1 6266 102 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 2 2096 36 EPIGENETIC EFFECTS OF CHILDHOOD ADVERSITY IN THE BRAIN AND SUICIDE RISK. WITH PREVALENCE ESTIMATES RANGING BETWEEN 6.4% AND 10.1% [-5], MAJOR DEPRESSION RANKS FIRST AMONG THE MOST SIGNIFICANT CAUSES OF DISABILITY AND PREMATURE DEATH, THUS IMPOSING A CONTINUAL ECONOMIC BURDEN ON SOCIETY. FOR INSTANCE, IN THE UNITED STATES, THE DIRECT AND INDIRECT COSTS ARE ESTIMATED AT U.S.$44 BILLION/YEAR [6]. THE GREATEST LOSS TO OUR SOCIETY, HOWEVER, IS THE ASSOCIATED MORTALITY BY SUICIDE RELATED TO MAJOR DEPRESSION. INDEED, IT HAS BEEN ESTIMATED THAT BETWEEN 50% AND 70% OF SUICIDE COMPLETERS WILL DIE DURING AN EPISODE OF MAJOR DEPRESSION [7,8] AND PROSPECTIVE FOLLOW-UP STUDIES OF MAJOR DEPRESSION SUGGEST THAT BETWEEN 7% AND 15% OF THESE PATIENTS WILL DIE BY SUICIDE [-12]. SUICIDE IS A COMPLEX PROBLEM, WHICH IS BELIEVED TO RESULT FROM THE INTERACTION OF SEVERAL DIFFERENT FACTORS [13,14]. INDEED, PSYCHOLOGICAL FACTORS AND PERSONALITY TRAITS SUCH AS IMPULSIVITY AND NEGATIVE AFFECT [14,15], SOCIAL FACTORS [16,17], ENVIRONMENTAL FACTORS SUCH AS EARLY-LIFE ADVERSITY [-20], GENETIC FACTORS [21], AND NEUROBIOLOGICAL FACTORS [22] HAVE BEEN PROPOSED TO INDUCE BEHAVIORAL ALTERATIONS, WHICH IN TURN MAY PREDISPOSE CERTAIN INDIVIDUALS TO DEVELOP DEPRESSIVE AND SUICIDAL BEHAVIORS. HOWEVER, SINCE THESE FACTORS ALONE ARE UNLIKELY TO EXPLAIN SUICIDE AND SUICIDE RISK, IT MAY BE MORE READILY EXPLAINED WHEN CONSIDERING THE INTERACTION BETWEEN THESE DIFFERENT SOURCES OF VARIATION [23,24]. AMONG THESE RISK FACTORS, EARLY-LIFE ADVERSITY, PARTICULARLY CHILDHOOD SEXUAL ABUSE (CSA) AND CHILDHOOD PHYSICAL ABUSE (CPA), IS ONE OF THE STRONGEST PREDICTORS OF MENTAL DISORDERS [25,26] AND SUICIDE [18,19]. FOR EXAMPLE, STUDIES HAVE SHOWN THAT CSA IS ASSOCIATED WITH EARLY ONSET OF DEPRESSION, CHRONIC COURSE, AND MORE SEVERE DEPRESSIVE OUTCOME [-29] BUT, MORE IMPORTANTLY, WITH 12 TIMES HIGHER ODDS OF SUICIDAL BEHAVIORS [26,30]. ALTHOUGH LESS CONSISTENTLY, CPA AND NEGLECT HAVE ALSO BEEN ASSOCIATED WITH SUICIDAL BEHAVIORS [19,31]. CSA AND CPA HAVE BEEN ASSOCIATED WITH HIGHER ODDS OF SELF-HARM [,,-34], SUICIDAL IDEATION [35,36], AND SUICIDE ATTEMPTS [,-39]. MOREOVER, THE PREVALENCE OF SUICIDAL IDEATION AND SUICIDE ATTEMPTS HAS BEEN SHOWN TO INCREASE WITH THE SEVERITY AND INTENSITY OF THE ABUSE [35,36,38]. 2012 3 576 21 BDNF METHYLATION AND SUICIDAL IDEATION IN PATIENTS WITH ACUTE CORONARY SYNDROME. OBJECTIVE: PATIENTS WITH ACUTE CORONARY SYNDROME (ACS) ARE AT AN INCREASED RISK OF SUICIDE. IT IS WELL KNOWN THAT EPIGENETIC MECHANISMS MAY EXPLAIN THE PATHOPHYSIOLOGY OF SUICIDAL BEHAVIOR INCLUDING SUICIDAL IDEATION (SI), BUT NO STUDY HAS EXPLORED THESE MECHANISMS IN ACS POPULATIONS. METHODS: IN TOTAL, 969 PATIENTS WERE INITIALLY RECRUITED WITHIN 2 WEEKS OF THE ACUTE CORONARY EVENT AND, 711 PATIENTS WERE SUCCESSFULLY FOLLOWED UP 1 YEAR AFTER ACS. SI WAS EVALUATED USING THE RELEVANT ITEMS ON THE MONTGOMERY-ASBERG DEPRESSION RATING SCALE AND COVARIATES POTENTIALLY AFFECTING SI WERE ESTIMATED. RESULTS: BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) HYPERMETHYLATION WAS ASSOCIATED WITH SI IN BOTH THE ACUTE AND CHRONIC PHASES OF ACS, ALTHOUGH THE ASSOCIATION WAS NOT STATISTICALLY SIGNIFICANT IN THE ACUTE PHASE AFTER APPLYING BONFERRONI'S CORRECTION. CONCLUSION: THESE RESULTS SUGGESTED THAT BDNF HYPERMETHYLATION MAY HAVE PLAYED A ROLE IN AN EPIGENETIC PREDISPOSITION FOR SI IN ACS PATIENTS, PARTICULARLY DURING THE CHRONIC PHASE. 