1 5331 229 PUTTING THE PIECES TOGETHER IN GILLES DE LA TOURETTE SYNDROME: EXPLORING THE LINK BETWEEN CLINICAL OBSERVATIONS AND THE BIOLOGICAL BASIS OF DYSFUNCTION. GILLES DE LA TOURETTE SYNDROME IS A COMPLEX, IDIOPATHIC NEUROPSYCHIATRIC DISORDER WHOSE PATHOPHYSIOLOGICAL MECHANISMS HAVE YET TO BE ELUCIDATED. IT IS PHENOTYPICALLY HETEROGENEOUS AND MANIFESTS MORE OFTEN THAN NOT WITH BOTH MOTOR AND BEHAVIORAL IMPAIRMENT, ALTHOUGH TICS ARE ITS CLINICAL HALLMARK. TICS THEMSELVES PRESENT WITH A COMPLEX PROFILE AS THEY CHARACTERISTICALLY WAX AND WANE AND ARE OFTEN PRECEDED BY PREMONITORY SOMATOSENSORY SENSATIONS TO WHICH IT IS SAID A TIC IS THE RESPONSE. HIGHLY COMORBID WITH OBSESSIVE-COMPULSIVE DISORDER AND ATTENTION DEFICIT-HYPERACTIVITY DISORDER, IT IS PURPORTED TO BE AN EPIGENETIC, NEURODEVELOPMENTAL SPECTRUM DISORDER WITH A COMPLEX GENETIC PROFILE. IT HAS A CHILDHOOD ONSET, OCCURS DISPROPORTIONATELY IN MALES, AND SHOWS SPONTANEOUS SYMPTOMATIC ATTENUATION BY ADULTHOOD IN THE MAJORITY OF THOSE AFFLICTED. ALTHOUGH NOT FULLY UNDERSTOOD, ITS NEUROBIOLOGICAL BASIS IS LINKED TO DYSFUNCTION IN THE CORTICO-BASAL GANGLIA-THALAMO-CORTICAL NETWORK. TREATMENT MODALITIES FOR TOURETTE SYNDROME INCLUDE BEHAVIORAL, PHARMACOLOGICAL AND SURGICAL INTERVENTIONS, BUT THERE IS PRESENTLY NO CURE FOR THE DISORDER. FOR THOSE SEVERELY AFFECTED, DEEP BRAIN STIMULATION (DBS) HAS RECENTLY BECOME A VIABLE THERAPEUTIC OPTION. A KEY FACTOR TO ATTAINING OPTIMAL RESULTS FROM THIS SURGERY IS TARGET SELECTION, A TOPIC STILL UNDER DEBATE DUE TO THE COMPLEX CLINICAL PROFILE PRESENTED BY GTS PATIENTS. DEPENDING ON ITS PHENOTYPIC EXPRESSION AND THE MOST PROBLEMATIC ASPECT OF THE DISORDER FOR THE INDIVIDUAL, ONE OF THREE BRAIN REGIONS IS MOST COMMONLY CHOSEN FOR STIMULATION: THE THALAMUS, GLOBUS PALLIDUS, OR NUCLEUS ACCUMBENS. NEUROPHYSIOLOGICAL ANALYSES OF INTRA- AND POST-OPERATIVE HUMAN ELECTROPHYSIOLOGICAL RECORDINGS FROM CLINICAL DBS STUDIES SUGGEST A LINK BETWEEN TIC BEHAVIOR AND ACTIVITY IN BOTH THE THALAMUS AND GLOBUS PALLIDUS. IN PARTICULAR, CHRONIC RECORDINGS FROM THE THALAMUS HAVE SHOWN A CORRELATION BETWEEN SYMPTOMATOLOGY AND (1) SPECTRAL ACTIVITY IN GAMMA BAND POWER AND (2) THETA/GAMMA CROSS FREQUENCY COHERENCE. THESE RESULTS SUGGEST GAMMA OSCILLATIONS AND THETA/GAMMA CROSS CORRELATION DYNAMICS MAY SERVE AS BIOMARKERS FOR DYSFUNCTION. WHILE ACUTE AND CHRONIC RECORDINGS FROM HUMAN SUBJECTS UNDERGOING DBS HAVE PROVIDED BETTER INSIGHT INTO TIC GENESIS AND THE NEUROPATHOPHYSIOLOGICAL MECHANISMS UNDERLYING TOURETTE SYNDROME, THESE STUDIES ARE STILL SPARSE AND THE FIELD WOULD GREATLY BENEFIT FROM FURTHER INVESTIGATIONS. THIS REVIEW REPORTS DATA AND DISCOVERIES OF SCIENTIFIC AND CLINICAL RELEVANCE FROM A WIDE VARIETY OF METHODS AND PROVIDES UP-TO-DATE INFORMATION ABOUT OUR CURRENT UNDERSTANDING OF THE PATHOMECHANISMS UNDERLYING TOURETTE SYNDROME. IT GIVES A COMPREHENSIVE OVERVIEW OF THE CURRENT STATE OF KNOWLEDGE AND ADDRESSES OPEN QUESTIONS IN THE FIELD. 