Emma Pendleton Bradley Hospital

COBRE CENTER FOR SLEEP AND CIRCADIAN RHYTHMS IN CHILD AND ADOLESCENT MENTAL HEALTH - PROJECT SUMMARY ABSTRACT THIS COBRE WILL ESTABLISH A CENTER ON SLEEP AND CIRCADIAN RHYTHMS IN CHILD AND ADOLESCENT MENTAL HEALTH AT THE EP BRADLEY HOSPITAL IN RHODE ISLAND. BRADLEY HOSPITAL IS UNIQUE IN THE US AS A PSYCHIATRIC INSTITUTION EXCLUSIVELY FOCUSED ON CHILDREN AND A NATIONAL RESOURCE FOR RESEARCH IN CHILD AND ADOLESCENT PSYCHIATRY. LINKS BETWEEN MENTAL ILLNESS AND SLEEP ARE INDISPUTABLE; PROBING AND IDENTIFYING THE LINKS FROM SLEEP AND CIRCADIAN RHYTHMS TO PEDIATRIC MENTAL ILLNESS AND MENTAL HEALTH CAN IDENTIFY IMPORTANT PATHWAYS TO PREVENTION AND EARLY INTERVENTION, NOT THE LEAST BECAUSE THESE FACTORS ARE AMENABLE TO BEHAVIORAL CHANGE AND TO DEFINED THERAPEUTIC TARGETING. THIS COBRE AIMS TO BUILD A BRIDGE FROM THE SLEEP AND CIRCADIAN KNOWLEDGE BASE AND RELEVANT RESEARCH METHODS TO THE OUTSTANDING MENTAL HEALTH RESEARCH AND CLINICAL CARE THAT CHARACTERIZE BRADLEY HOSPITAL. THE PROPOSED COBRE CENTER WOULD BE THE FIRST AND ONLY NIH-FUNDED RESEARCH CENTER TO HAVE AN EXPLICIT FOCUS ON SLEEP, CIRCADIAN RHYTHMS, AND PEDIATRIC MENTAL HEALTH. THE CENTER WILL TRAIN, MENTOR, AND SUPPORT JUNIOR INVESTIGATORS TOWARD INDEPENDENT RESEARCH CAREERS. THE CENTER’S RESEARCH CORES WILL HOST TRAINING IN THE ASSESSMENT OF PEDIATRIC MENTAL HEALTH AND IN SLEEP AND CIRCADIAN THEORY, SCIENCE, AND METHODS. THE OBJECTIVE OF THIS COBRE CENTER IS TO ESTABLISH AND BUILD A COMPREHENSIVE AND SUSTAINABLE RESOURCE TO SUPPORT THE GROWTH OF RESEARCH IN PEDIATRIC SLEEP, CIRCADIAN RHYTHMS, AND MENTAL HEALTH WHILE PROVIDING MENTORSHIP OF JUNIOR PROJECT LEADERS FOR RESEARCH AND FOR TRANSITIONING TO INDEPENDENT SCIENTIFIC CAREERS WITH EXTERNAL FUNDING. THE CENTER IS COMMITTED TO DIVERSITY IN FACULTY, MENTORS, INVESTIGATORS, RESEARCH APPROACHES AND METHODS, AND RESEARCH PARTICIPANTS. FOUR PROMISING YOUNG INVESTIGATORS HAVE EACH PROPOSED A PROJECT THAT HIGHLIGHTS THE DIVERSE AND COMPLEX NATURE OF THIS ENDEAVOR. PROJECT 1 WILL MEASURE SLEEP, CIRCADIAN TIMING, AND FMRI TO ASSESS SELF CRITICAL RUMINATION AND SELF REASSURANCE IN ADOLESCENTS AT RISK FOR SUICIDAL THOUGHTS AND ACTIONS. PROJECT 2 EVALUATES SLEEP PATTERNS AND CIRCADIAN TIMING IN YOUTH WHO HAVE A RARE DNA COPY NUMBER VARIANT ASSOCIATED WITH AUTISM AND SCHIZOPHRENIA AND INCLUDES A CIRCADIAN CLOCK GENE. PROJECT 3 ASSESS IN SCHOOL CHILDREN (GRADES 1-3) HOW GREEN SPACE USE IMPACTS SLEEP AND MENTAL HEALTH. PROJECT 4 USES AN INTENSIVE SLEEP AND CHRONOBIOLOGY IN-LAB APPROACH TO DETERMINE HOW SLEEPINESS AND MEMORY IN EARLY ADOLESCENTS WITH ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD) ARE AFFECTED BY SLEEP BIOREGULATORY FACTORS. THE ULTIMATE GOAL OF THIS COBRE IS TO EASE THE BURDEN OF THESE ISSUES FOR CHILDREN, ADOLESCENTS, AND THEIR FAMILIES THROUGH ENHANCING THE RESEARCH WORKFORCE AND CAPABILITIES. THE PROMISE OF THIS COBRE TO FULFILL ITS PLACE AS A TRUE CENTER OF BIOMEDICAL RESEARCH EXCELLENCE IS STRONG, AND THE MOST IMPORTANT, SPECIAL, AND NOTABLE ASPECT OF THIS PROPOSED CENTER IS THE VULNERABLE POPULATION THAT FORMS THE HEART OF OUR WORK.

BRADLEY HOSPITAL INTEGRATIVE RESEARCH LABORATORIES - PROJECT SUMMARY/ABSTRACT THE PROPOSED RESEARCH FACILITY WILL PROVIDE BIOMEDICAL RESEARCH FACILITIES AND OPPORTUNITIES FOR EXCEPTIONAL STATE-OF-THE-ART PEDIATRIC PSYCHIATRY RESEARCH TO BRADLEY HOSPITAL, THE NATION'S FIRST PSYCHIATRY HOSPITAL EXCLUSIVELY SERVING CHILDREN AND ADOLESCENTS. THE NEW INTEGRATIVE RESEARCH LABORATORIES, LOCATED ON THE CAMPUS OF BRADLEY HOSPITAL IN EAST PROVIDENCE, RI, WILL CREATE A CENTRALIZED FACILITY FOR SCIENTISTS AND THEIR RESEARCH ACTIVITIES ON THE HOSPITAL CAMPUS—STEPS AWAY FROM PATIENTS WHO PARTICIPATE IN SCIENCE AND WHO MAY BENEFIT THE MOST FROM NEW DISCOVERIES. THE PROPOSED FACILITY ADDRESSES FOUR CORE NEEDS: (A) CENTRALIZING MULTIPLE RESEARCH GROUPS IN A COHESIVE FACILITY IMMEDIATELY ACCESSIBLE TO BRADLEY'S PATIENT POPULATIONS WHO PARTICIPATE IN RESEARCH; (B) MODERNIZE AND EXPAND THE CAPACITIES OF OUR AGING SLEEP AND CHRONOBIOLOGY RESEARCH FACILITY; (C) BUILD A STATE-OF-THE-SCIENCE CHILD AND ADOLESCENT PSYCHIATRY ORIENTED BIOMARKERS AND BIOSPECIMEN ASSESSMENT AND PROCESSING LABORATORY; AND (D) CREATE NEW JOINT-USE ASSESSMENT SPACES THAT COMBINE THE BREADTH OF MODERN PSYCHIATRIC RESEARCH (E.G., OBSERVATION STUDIES, NEUROCOGNITIVE TESTING, ELECTROPHYSIOLOGICAL AND PSYCHOPHYSIOLOGICAL RECORDINGS, NEUROMODULATION) INTO A SINGLE FACILITY TO FACILITATE DYNAMIC SCIENCE AND NEW COLLABORATIONS. WE PROPOSE CONSTRUCTION OF A 13,856 SQUARE-FOOT FACILITY THAT WILL OCCUPY THE SECOND FLOOR OF A NEW BUILDING ON BRADLEY'S CAMPUS (WITH EXCESS CAPITAL COSTS SECURED FROM HOSPITAL AND CORPORATE FUNDS). THESE NEW INTEGRATIVE RESEARCH LABORATORIES WILL INCLUDE: PURPOSE-BUILT 24- HOUR-OPERATIONAL ENVIRONMENTALLY CONTROLLED SLEEP AND CIRCADIAN RESEARCH SUITES, SAMPLE COLLECTION, STORAGE AND ANALYSIS FACILITIES, ASSESSMENT ROOMS FOCUSING ON CHILD, FAMILY, AND GROUP OBSERVATION AND RESEARCH, CENTRALIZED PERFORMANCE TESTING LABORATORIES, 3 PURPOSE-BUILT PHYSIOLOGICAL LABS (EEG, PSYCHOPHYSIOLOGY AND NEUROMODULATION), AMPLE INSTRUMENTATION STORAGE AND FREEZER SPACE, AND DEDICATED FIXED EQUIPMENT TO FACILITATE RESEARCH SUCCESS. TOGETHER, THIS NEW FACILITY WILL TRANSFORM THE RESEARCH CAPACITIES OF BRADLEY HOSPITAL, SOLVING MULTIPLE LONG-STANDING CHALLENGES TO OUR SCIENTIFIC ENDEAVORS. RESEARCH ACCOMPLISHED IN THESE LABORATORIES WILL BENEFIT THE CHILDREN AND FAMILIES IN RI, GREATER NEW ENGLAND, AND ACROSS THE NATION BY ENHANCING KNOWLEDGE AND UNDERSTANDING OF PEDIATRIC MENTAL HEALTH. OUR CONSTRUCTION AND DESIGN PLAN MEETS THE HIGHEST STANDARDS OF MODERN FACILITIES TO ENSURE THE LONG-TERM UTILITY OF THIS SPACE. WE NOTE THAT THE HOSPITAL AND CORPORATE INSTITUTION (BROWN UNIVERSITY HEALTH) HAVE PLEDGED APPROXIMATELY $13.7 MILLION TO ENSURE THE VIABILITY OF THIS BIOMEDICAL RESEARCH FACILITY. OUR NEW INTEGRATIVE RESEARCH LABORATORIES FACILITY WILL PROVIDE THE INFRASTRUCTURE TO SUPPORT BRADLEY HOSPITAL AS A NATIONAL AND INTERNATIONAL LEADER IN CHILD AND ADOLESCENT PSYCHIATRY RESEARCH WELL INTO THE 21ST CENTURY.