2018 4 5500 19 REVISITING MIGRAINE: THE EVOLVING PATHOPHYSIOLOGY AND THE EXPANDING MANAGEMENT ARMAMENTARIUM. MIGRAINE AFFECTS ABOUT ONE BILLION PEOPLE WORLDWIDE YEARLY AND IS ONE OF THE MOST COMMON NEUROLOGIC ILLNESSES, WITH A HIGH PREVALENCE AND MORBIDITY, PARTICULARLY AMONG YOUNG ADULTS AND FEMALES. MIGRAINE IS ASSOCIATED WITH MANY COMORBIDITIES, INCLUDING STRESS, SLEEP DIFFICULTIES, AND SUICIDAL IDEATION. MIGRAINE, DESPITE ITS WIDESPREAD OCCURRENCE, IS UNDERDIAGNOSED AND UNDERTREATED. BECAUSE OF THE COMPLICATED AND PRIMARILY UNKNOWN MECHANISMS OF MIGRAINE FORMATION, SEVERAL SOCIAL AND BIOLOGICAL RISK FACTORS, SUCH AS HORMONE IMBALANCES, GENETIC AND EPIGENETIC IMPACTS, AND CARDIOVASCULAR, NEUROLOGICAL, AND AUTOIMMUNE ILLNESSES, HAVE BEEN PROPOSED. THROUGH THE MID-20TH CENTURY DIVERSION OF THE NOW-DEFUNCT VASCULAR THEORY, THE PATHOPHYSIOLOGY OF MIGRAINE HAS DEVELOPED FROM A HISTORICAL STUDY OF THE "HUMOURS" TO A DISTINCT ENTITY AS A NEUROLOGICAL DISORDER. THE RANGE OF THERAPEUTIC TARGETS HAS BROADENED SIGNIFICANTLY, INCREASING THE NUMBER OF SPECIALIZED CLINICAL TRIALS. UNDERSTANDING THE BIOLOGY OF MIGRAINE THROUGH CAREFUL RESEARCH HAS RESULTED IN THE IDENTIFICATION OF MAJOR THERAPEUTIC CLASSES: (I) TRIPTANS, SEROTONIN 5-HT1B/1D RECEPTOR AGONISTS, (II) GEPANTS, CALCITONIN GENE-RELATED PEPTIDE (CGRP) RECEPTOR ANTAGONISTS, (III) DITANS, 5-HT1F RECEPTOR AGONISTS, (IV) CGRP MONOCLONAL ANTIBODIES, AND (V) GLURANTS, MGLU5 MODULATORS, WITH FURTHER TARGETS BEING EXPLORED. THIS REVIEW PROVIDES A COMPREHENSIVE OVERVIEW OF THE MOST RECENT LITERATURE ON EPIDEMIOLOGY AND RISK FACTORS AND EXPOSES KNOWLEDGE GAPS. 2023 5 5302 28 PROTEIN-C REACTIVE AS BIOMARKER PREDICTOR OF SCHIZOPHRENIA PHASES OF ILLNESS? A SYSTEMATIC REVIEW. BACKGROUND: SCHIZOPHRENIA IS A COMPLEX ILLNESS IN WHICH GENETIC, ENVIRONMENTAL, AND EPIGENETIC COMPONENTS HAVE BEEN IMPLICATED. HOWEVER, RECENTLY, PSYCHIATRIC DISORDERS APPEAR TO BE RELATED TO A CHRONIC INFLAMMATORY STATE, AT THE LEVEL OF SPECIFIC CEREBRAL AREAS WHICH HAVE BEEN FOUND AS WELL IMPAIRED AND RESPONSIBLE FOR SCHIZOPHRENIA SYMPTOMATOLOGY. HENCE, A ROLE OF INFLAMMATORY MEDIATORS AND CYTOKINES HAS BEEN AS WELL DEFINED. ACCORDINGLY, THE ROLE OF AN ACUTE INFLAMMATORY PHASE PROTEIN, THE C-REACTIVE PROTEIN (CRP) HAS BEEN RECENTLY INVESTIGATED. OBJECTIVE: THE OBJECTIVE OF THE PRESENT STUDY IS TO EVALUATE HOW PCR MAY REPRESENT A BIOMARKER IN SCHIZOPHRENIA, I.E. CORRELATED WITH ILLNESS PHASES AND/OR CLINICAL MANIFESTATION AND/OR PSYCHOPATHOLOGICAL SEVERITY. METHODS: A SYSTEMATIC REVIEW WAS HERE CARRIED OUT BY SEARCHING THE FOLLOWING KEYWORDS ((C-REACTIVE PROTEIN AND ((SCHIZOPHRENIA) OR (PSYCHOTIC DISORDER))) FOR THE TOPICS 'PCR' AND 'SCHIZOPHRENIA', BY USING MESH TERMS. RESULTS: AN IMMUNE DYSFUNCTION AND INFLAMMATION HAVE BEEN DESCRIBED AMONGST SCHIZOPHRENIC PATIENTS. FINDINGS REPORTED ELEVATED CRP LEVELS