HIGH RISK OF APNS IN THE IMMEDIATE AFTERMATH OF TRAUMA, AND AN INABILITY TO IDENTIFY OPTIMAL TREATMENTS FOR INDIVIDUAL PATIENTS. OUR PURPOSE IS TO PROVIDE A COMPREHENSIVE REVIEW DESCRIBING CANDIDATE BLOOD-BASED BIOMARKERS THAT MAY HELP TO IDENTIFY THOSE AT HIGH RISK OF APNS AND/OR GUIDE INDIVIDUAL INTERVENTION DECISION-MAKING. SUCH BLOOD-BASED BIOMARKERS INCLUDE CIRCULATING BIOLOGICAL FACTORS SUCH AS HORMONES, PROTEINS, IMMUNE MOLECULES, NEUROPEPTIDES, NEUROTRANSMITTERS, MRNA, AND NONCODING RNA EXPRESSION SIGNATURES, WHILE WE DO NOT REVIEW GENETIC AND EPIGENETIC BIOMARKERS DUE TO OTHER RECENT REVIEWS OF THIS TOPIC. THE CURRENT STATE OF THE LITERATURE ON CIRCULATING RISK BIOMARKERS OF APNS IS SUMMARIZED, AND KEY CONSIDERATIONS AND CHALLENGES FOR THEIR DISCOVERY AND TRANSLATION ARE DISCUSSED. WE ALSO DESCRIBE THE AURORA STUDY, A SPECIFIC EXAMPLE OF CURRENT SCIENTIFIC EFFORTS TO IDENTIFY SUCH CIRCULATING RISK BIOMARKERS AND THE LARGEST STUDY TO DATE FOCUSED ON IDENTIFYING RISK AND PROGNOSTIC FACTORS IN THE AFTERMATH OF TRAUMA EXPOSURE.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
9   243  43 ADOLESCENT CHRONIC INTERMITTENT TOLUENE INHALATION DYNAMICALLY REGULATES THE TRANSCRIPTOME AND NEURONAL METHYLOME WITHIN THE RAT MEDIAL PREFRONTAL CORTEX. INHALANTS CONTAINING THE VOLATILE SOLVENT TOLUENE ARE MISUSED TO INDUCE EUPHORIA OR INTOXICATION. INHALANT ABUSE IS MOST COMMON DURING ADOLESCENCE AND CAN RESULT IN COGNITIVE IMPAIRMENTS DURING AN IMPORTANT MATURATIONAL PERIOD. DESPITE EVIDENCE SUGGESTING THAT EPIGENETIC MODIFICATIONS MAY UNDERPIN THE COGNITIVE EFFECTS OF INHALANTS, NO STUDIES TO DATE HAVE THOROUGHLY INVESTIGATED TOLUENE-INDUCED REGULATION OF THE TRANSCRIPTOME OR DISCRETE EPIGENETIC MODIFICATIONS WITHIN THE BRAIN. TO ADDRESS THIS, WE INVESTIGATED EFFECTS OF ADOLESCENT CHRONIC INTERMITTENT TOLUENE (CIT) INHALATION ON GENE EXPRESSION AND DNA METHYLATION PROFILES WITHIN THE RAT MEDIAL PREFRONTAL CORTEX (MPFC), WHICH UNDERGOES MATURATION THROUGHOUT ADOLESCENCE AND HAS BEEN IMPLICATED IN TOLUENE-INDUCED COGNITIVE DEFICITS. EMPLOYING BOTH RNA-SEQ AND GENOME-WIDE METHYL CPG BINDING DOMAIN (MBD) ULTRA-SEQ ANALYSIS, WE DEMONSTRATE THAT ADOLESCENT CIT INHALATION (10 000 PPM FOR 1 H/DAY, 3 DAYS/WEEK FOR 4 WEEKS) INDUCES BOTH TRANSIENT AND PERSISTENT CHANGES TO THE TRANSCRIPTOME AND DNA METHYLOME WITHIN THE RAT MPFC FOR AT LEAST 2 WEEKS FOLLOWING TOLUENE EXPOSURE. WE DEMONSTRATE FOR THE FIRST TIME THAT ADOLESCENT CIT EXPOSURE RESULTS IN DYNAMIC REGULATION OF THE MPFC TRANSCRIPTOME LIKELY RELATING TO ACUTE INFLAMMATORY RESPONSES AND PERSISTENT DEFICITS IN SYNAPTIC PLASTICITY. THESE ADAPTATIONS MAY CONTRIBUTE TO THE COGNITIVE DEFICITS ASSOCIATED WITH CHRONIC TOLUENE EXPOSURE AND PROVIDE NOVEL MOLECULAR TARGETS FOR PREVENTING LONG-TERM NEUROPHYSIOLOGICAL ABNORMALITIES FOLLOWING CHRONIC TOLUENE INHALATION.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