2017 2 6073 34 THE DRESDEN BURNOUT STUDY: PROTOCOL OF A PROSPECTIVE COHORT STUDY FOR THE BIO-PSYCHOLOGICAL INVESTIGATION OF BURNOUT. OBJECTIVES: THE DRESDEN BURNOUT STUDY (DBS) IS A 12-YEAR LONGITUDINAL COHORT STUDY THAT AIMS TO PROVIDE A DESCRIPTION OF THE BURNOUT SYNDROME ON THE BASIS OF TIME AND SYMPTOM CRITERIA WITH A SPECIAL FOCUS ON THE SEARCH FOR BIOMARKERS. BIOLOGICAL AND PSYCHOSOCIAL APPROACHES ARE APPLIED TO EXAMINE THE LONG-TERM COURSE AND CONSEQUENCES OF BURNOUT WITHIN A POPULATION-BASED GERMAN-SPEAKING SAMPLE AGED 18 TO 68 YEARS. METHODS: DEMOGRAPHICS AND PSYCHOSOCIAL DATA ARE GENERATED BY ONLINE ASSESSMENTS, INCLUDING DEMOGRAPHICS AND QUESTIONNAIRES ON BURNOUT, BURNOUT-RELATED CONSTRUCTS, WORK-ENVIRONMENT, AND HEALTH-RELATED FACTORS. THE LAB-BASED BIOMARKER ASSESSMENT INCLUDES ENDOCRINE, PHYSIOLOGICAL, IMMUNOLOGICAL, AND EPIGENETIC MARKERS OBTAINED FROM BLOOD AND HAIR SAMPLES. IN ADDITION, HEART RATE VARIABILITY IS ALSO MEASURED REPEATEDLY. WITHIN THE FIRST 2 YEARS, THE DBS COLLECTED PSYCHOSOCIAL DATA FROM OVER 7,600 PARTICIPANTS WITH BIOLOGICAL DATA OBTAINED FROM MORE THAN 800 INDIVIDUALS. DURING THE FOLLOWING 10 YEARS, DETAILED ASSESSMENTS OF BIOMARKERS AND PSYCHOSOCIAL FACTORS WILL BE COLLECTED IN ANNUAL STUDY WAVES. RESULTS: RESULTS WILL BE GENERATED DURING THE FOLLOWING DECADE. CONCLUSION: THE FINDINGS OF THE DBS ARE EXPECTED TO PAVE THE ROAD FOR AN IN-DEPTH BIOPSYCHOSOCIAL CHARACTERIZATION OF BURNOUT AND TO GIVE INSIGHT INTO THE LONG-TERM COURSE AND POTENTIAL MENTAL AND PHYSICAL HEALTH CONSEQUENCES OF THE BURNOUT SYNDROME. 2018 3 6827 36 [GILLES DE LA TOURETTE'S DISEASE. SYMPTOMS, ETIOPATHOGENESIS AND THERAPEUTIC APPROACHES]. THE GILLES DE LA TOURETTE SYNDROME IS A USUALLY CHRONIC NEUROPSYCHIATRIC DISORDER WITH AN EARLY CHILDHOOD ONSET FEATURING MAINLY MOTOR AND VOCAL TICS. IT SEEMS THAT STRONG GENETIC FACTORS MAKE A MAJOR CONTRIBUTION TO THE ETIOLOGY OF THIS DISORDER, BUT THERE ARE ALSO CLUES THAT EPIGENETIC FACTORS ARE INVOLVED IN THE PATHOGENESIS OF TOURETTE'S SYNDROME, SUCH AS MATERNAL STRESS DURING PREGNANCY, BIRTH COMPLICATIONS AND HORMONAL INFLUENCES. FIRST IN LINE FOR ADEQUATE TREATMENT ARE NEUROLEPTIC COMPOUNDS OF HIGH POTENCY, BESIDES, SEVERAL OTHER PSYCHOACTIVE DRUGS HAVE SHOWN SOME THERAPEUTIC EFFECTS. LESS EVIDENT IS THE EFFICACY OF NEUROSURGICAL AND PSYCHOTHERAPEUTIC INTERVENTIONS. 1997 4 1946 51 EPIGENETIC ABNORMALITIES ASSOCIATED WITH A CHROMOSOME 18(Q21-Q22) INVERSION AND A GILLES DE LA TOURETTE SYNDROME PHENOTYPE. GILLES DE LA TOURETTE SYNDROME (GTS) IS A POTENTIALLY DEBILITATING NEUROPSYCHIATRIC DISORDER DEFINED BY THE PRESENCE OF BOTH VOCAL AND MOTOR TICS. DESPITE EVIDENCE THAT THIS AND A RELATED PHENOTYPIC SPECTRUM, INCLUDING CHRONIC TICS (CT) AND OBSESSIVE COMPULSIVE DISORDER (OCD), ARE GENETICALLY MEDIATED, NO GENE INVOLVED IN DISEASE ETIOLOGY HAS BEEN IDENTIFIED. CHROMOSOMAL ABNORMALITIES HAVE LONG BEEN PROPOSED TO PLAY A CAUSATIVE ROLE IN ISOLATED CASES OF GTS SPECTRUM PHENOMENA, BUT CONFIRMATION OF THIS HYPOTHESIS HAS YET TO BE FORTHCOMING. WE DESCRIBE AN I(18Q21.1-Q22.2) INVERSION IN A PATIENT WITH CT AND OCD. WE HAVE FINE MAPPED THE