PROJECT AWARE BRADLEY 2022 - THE EMMA PENDLETON BRADLEY HOSPITAL (BRADLEY) IN PARTNERSHIP WITH THE RHODE ISLAND DEPARTMENT OF EDUCATION (RIDE), THE RHODE ISLAND DEPARTMENT OF CHILDREN YOUTH AND FAMILIES (DCYF), OTHER COMMUNITY-BASED PROVIDERS OF BEHAVIORAL HEALTH SERVICES, SCHOOL PERSONNEL, COMMUNITY ORGANIZATIONS, FAMILIES AND SCHOOL AGED YOUTH PROPOSE TO WORK ON DEVELOPING A SUSTAINABLE INFRASTRUCTURE FOR SCHOOL-BASED MENTAL WELLNESS PROGRAMS AND SERVICES. BRADLEY AND ITS PARTNERS PROPOSE TO BUILD ON EFFORTS UNDERWAY TOWARD THIS GOAL AS THE PANDEMIC HAS INCREASED BOTH THE CHALLENGES IN IMPLEMENTATION AND THE NEED FOR THE SERVICES. BASED ON A PUBLIC HEALTH MODEL, THIS FIVE-YEAR EFFORT WILL BE FOCUSED IN THREE SCHOOL DISTRICTS; NAMELY, PAWTUCKET, PROVIDENCE, AND WOONSOCKET. FOCUSING ON THESE THREE DISTRICTS WILL ANNUALLY IMPACT 35,447 STUDENTS AND 3,051 SCHOOL PERSONNEL AS THE PARTNERS IMPLEMENT PROFESSIONAL AND PARAPROFESSIONAL TRAINING, MENTAL HEALTH RELATED PROMOTIONS, AWARENESS, PREVENTION, INTERVENTION, AND RESILIENCE ACTIVITIES TO ENSURE THAT STUDENTS HAVE ACCESS AND ARE CONNECTED TO APPROPRIATE AND EFFECTIVE BEHAVIORAL HEALTH SERVICES. IN RHODE ISLAND, ONE IN FIVE (19%) CHILDREN AGES 6-17 HAS A DIAGNOSABLE MENTAL HEALTH PROBLEM AND ONE IN 10 (10%) HAS A SIGNIFICANT FUNCTIONAL IMPAIRMENT. BRADLEY, RIDE, DCYF, AND ITS PARTNERS SUPPORTED BY THIS GRANT FUNDING WILL CONTINUE TO BUILD STRONG COLLABORATIVE PARTNERSHIPS TO OVERSEE BEHAVIORAL HEALTH EFFORTS IN TARGET DISTRICTS IN SERVICE OF SCHOOL-AGED YOUTH WITH MENTAL DISORDERS. THE COLLECTIVE IMPACT OF OUR STATE PARTNERSHIP WILL BE MIRRORED BY A SIMILAR PARTNERSHIP WITHIN THE THREE SCHOOL DISTRICTS, IN COLLABORATION WITH LOCAL COMMUNITY MENTAL HEALTH TREATMENT PROVIDER AGENCIES, TO ENSURE THAT SCHOOL PREVENTION AND INTERVENTION PROGRAMS AND SERVICES ARE LINKED TO EXISTING RESOURCES AND/OR NEW CAPACITY TO SUPPORT STUDENTS IS CREATED. THE FOLLOWING GOALS WILL SUPPORT THE PROCESS. DETAILED CORRESPONDING MEASURABLE OBJECTIVES TO EACH GOAL HAVE BEEN DEVELOPED. GOAL 1 THROUGH SYSTEMIC ENHANCEMENTS BRADLEY, AND ITS PARTNERS, WILL INCREASE AWARENESS AND IDENTIFICATION OF MH, SUBSTANCE USE, AND CO-OCCURRING ISSUES AMONG SCHOOL-AGED YOUTH. GOAL 2 BRADLEY, AND ITS PARTNERS, WILL CONTINUE TO INCREASE THE KNOWLEDGE OF INDIVIDUALS WHO INTERACT WITH SCHOOL-AGED YOUTH TO UNDERSTAND AND DETECT THE SIGNS AND SYMPTOMS OF MENTAL HEALTH, SUBSTANCE USE, AND CO-OCCURRING DISORDERS. THIS WILL INCLUDE ALL FACULTY AND STAFF AT THE SCHOOL AND DISTRICT LEVEL AND COMMUNITY MEMBERS. GOAL 3 BRADLEY AND PARTNERS WILL HAVE THE CAPACITY TO SUPPORT LEAS IN HELPING SCHOOL-AGED YOUTH PROMOTE RESILIENCE BUILDING AND MENTAL HEALTH WELL-BEING THROUGH THE DEVELOPMENT OF SKILLS THAT WILL WORK TO AVERT DEVELOPMENT OF MENTAL AND BEHAVIORAL HEALTH DISORDERS AND PREVENT YOUTH VIOLENCE. GOAL 4 BRADLEY, AND ITS PARTNERS, WILL ENHANCE AND SUSTAIN THE SCHOOL-BASED MENTAL HEALTH SYSTEM THAT IS BASED ON A THREE-TIERED PUBLIC HEALTH MODEL. GOAL 5 BRADLEY, AND ITS PARTNERS, WILL DEVELOP AND ENHANCE REFERRAL PATHWAY SYSTEMS THAT CONNECT SCHOOL-AGED YOUTH WHO MAY HAVE BEHAVIORAL HEALTH ISSUES, INCLUDING SYMPTOMS CONSISTENT WITH A SMI OR SED, AND THEIR FAMILIES TO NEEDED SERVICES. GOAL 6 THROUGH PROGRAMS, POLICIES, AND SYSTEM CHANGES, BRADLEY, RIDE, DCYF AND ITS PARTNERS WILL INCREASE ACCESS TO CULTURALLY COMPETENT, DEVELOPMENTALLY APPROPRIATE, AND TRAUMA INFORMED SCHOOL- AND COMMUNITY-BASED BH SERVICES.

INVESTIGATING MECHANISMS UNDERPINNING OUTCOMES IN PEOPLE ON OPIOID AGONIST TREATMENT FOR OUD: DISENTANGLING SLEEP AND CIRCADIAN RHYTHM INFLUENCES ON CRAVING AND EMOTION REGULATION - PROJECT SUMMARY/ABSTRACT THE US OPIOID EPIDEMIC COSTS OVER $1.5T AND OVER 75,000 DEATHS ANNUALLY. AN UNDERSTUDIED RISK FACTOR FOR OPIOID USE DISORDER (OUD) AND ITS TREATMENT IS THE IMPORTANCE OF SLEEP AND CIRCADIAN RHYTHMS (CR). OPIOIDS IMPACT SLEEP QUALITY IN A FASHION THAT INHIBITS RECOVERY, AND SLEEP REMAINS A CRITICAL FACTOR EVEN WHEN PATIENTS ENTER TREATMENT: THE TWO MOST EFFICACIOUS MEDICATIONS FOR OUD (MOUD) ALSO CAUSE SLEEP PROBLEMS THAT CONTRIBUTE TO SUBOPTIMAL OUTCOMES. TO ADDRESS THE ENORMOUS COSTS OF THE OPIOID EPIDEMIC, IT IS ESSENTIAL TO UNDERSTAND THE MECHANISMS UNDERLYING THE RELATIONSHIP BETWEEN MOUD, POOR SLEEP, AND NEGATIVE OUTCOMES. THUS, OUR CENTRAL HYPOTHESIS IS THAT EXAMINATION OF SLEEP AND CIRCADIAN PHENOTYPES, WILL HELP TO IDENTIFY INDIVIDUALS ON MOUD WHO WILL BENEFIT FROM SPECIFIC INTERVENTIONS. CHARACTERIZATION OF THE BIDIRECTIONAL INTERPLAY BETWEEN SLEEP BEHAVIORS, SLEEP ARCHITECTURE, CIRCADIAN RHYTHMS, AND NEUROCOGNITIVE MEASURES IN INDIVIDUALS ON MOUD IS A CRUCIAL FIRST STEP IN IDENTIFYING POTENTIAL MECHANISMS OR MODIFIABLE VARIABLES TO IMPROVE MOUD OUTCOMES. IDENTIFYING THE SPECIFIC TYPE OF SLEEP/CIRCADIAN DISRUPTION BY MOUD MAY HIGHLIGHT ADJUNCTIVE TREATMENT OPTIONS TO ADDRESS THE RELEVANT SLEEP PROBLEM (E.G., COGNITIVE BEHAVIORAL THERAPY FOR INSOMNIA). MOREOVER, MOUDS DISRUPT SLEEP, BUT IT IS NOT KNOWN WHETHER THIS IS VIA ALTERATIONS OF CR OR ALTERATIONS OF SLEEP BEHAVIOR/ARCHITECTURE. SLEEP/CR SCIENCE PROVIDES EXPERIMENTAL METHODS FOR SEPARATING CIRCADIAN TIMING FROM SLEEP PHYSIOLOGY IN THE FORM OF THE 90-MINUTE DAY. PRIOR WORK HIGHLIGHTS NEUROCOGNITIVE PHENOTYPES, CRAVING AND EMOTION REGULATION (ER), THAT ARE CRITICAL FOR SUCCESSFUL MOUD OUTCOMES. CRAVINGS ARE BOTH AN OUD SYMPTOM AND FREQUENT PREDICTOR OF RELAPSE. SLEEP QUALITY AFFECTS CRAVING POSSIBLY THROUGH POSITIVE AND NEGATIVE AFFECT, EMPHASIZING THAT ER IS OF CRITICAL CONCERN WITH MOUD, AS PATIENTS REPORT AN INABILITY TO REGULATE EMOTIONS AS A PRIMARY MOTIVATION FOR USE AND FOR RELAPSE. POOR SLEEP IS ASSOCIATED WITH DIMINISHED ER. IN 100 INDIVIDUALS ON MOUD WE WILL 1) EVALUATE (A) NATURALLY OCCURRING SLEEP PATTERNS USING ACTIVITY MONITORING FOR ONE WEEK AND (B) SLEEP PHYSIOLOGY THROUGH POLYSOMNOGRAPHIC RECORDING IN THE SLEEP LAB TO CONTRIBUTE TO THE COMMON AIM ACROSS RESEARCH SITES AND TO PROVIDE DESCRIPTIVE ANALYSES; 2) EXAMINE SLEEP AND CIRCADIAN PHENOTYPES USING VARIABLES COLLECTED VIA ACTIGRAPHY, PSG, AND THE 90-MIN DAY PROTOCOL TO EXAMINE ASSOCIATIONS OF THESE PHENOTYPES WITH NEUROCOGNITIVE MECHANISMS THAT MAY IMPACT OUTCOME OF OUD TREATMENT INCLUDING CRAVING AND EMOTION REGULATION; AND 3) USE QUALITATIVE METHODS TO INVESTIGATE THE ACCEPTABILITY, FEASIBILITY, AND PERCEIVED UTILITY OF INTERVENTIONS TARGETING THE SPECIFIC MECHANISTIC RELATIONSHIPS HYPOTHESIZED. IN SUMMARY, WE PLAN A COMPREHENSIVE EXAMINATION OF NOVEL PATHWAYS BETWEEN SLEEP/CIRCADIAN RHYTHMS AND NEUROCOGNITIVE FACTORS —CRAVING AND EMOTION REGULATION—CRITICAL TO SUCCESS IN MOUD AS PUTATIVE MECHANISMS UNDERPINNING THE ASSOCIATION OF POOR SLEEP AND SUBOPTIMAL TREATMENT OUTCOMES.