10  1058  25 CLINICAL MEASURES OF ALLOSTATIC LOAD IN CHILDREN AND ADOLESCENTS WITH FOOD ALLERGY, DEPRESSION, OR ANXIETY. PURPOSE: SUSTAINED HIGH STRESS EXPOSURE RESULTS IN CHRONIC ACTIVATION OF THE STRESS RESPONSE SYSTEM, DYSREGULATED STRESS RESPONSES, HIGH ALLOSTATIC LOAD, AND POOR LATER-LIFE HEALTH. CHILDREN AND ADOLESCENTS WITH CHRONIC HEALTH CONDITIONS FACE STRESSORS RELATED TO THEIR CONDITION IN ADDITION TO THOSE TYPICAL OF CHILDHOOD AND ADOLESCENCE, PLACING THEM AT RISK OF HIGH ALLOSTATIC LOAD. THE PURPOSE OF THIS SECONDARY ANALYSIS WAS TO EXAMINE WHETHER YOUTH WITH CHRONIC HEALTH CONDITIONS DIFFER FROM CONTROLS ON CLINICAL MEASURES OF ALLOSTATIC LOAD. DESIGN AND METHODS: A SECONDARY ANALYSIS OF TWO DATASETS, THE ELECTRONIC HEALTH RECORD OF A TERTIARY CHILDREN'S HOSPITAL AND DATA FROM THE SURVEY OF THE HEALTH OF WISCONSIN, COMPARED YOUTH WITH CHRONIC HEALTH CONDITIONS TO CONTROLS ON CLINICAL MEASURES OF ALLOSTATIC LOAD. ADDITIONAL ANALYSES EXPLORED WHETHER PARENTAL STRESS AND MENTAL HEALTH INFLUENCED THESE RELATIONSHIPS. RESULTS: ANALYSES IDENTIFIED DIFFERENCES IN BMI, BLOOD PRESSURE, AND WAIST CIRCUMFERENCE BETWEEN YOUTH WITH FOOD ALLERGY, ANXIETY, OR DEPRESSION, AND CONTROLS. THESE RELATIONSHIPS DIFFERED FOR MALES AND FEMALES AND FOR THOSE WITH COMORBID MENTAL AND PHYSICAL CONDITIONS, AND WERE INFLUENCED BY PARENT STRESS AND MENTAL HEALTH. CONCLUSIONS: RESULTS SUPPORT FUTURE STUDIES EXPLORING WHETHER HIGH STRESS IN YOUTH WITH CHRONIC HEALTH CONDITIONS LEADS TO INCREASED ALLOSTATIC LOAD. INCORPORATING BIOMARKERS AS WELL AS GENETIC AND EPIGENETIC FACTORS WILL PROVIDE CRITICAL INSIGHTS. PRACTICE IMPLICATIONS: YOUTH WITH MENTAL AND PHYSICAL CHCS MAY BE AT INCREASED RISK OF HIGH ALLOSTATIC LOAD, REFLECTED IN CLINICAL MEASURES OF METABOLISM, AND SHOULD HAVE REGULAR ASSESSMENTS OF THEIR METABOLIC HEALTH.	2021	
                                                                                                                                                                                                                                                                                                                                                                                
11  2509  31 EPIGENETICS AND PAIN: NEW INSIGHTS TO AN OLD PROBLEM. PHYSICIANS AND NEUROSCIENTISTS HAVE LONG OBSERVED THAT FACTORS SUCH AS THOUGHTS, EMOTIONS, AND EXPECTATIONS CAN INFLUENCE THE PERCEPTION OF PAIN. PAIN CAN BE DESCRIBED AS AN UNPLEASANT SENSATION THAT CAUSES PHYSICAL DISCOMFORT AND EMOTIONAL DISTRESS. IT ALERTS AN INDIVIDUAL TO SEEK HELP AND IS THE MAIN COMPLAINT THAT BRINGS INDIVIDUALS TO PHYSICIANS. THOUGH