IN SCHIZOPHRENIA, MAINLY CORRELATED WITH THE SEVERITY OF ILLNESS AND DURING THE RECRUDESCENT PHASE. CRP LEVELS ARE HIGHER WHEN CATATONIC FEATURES, NEGATIVE SYMPTOMATOLOGY AND AGGRESSIVENESS ARE ASSOCIATED. CRP LEVELS APPEARED NOT TO BE RELATED TO SUICIDAL BEHAVIOUR AND IDEATION. CONCLUSION: CRP AND ITS BLOOD LEVELS HAVE BEEN REPORTED HIGHER AMONGST SCHIZOPHRENIC PATIENTS, BY SUGGESTING A ROLE OF INFLAMMATION IN THE PATHOGENESIS OF SCHIZOPHRENIA. FURTHER STUDIES ARE NEEDED TO BETTER UNDERSTAND IF CRP MAY BE CONSIDERED A BIOMARKER IN SCHIZOPHRENIA. 2018 6 5520 28 RISK FACTORS OF POSTPARTUM DEPRESSION. POSTPARTUM DEPRESSION (PPD) IS A WIDESPREAD MENTAL HEALTH PROBLEM AND ONE OF THE PRIME CAUSES OF MATERNAL SUFFERING AND ILL HEALTH. ON A GLOBAL LEVEL, THE PREVALENCE OF THE DISORDER IS ABOUT 10 TO 15%. SYMPTOMS GENERALLY APPEAR WITHIN THE FIRST FOUR TO SIX WEEKS, WHICH IS THE HIGH-RISK PERIOD. HOWEVER, IT MAY DEVELOP UP TO ONE YEAR POST-DELIVERY. PPD PRESENTS WITH SYMPTOMS OF CLASSICAL DEPRESSION, INCLUDING MOOD FLUCTUATIONS, BOUTS OF CRYING, LACK OF INTEREST IN THE CHILD, AND EVEN THOUGHTS OF SUICIDE. PPD NOT ONLY HAS ADVERSE EFFECTS ON THE MOTHER'S HEALTH BUT ALSO HAMPERS THE GROWTH AND DEVELOPMENT OF THE CHILD. IT HAMPERS THE FORMATION OF A HEALTHY MOTHER-CHILD BOND, WHICH IN TURN MAY IMPACT FEEDING PRACTICES. THE SOCIAL ENVIRONMENT OF THE INFANT DURING THE FIRST FEW MONTHS IS PRIMARILY PROVIDED BY THE MOTHER, AND PPD MAY THUS IMPACT THE CHILD'S DEVELOPMENT. IT ALSO INCREASES THE CHILD'S SUSCEPTIBILITY TO MALNUTRITION. RESEARCH ON POSTPARTUM DEPRESSION HAS GARNERED MOMENTUM WITHIN THE LAST FEW YEARS. HOWEVER, THE MASSES ARE STILL LARGELY UNAWARE OF THE DISORDER AND ITS IMPLICATIONS. THERE IS ALSO AN INADEQUACY OF AWARENESS OF THE RISK FACTORS OF PPD. THE CROSS-CULTURAL DIFFERENCES IN MANIFESTATIONS AND APPROPRIATE PREVENTIVE MEASURES HAVE NOT BEEN EXTENSIVELY STUDIED. SOME RISK FACTORS FOR PPD ARE SIMILAR TO THOSE FOR CLASSIC DEPRESSION; HOWEVER, OBSTETRICAL AND PEDIATRIC FACTORS ARE ALSO INVOLVED. THIS LITERATURE REVIEW AIMS TO ASSESS THE CURRENTLY KNOWN RISK FACTORS FOR PPD, THEIR STRENGTH OF ASSOCIATION, AND PROBABLE MECHANISMS TO HELP IDENTIFY THE HIGH-RISK GROUP AND ENABLE THE IMPLEMENTATION OF PREVENTIVE MEASURES OR FACILITATE EARLY DIAGNOSIS. THE FACTORS IDENTIFIED SPANNED SOCIODEMOGRAPHIC, BIOLOGICAL, PSYCHOLOGICAL, AND OBSTETRIC DOMAINS. THESE INCLUDED SOCIOECONOMIC STANDING, MARITAL RELATIONSHIP, HISTORY OF PSYCHIATRIC ILLNESS, SOCIAL SUPPORT, GESTATIONAL DIABETES, VITAMIN D DEFICIENCY, IMMIGRATION STATUS, DELIVERY METHOD, VIOLENCE AND ABUSE, BIRTH EXPERIENCE, AND BIOLOGICAL AND EPIGENETIC MARKERS. THE RISK FACTORS FOR POSTPARTUM DEPRESSION ARE NUMEROUS AND MAY HAVE STRONG TO WEAK ASSOCIATIONS WITH THE DEVELOPMENT OF PPD. A PREVIOUS HISTORY OF DEPRESSION OR PSYCHIATRIC ILLNESS, DEPRESSIVE SYMPTOMS DURING PREGNANCY, GESTATIONAL DIABETES, AND A LACK OF SPOUSAL AND SOCIAL SUPPORT WERE THE MOST POWERFUL RISK FACTORS. OTHER SIGNIFICANT FACTORS INCLUDE COMPLICATIONS DURING PREGNANCY, LOW SOCIOECONOMIC STATUS, AND STRESSFUL LIFE EVENTS. STUDIES ON MATERNAL AGE AND CHRONIC ILLNESS AS RISK FACTORS WERE INCONCLUSIVE. THE ROLES OF GENETIC AND EPIGENETIC MARKERS, CULTURAL FACTORS, AND VITAMIN D INSUFFICIENCY REQUIRE FURTHER INVESTIGATION. 