TELOMERIC ASPECT OF THE REARRANGEMENT TO WITHIN 1 MB OF A PREVIOUSLY REPORTED 18Q22 BREAKPOINT THAT COSEGREGATED IN A FAMILY WITH GTS AND RELATED PHENOTYPES. A COMPREHENSIVE CHARACTERIZATION OF THIS GENOMIC INTERVAL LED TO THE IDENTIFICATION OF TWO TRANSCRIPTS, NEITHER OF WHICH WAS FOUND TO BE STRUCTURALLY DISRUPTED. ANALYSIS OF THE EPIGENETIC CHARACTERISTICS OF THE REGION DEMONSTRATED A SIGNIFICANT INCREASE IN REPLICATION ASYNCHRONY IN THE PATIENT COMPARED TO CONTROLS, WITH THE INVERTED CHROMOSOME SHOWING DELAYED REPLICATION TIMING ACROSS AT LEAST A 500-KB INTERVAL. THESE FINDINGS ARE CONSISTENT WITH LONG-RANGE FUNCTIONAL DYSREGULATION OF ONE OR MORE GENES IN THE REGION. OUR DATA SUPPORT A LINK BETWEEN CHROMOSOMAL ABERRATIONS AND EPIGENETIC MECHANISMS IN GTS AND SUGGEST THAT THE STUDY OF THE FUNCTIONAL CONSEQUENCES OF BALANCED CHROMOSOMAL REARRANGEMENTS IS WARRANTED IN PATIENTS WITH PHENOTYPES OF INTEREST, IRRESPECTIVE OF THE FINDINGS REGARDING STRUCTURALLY DISRUPTED TRANSCRIPTS. 2003 5 4491 41 MONOSOMY 7 MYELOPROLIFERATIVE DISEASE IN CHILDREN WITH NEUROFIBROMATOSIS, TYPE 1: EPIDEMIOLOGY AND MOLECULAR ANALYSIS. LOSS OF CONSTITUTIONAL HETEROZYGOSITY IS A COMMON MOLECULAR FEATURE OF CANCERS IN WHICH INACTIVATION OF ONE OR MORE TUMOR SUPPRESSOR GENES IS THOUGHT TO CONTRIBUTE TO TUMORIGENESIS. RECENT EVIDENCE SUGGESTS THAT THE GENE RESPONSIBLE FOR NEUROFIBROMATOSIS, TYPE 1 (NF-1), BELONGS TO THIS CLASS OF HERITABLE CANCER GENES. CHILDREN WITH NF-1 SHOW AN INCREASED INCIDENCE OF MYELOID LEUKEMIA, INCLUDING JUVENILE CHRONIC MYELOGENOUS LEUKEMIA (JCML) AND, PERHAPS, THE MYELOPROLIFERATIVE SYNDROME (MPS) ASSOCIATED WITH BONE MARROW MONOSOMY 7 (MO 7). WE HAVE INVESTIGATED FIVE CHILDREN WITH MO 7: THREE WITH NF-1 AND TWO OTHERS WITH SUGGESTIVE EVIDENCE OF NF-1. SOUTHERN BLOTTING EXPERIMENTS PERFORMED IN FOUR PATIENTS SHOWED NO LOSS OF HETEROZYGOSITY IN BONE MARROW SPECIMENS USING PROBES LINKED TO THE NF-1 LOCUS ON THE LONG ARM OF CHROMOSOME 17. BOTH OF OUR PATIENTS WITH FAMILIAL NF-1 INHERITED THE DISEASE FROM THEIR MOTHERS, AS DID 14 OF 19 OTHER CASES OF MYELOID LEUKEMIA IN CHILDREN WITH FAMILIAL NF-1. SEVENTEEN OF THESE 21 CHILDREN WERE BOYS. MYELOID LEUKEMIA DEVELOPED IN 12 BOYS AND FOUR GIRLS WHO INHERITED NF-1 FROM THEIR MOTHERS, AND IN FIVE BOYS WHO INHERITED THE DISEASE FROM THEIR FATHERS. FATHER-TO-DAUGHTER TRANSMISSION WAS NOT OBSERVED. TAKEN TOGETHER, THE PRESENCE OF CHROMOSOME 7 DELETIONS IN THE LEUKEMIAS OF CHILDREN WITH NF-1, A PATTERN OF INHERITANCE FAVORING MATERNAL TRANSMISSION OF NF-1, AND THE MARKED PREDILECTION FOR BOYS TO DEVELOP JCML AND MO 7 SUGGEST A MULTISTEP MECHANISM OF ONCOGENESIS IN WHICH EPIGENETIC FACTORS MIGHT PLAY A ROLE. FURTHER INVESTIGATION IS REQUIRED TO DETERMINE IF THE NF-1 GENES IN THE LEUKEMIC BONE MARROWS OF THESE PATIENTS HAVE ACQUIRED POINT MUTATIONS OR SMALL DELETIONS. 