IT IS ASSOCIATED WITH PROBABLE TISSUE DAMAGE, SUCH DAMAGE MAY BE SUBTLE, SOMETIMES INVOLVING THE RELEASE OF ALGESIC CHEMICALS, AND ALSO INFLUENCED BY ATTITUDES, BELIEFS, PERSONALITY, AND SOCIAL FACTORS. THE PERCEPTION OF PAIN MAY VARY DUE TO A MULTITUDE OF THESE FACTORS INFLUENCING THE ASCENDING SENSORY IMPULSE PROPAGATION TO THE PRIMARY SOMATOSENSORY CORTEX. THE GENETICS AND EPIGENETICS OF PAIN MODULATORS HAVE BEEN PREVIOUSLY STUDIED, BUT THERE IS A LACK OF APPLICATION IN THE EVERYDAY MANAGEMENT AND TREATMENT OF PAIN DUE TO THE PAUCITY OF VALID EVIDENCE-BASED DATA. WE USED THE PUBMED DATABASE AS OUR PRIMARY TOOL FOR RESEARCHING CURRENT LITERATURE ON THIS TOPIC. THE MESH TERMS USED INCLUDED: GENE MODIFICATION, EPIGENETICS, GENES, PAIN, ANALGESIA, "TYPES OF PAIN, AND THEORIES OF PAIN. THE RESULTS WERE FILTERED AS FOLLOWS: PUBLICATIONS WITHIN THE LAST 10 YEARS, GENERALIZED PAIN STUDIES REGARDING THE BIOPSYCHOSOCIAL ASPECT OF PAIN, PERTINENT GENES, AND EPIGENETIC MODULATION OF THOSE GENES; 52 PUBLICATIONS WERE SELECTED FOR REVIEW. BY ADDRESSING THE EXTERNAL FACTORIAL CAUSES AND THE APPROPRIATE APPLICATION OF EPIGENETIC PRINCIPLES WHICH AFFECT PAIN PERCEPTION, IT IS HOPED THAT THIS REVIEW WILL MOTIVATE FUTURE ADVANCEMENTS IN THE MANAGEMENT OF ACUTE AND/OR CHRONIC PAIN.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
12  2850  30 FROM CHILD ABUSE TO DEVELOPING BORDERLINE PERSONALITY DISORDER INTO ADULTHOOD: EXPLORING THE NEUROMORPHOLOGICAL AND EPIGENETIC PATHWAY. BORDERLINE PERSONALITY DISORDER (BPD) IS ONE OF THE MOST COMMON PERSONALITY DISORDERS SEEN IN THE GENERAL POPULATION. AMONG MULTIPLE IDENTIFIED RISK FACTORS, ONE OF THE MOST INFLUENTIAL ELEMENTS IS EXPOSURE TO AN ADVERSE CHILDHOOD EXPERIENCE IN TERMS OF EMOTIONAL, PHYSICAL, OR SEXUAL ABUSE. A CASCADE OF NEUROMORPHOLOGICAL AND EPIGENETIC CHANGES OCCURS IN RESPONSE TO THESE CHILDHOOD STRESSORS, WHICH MAY HAVE A STRONG LINK TO THE DEVELOPMENT OF BPD. PUBMED AND GOOGLE SCHOLAR WERE SEARCHED FOR ARTICLES RELEVANT TO CHILD ABUSE AND THE DEVELOPMENT OF BPD. THE SEARCH WAS NOT RESTRICTED TO ANY TIME FRAME OR GEOGRAPHIC LOCATION. SIGNIFICANT EPIGENETIC AND NEUROMORPHOLOGICAL CHANGES ARE SEEN WITH CHILD ABUSE, CONTRIBUTING TO THE DEVELOPMENT OF BPD. CHRONIC STRESSORS LEAD TO HYPOTHALAMIC-PITUITARY AXIS (HPA) ACTIVATION, RELEASING CORTISOL THAT ACTS ON THE PREFRONTAL CORTEX, AMYGDALA, AND HIPPOCAMPUS, PRODUCING THE BEHAVIORAL PATTERNS SEEN IN BPD. OVERSTIMULATION OF GRAY MATTER LEADS TO PERMANENT NEUROMORPHOLOGICAL CHANGES, WHICH CAN BE VISUALIZED IN FUNCTIONAL MRI/BRAIN SCANS. HYPERMETHYLATION OF MESSENGER RIBONUCLEIC ACID IN VARIOUS SITES SUGGESTS THE IMPACT OF CHILD ABUSE ON THE GENETIC LEVEL. INTERESTINGLY, THE PREVALENCE OF BPD IS SEEN EQUALLY IN BOTH GENDERS BUT IS