2022 7 6478 21 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 8 747 19 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 9 5658 26 SEX-DIMORPHIC PATHWAYS IN THE ASSOCIATIONS BETWEEN MATERNAL TRAIT ANXIETY, INFANT BDNF METHYLATION, AND NEGATIVE EMOTIONALITY. MATERNAL ANTENATAL ANXIETY IS AN EMERGING RISK FACTOR FOR CHILD EMOTIONAL DEVELOPMENT. BOTH SEX AND EPIGENETIC MECHANISMS, SUCH AS DNA METHYLATION, MAY CONTRIBUTE TO THE EMBEDDING OF MATERNAL DISTRESS INTO EMOTIONAL OUTCOMES. HERE, WE INVESTIGATED SEX-DEPENDENT PATTERNS IN THE ASSOCIATION BETWEEN ANTENATAL MATERNAL TRAIT ANXIETY, METHYLATION OF THE BRAIN-DERIVED NEUROTROPHIC FACTOR GENE (BDNF DNAM), AND INFANT NEGATIVE EMOTIONALITY (NE). MOTHER-INFANT DYADS (N = 276) WERE RECRUITED AT DELIVERY. MATERNAL TRAIT ANXIETY, AS A MARKER OF ANTENATAL CHRONIC STRESS EXPOSURE, WAS ASSESSED SOON AFTER DELIVERY USING THE STAIT-TRAIT ANXIETY INVENTORY (STAI-Y). INFANTS' BDNF DNAM AT BIRTH WAS ASSESSED IN 11 CPG SITES IN BUCCAL CELLS WHEREAS INFANTS' NE WAS ASSESSED AT 3 (N = 225) AND 6 MONTHS (N = 189) USING THE INFANT BEHAVIOR QUESTIONNAIRE-REVISED (IBQ-R). HIERARCHICAL LINEAR ANALYSES SHOWED THAT HIGHER MATERNAL ANTENATAL ANXIETY WAS ASSOCIATED WITH GREATER 6-MONTH-OLDS' NE. FURTHERMORE, MATERNAL ANTENATAL ANXIETY PREDICTED GREATER INFANTS' BDNF DNAM IN FIVE CPG SITES IN MALES BUT NOT IN FEMALES. HIGHER METHYLATION AT THESE SITES WAS ASSOCIATED WITH GREATER 3-TO-6-MONTH NE INCREASE, INDEPENDENTLY OF INFANTS' SEX. MATERNAL ANTENATAL ANXIETY EMERGED AS A RISK FACTOR FOR INFANT'S NE. BDNF DNAM MIGHT MEDIATE THIS EFFECT IN MALES. THESE RESULTS MAY INFORM THE DEVELOPMENT OF STRATEGIES TO PROMOTE MOTHERS AND INFANTS' EMOTIONAL WELL-BEING. 2023 10 2949 23 GENETIC AND EPIGENETIC CONSEQUENCE OF EARLY-LIFE SOCIAL STRESS ON DEPRESSION: ROLE OF SEROTONIN-ASSOCIATED GENES. EARLY-LIFE ADVERSITY CAUSED BY POOR SOCIAL BONDING AND DEPRIVED MATERNAL CARE IS KNOWN TO AFFECT MENTAL WELLBEING AND PHYSICAL HEALTH. IT IS A FORM OF CHRONIC SOCIAL STRESS THAT PERSISTS BECAUSE OF A NEGATIVE ENVIRONMENT, AND THE CONSEQUENCES ARE LONG-LASTING ON MENTAL HEALTH. THE PRESENCE OF SOCIAL STRESS DURING EARLY LIFE CAN HAVE AN EPIGENETIC EFFECT ON THE BODY, POSSIBLY RESULTING IN MANY COMPLEX MENTAL DISORDERS, INCLUDING DEPRESSION IN LATER LIFE. HERE, WE REVIEW THE EVIDENCE FOR EARLY-LIFE SOCIAL STRESS-INDUCED EPIGENETIC CHANGES THAT MODULATE JUVENILE AND ADULT SOCIAL BEHAVIOR (DEPRESSION AND ANXIETY). THIS REVIEW HAS A PARTICULAR EMPHASIS ON THE INTERACTION BETWEEN EARLY-LIFE SOCIAL STRESS AND GENETIC VARIATION OF SEROTONIN ASSOCIATE GENES INCLUDING THE SEROTONIN TRANSPORTER GENE (5-HTT; ALSO KNOWN AS SLC6A4), WHICH ARE KEY MOLECULES INVOLVED IN DEPRESSION. 