1992 6 6266 29 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 7 3606 44 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 8 5827 39 STRESS, BURNOUT AND DEPRESSION: A SYSTEMATIC REVIEW ON DNA METHYLATION MECHANISMS. DESPITE THAT BURNOUT PRESENTS A SERIOUS BURDEN FOR MODERN SOCIETY, THERE ARE NO DIAGNOSTIC CRITERIA. ADDITIONAL DIFFICULTY IS THE DIFFERENTIAL DIAGNOSIS WITH DEPRESSION. CONSEQUENTLY, THERE IS A NEED TO DISPOSE OF A BURNOUT BIOMARKER. EPIGENETIC STUDIES SUGGEST THAT DNA METHYLATION IS A POSSIBLE MEDIATOR LINKING INDIVIDUAL RESPONSE TO STRESS AND PSYCHOPATHOLOGY AND COULD BE CONSIDERED AS A POTENTIAL BIOMARKER OF STRESS-RELATED MENTAL DISORDERS. THUS, THE AIM OF THIS REVIEW IS TO PROVIDE AN OVERVIEW OF DNA METHYLATION MECHANISMS IN STRESS, BURNOUT AND DEPRESSION. IN ADDITION TO STATE-OF-THE-ART OVERVIEW, THE GOAL OF THIS REVIEW IS TO PROVIDE A SCIENTIFIC BASE FOR BURNOUT BIOMARKER RESEARCH. WE PERFORMED A SYSTEMATIC LITERATURE SEARCH AND IDENTIFIED 25 PERTINENT ARTICLES. AMONG THESE, 15 FOCUSED ON DEPRESSION, 7 ON CHRONIC STRESS AND ONLY 3 ON WORK STRESS/BURNOUT. THREE EPIGENOME-WIDE STUDIES WERE IDENTIFIED AND THE MAJORITY OF STUDIES USED THE CANDIDATE-GENE APPROACH, ASSESSING 12 DIFFERENT GENES. THE GLUCOCORTICOID RECEPTOR GENE (NR3C1) DISPLAYED DIFFERENT METHYLATION PATTERNS IN CHRONIC STRESS AND DEPRESSION. THE SEROTONIN TRANSPORTER GENE (SLC6A4) METHYLATION WAS SIMILARLY AFFECTED IN STRESS, DEPRESSION AND BURNOUT. WORK-RELATED STRESS AND DEPRESSIVE SYMPTOMS WERE ASSOCIATED WITH DIFFERENT METHYLATION PATTERNS OF THE BRAIN DERIVED NEUROTROPHIC FACTOR GENE (BDNF) IN THE SAME HUMAN SAMPLE. THE TYROSINE HYDROXYLASE (TH) METHYLATION WAS CORRELATED WITH WORK STRESS IN A SINGLE STUDY. ADDITIONAL, THOROUGHLY DESIGNED LONGITUDINAL STUDIES ARE NECESSARY FOR REVEALING THE CAUSE-EFFECT RELATIONSHIP OF WORK STRESS, EPIGENETICS AND BURNOUT, INCLUDING ITS OVERLAP WITH DEPRESSION. 2017 9 5515 43 RILUZOLE ADMINISTRATION TO RATS WITH LEVODOPA-INDUCED DYSKINESIA LEADS TO LOSS OF DNA METHYLATION IN NEURONAL GENES. DYSKINESIAS ARE CHARACTERIZED BY ABNORMAL REPETITIVE INVOLUNTARY MOVEMENTS DUE TO DYSFUNCTIONAL NEURONAL ACTIVITY. ALTHOUGH LEVODOPA-INDUCED DYSKINESIA, CHARACTERIZED BY TIC-LIKE ABNORMAL INVOLUNTARY MOVEMENTS, HAS NO CLINICAL TREATMENT FOR PARKINSON'S DISEASE PATIENTS, ANIMAL STUDIES INDICATE THAT RILUZOLE, WHICH INTERFERES WITH GLUTAMATERGIC NEUROTRANSMISSION, CAN IMPROVE THE PHENOTYPE. THE RAT MODEL OF LEVODOPA-INDUCED DYSKINESIA IS A UNILATERAL LESION WITH 6-HYDROXYDOPAMINE IN THE MEDIAL FOREBRAIN BUNDLE, FOLLOWED BY THE REPEATED ADMINISTRATION OF LEVODOPA. THE MOLECULAR PATHOMECHANISM OF LEVODOPA-INDUCED DYSKINESIA IS STILL NOT DECIPHERED; HOWEVER, THE IMPLICATION OF EPIGENETIC MECHANISMS WAS SUGGESTED. IN THIS STUDY, WE INVESTIGATED THE STRIATUM FOR DNA METHYLATION ALTERATIONS UNDER CHRONIC LEVODOPA TREATMENT WITH OR WITHOUT CO-TREATMENT WITH RILUZOLE. OUR DATA SHOW THAT THE LESIONED AND CONTRALATERAL STRIATA HAVE NEARLY IDENTICAL DNA METHYLATION PROFILES. CHRONIC LEVODOPA AND LEVODOPA + RILUZOLE TREATMENTS LED TO DNA METHYLATION LOSS, PARTICULARLY OUTSIDE OF PROMOTERS, IN GENE BODIES AND CPG POOR REGIONS. WE OBSERVED THAT SEVERAL GENES INVOLVED IN THE LEVODOPA-INDUCED DYSKINESIA UNDERWENT METHYLATION CHANGES. FURTHERMORE, THE RILUZOLE CO-TREATMENT, WHICH IMPROVED THE PHENOTYPE, PINPOINTED SPECIFIC METHYLATION TARGETS, WITH A MORE THAN 20% METHYLATION DIFFERENCE RELATIVE TO LEVODOPA TREATMENT ALONE. THESE FINDINGS INDICATE POTENTIAL NEW DRUGGABLE TARGETS FOR LEVODOPA-INDUCED DYSKINESIA. 