INTRINSIC CIRCADIAN PERIOD: DEVELOPMENT DELAYED PHASE AND GENETIC ASSOCIATIONS

PROSPECTIVE STUDY OF DEPRESSED MOOD, SHORT SLEEP AND SEROTONERGIC GENES

LONGITUDINAL EXAMINATION OF DNA METHYLATION IN MALTREATED CHILDREN

BRAIN-BEHAVIOR VULNERABILITY TO SLEEP LOSS IN CHILDREN: A DIMENSIONAL STUDY OF ATTENTION AND IMPULSIVITY - PROJECT SUMMARY CHILDREN AND ADOLESCENTS INCREASINGLY EXPERIENCE INSUFFICIENT OR POORLY TIMED SLEEP AS EARLY SCHOOL START TIMES COLLIDE WITH MATURATIONAL CHANGES IN SLEEP REGULATION. HOWEVER, WE LACK A DEEP UNDERSTANDING OF BOTH THE BRAIN-BEHAVIOR CONSEQUENCES OF THIS SLEEP LOSS AND THE FACTORS THAT DISTINGUISH WHICH CHILDREN MAY BE INCREASINGLY VULNERABLE AND WHICH ARE COMPARATIVELY RESILIENT TO ITS EFFECTS. THIS IS PARTICULARLY SALIENT FOR THE BRAIN-BEHAVIOR MECHANISMS UNDERLYING ATTENTION AND IMPULSIVITY: TWO COGNITIVE DOMAINS WHICH ARE ACUTELY IMPACTED BY SLEEP LOSS, ARE CRITICAL FOR ACADEMIC SUCCESS, AND ARE CORE ASPECTS OF NEURODEVELOPMENTAL DISORDERS SUCH AS ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER (ADHD). ATTEMPTS TO ADDRESS THESE ISSUES ARE HINDERED BY LIMITED MECHANISTIC STUDIES, OVERRELIANCE ON DATA FROM ADULTS, AND THE USE OF NEUROTYPICAL SAMPLES ONLY. THUS, THIS R01 PROJECT TACKLES THESE CHALLENGES WITH A WITHIN-SUBJECT AT-HOME SLEEP RESTRICTION EXPERIMENT WITH COMBINED METHODS OF FMRI, NEUROCOGNITIVE TESTING, EEG, AND CIRCADIAN PHYSIOLOGY TO BEAR ON THIS IMPORTANT PROBLEM. WE AIM TO ENROLL (OVER FIVE YEARS) 150, 10-13-YEAR-OLD CHILDREN ACROSS LEVELS OF INATTENTION AND IMPULSIVITY. WE WILL COMPARE A SLEEP OPTIMIZED BASELINE TO 5 NIGHTS OF SLEEP RESTRICTION. EACH CHILD IS CHARACTERIZED ON SEVERAL ATTENTION AND IMPULSIVITY METRICS TO COMPILE BASELINE RISK SCORES FOR EACH DOMAIN. RESTING NEURAL AROUSAL (WAKING FRONTAL EEG THETA POWER) AND CIRCADIAN TIMING (MELATONIN ONSET PHASE ANGLE) INDEX SLEEP-RELEVANT PHYSIOLOGY AS CANDIDATE MECHANISMS ALTERING A CHILD’S RESILIENCE TO SLEEP LOSS. REPEATED FUNCTIONAL MAGNETIC RESONANCE IMAGING USING TASK-BASED AND RESTING PARADIGMS, WITH COMPLEX MODELING OF BEHAVIOR VARIABILITY CHARACTERIZES SLEEP LOSS’S IMPACT ON ATTENTION AND IMPULSIVITY. A PERFORMANCE BATTERY INDEXES NEUROCOGNITIVE IMPAIRMENTS RELEVANT FOR ACADEMIC ACHIEVEMENT. FINALLY, MACHINE LEARNING IS USED TO DETERMINE EXAMINE DISTINCT PHENOTYPES OF BASELINE RISK FACTORS AND SLEEP-LOSS VULNERABILITY IN OUR SAMPLE. IN SUM, THIS PROJECT WILL ADVANCE BOTH NICHD AND NIMH’S GOAL TO UNDERSTAND MECHANISMS OF COMPLEX BEHAVIOR; HERE, CONSEQUENCES AND MEDIATORS OF SLEEP LOSS FOR CHILDREN.

A CULTURALLY CENTERED CBT PROTOCOL FOR SUICIDAL IDEATION AND SUICIDE ATTEMPTS AMONG LATINX YOUTH

FOOD CHOICES IN OVERWEIGHT & NORMAL WEIGHT ADOLESCENTS - SLEEP & CIRCADIAN RHYTHM

TRANSCRANIAL MAGNETIC STIMULATION TO AUGMENT EXPOSURE AND RESPONSE PREVENTION FOR PEDIATRIC OCD - PROJECT SUMMARY PEDIATRIC OCD IS A PUBLIC HEALTH PROBLEM AND MANY REMAIN SYMPTOMATIC EVEN AFTER RECEIVING EFFICACIOUS TREATMENTS. THE SUCCESS OF EXPOSURE AND RESPONSE PREVENTION (ERP), A FIRST-LINE BEHAVIORAL TREATMENT, DEPENDS ON THE ABILITY TO REFRAIN FROM COMPULSIONS DURING EXPOSURE TASKS. IMPROVING THIS “THERAPY CRITICAL BEHAVIOR” IS A POTENTIALLY IMPORTANT STRATEGY FOR ERP AUGMENTATION. REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION (RTMS) CAN BE LEVERAGED TO STIMULATE HEALTHIER FUNCTIONING OF BRAIN CIRCUITS UNDERLYING THERAPY CRITICAL BEHAVIORS. THE OVERALL OBJECTIVE OF THIS R61/R33 IS TO TEST WHETHER AUGMENTING ERP WITH RTMS OVER CORTICAL NODES OF SELECT CORTICO-STRIATAL CIRCUITS IMPLICATED IN COMPULSIVITY CAN NORMALIZE CONNECTIVITY AND ENHANCE RESPONSE PREVENTION IN YOUTH AND YOUNG ADULTS WITH OCD. THE R61 PHASE OF THIS PROJECT WILL USE A MASKED RCT DESIGN TO TEST WHETHER ERP+TMS ENGAGES 1) HYPOTHESIZED CIRCUITS INVOLVED IN COMPULSIVITY AND 2) OBSERVED RESPONSE PREVENTION DURING ERP EXPOSURE TASKS. YOUTH AGES 12-21 YEARS WITH OCD WILL COMPLETE A FULL COURSE OF ERP PLUS RANDOMLY ASSIGNED TMS REGIMENS OF SHAM, ITBS TO DLPFC, OR CTBS TO PSMA (N=20 PER GROUP). MILESTONES FOR THE R61 PHASE ARE DETERMINATION THAT AT LEAST ONE ACTIVE RTMS CONDITION A) CHANGES RSFC IN THE HYPOTHESIZED CIRCUIT WITHIN- AND BETWEEN-SUBJECTS AND B) IS SAFE AND FEASIBLE. THE R33 PHASE WILL USE A MASKED RCT DESIGN TO ESTABLISH WHETHER ERP+TMS ENGAGEMENT OF THE CIRCUIT AND BEHAVIORAL TARGETS MEDIATES CHANGES IN OCD SYMPTOM SEVERITY. A NEW SAMPLE OF YOUTH AGES 12-21 WITH OCD WILL RECEIVE ERP PLUS EITHER SHAM OR ACTIVE TMS STIMULATION, USING THE OPTIMAL TMS REGIMEN IDENTIFIED IN THE R61 (N=30 PER GROUP). EXPLORATORY ANALYSES IN BOTH PHASES WILL EXAMINE WHETHER NEUROCOGNITIVE TASK PERFORMANCE PREDICTS SYMPTOM CHANGE, CHANGES DIFFERENTIALLY BY TREATMENT ARM, AND CORRESPONDS WITH FMRI- MEASURED METRICS OF CORTICO-STRIATAL CIRCUITRY. AT THE END OF THIS AWARD, WE WILL HAVE DETERMINED WHETHER RTMS IS EFFECTIVE FOR IMPROVING COMPULSIVE BEHAVIOR AND FUNCTIONAL CONNECTIVITY IN CIRCUITS UNDERLYING COMPULSIVITY, AND WHETHER THESE MEDIATE CHANGE IN CLINICAL OUTCOMES. IF SUCCESSFUL, WE WILL BE POISED TO CONDUCT A LARGE-SCALE TRIAL OF RTMS WITH ERP FOR PEDIATRIC OCD, INCLUDING A CONFIRMATORY TEST OF THE LINKED MECHANISMS OF BOTH TREATMENTS. ULTIMATELY, RESULTS FROM THIS LINE OF RESEARCH WILL INFORM UNDERSTANDING OF NEURAL MECHANISMS IN RTMS AND OCD AND WILL PROVIDE A MODEL FOR STUDYING LINKED MECHANISMS IN AUGMENTATION TRIALS.