DIAGNOSED MORE FREQUENTLY IN FEMALES BECAUSE THEY TEND TO BE MORE LIKELY TO SEEK HELP. UNDERSTANDING THE IMPACT OF EARLY AGE LIFE STRESSORS INTO ADULTHOOD CALLS FOR SERIOUS FOCUS ON EARLY DIAGNOSIS AND INTERVENTION. THIS IMPLIES THE NEED FOR MORE STUDIES IN PATIENTS WITH BPD WITH OR WITHOUT ANY CHILDHOOD TRAUMATIC EXPERIENCE AND A BETTER UNDERSTANDING OF THE CHANGES THAT OCCUR BIOPSYCHOLOGICALLY AND GENETICALLY IN RESPONSE TO TRAUMA.	2020	
                                                                                                                                                                                                                                                                                                                                                 
13    92  29 A PILOT STUDY INVESTIGATING THE ROLE OF GENDER IN THE INTERGENERATIONAL RELATIONSHIPS BETWEEN GENE EXPRESSION, CHRONIC PAIN, AND ADVERSE CHILDHOOD EXPERIENCES IN A CLINICAL SAMPLE OF YOUTH WITH CHRONIC PAIN. CHRONIC PAIN IS A HIGHLY PREVALENT AND COSTLY ISSUE THAT OFTEN EMERGES DURING CHILDHOOD OR ADOLESCENCE AND PERSISTS INTO ADULTHOOD. ADVERSE CHILDHOOD EXPERIENCES (ACES) INCREASE RISK FOR SEVERAL ADVERSE HEALTH CONDITIONS, INCLUDING CHRONIC PAIN. RECENT EVIDENCE SUGGESTS THAT PARENTAL TRAUMA (ACES, POST-TRAUMATIC STRESS DISORDER (PTSD) SYMPTOMS) CONFERS RISK OF POOR HEALTH OUTCOMES IN THEIR CHILDREN. INTERGENERATIONAL RELATIONSHIPS BETWEEN PARENTAL TRAUMA AND CHILD CHRONIC PAIN MAY BE MEDIATED BY EPIGENETIC MECHANISMS. A CLINICAL SAMPLE OF YOUTH WITH CHRONIC PAIN AND THEIR PARENTS COMPLETED PSYCHOMETRICALLY SOUND QUESTIONNAIRES ASSESSING ACES, PTSD SYMPTOMS, AND CHRONIC PAIN, AND PROVIDED A SALIVA SAMPLE. THESE WERE USED TO INVESTIGATE THE INTERGENERATIONAL RELATIONSHIPS BETWEEN FOUR EPIGENETIC BIOMARKERS (COMT, DRD2, GR, AND SERT), TRAUMA, AND CHRONIC PAIN. THE RESULTS INDICATED THAT THE SIGNIFICANT BIOMARKERS WERE DEPENDENT UPON THE GENDER OF THE CHILD, WHEREIN PARENTAL ACES SIGNIFICANTLY CORRELATED WITH CHANGES IN DRD2 EXPRESSION IN FEMALE CHILDREN AND ALTERED COMT EXPRESSION IN THE PARENTS OF MALE CHILDREN. ADDITIONALLY, THE NATURE OF THE ACE (MALTREATMENT VS. HOUSEHOLD DYSFUNCTION) WAS ASSOCIATED WITH THE SPECIFIC EPIGENETIC CHANGES. THERE MAY BE DIFFERENT PATHWAYS THROUGH WHICH PARENTAL ACES CONFER RISK FOR POOR OUTCOMES FOR MALES AND FEMALES, HIGHLIGHTING THE IMPORTANCE OF CHILD GENDER IN FUTURE INVESTIGATIONS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