2020 11 4525 20 MULTIFACTORIAL CAUSES OF PARANOID SCHIZOPHRENIA WITH AUDITORY-VISUAL HALLUCINATIONS IN A 31-YEAR-OLD MALE WITH HISTORY OF TRAUMATIC BRAIN INJURY AND SUBSTANCE ABUSE. SCHIZOPHRENIA IS A CHRONIC PSYCHIATRIC DISORDER THAT CLASSICALLY PRESENTS WITH DISTORTIONS OF THOUGHT, BEHAVIOR, AND PERCEPTIONS THAT ARE OFTEN MISDIAGNOSED. ONE DIFFICULTY IN DIAGNOSING SCHIZOPHRENIA IS DUE TO ITS PHENOTYPICALLY HETEROGENEOUS CONDITION THAT CAN BE PRECIPITATED BY A COMBINATION OF GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS. THE PREVALENCE OF SCHIZOPHRENIA IS ROUGHLY 1%, BUT IT IS OFTEN MISDIAGNOSED. POSSIBLE DIFFERENTIAL DIAGNOSES INCLUDE DEPRESSION OR BIPOLAR DISORDER WITH PSYCHOSIS, PSYCHOSIS DUE TO A MEDICAL CONDITION, SCHIZOTYPAL AND SCHIZOID PERSONALITY DISORDERS, AND NEUROCOGNITIVE DISORDERS. IN THIS CASE REPORT, A 31-YEAR-OLD MALE PRESENTS WITH THOUGHTS OF SUICIDE FOLLOWING A RECENT EXACERBATION OF HIS HALLUCINATIONS. ON PRESENTATION, THE PATIENT PRESENTED WITH A HISTORICAL DIAGNOSIS OF "PARANOID SCHIZOPHRENIA" AS WELL AS A HISTORY OF TRAUMATIC BRAIN INJURY (TBI), POLY-SUBSTANCE USE DISORDER, AND A FAMILY HISTORY OF SCHIZOPHRENIA. THIS CASE SERVES TO HIGHLIGHT THE DIFFICULTIES OF MAKING AN ACCURATE DIAGNOSIS AND PROVIDING EVIDENCED-BASED TREATMENT. 2022 12 6329 33 THE ROLE OF CHILDHOOD TRAUMA IN BIPOLAR DISORDERS. THIS REVIEW WILL DISCUSS THE ROLE OF CHILDHOOD TRAUMA IN BIPOLAR DISORDERS. RELEVANT STUDIES WERE IDENTIFIED VIA MEDLINE (PUBMED) AND PSYCINFO DATABASES PUBLISHED UP TO AND INCLUDING JULY 2015. THIS REVIEW CONTRIBUTES TO A NEW UNDERSTANDING OF THE NEGATIVE CONSEQUENCES OF EARLY LIFE STRESS, AS WELL AS SETTING CHILDHOOD TRAUMA IN A BIOLOGICAL CONTEXT OF SUSCEPTIBILITY AND DISCUSSING NOVEL LONG-TERM PATHOPHYSIOLOGICAL CONSEQUENCES IN BIPOLAR DISORDERS. CHILDHOOD TRAUMATIC EVENTS ARE RISK FACTORS FOR DEVELOPING BIPOLAR DISORDERS, IN ADDITION TO A MORE SEVERE CLINICAL PRESENTATION OVER TIME (PRIMARILY AN EARLIER AGE AT ONSET AND AN INCREASED RISK OF SUICIDE ATTEMPT AND SUBSTANCE MISUSE). CHILDHOOD TRAUMA LEADS TO ALTERATIONS OF AFFECT REGULATION, IMPULSE CONTROL, AND COGNITIVE FUNCTIONING THAT MIGHT DECREASE THE ABILITY TO COPE WITH LATER STRESSORS. CHILDHOOD TRAUMA INTERACTS WITH SEVERAL GENES BELONGING TO SEVERAL DIFFERENT BIOLOGICAL PATHWAYS [HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS, SEROTONERGIC TRANSMISSION, NEUROPLASTICITY, IMMUNITY, CALCIUM SIGNALING, AND CIRCADIAN RHYTHMS] TO DECREASE THE AGE AT THE ONSET OF THE DISORDER OR INCREASE THE RISK OF SUICIDE. EPIGENETIC FACTORS MAY ALSO BE INVOLVED IN THE NEUROBIOLOGICAL CONSEQUENCES OF CHILDHOOD TRAUMA IN BIPOLAR DISORDER. BIOLOGICAL SEQUELAE SUCH AS CHRONIC INFLAMMATION, SLEEP DISTURBANCE, OR TELOMERE SHORTENING ARE POTENTIAL MEDIATORS OF THE NEGATIVE EFFECTS OF CHILDHOOD TRAUMA IN BIPOLAR DISORDERS, IN PARTICULAR WITH REGARD TO PHYSICAL HEALTH. THE MAIN CLINICAL IMPLICATION IS TO SYSTEMATICALLY ASSESS CHILDHOOD TRAUMA IN PATIENTS WITH BIPOLAR DISORDERS, OR AT LEAST IN THOSE WITH A SEVERE OR INSTABLE COURSE. THE CHALLENGE FOR THE NEXT YEARS WILL BE TO FILL THE GAP BETWEEN CLINICAL AND FUNDAMENTAL RESEARCH AND ROUTINE PRACTICE, SINCE RECOMMENDATIONS FOR MANAGING THIS SPECIFIC POPULATION ARE LACKING. IN PARTICULAR, LITTLE IS KNOWN ON WHICH PSYCHOTHERAPIES SHOULD BE PROVIDED OR WHICH TARGETS THERAPISTS SHOULD FOCUS ON, AS WELL AS HOW CHILDHOOD TRAUMA COULD EXPLAIN THE RESISTANCE TO MOOD STABILIZERS. 