CHILDREN'S HOSPITALS GRADUATE MEDICAL EDUCATION PAYMENT PROGRAM

SERIAL NIGHTS OF ALCOHOL ADMINISTRATION: IMPACT ON SLEEP AND NEXT-DAY NEUROCOGNITIVE FUNCTION AND ALERTNESS

LIFE STRESSORS, IMPULSIVITY, AND ADOLESCENT SUICIDAL BEHAVIOR

QUALITY ASSESSMENT IN EXPOSURE THERAPY

AUTOMATED CODING OF EXPOSURE THERAPY QUALITY USING NATURAL LANGUAGE PROCESSING - PROJECT SUMMARY QUALITY MONITORING IS ESSENTIAL IN PSYCHOTHERAPY CLINICAL TRIALS AND FOR SUPPORTING THE USE OF EVIDENCE-BASED INTERVENTIONS (EBI) IN MENTAL HEALTH SERVICE SETTINGS, BUT FEW ARE AVAILABLE, AND THESE REQUIRE COSTLY AND LABORIOUS PROCEDURES. WITHOUT PRAGMATIC, SPECIFIC MEASURES OF QUALITY, IT IS IMPOSSIBLE TO KNOW WHETHER KEY QUALITY COMPONENTS ARE BEING DELIVERED, AND TO WHAT EFFECT. NATURAL LANGUAGE PROCESSING (NLP), A TYPE OF ARTIFICIAL INTELLIGENCE, HAS EXTRAORDINARY POTENTIAL TO REDUCE BURDEN BY AUTOMATING THE PROCESS OF QUALITY CODING. EXPOSURE THERAPY FOR ANXIETY IS AN IDEAL PROTOTYPE FOR TESTING AUTOMATED QUALITY CODING USING NLP, GIVEN ITS POTENTIAL FOR PUBLIC HEALTH IMPACT AND CLEAR THEORY OF MECHANISM TO GUIDE QUALITY MEASUREMENT. BUILDING ON PILOT WORK, THIS STUDY WILL REFINE AND TEST AUTOMATED QUALITY CODING WITH AUDIO DATA (N =1,286 PATIENTS AND 11,213 SESSIONS) FROM 6 EXISTING CLINICAL TRIALS OF EXPOSURE THERAPY FOR YOUTH AND ADULTS, ACROSS BOTH RESEARCH AND COMMUNITY SETTINGS. TO ENHANCE PROJECT EFFICIENCY AND FUTURE UTILITY OF FINDINGS, WE WILL LEVERAGE STRONG EXISTING PARTNERSHIPS WITH 1) NIMH INTRAMURAL RESEARCHERS BRINGING EXPERTISE IN THE QUANTITATIVE STUDY OF ANXIETY AND DEEP LEARNING METHODS INCLUDING NLP, 2) THE INTERNATIONAL EXPOSURE THERAPY CONSORTIUM (ETC), WHOSE MISSION IS TO SUPPORT CENTRALIZED TOOLS FOR RESEARCHERS STUDYING DELIVERY AND MECHANISMS OF EXPOSURE THERAPY, AND 3) A DIVERSE SET OF STAKEHOLDERS INCLUDING PATIENTS/FAMILIES, PROVIDERS, AGENCY LEADERS, PAYERS, POLICY MAKERS, AND TECHNOLOGY DEVELOPERS. SPECIFIC AIMS ARE DESIGNED TO VALIDATE AUTOMATED CODING WITH NLP AGAINST HUMAN CODERS, TEST PREDICTIVE UTILITY, AND INCORPORATE STAKEHOLDER FEEDBACK TO FACILITATE NEAR-TERM USABILITY OF FINDINGS.

WHAT WORKS FOR WHOM IN PEDIATRIC OCD - PROJECT SUMMARY/ABSTRACT IMPROVING PATIENT OUTCOMES WILL BE ENHANCED BY UNDERSTANDING “WHAT WORKS, FOR WHOM?” ENABLING BETTER MATCHING OF PATIENTS TO AVAILABLE TREATMENTS. DESPITE A WEALTH OF RESEARCH SEEKING TO OPTIMIZE CBT OUTCOMES FOR PEDIATRIC OBSESSIVE-COMPULSIVE DISORDER (OCD), WE HAVE LIMITED UNDERSTANDING ABOUT HOW TO MATCH PATIENTS WITH THE APPROPRIATE TREATMENT PACKAGE. PAST RESEARCH HAS IDENTIFIED PATIENT CHARACTERISTICS THAT MAY INFLUENCE TREATMENT RESPONSE, INCLUDING AGE, SYMPTOM SEVERITY, COMORBIDITIES, AND PREVIOUS TREATMENT HISTORY. UNFORTUNATELY, FINDINGS HAVE BEEN INCONSISTENT DUE TO LIMITED SAMPLE SIZE, A FOCUS ON ONE MODIFIER AT A TIME, AND DIFFICULTY INTEGRATING RESULTS ACROSS TRIALS WITH DIFFERENT SAMPLE CHARACTERISTICS. BETWEEN-TRIAL DIFFERENCES IN SAMPLE CHARACTERISTICS SEVERELY LIMIT CONVENTIONAL META-ANALYTIC TOOLS, GREATLY COMPLICATING CROSS-TRIAL COMPARISONS OF TREATMENT EFFICACY. THIS PROJECT WILL USE INDIVIDUAL-PARTICIPANT-DATA FROM 27 TRIALS AND DATA FROM TWO CLINICAL POPULATIONS AND UTILIZE RECENT ADVANCEMENTS IN TRANSPORTABILITY METHODS FACILITATES UNDERSTANDING “WHAT WORKS, FOR WHOM?” TRANSPORTABILITY METHODS INCLUDE CAUSAL ANALYTIC APPROACHES TO EXTEND INFERENCES FROM TRIAL SAMPLES TO TARGET POPULATIONS WHEN THERE ARE MARKED DIFFERENCES IN THE DISTRIBUTION OF SAMPLE CHARACTERISTICS BETWEEN TRIALS AND THE TARGET POPULATION. ROBUST STATISTICAL MODELS ARE USED TO ADDRESS BETWEEN-TRIAL DIFFERENCES IN COVARIATES, ENABLING THE TRANSPORTATION OF CAUSAL ESTIMATES FROM TRIAL SAMPLES TO TARGET POPULATIONS. UNDER EXPLICIT CAUSAL AND STATISTICAL ASSUMPTIONS, THE TRANSPORTED ANALYSES PROVIDE UNBIASED ESTIMATES OF HOW INTERVENTIONS WILL FAIR IN THE TARGET POPULATION(S), ENABLING APPLES-TO-APPLES COMPARISONS OF INTERVENTIONS EVEN WHEN TWO INTERVENTIONS HAVE NOT BEEN COMPARED IN A HEAD-TO-HEAD TRIAL. IN ADDITION, THE TARGET POPULATION CAN BE DEFINED AS SUB-POPULATIONS (E.G., YOUNGER CHILDREN WITH HIGH ILLNESS SEVERITY, COMORBIDITIES), ENABLING EVALUATION OF RELEVANT INTERVENTIONS FOR THAT SUB-POPULATION, EFFECTIVELY PROVIDING INSIGHT INTO THE QUESTION OF “WHAT WORKS FOR WHOM?”