14  2900  25 GENDER BIAS IN THERAPEUTIC EFFORT: FROM RESEARCH TO HEALTH CARE. THERE ARE RELEVANT DIMENSIONS FROM A GENDER PERSPECTIVE RELATED TO THERAPEUTIC EFFORT. TO ILLUSTRATE AND DISCUSS POSSIBLE GENDER BIAS RELATED TO MEDICINES, THROUGH THE CONSUMPTION ANALYSIS IN WOMEN, THE PRESCRIPTION OF BIOLOGICAL DRUGS ACCORDING TO SEX, THE POTENTIAL GENDER INEQUALITY IN ADVERSE DRUG REACTIONS, AND RESEARCH WITH CLINICAL TRIALS, AS WELL AS THE DECISIONS OF INTERNATIONAL INSTITUTIONS IN THE MARKETING OF MEDICINAL PRODUCTS. THERE IS GREATER TENDENCY TO PRESCRIBE PAIN RELIEVERS, REGARDLESS OF PAIN, AND DRUGS FOR LOW INTENSITY DEPRESSIVE SYMPTOMS IN WOMEN THAN IN MEN. THE OPPOSITE OCCURS IN THE PRESCRIPTION OF STATINS AND ADEQUATE DOSES, AND WITH THE GREATER PROBABILITY OF PRESCRIBING ANTI-TUMOR NECROSIS FACTOR IN MEN THAN IN WOMEN WITH ANKYLOSING SPONDYLITIS, DESPITE A SIMILAR DISEASE BURDEN. ADVERSE DRUG REACTIONS ARE OBSERVED MORE FREQUENTLY IN WOMEN THAN IN MEN, WHERE DETERMINANTS SUCH AS BODY WEIGHT ARE HAVING LITTLE INFLUENCE ON THE DOSAGE. IT IS CURRENTLY SCARCELY CONSIDERED IN THE PRESCRIPTION THAT WOMEN HAVE DIFFERENCES IN THE ACTIVITY OF CYTOCHROME CYPP450 ENZYMES, WHICH CAN AFFECT THE LIVER'S METABOLISM RATE. THERE ARE EVEN IMMUNOLOGICAL, GENETIC AND EPIGENETIC EFFECTS (DUE TO HEREDITY AND UNEVEN GENE DOSING LOCATED IN THE X AND Y CHROMOSOMES) THAT CAN INFLUENCE THESE DIFFERENCES BY SEX. FINALLY, THROUGH CASES OF HORMONAL THERAPY CLINICAL TRIALS, A DRUG FOR WOMEN'S INHIBITED SEXUAL DESIRE AND A CONTRACEPTIVE FOR MEN, GENDER BIAS AND STEREOTYPES ARE SHOWN TO INFLUENCE A POTENTIAL GENERATION OF INEQUALITIES, ESPECIALLY IN ADVERSE DRUG REACTIONS TO THE DETRIMENT OF WOMEN. IN CONCLUSION, HEALTH PROFESSIONALS FREQUENTLY ATTRIBUTE PHYSICAL SYMPTOMS TO WOMEN'S EMOTIONALITY, INFLUENCING THEIR GREATER PRESCRIPTION OF SYMPTOMATIC DRUGS. WHETHER THE SAME REASON INFLUENCES THE LOWER PRESCRIPTION OF THERAPEUTIC DRUGS IN WOMEN THAN IN MEN SHOULD BE ANALYZED. THERE ARE BIOLOGICAL DETERMINANTS TO CONSIDER DUE TO THEIR INFLUENCE ON A GREATER PHARMACOLOGICAL TOXICITY IN WOMEN. CLINICAL TRIALS SHOULD IMPROVE ACCORDING TO THE GENDER RECOMMENDATIONS BY THE FOOD AND DRUGS ADMINISTRATION.	2020	

15   380  15 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
16    23  36 60 YEARS OF NEUROENDOCRINOLOGY: REDEFINING NEUROENDOCRINOLOGY: STRESS, SEX AND COGNITIVE AND EMOTIONAL REGULATION. THE DISCOVERY OF STEROID HORMONE RECEPTORS IN BRAIN REGIONS THAT MEDIATE EVERY ASPECT OF BRAIN FUNCTION HAS BROADENED THE DEFINITION OF 'NEUROENDOCRINOLOGY' TO INCLUDE THE RECIPROCAL COMMUNICATION BETWEEN THE BRAIN AND THE BODY VIA HORMONAL AND NEURAL PATHWAYS. THE BRAIN IS THE CENTRAL ORGAN OF STRESS AND ADAPTATION TO STRESS BECAUSE IT PERCEIVES AND DETERMINES WHAT IS THREATENING, AS WELL AS THE BEHAVIORAL AND PHYSIOLOGICAL RESPONSES TO THE STRESSOR. THE ADULT AND DEVELOPING BRAIN POSSESS REMARKABLE STRUCTURAL AND FUNCTIONAL PLASTICITY IN RESPONSE TO STRESS, INCLUDING NEURONAL REPLACEMENT, DENDRITIC REMODELING, AND SYNAPSE