2016 13 5311 25 PSYCHOLOGICAL AND BIOLOGICAL RESILIENCE MODULATES THE EFFECTS OF STRESS ON EPIGENETIC AGING. OUR SOCIETY IS EXPERIENCING MORE STRESS THAN EVER BEFORE, LEADING TO BOTH NEGATIVE PSYCHIATRIC AND PHYSICAL OUTCOMES. CHRONIC STRESS IS LINKED TO NEGATIVE LONG-TERM HEALTH CONSEQUENCES, RAISING THE POSSIBILITY THAT STRESS IS RELATED TO ACCELERATED AGING. IN THIS STUDY, WE EXAMINE WHETHER RESILIENCE FACTORS AFFECT STRESS-ASSOCIATED BIOLOGICAL AGE ACCELERATION. RECENTLY DEVELOPED "EPIGENETIC CLOCKS" SUCH AS GRIMAGE HAVE SHOWN UTILITY IN PREDICTING BIOLOGICAL AGE AND MORTALITY. HERE, WE ASSESSED THE IMPACT OF CUMULATIVE STRESS, STRESS PHYSIOLOGY, AND RESILIENCE ON ACCELERATED AGING IN A COMMUNITY SAMPLE (N = 444). CUMULATIVE STRESS WAS ASSOCIATED WITH ACCELERATED GRIMAGE (P = 0.0388) AND STRESS-RELATED PHYSIOLOGIC MEASURES OF ADRENAL SENSITIVITY (CORTISOL/ACTH RATIO) AND INSULIN RESISTANCE (HOMA). AFTER CONTROLLING FOR DEMOGRAPHIC AND BEHAVIORAL FACTORS, HOMA CORRELATED WITH ACCELERATED GRIMAGE (P = 0.0186). REMARKABLY, PSYCHOLOGICAL RESILIENCE FACTORS OF EMOTION REGULATION AND SELF-CONTROL MODERATED THESE RELATIONSHIPS. EMOTION REGULATION MODERATED THE ASSOCIATION BETWEEN STRESS AND AGING (P = 8.82E-4) SUCH THAT WITH WORSE EMOTION REGULATION, THERE WAS GREATER STRESS-RELATED AGE ACCELERATION, WHILE STRONGER EMOTION REGULATION PREVENTED ANY SIGNIFICANT EFFECT OF STRESS ON GRIMAGE. SELF-CONTROL MODERATED THE RELATIONSHIP BETWEEN STRESS AND INSULIN RESISTANCE (P = 0.00732), WITH HIGH SELF-CONTROL BLUNTING THIS RELATIONSHIP. IN THE FINAL MODEL, IN THOSE WITH POOR EMOTION REGULATION, CUMULATIVE STRESS CONTINUED TO PREDICT ADDITIONAL GRIMAGE ACCELERATION EVEN WHILE ACCOUNTING FOR DEMOGRAPHIC, PHYSIOLOGIC, AND BEHAVIORAL COVARIATES. THESE RESULTS DEMONSTRATE THAT CUMULATIVE STRESS IS ASSOCIATED WITH EPIGENETIC AGING IN A HEALTHY POPULATION, AND THESE ASSOCIATIONS ARE MODIFIED BY BIOBEHAVIORAL RESILIENCE FACTORS. 2021 14 4402 22 MODULATION OF NOCICEPTION BY SOCIAL FACTORS IN RODENTS: CONTRIBUTION OF THE OPIOID SYSTEM. RATIONALE: THE OPIOID SYSTEM IS INVOLVED IN THE REGULATION OF SEVERAL BEHAVIORAL AND PHYSIOLOGICAL RESPONSES, CONTROLLING PAIN, REWARD, AND ADDICTIVE BEHAVIORS. OPIOID ADMINISTRATION, DEPENDING ON DRUGS AND DOSES, USUALLY AFFECTS SOCIABILITY REDUCING INTERACTIONS BETWEEN CONSPECIFICS, WHEREAS SOME AFFILIATIVE BEHAVIORS SUCH AS SEXUAL ACTIVITY, SOCIAL GROOMING, AND PLAY BEHAVIOR INCREASE THE ENDOGENOUS OPIOID ACTIVITY. OBJECTIVES: THE POSSIBLE INTERACTION BETWEEN ENDOGENOUS OPIOIDS RELEASED DURING SOCIO/SEXUAL BEHAVIOR AND THEIR ANALGESIC EFFECT ON PAIN RESPONSE IS REVIEWED IN THE RODENT LITERATURE. RESULTS: DIRECT EVIDENCE FOR SOCIALLY MEDIATED OPIOID CHANGES RESULTING IN INCREASE IN NOCICEPTIVE THRESHOLD DERIVES FROM STUDIES EXPLORING THE EFFECTS OF DEFEAT EXPERIENCES, SOCIAL ISOLATION, MATERNAL, SEXUAL BEHAVIOR, AND SOCIAL REUNION AMONG KIN OR FAMILIAR ANIMALS IN LABORATORY RODENTS. INDIRECT EVIDENCE FOR ENDOGENOUS ACTIVATION OF THE OPIOID SYSTEM, POSSIBLY AFFECTING PAIN SENSITIVITY, DERIVES FROM STUDIES INVESTIGATING THE RELEVANCE OF NATURAL SOCIAL REWARD USING THE CONDITIONED PLACE PREFERENCE PROTOCOLS OR ANALYZING ULTRASONIC VOCALIZATIONS ASSOCIATED TO POSITIVE AFFECTIVE CONTEXTS. FINALLY, GENETIC AND EPIGENETIC FACTORS THAT AFFECT THE OPIOID SYSTEM DURING DEVELOPMENT ARE REPORTED TO BE INVOLVED IN MODULATING THE RESPONSE TO SOCIAL STIMULI AS WELL AS NOCICEPTION. CONCLUSIONS: ALL STUDIES HIGHLIGHT THE RELEVANCE OF AFFILIATIVE CONTACT BEHAVIOR BETWEEN CONSPECIFICS THAT IS RESPONSIBLE FOR THE ACTIVATION OF THE ENDOGENOUS MU-OPIOID SYSTEM, INDUCING NOCICEPTIVE THRESHOLD INCREASE. 