EMBEDDING MENTAL HEALTH CONSULTATION WITHIN PRENATAL HOME VISITING TO PREVENT CHILD MALTREATMENT AND VIOLENCE EXPOSURE

NEURAL MECHANISMS UNDERLYING SELF-CRITICAL RUMINATION AND SELF-REASSURANCE AND SUICIDAL THOUGHTS AND BEHAVIOR IN YOUTH

MODULATION OF FRONTOPARIETAL DYNAMICS IN ADOLESCENT WORKING MEMORY DEFICITS - PROJECT SUMMARY/ABSTRACT DEFICITS IN WORKING MEMORY (WM) COMPRISE A CORE, TRANSDIAGNOSTIC FEATURE OF CHILDHOOD AND ADOLESCENT PSYCHOPATHOLOGY. WM IS ONE OF THE STRONGEST PREDICTORS OF CLINICAL AND FUNCTIONAL OUTCOMES, YET THERE REMAINS A DEARTH OF TREATMENTS AVAILABLE FOR WM DEFICITS. WM WAS HISTORICALLY CONCEPTUALIZED AS SOLELY LOCALIZED TO THE DORSOLATERAL PREFRONTAL CORTEX, WHILE MODERN TECHNOLOGY HAS ESTABLISHED THE BROADER ROLE OF THE PREFRONTAL CORTEX (PFC) AND POSTERIOR PARIETAL CORTEX (PPC). THERE IS EVIDENCE TO SUGGEST THAT PPC RECEIVES DIRECT INPUT FROM PFC, ALTHOUGH OTHER EVIDENCE SUGGESTS THE PPC ENCODES INCOMING STIMULI AND FEEDS FORWARD TO THE PFC FOR THE INITIATION OF CONTROL FUNCTIONS. I HAVE PREVIOUSLY FOUND THAT FRONTOPARIETAL THETA/GAMMA OSCILLATIONS, PARTICULARLY THETA-GAMMA COUPLING, IS A NEURAL MECHANISM UNDERLYING WM PROCESSES. NOVEL APPROACHES TO NON-INVASIVE BRAIN STIMULATION, SUCH AS INTERMITTENT THETA BURST STIMULATION (ITBS) CAN NOW MODULATE THESE DISTINCT OSCILLATORY DYNAMICS AND SUBSEQUENTLY EXAMINE POSSIBLE CAUSAL OR TEMPORAL RELATIONSHIPS. THIS AWARD WOULD BUILD ON MY PRELIMINARY FINDINGS AND TRANSITION MY CAREER FROM A CLINICIAN TO AN INDEPENDENT RESEARCHER. THE OBJECTIVE OF THIS PATIENT-ORIENTED RESEARCH CAREER DEVELOPMENT AWARD (K23) IS TO PROVIDE THE NECESSARY TRAINING FOR ME TO OBTAIN MY CAREER GOAL OF UTILIZING A MULTIMODAL NEUROSCIENTIFIC APPROACH TO MEASURE AND MODULATE THE NEURAL DYNAMICS UNDERLYING NEUROCOGNITIVE DEFICITS IN CHILDHOOD AND ADOLESCENT PSYCHOPATHOLOGY. IN LINE WITH NIMH PRIORITIES, THE TRAINING PLAN PROPOSED WILL BUILD UPON MY CLINICAL NEUROPSYCHOLOGY AND CLINICAL RESEARCH FOUNDATION TO PROVIDE COMPREHENSIVE TRAINING AND MENTORSHIP IN TWO CORE AREAS: 1) NEUROMODULATION AND 2) COMPUTATIONAL NEUROSCIENCE. IN A 2X2 FACTORIAL DOUBLE-BLIND DESIGN, WE WILL RANDOMIZE A SAMPLE OF 40 ADOLESCENTS (13-17 YEARS) WITH WM DEFICITS TO ITBS AT THE LEFT DLPFC OR INFERIOR PARIETAL LOBULE (IPL). PARTICIPANTS WILL COMPLETE AN ACTIVE ITBS SESSION AND A SHAM ITBS SESSION. THE PRIMARY OUTCOME WILL BE THETA-GAMMA COUPLING DURING WM DEMANDS, AS MEASURED VIA ELECTROENCEPHALOGRAPHY DURING A SPATIAL WM TASK IMMEDIATELY BEFORE AND AFTER ITBS. AIM 1 WILL EXAMINE THE EFFECT OF ITBS TO THE PPC ON THE ENCODING STAGE OF WM, WHILE AIM 2 WILL EXAMINE THE EFFECT OF ITBS TO THE PFC ON THE MAINTENANCE STAGE OF WM. AIM 3 WILL UTILIZE COMPUTATIONAL NEURAL MODELING TO IDENTIFY THE NEOCORTICAL CIRCUITRY UNDERLYING OSCILLATORY MODULATION. MY CENTRAL HYPOTHESIS IS THAT THE PFC AND PPC REGIONS HAVE COMPLIMENTARY ROLES IN EXECUTING WM PROCESSES. FURTHER, ITBS CAN MODULATE THETA-GAMMA COUPLING IN THESE REGIONS TO IMPROVE BEHAVIORAL PERFORMANCE. WE WILL ESTABLISH A FRAMEWORK FOR MODULATING OSCILLATORY DYNAMICS IN CHILD PSYCHIATRY AND SET THE STAGE FOR MY FIRST R01 ON WM-RELATED FRONTOPARIETAL OSCILLATORY DYNAMICS AND OPTIMAL TREATMENT PARAMETERS FOR ADOLESCENT WM DEFICITS. THIS WILL PROVIDE THE FOUNDATION REQUIRED TO DEDICATE MY CAREER TO MEASURING AND MODULATING OSCILLATORY ABNORMALITIES IN CHILD PSYCHIATRY.

MCH RESEARCH

ENHANCING EARLY CARE AND EDUCATION THROUGH REFLECTIVE SUPERVISION TO PROMOTE ADAPTIVE EMOTION REGULATION IN YOUNG CHILDREN - PROJECT SUMMARY GROWING UP IN POVERTY IS ASSOCIATED WITH EMOTION REGULATION (ER) PROBLEMS, WHICH INCREASE RISK FOR PSYCHOPATHOLOGY AND DISEASE AS CHILDREN AGE. HIGH QUALITY EARLY CARE AND EDUCATION (ECE) PROGRAMS WERE DESIGNED TO PREVENT THE NEGATIVE EFFECTS OF POVERTY AND ITS ASSOCIATED STRESSORS BY STRENGTHENING YOUNG CHILDREN’S ER CAPACITY, THROUGH RESPONSIVE AND NURTURING RELATIONSHIPS WITH TEACHERS AND EVIDENCE-BASED TEACHING PRACTICES AND CURRICULUM. HOWEVER, REAL-WORLD ECE PROGRAMS LACK THE INTERNAL SUPPORT TO SUSTAIN BEST PRACTICES THAT ARE LINKED TO POSITIVE CHILD OUTCOMES. TEACHERS ARE TRAINED TO USE EVIDENCE-BASED SKILLS BY EXTERNAL CONSULTANTS OR INTERVENTIONISTS, BUT THEN DRIFT FROM THESE PRACTICES ONCE THOSE SUPPORTS ARE NO LONGER AVAILABLE. THUS, THE PUBLIC HEALTH NEED TO INCREASE QUALITY OF SUPPORT FOR TEACHERS WITHIN AN ECE PROGRAM CANNOT BE OVERSTATED, ESPECIALLY GIVEN FINDINGS THAT LACK OF SUPPORT FROM PROGRAM DIRECTORS IS ASSOCIATED WITH REDUCED USE OF EVIDENCE-BASED PRACTICES OVER TIME, AND TEACHER STRESS, BURNOUT, AND TURNOVER, WHICH LEADS TO POOR SOCIOEMOTIONAL ENVIRONMENTS FOR CHILDREN. THEREFORE, THE PROPOSED STUDY AIMS TO TRAIN ECE DIRECTORS TO USE REFLECTIVE PRACTICE AND SUPERVISION (RP/S), A RELATIONSHIP-BASED, CULTURALLY RESPONSIVE MODEL OF SUPERVISION, WITH THEIR TEACHERS TO IMPROVE TEACHING QUALITY AND INCREASE USE OF EVIDENCE-BASED SKILLS TO PROMOTE ADAPTIVE ER IN CHILDREN. THIS INNOVATIVE RESEARCH WILL BE CONDUCTED IN TWO PHASES: AN OPEN TRIAL AND A FULLY POWERED CLUSTER RANDOMIZED CONTROLLED TRIAL (CRT). THE GOAL OF THE AIM 1 OPEN TRIAL IS TO ASSESS FEASIBILITY, ACCEPTABILITY, AND IMPLEMENTATION BARRIERS AND FACILITATORS. QUANTITATIVE AND QUALITATIVE DATA WILL BE USED TO REFINE RP/S PRIOR TO THE CRT. THE SECOND PHASE WILL TEST RP/S AGAINST A WAITLIST CONTROL CONDITION (I.E., STANDARD ADMINISTRATIVE SUPERVISION). AIM 2 WILL DETERMINE WHETHER RP/S IS ASSOCIATED WITH INCREASES IN TEACHING QUALITY AND TEACHER USE OF EVIDENCE-BASED SKILLS FROM PRE- TO POST, AND AT 3-MONTH FOLLOW-UP. AIM 3 WILL DETERMINE WHETHER RP/S IS ASSOCIATED WITH INCREASES IN ADAPTIVE ER AMONG CHILDREN, MEASURED WITH A MULTI-METHOD ASSESSMENT BATTERY. THIS WILL BE THE FIRST RIGOROUS EVALUATION OF RP/S AS AN ENHANCEMENT TO ECE PROGRAMMING, AND RESULTS WILL BE OF HIGH INTEREST TO LOCAL AND NATIONAL STAKEHOLDERS. A HIGHLY STRUCTURED TRAINING PLAN WILL ENSURE ACHIEVEMENT OF THE PROPOSED RESEARCH AIMS. SPECIFICALLY, THE PI WILL RECEIVE SPECIALIZED TRAINING IN (1) INFANT MENTAL HEALTH, (2) IMPLEMENTATION WITHIN ECE SYSTEMS, (3) PRAGMATIC CRT DEVELOPMENT, DELIVERY, AND EVALUATION, (4) CLINICAL TRIAL AND MULTILEVEL MODELING METHODS, AND (5) MENTORING AND LEADERSHIP SKILLS. TRAINING WILL BE GUIDED BY AN OUTSTANDING MENTORSHIP TEAM WITH HIGHLY RELEVANT EXPERTISE AND OUTSTANDING TRACK RECORDS OF MENTORSHIP AND COLLABORATION. THE PROPOSED RESEARCH AND TRAINING PLAN IS FURTHER SUPPORTED BY THE RICH TRAINING ENVIRONMENT IN THE BROWN MEDICAL SCHOOL AND BRADLEY HOSPITAL. THROUGH THIS K23, THE PI WILL LAUNCH HER CAREER AS AN INDEPENDENT CLINICAL SCIENTIST FOCUSED ON DEVELOPING AND EVALUATING SYSTEMS-BASED PREVENTIVE INTERVENTIONS IN COMMUNITY SETTINGS TO IMPROVE EMOTION REGULATION IN YOUNG CHILDREN EXPOSED TO ADVERSITY.