2021 10 6457 65 TIC DISORDERS: WHEN HABIT FORMING NEURAL SYSTEMS FORM HABITS OF THEIR OWN? TOURETTE SYNDROME (TS), OBSESSIVE-COMPULSIVE DISORDER (OCD) AND RELATED CONDITIONS ARE PREVALENT DISORDERS AFFECTING AS MANY AS 0.3-3% OF THE POPULATION. THEY ARE FREQUENTLY CHRONIC AND CAN BE ASSOCIATED WITH MARKED IMPAIRMENT AND DISABILITY. ALTHOUGH CLINICAL CARE HAS IMPROVED OVER THE PAST DECADE, A SIGNIFICANT NUMBER OF PATIENTS FAIL TO RESPOND ADEQUATELY OR EXPERIENCE INTOLERABLE SIDE EFFECTS. THE ETIOLOGY OF THESE DISORDERS IS UNKNOWN. COMPELLING EVIDENCE SUGGESTS THAT THE VULNERABILITY TO DEVELOP TS AND OCD IS MEDIATED BY BOTH GENETIC AND ENVIRONMENTAL FACTORS, AND THAT NEURAL SYSTEMS LOCATED IN THE BASAL GANGLIA AND FUNCTIONALLY RELATED BRAIN STRUCTURES ARE INVOLVED IN THEIR PATHOGENESIS. BASED ON EXPLICIT MODELS OF PATHOGENESIS FOR TS AND OCD AND BUILDING ON WORK ACCOMPLISHED OVER THE PAST TWO DECADES, AN ARRAY OF CLINICAL, NEUROPSYCHOLOGICAL, GENETIC, NEUROIMAGING, EPIDEMIOLOGICAL NEUROBIOLOGICAL, AND TREATMENT STUDIES HAVE BEEN COMPLETED OR ARE UNDERWAY AT THE CHILD STUDY CENTER AT YALE UNIVERSITY. A MULTIDISCIPLINARY TEAM OF INVESTIGATORS HAS JOINED FORCES TO TEST SPECIFIC HYPOTHESES THROUGH THE INTEGRATION AND TRANSLATION OF BASIC AND CLINICAL NEUROSCIENCE RESEARCH. ALL SUBJECTS HAVE BEEN STUDIED USING IDENTICAL CLINICAL, NEUROPSYCHOLOGICAL, GENETIC, NEUROBIOLOGICAL, AND PHARMACOLOGICAL TECHNIQUES. CURRENT CONCEPTUALIZATIONS OF TS HAVE BEEN SHAPED BY ADVANCES IN CLINICAL PHENOMENOLOGY, GENETICS, SYSTEMS NEUROSCIENCE AND THE EMERGING UNDERSTANDING OF THE ROLE OF THE BASAL GANGLIA IN IMPLICIT LEARNING AND HABIT FORMATION, NEUROIMMUNOLOGY AND PSYCHOPHARMACOLOGY. AN APPRECIATION OF THE PREMONITORY URGES THAT PRECEDE TICS AND TEMPORAL DYNAMICS OF TICS HAVE PROVIDED USEFUL VIEWPOINTS FROM WHICH TO REGARD THE NATURAL HISTORY OF TS. WHILE THE LONG-TERM OUTCOME OF TS CAN BE RELATIVELY BENIGN, THE PRESENCE OF COMORBID CONDITIONS SUCH AS ATTENTION DEFICIT/HYPERACTIVITY DISORDER (ADHD), OCD OR A MAJOR AFFECTIVE DISORDER CAN HAVE LASTING UNTOWARD CONSEQUENCES. THE IDENTIFICATION OF SUSCEPTIBILITY GENES IN TS WILL DOUBTLESS POINT IN NEW THERAPEUTIC DIRECTIONS FOR TREATMENT, AS WILL THE CHARACTERIZATION OF THE PUTATIVE AUTOIMMUNE MECHANISMS ACTIVE IN SUBGROUP OF PATIENTS. CONTINUED SUCCESS IN FUNCTIONAL IN VIVO NEUROIMAGING STUDIES WILL LEAD TO THE TARGETING OF SPECIFIC BRAIN CIRCUITS FOR MORE INTENSIVE STUDY. ALTHOUGH IDEAL ANTI-TIC THERAPIES ARE NOT AVAILABLE, RECENTLY COMPLETED CLINICAL TRIALS WITH ALPHA-ADRENERGIC AGENTS AND ATYPICAL NEUROLEPTICS ARE ENCOURAGING. GIVEN THESE DEVELOPMENTS, TS CAN BE CONSIDERED A MODEL DISORDER TO STUDY THE DYNAMIC INTERPLAY OF GENETIC VULNERABILITIES, EPIGENETIC EVENTS, AND NEUROBIOLOGICAL SYSTEMS ACTIVE DURING EARLY BRAIN DEVELOPMENT. IT IS LIKELY THAT THE RESEARCH PARADIGMS UTILIZED IN THESE STUDIES AND MANY OF THE EMPIRICAL FINDINGS RESULTING FROM THEM, WILL BE RELEVANT TO OTHER DISORDERS OF CHILDHOOD ONSET AND TO OUR UNDERSTANDING OF NORMAL DEVELOPMENT. 