TURNOVER. STRESS CAUSES AN IMBALANCE OF NEURAL CIRCUITRY SUBSERVING COGNITION, DECISION-MAKING, ANXIETY AND MOOD THAT CAN ALTER EXPRESSION OF THOSE BEHAVIORS AND BEHAVIORAL STATES. THIS IMBALANCE, IN TURN, AFFECTS SYSTEMIC PHYSIOLOGY VIA NEUROENDOCRINE, AUTONOMIC, IMMUNE AND METABOLIC MEDIATORS. IN THE SHORT TERM, AS FOR INCREASED FEARFUL VIGILANCE AND ANXIETY IN A THREATENING ENVIRONMENT, THESE CHANGES MAY BE ADAPTIVE. BUT, IF THE DANGER PASSES AND THE BEHAVIORAL STATE PERSISTS ALONG WITH THE CHANGES IN NEURAL CIRCUITRY, SUCH MALADAPTATION MAY NEED INTERVENTION WITH A COMBINATION OF PHARMACOLOGICAL AND BEHAVIORAL THERAPIES, AS IS THE CASE FOR CHRONIC ANXIETY AND DEPRESSION. THERE ARE IMPORTANT SEX DIFFERENCES IN THE BRAIN RESPONSES TO STRESSORS THAT ARE IN URGENT NEED OF FURTHER EXPLORATION. MOREOVER, ADVERSE EARLY-LIFE EXPERIENCE, INTERACTING WITH ALLELES OF CERTAIN GENES, PRODUCE LASTING EFFECTS ON BRAIN AND BODY OVER THE LIFE-COURSE VIA EPIGENETIC MECHANISMS. WHILE PREVENTION IS MOST IMPORTANT, THE PLASTICITY OF THE BRAIN GIVES HOPE FOR THERAPIES THAT TAKE INTO CONSIDERATION BRAIN-BODY INTERACTIONS.	2015	
                                                                                                                                                                                                                                                                                                                                    
17  1760  24 EARLY PREDICTORS OF ASTHMA AND ALLERGY IN CHILDREN: THE ROLE OF EPIGENETICS. PURPOSE OF REVIEW: ASTHMA AND ALLERGIC DISEASES ARE AMONG THE MOST PREVALENT CHRONIC NONCOMMUNICABLE DISEASES OF CHILDHOOD. ALTHOUGH EPIDEMIOLOGIC STUDIES SUGGEST THAT ASTHMA BEGINS IN THE PRESCHOOL YEARS, THE LACK OF FIRM DIAGNOSTIC CRITERIA TO DISTINGUISH CHILDREN WHO WILL WHEEZE ONLY TRANSIENTLY DURING EARLY-LIFE LOWER RESPIRATORY ILLNESSES FROM CHILDREN WHO WILL WHEEZE PERSISTENTLY AND DEVELOP ASTHMA PREVENTS PINPOINTING THE TIME AT WHICH DISEASE TRULY BEGINS. EPIGENETIC MECHANISMS LINK GENE REGULATION TO ENVIRONMENTAL CUES AND DEVELOPMENTAL TRAJECTORIES. THIS ARTICLE REVIEWS, THE SEARCH FOR EPIGENETIC PREDICTORS OF ASTHMA AND/OR ALLERGY THAT CAN BE IDENTIFIED ALREADY AT BIRTH AND/OR IN EARLY LIFE. RECENT FINDINGS: DNA METHYLATION SIGNATURES ASSOCIATED WITH ASTHMA AND/OR ALLERGY AT BIRTH, AND TIME-DEPENDENT DNA METHYLATION SIGNATURES ASSOCIATED WITH ALLERGIC DISEASE PHENOTYPES IN EARLY LIFE HAVE BEEN IDENTIFIED. SUMMARY: THE IDENTIFICATION OF EARLY EPIGENETIC PREDICTORS OF ALLERGIC DISEASES POINTS TO A POTENTIAL ROLE OF EPIGENETIC MECHANISMS IN REGULATING THE INCEPTION OF AND THE SUSCEPTIBILITY TO THESE DISEASES. PREDICTIVE SIGNATURES TO MORE ACCURATELY ESTIMATE A CHILD'S RISK FOR ASTHMA AND ALLERGY MAY IMPROVE CHILDHOOD ASTHMA DIAGNOSIS. MOREOVER, UNDERSTANDING THE BIOLOGICAL IMPLICATIONS OF THESE SIGNATURES MAY HELP ELUCIDATE NOVEL DISEASE PATHWAYS AND ENDOTYPES.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