COGNITIVE FLEXIBILITY AND REWARD MOTIVATION IN ADOLESCENT CANNABIS USE: AN INVESTIGATION OF NEUROBEHAVIORAL MECHANISMS AND INTRINSIC RESTING STATE CONNECTIVITY. - 7. PROJECT SUMMARY: CANNABIS USE (CU) INITIATED IN ADOLESCENCE IS ASSOCIATED WITH SUBSTANTIAL CONSEQUENCES, FROM COGNITIVE DECLINE TO ADDICTION. WHILE CU MAY DISRUPT NORMAL PROCESSES OF ADOLESCENT BRAIN DEVELOPMENT, RELATIVELY LITTLE IS KNOWN ABOUT HOW ADOLESCENT CU DISRUPTS CIRCUITS MEDIATING COGNITIVE FLEXIBILITY (ADAPTATION TO CHANGING REWARDS AND PUNISHMENTS) AND INTRINSIC RESTING STATE FUNCTIONAL CONNECTIVITY (RSFC), AND IMPACTS REWARD MOTIVATION (THE AMOUNT OF GOAL-DIRECTED BEHAVIOR TO EARN REINFORCEMENT). THESE DOMAINS ARE ALL UNDERSTUDIED AREAS RELATIVE TO ADULT CU YET ADVANCING KNOWLEDGE OF THESE PROCESSES MAY EXPLAIN WHY ADOLESCENT-ONSET CU IS LINKED TO FUNCTIONAL IMPAIRMENTS AND HIGHER RATES OF PROBLEMATIC SUBSTANCE USE. DR. THOMAS’S LONG-TERM CAREER GOAL IS TO BECOME AN INDEPENDENT RESEARCHER IDENTIFYING BIO-BEHAVIORAL MECHANISMS OF RISKS AND EFFECTS OF ADOLESCENT DRUG USE IN ORDER TO IMPROVE IDENTIFICATION METHODS FOR TARGETED PREVENTION AND TREATMENT. THE CENTRAL HYPOTHESIS TO BE TESTED IN THIS 4-YEAR PATIENT-ORIENTED MENTORED CAREER AWARD IS THAT CU IN THE CONTEXT OF ADOLESCENT BRAIN DEVELOPMENT IS LINKED TO FRONTOSTRIATAL ALTERATIONS AND IMPAIRED COGNITIVE FLEXIBILITY, REWARD MOTIVATION, AND INTRINSIC RSFC THAT WILL VARY AS A FUNCTION OF CU EXPOSURE. THE CENTRAL METHODOLOGY IS TO USE SYMPTOM, CIRCUIT, AND BEHAVIORAL DATA IN 14-17 YEAR OLD ADOLESCENTS WHO ARE ENGAGED IN CU AND ALSO TYPICALLY- DEVELOPING CONTROL ADOLESCENTS (N=40 OF EACH). THE CAREER DEVELOPMENT OBJECTIVES OF THIS NIDA K23 APPLICATION ARE TO GAIN HANDS-ON MENTORSHIP IN (A) PHENOMENOLOGY AND ASSESSMENT OF ADOLESCENT CU, (B) THE USE OF FMRI TO MEASURE BRAIN/BEHAVIOR ALTERATIONS UNDERLYING ADOLESCENT CU, AND (C) ADVANCED STATISTICAL METHODS FOR GREATER LEVEL OF INFERENCE FROM THESE DATA, BY LEARNING A COMPUTATIONAL PSYCHIATRY MODEL. THE RESEARCH OBJECTIVES OF THIS K23 ARE TO: (1) TO IDENTIFY THE BRAIN/BEHAVIOR MECHANISMS OF COGNITIVE FLEXIBILITY AND RSFC ASSOCIATED WITH CU USING FMRI; (2) TO DEFINE BEHAVIORAL ALTERATIONS IN REWARD MOTIVATION; (3) TO USE ADVANCED STATISTICAL METHODS, INCLUDING A SPECIFIC COMPUTATIONAL MODEL, TO INTEGRATE THE NEURAL AND BEHAVIORAL CONTRIBUTIONS TO DECISION-MAKING DURING A COGNITIVE FLEXIBILITY TASK AND DETERMINE HOW DECISION-MAKING COMPONENTS VARY FOR CU ADOLESCENTS AND CONTROL ADOLESCENTS. BROWN UNIVERSITY IS A RICH SCIENTIFIC ENVIRONMENT TO CONDUCT THIS RESEARCH DUE TO THE EXPERTISE OF MENTORS IN ADOLESCENT SUBSTANCE USE, NEUROSCIENCE, AND ADVANCED STATISTICAL METHODS WITH AMPLE RESOURCES TO CARRY OUT DR. THOMAS’S TRAINING PLAN CONSISTING OF HANDS- ON MENTORSHIP, WORKSHOPS, COURSEWORK (E.G., NEUROANATOMY), AND PROFESSIONAL DEVELOPMENT (CONFERENCE PRESENTATIONS, PUBLICATIONS). THIS PROJECT IS SIGNIFICANT BECAUSE ADDRESSING THE DEARTH OF KNOWLEDGE ABOUT COGNITIVE FLEXIBILITY, REWARD MOTIVATION, AND RSFC IS THE FIRST STEP TOWARDS FACILITATING MECHANISM-BASED (A) PREDICTORS OF PROGRESSION FROM REGULAR CU TO ADDICTION, AND (B) TREATMENTS FOR CU AMONG ADOLESCENTS. THIS PROJECT IS INNOVATIVE IN ITS USE OF FMRI TO PROBE THE RELATIVELY UNDERSTUDIED DOMAINS OF COGNITIVE FLEXIBILITY AND REWARD MOTIVATION AMONG ADOLESCENTS WITH AND WITHOUT CU USING COMPUTATIONAL PSYCHIATRY ANALYSES.

NEURAL MECHANISMS OF DEPRESSIVE SYMPTOMS IN YOUTH WITH AUTISM SPECTRUMDISORDER - PROJECT SUMMARY/ABSTRACT AUTISM SPECTRUM DISORDER (ASD) IS COMMON (1 IN 59 US CHILDREN) AND IMPAIRING. YET, CO-OCCURRING PSYCHIATRIC DISORDERS—ESPECIALLY DEPRESSION—IN ASD REMAIN UNDERSTUDIED, HINDERING CLINICAL CARE. THIS K23 SEEKS TO ADDRESS AN IMPORTANT GAP IN KNOWLEDGE ABOUT THE NEURAL MECHANISMS UNDERLYING DEPRESSIVE SYMPTOMS IN ASD, WHICH COULD ULTIMATELY PROVIDE A PRECISION MEDICINE-BASED APPROACH TO NOVEL TREATMENT DEVELOPMENT. OUR CENTRAL HYPOTHESIS IS THAT DEPRESSIVE SYMPTOMS IN ADOLESCENTS WITH ASD WILL BE ASSOCIATED WITH FRONTO-LIMBIC, FRONTO-FRONTAL AND FRONTO-THALAMIC CONNECTIVITY THAT, IN TURN, ARE RELATED TO UNDERLYING DIFFERENCES IN WHITE MATTER INTEGRITY AND MYELINATION. OUR CENTRAL METHODOLOGY IS TO SCAN N=40 CHILDREN (AGES 12-16) WITH ASD AND N=40 AGE-MATCHED CONTROLS WITHOUT ASD. THE RESEARCH GOALS OF THIS K23 ARE TO: (I) IDENTIFY RESTING-STATE FUNCTIONAL MAGNETIC RESONANCE IMAGING (RS-FMRI) CORRELATES OF DEPRESSIVE SYMPTOMS IN ASD; (II) INVESTIGATE WHITE MATTER MICROSTRUCTURAL ALTERATIONS LINKED TO DEPRESSIVE SYMPTOMS IN ASD; (III) UTILIZE CONNECTOME-BASED APPROACHES TO EXPLORE THE INTERACTION BETWEEN DEPRESSIVE SYMPTOMS ACROSS MODALITIES. MY CAREER DEVELOPMENT GOALS ARE TO GAIN EXPERTISE IN: (I) RS-FMRI (AND DEEPER UNDERSTANDING OF PROMISING CIRCUIT-BASED APPROACHES TO TARGET ENGAGEMENT); (II) DIFFUSION SPECTRUM IMAGING/MYELIN IMAGING; (III) RESEARCH- GRADE DIAGNOSTIC EVALUATION OF ASD; (IV) CHARACTERIZATION OF MOOD DISORDERS IN INDIVIDUALS WITH ASD; AND (V) PROFESSIONAL DEVELOPMENT TO BECOME AN INDEPENDENT INVESTIGATOR. THIS PROPOSAL IS SIGNIFICANT BECAUSE IT WILL ADDRESS NIMH STRATEGIC PLAN OBJECTIVE 1.3 TO CHARACTERIZE NEURAL CIRCUIT MECHANISM DISRUPTION UNDERLYING DEPRESSIVE SYMPTOMS IN ASD, USING NEUROIMAGING AND DETAILED PSYCHOPATHOLOGY PHENOTYPING. THIS K23 IS INNOVATIVE BECAUSE IT WILL BE THE FIRST TO USE MULTIMODAL IMAGING METHODS, INCLUDING RS-FMRI, DIFFUSION SPECTRUM IMAGING, AND MYELIN IMAGING, TO DEFINE NEURAL MECHANISMS OF DEPRESSIVE SYMPTOMS IN A SEX-BALANCED SAMPLE OF ADOLESCENTS WITH ASD. LEVERAGING VITAL DATA AND CAREER DEVELOPMENT FROM THIS K23, I WILL SUBMIT FUTURE R01S AS AN INDEPENDENT INVESTIGATOR THAT FOCUSES ON: (I) DEEPER UNDERSTANDING OF THE NEURAL MECHANISMS OF CO-OCCURRING DEPRESSIVE DISORDERS (INCLUDING MAJOR DEPRESSIVE DISORDER, PERSISTENT DEPRESSIVE DISORDER) IN INDIVIDUALS WITH ASD, AND (II) EXAMINATION OF HOW CIRCUITS CHANGE ACROSS DEVELOPMENT (EXPANDING THE AGE RANGE TO EARLY CHILDHOOD AND YOUNG ADULTHOOD) IN INDIVIDUALS WITH ASD WITH OR WITHOUT DEPRESSIVE DISORDERS.

THE INTERACTION OF BRAIN STRUCTURE AND SLEEP NEUROPHYSIOLOGY IN REGULATING THE NEURAL SUBSTRATES OF INATTENTION SYMPTOMS IN PEDIATRIC ADHD