2001 11 4632 36 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 12 4006 34 LOST AMONG THE TREES? THE AUTONOMIC NERVOUS SYSTEM AND PAEDIATRICS. THE AUTONOMIC NERVOUS SYSTEM (ANS) HAS BEEN STRIKINGLY NEGLECTED IN WESTERN MEDICINE. DESPITE ITS PROFOUND IMPORTANCE FOR REGULATION, ADJUSTMENT AND COORDINATION OF BODY SYSTEMS, IT LACKS PRIORITY IN TRAINING AND PRACTICE AND RECEIVES SCANT ATTENTION IN NUMEROUS MAJOR TEXTBOOKS. THE ANS IS INTEGRAL TO MANIFESTATIONS OF ILLNESS, UNDERLYING FAMILIAR PHYSICAL AND PSYCHOLOGICAL SYMPTOMS. WHEN ANS ACTIVITY IS ITSELF DYSFUNCTIONAL, USUAL INDICATORS OF ACUTE ILLNESS MAY PROVE DECEPTIVE. RECOGNISING THE RELEVANCE OF THE ANS CAN INVOLVE SEEING THE FAMILIAR THROUGH FRESH EYES, CHALLENGING ASSUMPTIONS IN CLINICAL ASSESSMENT AND IN APPROACHES TO PRACTICE. ITS IMPORTANCE EXTENDS FROM PHYSICAL AND PSYCHOLOGICAL WELL-BEING TO PARENTING AND SAFEGUARDING, PUBLIC SERVICES AND THE FUNCTIONING OF SOCIETY. EXPLORATION OF ITS ROLE IN CONDITIONS RANGING FROM NEUROLOGICAL, GASTROINTESTINAL AND CONNECTIVE TISSUE DISORDERS, DIABETES AND CHRONIC FATIGUE SYNDROME, TO AUTISM, BEHAVIOURAL AND MENTAL HEALTH DIFFICULTIES MAY OPEN THERAPEUTIC AVENUES. THE ANS OFFERS A MECHANISM FOR SO-CALLED FUNCTIONAL ILLNESSES AND ILLUSTRATES THE IMPORTANCE OF RECOGNISING THAT 'STRESS' TAKES MANY FORMS, PHYSICAL, PSYCHOLOGICAL AND ENVIRONMENTAL, DESIRABLE AND OTHERWISE. EVIDENCE OF INTRAUTERINE AND POST-NATAL PROGRAMMING OF ANS REACTIVITY SUGGESTS THAT NEONATAL CARE AND SAFEGUARDING PRACTICE MAY OFFER PREVENTIVE OPPORTUNITY, AS MAY GREATER UNDERSTANDING OF EPIGENETIC CHANGE OF ANS ACTIVITY THROUGH, FOR EXAMPLE, ACCIDENTAL OR PSYCHOLOGICAL TRAUMA OR INFECTION. THE AIM OF THIS ARTICLE IS TO ACCELERATE RECOGNITION OF THE IMPORTANCE OF THE ANS THROUGHOUT PAEDIATRICS, AND OF THE POTENTIAL PHYSICAL AND PSYCHOLOGICAL COST OF NEGLECTING IT. 2014 13 6779 20 [BIO-PSYCHO-SOCIAL THERAPY FOR STRESS-INDUCED CHRONIC PAIN]. BIO-PSYCHO-SOCIAL THERAPY FOR STRESS-INDUCED CHRONIC PAIN ABSTRACT. AGAINST THE BACKGROUND OF LATEST NEUROBIOLOGICAL AND EPIGENETIC FINDINGS THE BIO-PSYCHO-SOCIAL MODEL OF DISEASE IS OUTLINED OFTEN MISINTERPRETED IN THE CONTEXT OF CHRONIC PAIN. IT REPRESENTS THE BASIC PRINCIPLE FOR A PERSONALIZED TREATMENT OF STRESS-INDUCED CHRONIC PAIN. CONSEQUENCES FOR DIAGNOSTIC PROCEDURES ARE DELINEATED TO DETECT THIS PATHOGENETIC SUBGROUP OF CHRONIC PAIN PATIENTS (E.G. FIBROMYALGIA, BACK PAIN, TEMPOROMANDIBULAR DYSFUNCTION, TENSION HEADACHE). FINALLY, THE PRINCIPLES OF A BIO-PSYCHO-SOCIAL TREATMENT PROGRAM WITH HIGH EFFICIENCY ARE PRESENTED. 