2012 15 4006 22 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 16 5855 29 SUBSTANCE USE DISORDER A BIO-DIRECTIONAL SUBSET OF REWARD DEFICIENCY SYNDROME. THIS COMMENTARY IS TO INFORM CLINICIANS CHALLENGED WITH AN INCREASE IN PEOPLE SEEKING TREATMENT FOR SUBSTANCE USE DISORDER (SUD), THAT THE NINETY PERCENT REVOLVING DOOR, IS, IN PART, DUE TO POST-WITHDRAWAL, UNTREATED NEUROTOXICITY. THIS IMPAIRMENT ATTENUATES NEUROTRANSMITTER SIGNALING AND COMPROMISES RESTING STATE FUNCTIONAL CONNECTIVITY, LEADING TO UNWANTED SEQUELAE INCLUDING DEPRESSION, SLEEP DISTURBANCES, SENSATION SEEKING, LACK OF SATISFACTION AND IMPULSIVITY. NEUROIMAGING STUDIES INDICATE THAT NEUROBIOLOGICAL RECOVERY CAN TAKE YEARS. LIKE A "DOUBLE EDGE SWORD" SUD HAS A BIOLOGICAL BI -DIRECTIONAL (BIO-DIRECTIONAL) EFFECT ON THE BRAIN REWARD CIRCUITRY. THE ACUTE INTAKE OF PSYCHOACTIVE DRUGS RESULTS IN HEIGHTENED DOPAMINERGIC ACTIVITY, WHILE, THE OPPOSITE, HYPODOPAMINERGIA OCCURS FOLLOWING CHRONIC ABUSE. INDIVIDUALS WITH SUD CAN HAVE A GENETIC PREDISPOSITION, COMPOUNDED BY STRESS AND NEUROTOXICALLY INDUCED, EPIGENETIC INSULTS THAT IMPACT RECOVERY FROM PROTRACTED ABSTINENCE. FOLLOW-UP POST -SHORT-TERM RECOVERY USUALLY INCLUDES SUPPORTIVE THERAPIES AND PROGRAMS LIKE 12 -STEPS AND OTHER FELLOWSHIPS. HOWEVER, RELAPSE WILL USUALLY OCCUR IF POST -SHORT-TERM RECOVERY HYPODOPAMINERGIA IS NOT TREATED WITH ATTEMPTS AT EPIGENETIC MANIPULATION OF COMPROMISED BRAIN NEUROCHEMISTRY USING SOME MANNER OF PRO-DOPAMINE REGULATION. 2017 17 3664 20 INFANT NEUROBEHAVIORAL DEVELOPMENT. THE TREND TOWARD SINGLE-ROOM NEONATAL INTENSIVE CARE UNITS (NICUS) IS INCREASING; HOWEVER SCIENTIFIC EVIDENCE IS, AT THIS POINT, MOSTLY ANECDOTAL. THIS IS A CRITICAL TIME TO ASSESS THE IMPACT OF THE SINGLE-ROOM NICU ON IMPROVING MEDICAL AND NEUROBEHAVIORAL OUTCOMES OF THE PRETERM INFANT. WE HAVE DEVELOPED A THEORETICAL MODEL THAT MAY BE USEFUL IN STUDYING HOW THE CHANGE FROM AN OPEN-BAY NICU TO A SINGLE-ROOM NICU COULD AFFECT INFANT MEDICAL AND NEUROBEHAVIORAL OUTCOME. THE MODEL IDENTIFIES MEDIATING FACTORS THAT ARE LIKELY TO ACCOMPANY THE CHANGE TO A SINGLE-ROOM NICU. THESE MEDIATING FACTORS INCLUDE FAMILY CENTERED CARE, DEVELOPMENTAL CARE, PARENTING AND FAMILY FACTORS, STAFF BEHAVIOR AND ATTITUDES, AND MEDICAL PRACTICES. MEDICAL OUTCOMES THAT PLAN TO BE MEASURED ARE SEPSIS, LENGTH OF STAY, GESTATIONAL AGE AT DISCHARGE, WEIGHT GAIN, ILLNESS SEVERITY, GESTATIONAL AGE AT ENTERAL FEEDING, AND NECROTIZING ENTEROCOLITIS (NEC). NEUROBEHAVIORAL OUTCOMES INCLUDE THE NICU NETWORK NEUROBEHAVIORAL SCALE (NNNS) SCORES, SLEEP STATE ORGANIZATION AND SLEEP PHYSIOLOGY, INFANT MOTHER FEEDING INTERACTION SCORES, AND PAIN SCORES. PRELIMINARY FINDINGS ON THE SAMPLE OF 150 PATIENTS IN THE OPEN-BAY NICU SHOWED A "BASELINE" OF EFFECTS OF FAMILY CENTERED