COGFLEX: PILOT TRANSLATIONAL INTERVENTION FOR PEDIATRIC BIPOLAR DISORDER

ENGAGING LOW-INCOME CAREGIVERS IN PREVENTIVE INTERVENTIONS FOR CONDUCT PROBLEMS

EXAMINING BEHAVIORAL STRATEGIES FOR ENHANCING THERAPISTS' DELIVERY OF EXPOSURE THERAPY

HEALTH CARE AND OTHER FACILITIES

A GENOMIC APPROACH TO AUTISM AND SCHIZOPHRENIA RISK THROUGH 17Q12 CNVS

CHILDHOOD ADVERSITY AND BIOLOGICAL MECHANISMS OF ACCELERATED AGING - PROJECT SUMMARY/ABSTRACT EARLY LIFE ADVERSITY, INCLUDING CHILDHOOD MALTREATMENT AND OTHER TRAUMAS, IS A MAJOR RISK FACTOR FOR A HOST OF HEALTH CONDITIONS, INCLUDING PSYCHIATRIC DISORDERS, OBESITY, DIABETES, AND CARDIOVASCULAR DISEASE. HEALTH BEHAVIORS, SUCH AS DIET, SLEEP, AND ACTIVITY, ARE LINKED TO CHILDHOOD ADVERSITY AND CAN FURTHER CONTRIBUTE TO RISK FOR THESE CONDITIONS. THESE EFFECTS COMPOUND OVER TIME AND POOR HEALTH OUTCOMES ARE MOST EVIDENT IN ADULTS WHEN BIOLOGICAL EFFECTS OF STRESS AND HEALTH BEHAVIORS COMBINE WITH AGE-RELATED DECLINE TO PRODUCE FRANK DISEASE. THERE IS NOW EVIDENCE THAT THESE PROCESSES BEGIN EARLY IN LIFE AND THAT SOME OF THE HEALTH OUTCOMES CAN BE OBSERVED IN CHILDHOOD. CONVERGING EVIDENCE FROM ANIMAL MODELS AND RECENT HUMAN STUDIES INDICATE THAT MITOCHONDRIA PLAY A KEY ROLE IN COORDINATING THE STRESS RESPONSE AND IN THE AGING PROCESS. HERE WE HYPOTHESIZE THAT EARLY STRESS ALTERS MITOCHONDRIAL DNA AND MITOCHONDRIAL FUNCTION AND THAT THIS MAY BE A MECHANISM OF RISK FOR STRESS- AND AGE-RELATED DISORDERS. THE PROPOSED STUDY LEVERAGES DATA AND SPECIMENS AVAILABLE IN A LONGITUDINAL DEVELOPMENTAL STUDY OF CHILDHOOD MALTREATMENT THAT INCLUDES RICH DATA ON EXPOSURES, BIOMARKERS OF AGING, AND HEALTH OUTCOMES. RESULTS OF THIS STUDY ARE EXPECTED TO PROVIDE INSIGHT INTO THE BIOLOGICAL MECHANISMS OF ADVERSITY-RELATED RISK FOR ACCELERATED AGING AND RISK FOR DISEASE, AND PROVIDE TARGETS FOR NEW TREATMENT AND PREVENTION APPROACHES.

COGFLEX: PILOT TRANSLATIONAL INTERVENTION FOR PEDIATRIC BIPOLAR DISORDER

DEEP PHENOTYPING OF SLEEP AND SYMPTOMS IN ADOLESCENTS WITH PSYCHOSIS-SPECTRUM CONDITIONS - PROJECT SUMMARY ADOLESCENTS EXPERIENCING PSYCHOSIS-SPECTRUM (PS) SYMPTOMS ARE AT HIGH RISK FOR LIFELONG MENTAL ILLNESS AND IMPAIRMENT, INCLUDING CONVERSION TO SCHIZOPHRENIA. MECHANISMS INFLUENCING THE ONSET OR PERSISTENCE OF PS SYMPTOMS IN ADOLESCENCE ARE UNCLEAR. SLEEP IS ALTERED IN YOUTH AT CLINICAL HIGH RISK FOR PSYCHOSIS (CHR) COMPARED TO CONTROLS, AND SLEEP PROBLEMS MAY PREDICT THE TRANSITION TO FULL-THRESHOLD PSYCHOSIS AND PERSIST IN FIRST EPISODE PSYCHOSIS (FEP). STUDIES OF SLEEP AND PS SYMPTOMS IN YOUTH SUFFER FROM THREE MAIN GAPS. FIRST, EXTANT STUDIES ARE OVERLY CORRELATIONAL, WITH FEW STUDIES USING DENSE SAMPLING ACROSS DAYS TO UNDERSTAND TEMPORAL FLUCTUATIONS BETWEEN PS SYMPTOMS AND SLEEP IN YOUTH. SECOND, NONSPECIFIC BEHAVIORAL INDICES OF SLEEP (FROM SELF-REPORT AND ACTIGRAPHY) MAY REVEAL THE CLINICAL PRESENTATION OF SLEEP DEFICITS BUT NOT THE ROOT MECHANISTIC CAUSE OF THESE DIFFICULTIES. FINALLY, STUDIES OF SLEEP IN THIS POPULATION HAVE OMITTED MEASUREMENT OF IMPORTANT CO-OCCURRING PROCESSES SUCH AS STRESS, WHICH MAY MEDIATE OR MODERATE THE SLEEP-PSYCHOSIS RELATIONSHIP IN WAYS IMPORTANT FOR TREATMENT DEVELOPMENT. THIS STUDY SEEKS TO ADDRESS THESE THREE CRITICAL GAPS BY INVESTIGATING DAILY FLUCTUATIONS IN PS SYMPTOMS, SLEEP AT BEHAVIORAL AND NEUROBIOLOGICAL LEVELS, AND PSYCHOLOGICAL STRESS IN ADOLESCENTS WITH PS CONDITIONS (N = 40, AGED 14-17 YEARS). ACROSS A 3-WEEK SAMPLING PERIOD, THIS STUDY WILL MEASURE PS SYMPTOMS (HALLUCINATIONS AND PARANOIA), SUBJECTIVE RATINGS OF STRESS, AND OBJECTIVELY MEASURED SLEEP CHARACTERISTICS, INCLUDING BEHAVIORAL (ACTIGRAPHY-ESTIMATED SLEEP DURATION, FRAGMENTATION, EFFICIENCY, TIMING, RHYTHMICITY, AND REGULARITY) AND BIOLOGICAL (SIMULTANEOUS PSG/EEG-INDEXED SLEEP SPINDLE DENSITY, AMPLITUDE, DURATION) MARKERS. PARTICIPANTS WILL FIRST COMPLETE A BASELINE INTERVIEW TO ASSESS ELIGIBILITY, PS SYMPTOMS, SLEEP, AND STRESS. FOR THE SUBSEQUENT 21 DAYS, ADOLESCENTS WILL (1) WEAR A PATCH-BASED ACTIGRAPHY MONITOR TO ASSESS SLEEP AND 24H REST-ACTIVITY RHYTHMS; (2) COMPLETE TWICE-DAILY DIGITAL DIARIES PROBING SLEEP, STRESS, AS WELL AS PS SYMPTOM TYPE (E.G., HALLUCINATIONS AND PARANOID THOUGHTS), SEVERITY, IMPAIRMENT, AND TIMING; AND (3) WEAR PSG AND WEARABLE EEG FOR 2 CONSECUTIVE NIGHTS TO INDEX SLEEP SPINDLES. THIS MEASUREMENT SUPPORTS 2 SPECIFIC AIMS: 1) EXAMINE HOW SUBJECTIVE RATINGS OF PS SYMPTOMS AND STRESS FLUCTUATE WITH RESPECT TO SLEEP ON A DAILY BASIS, AND 2) EXAMINE THE FEASIBILITY OF COLLECTING AT-HOME EEG DATA FROM ADOLESCENTS WITH EARLY PHASE PSYCHOSIS AND ESTABLISH EARLY LINKS AMONG SPINDLES, PS SYMPTOMS, AND STRESS. THIS STUDY ALIGNS WITH NIMH OBJECTIVES TO 1) DEFINE BRAIN MECHANISMS UNDERLYING COMPLEX BEHAVIOR BY CHARACTERIZING SLEEP SPINDLES IN EARLY PSYCHOSIS, AND 2) EXAMINE MENTAL ILLNESS TRAJECTORIES ACROSS THE LIFESPAN BY EXPLORING THESE MECHANISMS IN AN UNDERSTUDIED ADOLESCENT POPULATION. IF SUCCESSFUL, THIS WILL BE THE FIRST STUDY TO EMPLOY DEEP PHENOTYPING OF SLEEP IN ADOLESCENTS WITH EARLY PHASE PSYCHOSIS.

OVARIAN STEROID EFFECTS ON MOOD AND SLEEP ACROSS THE ADOLESCENT MENSTRUAL CYCLE - PROJECT SUMMARY/ABSTRACT AFTER MENARCHE, FEMALES ARE TWICE AS LIKELY TO DEVELOP DEPRESSION AND SLEEP PROBLEMS THAN MALES. OVARIAN STEROIDS HAVE BEEN HYPOTHESIZED TO PLAY A ROLE, BUT PRIOR WORK HAS FAILED TO CLARIFY THE EFFECT OF OVARIAN STEROIDS ON MOOD AND SLEEP PROBLEMS. HORMONE SENSITIVITY (NEURAL VULNERABILITY TO NORMAL FLUCTUATIONS IN HORMONES ACROSS THE MENSTRUAL CYCLE) IS A PROMISING CANDIDATE, PARTICULARLY SENSITIVITY TO ESTROGEN WITHDRAWAL (E2), BUT LITTLE IS KNOWN ABOUT HORMONE SENSITIVITY IN ADOLESCENTS. THIS WORK IS HINDERED BY TRADITIONAL STATISTICAL APPROACHES (MULTILEVEL MODELING (MLM) WITH PHASE CONTRASTS), AS THEY RELY ON THE ASSUMPTION OF A REGULAR, OVULATORY CYCLE, WHICH ADOLESCENTS OFTEN DO NOT HAVE. THE PROPOSED STUDY WILL CHARACTERIZE HORMONE SENSITIVITY IN ADOLESCENTS BY COLLECTING DAILY ASSESSMENTS OF MOOD RATINGS, SLEEP (VIA SELF-REPORT AND ACTIGRAPHY), AND OVARIAN STEROID HORMONES (VIA DRIED URINE STRIPS) FROM 50 FEMALE ADOLESCENTS, AGED 11-14, AT LEAST ONE-YEAR POST-MENARCHE, WITH REGULAR CYCLES (21-45 DAYS) AND ELEVATED DEPRESSIVE SYMPTOMS. FOR ADOLESCENTS WITH OVULATORY CYCLES, MULTILEVEL MODELS (MLM) WITH PHASE CONTRASTS WILL BE USED TO EVALUATE MENSTRUAL CYCLE EFFECTS ON SYMPTOMS AND SLEEP, AND THE CAROLINA PREMENSTRUAL ASSESSMENT SCORING SYSTEM (C-PASS) WILL BE USED TO IDENTIFY CLINICALLY SIGNIFICANT PREMENSTRUAL EXACERBATION OF SYMPTOMS (AIM 1). I HYPOTHESIZE THAT DEPRESSIVE SYMPTOMS AND SLEEP PROBLEMS WILL BE HIGHER IN THE PERIMENSTRUAL PHASE OF THE CYCLE COMPARED TO ALL OTHER PHASES. ACROSS THE FULL SAMPLE, LONGITUDINAL NETWORK MODELS WILL BE USED TO ADDRESS LIMITATIONS OF MULTILEVEL MODELING; NETWORKS OF ASSOCIATIONS BETWEEN E2, MOOD SYMPTOMS, AND SLEEP PROBLEMS ACROSS THE CYCLE WILL BE ESTIMATED (AIM 2), WITH THE HYPOTHESIS THAT DECREASES IN E2 WILL BE ASSOCIATED WITH SUBSEQUENT INCREASES IN SLEEP PROBLEMS FOLLOWED BY INCREASES IN MOOD SYMPTOMS. EXPLORATORY ANALYSES ESTIMATE THE INDIRECT EFFECT OF E2 ON MOOD SYMPTOMS VIA SLEEP PROBLEMS (AIM 3). THIS KNOWLEDGE COULD FACILITATE EARLIER IDENTIFICATION AND PREVENTION EFFORTS AND LAY THE GROUNDWORK FOR FUTURE RESEARCH ON THE DEVELOPMENTAL CONTRIBUTION OF HORMONE SENSITIVITY TO SEX DIFFERENCES IN DEPRESSION AND SLEEP PROBLEMS. THE TRAINING PLAN CLOSELY MATCHES THE PROPOSED RESEARCH AND LONG-TERM GOALS WITH AN EMPHASIS ON ACTIVITIES THAT WILL FACILITATE THE CANDIDATE’S DEVELOPMENT AS AN INDEPENDENT INVESTIGATOR. SPECIFICALLY, THE TRAINING GOALS ARE TO (1) GAIN IMMERSIVE TRAINING IN RESEARCH ON THE MENSTRUAL CYCLE AND HORMONE SENSITIVITY WITH ADOLESCENTS, (2) DEVELOP COMPETENCE IN THE ASSESSMENT OF SLEEP VIA ACTIGRAPHY AND SELF-REPORT IN ADOLESCENTS, AND (3) GAIN PROFICIENCY IN IDIOGRAPHIC LONGITUDINAL METHODS FOR USE WITH MENSTRUAL CYCLE DATA. A MENTORSHIP TEAM WITH EXPERTISE ACROSS THESE AREAS HAS BEEN ASSEMBLED, AND BROWN UNIVERSITY IS A WORLD-RENOWNED CLINICAL RESEARCH INSTITUTION WITH AN EXTENSIVE HISTORY OF NIH FUNDING AND SUPPORTING CAREER DEVELOPMENT AWARDS. OVERALL, THE BROAD AIM OF THESE RESEARCH AND TRAINING GOALS IS TO SUPPORT THE CANDIDATE’S DEVELOPMENT OF AN INDEPENDENT RESEARCH PROGRAM EXAMINING THE BIOLOGICAL MECHANISMS OF THE SEX DIFFERENCES IN DEPRESSION AND SLEEP PROBLEMS THAT EMERGE AFTER PUBERTY.