2020 14 3559 44 IMPACT OF CHRONIC CONDITIONS AND DEMENTIA IN RURAL WEST TEXAS: A HEALTHY AGING STUDY. ALZHEIMER'S DISEASE (AD) IS A DEVASTATING ILLNESS IN ELDERLY INDIVIDUALS, THAT CURRENTLY HAS NO KNOWN CURE. CAUSAL GENETIC FACTORS ONLY ACCOUNT FOR 1-2% OF AD PATIENTS. HOWEVER, OTHER CAUSAL FACTORS ARE STILL UNKNOWN FOR A MAJORITY OF AD PATIENTS. CURRENTLY, MULTIPLE FACTORS ARE IMPLICATED IN LATE-ONSET AD, INCLUDING UNHEALTHY DIET, PHYSICAL INACTIVITY, TRAUMATIC BRAIN INJURY, CHRONIC CONDITIONS, EPIGENETIC FACTORS, AND ENVIRONMENTAL EXPOSURES. ALTHOUGH CLINICAL SYMPTOMS OF DEMENTIA ARE COMMON TO ALL RACES AND ETHNIC GROUPS, CONDITIONS THAT LEAD TO DEMENTIA ARE DIFFERENT IN TERMS OF LIFESTYLE, GENETIC PROFILE, AND SOCIO-ECONOMIC CONDITIONS. INCREASING EVIDENCE ALSO SUGGESTS THAT SOME ELDERLY INDIVIDUALS AGE WITHOUT COGNITIVE IMPAIRMENTS IN THEIR 60-90S AS SEEN IN RURAL WEST TEXAS, WHILE SOME INDIVIDUALS PROGRESS WITH CHRONIC CONDITIONS AND COGNITIVE IMPAIRMENTS INTO THEIR 60S. TO UNDERSTAND THESE DISCRIMINATIONS, WE ASSESSED CURRENT LITERATURE ON DEMOGRAPHIC FEATURES OF HEALTH IN RURAL WEST TEXAS. THIS PAPER ALSO OUTLINES OUR INITIATED CLINICAL STUDY WITH A PURPOSE OF UNDERSTANDING THE FACTORS THAT ALLOW SOME INDIVIDUALS TO LIVE WITHOUT COGNITIVE IMPAIRMENTS AT THE AGE OF 60-90 YEARS, WHEREAS OTHERS DEVELOP DEFICITS IN COGNITIVE FUNCTION AROUND OR ABOVE 60 YEARS. OUR ONGOING STUDY HOPES TO DETERMINE THE FACTORS THAT DELAY AGING IN SOME INDIVIDUALS BY INVESTIGATING VARIOUS ASPECTS INCLUDING GENETICS, EPIGENETICS, ETHNICITY, BIOLOGY, CULTURE, AND LIFESTYLE. THIS WILL BE ACHIEVED BY GATHERING INFORMATION ABOUT PARTICIPANTS' ETHNOGRAPHIC PROFILES, COGNITIVE ASSESSMENTS, BLOOD-PROFILES, BRAIN SCANS, AND BLOOD-BASED GENOMIC ANALYSES IN RELATION TO LIFESTYLE. THE OUTCOMES OF OUR STUDY WILL PROVIDE INSIGHTS INTO HEALTHY AGING IN RURAL WEST TEXAS. 2022 15 747 27 CANNABIS-INDUCED HYPODOPAMINERGIC ANHEDONIA AND COGNITIVE DECLINE IN HUMANS: EMBRACING PUTATIVE INDUCTION OF DOPAMINE HOMEOSTASIS. OVER YEARS, THE REGULAR USE OF CANNABIS HAS SUBSTANTIALLY INCREASED AMONG YOUNG ADULTS, AS INDICATED BY THE RISE IN CANNABIS USE DISORDER (CUD), WITH AN ESTIMATED PREVALENCE OF 8. 3% IN THE UNITED STATES. RESEARCH SHOWS THAT EXPOSURE TO CANNABIS IS ASSOCIATED WITH HYPODOPAMINERGIC ANHEDONIA (DEPRESSION), COGNITIVE DECLINE, POOR MEMORY, INATTENTION, IMPAIRED LEARNING PERFORMANCE, REDUCED DOPAMINE BRAIN RESPONSE-ASSOCIATED EMOTIONALITY, AND INCREASED ADDICTION SEVERITY IN YOUNG ADULTS. THE ADDICTION MEDICINE COMMUNITY IS INCREASING CONCERN BECAUSE OF THE HIGH CONTENT OF DELTA-9-TETRAHYDROCANNABINOL (THC) CURRENTLY FOUND IN ORAL AND VAPING CANNABIS PRODUCTS, THE COGNITIVE EFFECTS OF CANNABIS MAY BECOME MORE PRONOUNCED IN YOUNG ADULTS WHO USE THESE CANNABIS PRODUCTS. PRELIMINARY RESEARCH SUGGESTS THAT IT IS POSSIBLE TO INDUCE 'DOPAMINE HOMEOSTASIS,' THAT IS, RESTORE DOPAMINE FUNCTION WITH DOPAMINE UPREGULATION WITH THE PROPOSED COMPOUND AND NORMALIZE BEHAVIOR IN CHRONIC CANNABIS USERS WITH CANNABIS-INDUCED HYPODOPAMINERGIC ANHEDONIA (DEPRESSION) AND COGNITIVE DECLINE. THIS PSYCHOLOGICAL, NEUROBIOLOGICAL, ANATOMICAL, GENETIC, AND EPIGENETIC RESEARCH ALSO COULD PROVIDE EVIDENCE TO USE FOR THE