18  1722  20 DYSREGULATION OF BRAIN DOPAMINE SYSTEMS IN MAJOR DEPRESSIVE DISORDER. MAJOR DEPRESSIVE DISORDER (MDD OR DEPRESSION) IS A DEBILITATING NEUROPSYCHIATRIC SYNDROME WITH GENETIC, EPIGENETIC, AND ENVIRONMENTAL CONTRIBUTIONS. DEPRESSION IS ONE OF THE LARGEST CONTRIBUTORS TO CHRONIC DISEASE BURDEN; IT AFFECTS MORE THAN ONE IN SIX INDIVIDUALS IN THE UNITED STATES. A WIDE ARRAY OF CELLULAR AND MOLECULAR MODIFICATIONS DISTRIBUTED ACROSS A VARIETY OF NEURONAL PROCESSES AND CIRCUITS UNDERLIE THE PATHOPHYSIOLOGY OF DEPRESSION-NO ESTABLISHED MECHANISM CAN EXPLAIN ALL ASPECTS OF THE DISEASE. MDD SUFFERS FROM A VAST TREATMENT GAP WORLDWIDE, AND LARGE NUMBERS OF INDIVIDUALS WHO REQUIRE TREATMENT DO NOT RECEIVE ADEQUATE CARE. THIS MINI-REVIEW FOCUSES ON DYSREGULATION OF BRAIN DOPAMINE (DA) SYSTEMS IN THE PATHOPHYSIOLOGY OF MDD AND DESCRIBING NEW CELLULAR TARGETS FOR POTENTIAL MEDICATION DEVELOPMENT FOCUSED ON DA-MODULATED MICRO-CIRCUITS. WE ALSO EXPLORE HOW NEURODEVELOPMENTAL FACTORS MAY MODIFY RISK FOR LATER EMERGENCE OF MDD, POSSIBLY THROUGH DOPAMINERGIC SUBSTRATES IN THE BRAIN.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
19  5161  22 PRECISION AND PERSONALIZED MEDICINE: HOW GENOMIC APPROACH IMPROVES THE MANAGEMENT OF CARDIOVASCULAR AND NEURODEGENERATIVE DISEASE. LIFE EXPECTANCY HAS GRADUALLY GROWN OVER THE LAST CENTURY. THIS HAS DEEPLY AFFECTED HEALTHCARE COSTS, SINCE THE GROWTH OF AN AGING POPULATION IS CORRELATED TO THE INCREASING BURDEN OF CHRONIC DISEASES. THIS REPRESENTS THE INTERESTING CHALLENGE OF HOW TO MANAGE PATIENTS WITH CHRONIC DISEASES IN ORDER TO IMPROVE HEALTH CARE BUDGETS. EFFECTIVE PRIMARY PREVENTION COULD REPRESENT A PROMISING ROUTE. TO THIS END, PRECISION, TOGETHER WITH PERSONALIZED MEDICINE, ARE USEFUL INSTRUMENTS IN ORDER TO INVESTIGATE PATHOLOGICAL PROCESSES BEFORE THE APPEARANCE OF CLINICAL SYMPTOMS AND TO GUIDE PHYSICIANS TO CHOOSE A TARGETED THERAPY TO MANAGE THE PATIENT. CARDIOVASCULAR AND NEURODEGENERATIVE DISEASES REPRESENT SUITABLE MODELS FOR TAKING FULL ADVANTAGE OF PRECISION MEDICINE TECHNOLOGIES APPLIED TO ALL STAGES OF DISEASE DEVELOPMENT. THE AVAILABILITY OF HIGH TECHNOLOGY INCORPORATING ARTIFICIAL INTELLIGENCE AND ADVANCEMENT PROGRESS MADE IN THE FIELD OF BIOMEDICAL RESEARCH HAVE BEEN SUBSTANTIAL TO UNDERSTAND HOW GENES, EPIGENETIC MODIFICATIONS, AGING, NUTRITION, DRUGS, MICROBIOME AND OTHER ENVIRONMENTAL FACTORS CAN IMPACT HEALTH AND CHRONIC DISORDERS. THE AIM OF THE PRESENT REVIEW IS TO ADDRESS HOW PRECISION AND PERSONALIZED MEDICINE CAN BRING GREATER CLARITY TO THE CLINICAL