CARE, DEVELOPMENTAL CARE, PARENT SATISFACTION, MATERNAL DEPRESSION, AND PARENTING STRESS ON THE NEUROBEHAVIORAL OUTCOMES OF THE NEWBORN. THE SINGLE-ROOM NICU HAS THE POTENTIAL TO IMPROVE THE NEUROBEHAVIORAL STATUS OF THE INFANT AT DISCHARGE. NEUROBEHAVIORAL ASSESSMENT CAN ASSIST WITH EARLY DETECTION AND THEREFORE PREVENTATIVE INTERVENTION TO MAXIMIZE DEVELOPMENTAL OUTCOME. WE ALSO PRESENT AN EPIGENETIC MODEL OF THE POTENTIAL EFFECTS OF MATERNAL CARE ON IMPROVING INFANT NEUROBEHAVIORAL STATUS. 2011 18 1754 29 EARLY LIFE STRESS, THE DEVELOPMENT OF AGGRESSION AND NEUROENDOCRINE AND NEUROBIOLOGICAL CORRELATES: WHAT CAN WE LEARN FROM ANIMAL MODELS? EARLY LIFE STRESS (CHILD AND ADOLESCENT ABUSE, NEGLECT AND TRAUMA) INDUCES ROBUST ALTERATIONS IN EMOTIONAL AND SOCIAL FUNCTIONING RESULTING IN ENHANCED RISK FOR THE DEVELOPMENT OF PSYCHOPATHOLOGIES SUCH AS MOOD AND AGGRESSIVE DISORDERS. HERE, AN OVERVIEW IS GIVEN ON RECENT FINDINGS IN PRIMATE AND RODENT MODELS OF EARLY LIFE STRESS, DEMONSTRATING THAT CHRONIC DEPRIVATION OF EARLY MATERNAL CARE AS WELL AS CHRONIC DEPRIVATION OF EARLY PHYSICAL INTERACTIONS WITH PEERS ARE PROFOUND RISK FACTORS FOR THE DEVELOPMENT OF INAPPROPRIATE AGGRESSIVE BEHAVIORS. ALTERATIONS IN THE HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL (HPA), VASOPRESSIN AND SEROTONIN SYSTEMS AND THEIR RELEVANCE FOR THE REGULATION OF AGGRESSION ARE DISCUSSED. DATA SUGGEST THAT SOCIAL DEPRIVATION-INDUCED INAPPROPRIATE FORMS OF AGGRESSION ARE ASSOCIATED WITH HIGH OR LOW HPA AXIS (RE)ACTIVITY AND A GENERALLY LOWER FUNCTIONING OF THE SEROTONIN SYSTEM IN ADULTHOOD. MOREOVER, GENETIC AND EPIGENETIC MODIFICATIONS IN HPA AND SEROTONIN SYSTEMS INFLUENCE THE OUTCOME OF EARLY LIFE STRESS AND MAY EVEN MODERATE ADVERSE EFFECTS OF EARLY SOCIAL DEPRIVATION ON AGGRESSION. A MORE COMPREHENSIVE STUDY OF AGGRESSION, NEUROENDOCRINE, NEUROBIOLOGICAL AND (EPI)GENETIC CORRELATES OF EARLY LIFE STRESS USING ANIMAL MODELS IS NECESSARY TO PROVIDE A BETTER UNDERSTANDING OF THE INVASIVE AGGRESSIVE DEFICITS OBSERVED IN HUMANS EXPOSED TO CHILD MALTREATMENT. 2009 19 1750 20 EARLY LIFE STRESS AND PEDIATRIC POSTTRAUMATIC STRESS DISORDER. TRAUMATIC STRESS EXPOSURE DURING CRITICAL PERIODS OF DEVELOPMENT MAY HAVE ESSENTIAL AND LONG-LASTING EFFECTS ON THE PHYSICAL AND MENTAL HEALTH OF INDIVIDUALS. TWO THIRDS OF YOUTH ARE EXPOSED TO POTENTIALLY TRAUMATIC EXPERIENCES BY THE AGE OF 17, AND APPROXIMATELY 5% OF ADOLESCENTS MEET LIFETIME CRITERIA FOR POSTTRAUMATIC STRESS DISORDER (PTSD). THE ROLE OF THE STRESS SYSTEM IS THE MAINTENANCE OF HOMEOSTASIS IN THE PRESENCE OF REAL/PERCEIVED AND ACUTE/CHRONIC STRESSORS. EARLY-LIFE STRESS (ELS) HAS AN IMPACT ON NEURONAL BRAIN NETWORKS INVOLVED IN STRESS REACTIONS, AND COULD EXERT A PROGRAMMING EFFECT ON GLUCOCORTICOID SIGNALING. STUDIES ON PEDIATRIC PTSD REVEAL DIVERSE NEUROENDOCRINE RESPONSES TO ADVERSE EVENTS AND RELATED LONG-TERM NEUROENDOCRINE AND EPIGENETIC ALTERATIONS. NEUROENDOCRINE, NEUROIMAGING, AND GENETIC STUDIES IN CHILDREN WITH PTSD AND ELS EXPERIENCES ARE CRUCIAL IN UNDERSTANDING RISK AND RESILIENCE FACTORS, AND ALSO THE NATURAL HISTORY OF PTSD. 2020 20 4622 20 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