DEVELOPMENT OF AN APPROPRIATE POLICY REGARDING THE DECRIMINALIZATION OF CANNABIS FOR RECREATIONAL USE. 2021 16 6894 25 [SOCIAL INEQUALITY AND MENTAL HEALTH]. SOCIAL INEQUALITY REFERS TO THE INEQUITABLE DISTRIBUTION OF SOCIAL PROSPERITY INCLUDING THE RESOURCE OF HEALTH. THE RELATIONSHIP BETWEEN SOCIAL INEQUALITY AND MENTAL HEALTH CAN BE ESTABLISHED BY MEANS OF INDICATORS OF SOCIAL INEQUALITY THROUGHOUT ALL AGE GROUPS IN GERMANY. THERE ARE SOCIAL GRADIENTS OF MENTAL HEALTH ON THE POPULATION LEVEL, I.E. THE LINEAR RELATIONSHIP BETWEEN SOCIAL CLASSES OR STATUS AND STATE OF HEALTH. FUNDAMENTAL DETERMINANTS OF HEALTH DISPARITY ARE CULTURAL, SOCIAL, POLITICAL, AND GEOGRAPHICAL CONDITIONS, WHICH INTERACT WITH THE GENETIC MAKE-UP AND EPIGENETIC PROCESSES. THESE DETERMINANTS ALSO INFLUENCE THE MANAGEMENT OF DEVELOPMENTAL TASKS DURING THE LIFE COURSE AND ARE OF UTMOST IMPORTANCE FOR THE DEVELOPMENT OF MENTAL DISORDERS. THE MALADAPTATION TO CHRONIC STRESS IS AT THE CORE OF HEALTH DISPARITY. INTERVENTIONS AT THE INDIVIDUAL BEHAVIORAL LEVEL SHOULD COMPRISE THE DEVELOPMENT OF STRESS MANAGEMENT AND COPING STRATEGIES. 2019 17 4067 25 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 18 29 36 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 19 6478 31 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 20 367 34 AMPLIFIED PAIN SYNDROMES IN CHILDREN: TREATMENT AND NEW INSIGHTS INTO DISEASE PATHOGENESIS. PURPOSE OF REVIEW: ALTHOUGH MANY DIAGNOSTIC TERMS ARE USED FOR PEDIATRIC CHRONIC PAIN, EVIDENCE SUGGESTS A COMMON THREAD OF SIGNAL AMPLIFICATION, LEADING TO THE UNIFYING TERM 'AMPLIFIED PAIN SYNDROMES'. ONGOING RESEARCH PROVIDES NEW INSIGHTS INTO BIOPSYCHOSOCIAL CONTRIBUTORS AND TREATMENTS FOR PEDIATRIC AMPLIFIED PAIN SYNDROMES. RECENT FINDINGS: BASIC SCIENCE INDICATES A COMPLEX INTERPLAY OF GENETIC, EPIGENETIC, NEUROCHEMICAL, ENDOCRINE, AND INFLAMMATORY CONTRIBUTORS, ALONG WITH ENVIRONMENTAL AND PSYCHOLOGICAL FACTORS. ALTHOUGH MEDICATIONS AND INTERVENTIONS REMAIN COMMON APPROACHES TO CHILDREN WITH CHRONIC PAIN, THEIR EVIDENCE IS LIMITED. PRELIMINARY EVIDENCE EXISTS FOR MINDFULNESS-BASED THERAPIES, YOGA, AND OTHER COMPLEMENTARY/ALTERNATIVE MEDICINE APPROACHES. THE STRONGEST EVIDENCE IS FOR EXERCISE-BASED AND COGNITIVE-BEHAVIORAL TREATMENTS, IN PARTICULAR, WHEN COMBINED IN A MULTIDISCIPLINARY FORMAT. INTENSIVE APPROACHES (PAIN REHABILITATION) HAVE THE POTENTIAL TO EFFECTIVELY AND EFFICIENTLY TREAT THOSE MOST DISABLED BY AMPLIFIED PAIN SYNDROMES, AND LEAD TO SUSTAINED IMPROVEMENT IN PAIN, FUNCTIONING, AND MEDICAL UTILIZATION. SUMMARY: ALTHOUGH UNDERSTANDING OF THE MECHANISMS UNDERLYING PEDIATRIC AMPLIFIED PAIN SYNDROMES EVOLVES, STANDARD OF CARE IS MULTIDISCIPLINARY EMPHASIZING EXERCISE THERAPY, COGNITIVE-BEHAVIORAL TREATMENT, AND SELF-REGULATION. TREATMENT SHOULD TARGET FULL RETURN TO PHYSICAL FUNCTION, WHICH LEADS TO SUBSEQUENT IMPROVEMENT OR RESOLUTION OF PAIN. MULTIDISCIPLINARY CARE CAN BE COORDINATED BY A RHEUMATOLOGIST OR OTHER PHYSICIAN WITH APPROPRIATE REFERRALS, OR THROUGH A MULTIDISCIPLINARY TEAM. 2014