AND BIOLOGICAL COMPLEXITY OF THESE TYPES OF DISORDERS ASSOCIATED WITH HIGH MORTALITY, INVOLVING TREMENDOUS HEALTH CARE COSTS, BY DESCRIBING IN DETAIL THE METHODS THAT CAN BE APPLIED. THIS MIGHT OFFER PRECIOUS TOOLS FOR PREVENTIVE STRATEGIES AND POSSIBLE CLUES ON THE EVOLUTION OF THE DISEASE AND COULD HELP IN PREDICTING MORBIDITY, MORTALITY AND DETECTING CHRONIC DISEASE INDICATORS MUCH EARLIER IN THE DISEASE COURSE. THIS, OF COURSE, WILL HAVE A MAJOR EFFECT ON BOTH IMPROVING THE QUALITY OF CARE AND QUALITY OF LIFE OF THE PATIENTS AND REDUCING TIME EFFORTS AND HEALTHCARE COSTS.	2020	
                                                                                                                                                                                                            
20  5812  39 STRESS AND ANXIETY: STRUCTURAL PLASTICITY AND EPIGENETIC REGULATION AS A CONSEQUENCE OF STRESS. THE BRAIN IS THE CENTRAL ORGAN OF STRESS AND ADAPTATION TO STRESS BECAUSE IT PERCEIVES AND DETERMINES WHAT IS THREATENING, AS WELL AS THE BEHAVIORAL AND PHYSIOLOGICAL RESPONSES TO THE STRESSOR. THE ADULT, AS WELL AS DEVELOPING BRAIN, POSSESS A REMARKABLE ABILITY TO SHOW REVERSIBLE STRUCTURAL AND FUNCTIONAL PLASTICITY IN RESPONSE TO STRESSFUL AND OTHER EXPERIENCES, INCLUDING NEURONAL REPLACEMENT, DENDRITIC REMODELING, AND SYNAPSE TURNOVER. THIS IS PARTICULARLY EVIDENT IN THE HIPPOCAMPUS, WHERE ALL THREE TYPES OF STRUCTURAL PLASTICITY HAVE BEEN RECOGNIZED AND INVESTIGATED, USING A COMBINATION OF MORPHOLOGICAL, MOLECULAR, PHARMACOLOGICAL, ELECTROPHYSIOLOGICAL AND BEHAVIORAL APPROACHES. THE AMYGDALA AND THE PREFRONTAL CORTEX, BRAIN REGIONS INVOLVED IN ANXIETY AND FEAR, MOOD, COGNITIVE FUNCTION AND BEHAVIORAL CONTROL, ALSO SHOW STRUCTURAL PLASTICITY. ACUTE AND CHRONIC STRESS CAUSE AN IMBALANCE OF NEURAL CIRCUITRY SUBSERVING COGNITION, DECISION MAKING, ANXIETY AND MOOD THAT CAN INCREASE OR DECREASE EXPRESSION OF THOSE BEHAVIORS AND BEHAVIORAL STATES. IN THE SHORT TERM, SUCH AS FOR INCREASED FEARFUL VIGILANCE AND ANXIETY IN A THREATENING ENVIRONMENT, THESE CHANGES MAY BE ADAPTIVE; BUT, IF THE DANGER PASSES AND THE BEHAVIORAL STATE PERSISTS ALONG WITH THE CHANGES IN NEURAL CIRCUITRY, SUCH MALADAPTATION MAY NEED INTERVENTION WITH A COMBINATION OF PHARMACOLOGICAL AND BEHAVIORAL THERAPIES, AS IS THE CASE FOR CHRONIC OR MOOD ANXIETY DISORDERS. WE SHALL REVIEW CELLULAR AND MOLECULAR MECHANISMS, AS WELL AS RECENT WORK ON INDIVIDUAL DIFFERENCES IN ANXIETY-LIKE BEHAVIOR AND ALSO DEVELOPMENTAL INFLUENCES THAT BIAS HOW THE BRAIN RESPONDS TO STRESSORS. FINALLY, WE SUGGEST THAT SUCH AN APPROACH NEEDS TO BE EXTENDED TO OTHER BRAIN AREAS THAT ARE ALSO INVOLVED IN ANXIETY AND MOOD. THIS ARTICLE IS PART OF A SPECIAL ISSUE ENTITLED 'ANXIETY AND DEPRESSION'.	2012