MODULATING IMPULSIVITY IN SUICIDAL ADOLESCENTS WITH TDCS: A PROOF CONCEPT STUDY

MITOCHONDRIAL SIGNALING, STRESS, AND SLEEP IN CHILDREN WITH INTERNALIZING DISORDERS - PROJECT SUMMARY PSYCHOSOCIAL STRESS IN CHILDHOOD IS A PROMINENT RISK FACTOR IN THE DEVELOPMENT, SEVERITY, AND OUTCOMES OF INTERNALIZING DISORDERS. STRESS MAY IMPACT PEDIATRIC MENTAL HEALTH BY DISRUPTING HOMEOSTATIC PATHWAYS, SUCH AS SLEEP AND ENERGY METABOLISM THAT CAN BE INDEXED USING MITOCHONDRIAL BIOMARKERS. MITOCHONDRIA, WITH BROAD ROLES IN CELLULAR ENERGY AND METABOLIC HOMEOSTASIS, MAY CONTRIBUTE TO STRESS-ASSOCIATED PHYSIOLOGICAL WEAR AND TEAR AND SERVE AS A TARGET FOR INTERVENTION IN CHILDREN WITH INTERNALIZING DISORDERS. MITOCHONDRIAL DNA (MTDNA) CONTAINS UNIQUE INFLAMMATORY AND CELL-SIGNALING PROPERTIES AND IS ACTIVELY RELEASED AS CELL-FREE MTDNA (CF- MTDNA) IN RESPONSE TO PSYCHOSOCIAL STRESSORS, PROMOTING INFLAMMATION AND OXIDATIVE DAMAGE. LEVELS OF CF- MTDNA APPEAR TO FLUCTUATE ACROSS DAYS AND THROUGHOUT THE DAY AND MAY HAVE A CIRCADIAN RHYTHM. IMPORTANTLY, PERVASIVE DISTURBANCES IN SLEEP ARE OBSERVED IN BOTH SEVERE STRESS AND MENTAL HEALTH DISORDERS AND SLEEP IMPAIRMENT INTERFERES WITH MITOCHONDRIAL MAINTENANCE. RECENT PRECLINICAL WORK INDICATES THAT SLEEP IS REQUIRED FOR HOMEOSTATIC OXIDATIVE RECOVERY OF MITOCHONDRIA AND EMERGING CLINICAL RESEARCH DEMONSTRATES THAT CIRCADIAN DISRUPTION IS ASSOCIATED WITH DYSREGULATION OF CF-MTDNA. TAKEN TOGETHER, THIS WORK SUGGESTS THAT STRESS- INDUCED CHANGES IN MITOCHONDRIAL SIGNALING MAY CONTRIBUTE TO PHYSIOLOGICAL DYSFUNCTION AND SYMPTOMS, POTENTIALLY DUE IN PART TO STRESS EFFECTS ON SLEEP. QUANTIFICATION OF CF-MTDNA IS NOW ACCESSIBLE THROUGH SALIVA AND MAY HOLD PROMISE AS A ROBUST BIOMARKER OF THE DYNAMIC EFFECTS OF STRESS AND BEHAVIOR ON PSYCHIATRIC SYMPTOMS. THE PROPOSED STUDY WILL RECRUIT N=60 CHILDREN AGES 9-12 WITH INTERNALIZING DISORDERS FROM A DAY HOSPITAL PROGRAM. AT THE TIME OF ADMISSION, CHILDREN AND CAREGIVERS WILL EACH PROVIDE BASELINE ASSESSMENTS OF CUMULATIVE STRESS HISTORY, SLEEP DISTURBANCES AND BEHAVIORAL HEALTH SYMPTOMS OVER THE PAST MONTH, AND ASSESSMENT OF A RANGE OF INTERNALIZING AND EXTERNALIZING SYMPTOMS. FOLLOWING RECRUITMENT, CHILDREN AND CAREGIVERS WILL PROVIDE DAILY DIARY ASSESSMENTS OF STRESS EXPOSURE, SLEEP, AND SYMPTOMS, AND SALIVARY SAMPLES ASSESSED FOR CF-MTDNA ACROSS TWO WEEKS. THIS STUDY WILL 1) CHARACTERIZE BASELINE CROSS-SECTIONAL ASSOCIATIONS OF LEVELS OF CF-MTDNA WITH CUMULATIVE EARLY LIFE STRESS, BASELINE SLEEP DISTURBANCES, AND BASELINE INTERNALIZING SYMPTOM SEVERITY AND 2) EXAMINE DAILY FLUCTUATIONS OF CF-MTDNA IN ASSOCIATION WITH DAILY STRESSORS (TYPE, SEVERITY, AND TIMING), SLEEP (DURATION, TIMING, REGULARITY AND QUALITY), AND MENTAL HEALTH SYMPTOMS. BY INVESTIGATING STRESS-ASSOCIATED MITOCHONDRIAL PROCESSES AND SLEEP IN CHILDREN WITH PSYCHOPATHOLOGY, THIS STUDY WILL YIELD CLINICALLY RELEVANT INFORMATION, CONSISTENT WITH NIMH STRATEGIC PLAN STRATEGY 2.2, TO IDENTIFY MECHANISMS OF RISK TO GUIDE THE DEVELOPMENT OF NOVEL TREATMENT TARGETS FOR CHILDREN WITH ACUTE PSYCHIATRIC PATHOLOGY. FURTHER, DATA FROM THIS STUDY WILL BE USED TO INFORM AN R01 APPLICATION INVESTIGATING CF-MTDNA AND ADDITIONAL MITOCHONDRIAL INDICES AND INFLAMMATORY TARGETS IN A LARGER, MORE DEFINITIVE STUDY OF CHILDREN WITH INTERNALIZING DISORDERS.

IMPLEMENTATION AND PILOT TESTING OF A CULTURALLY CENTERED CBT PROTOCOL FOR SUICIDAL BEHAVIORS AMONG YOUTH IN MEXICO CITY - PROJECT SUMMARY/ABSTRACT THE RISKS OF IDEATING, SUICIDE ATTEMPT (SA), AND DYING BY SUICIDE HAVE NEVER BEEN GREATER FOR MEXICAN TEENS. IN THE PAST TWO DECADES, THE RATES OF SUICIDAL BEHAVIORS (SB) AMONG MEXICAN YOUTH HAVE SHOWN A 3.4- FOLD INCREASE. TODAY, 2.8% OF MEXICAN TEENS AGES 15 TO 19 REPORT SA (3.8% FEMALES, 0.3% BOYS). EVEN THOUGH REPORTED SA ARE LOWER IN MEXICAN YOUTH COMPARED TO THEIR U.S. COUNTERPARTS, THIS HAS BECOME A CRITICAL ISSUE GIVEN ITS INCREASE IN MEXICO, THE LACK OF EVIDENCE BASED PRACTICES (EBP), AND ITS FUTURE CLINICAL IMPLICATIONS. SB HAVE SOBERING IMPLICATIONS FOR THE FUTURE WELL-BEING OF MEXICAN YOUTH, AS THEY ARE ASSOCIATED WITH A MYRIAD OF SHORT- AND LONG-TERM NEGATIVE OUTCOMES, INCLUDING PREMATURE DEATH. SUICIDAL YOUTH IN MEXICO, 50% OF THEM WHO ARE OR WERE IN CONTACT WITH PROVIDERS, DO NOT HAVE ACCESS TO THE QUALITY TREATMENTS DEVELOPED IN AND AVAILABLE TO THEIR COUNTERPARTS IN HIGH-INCOME NATIONS. THIS ACCESS DISPARITY IS NOT UNIQUE TO MEXICO; MOST SUICIDAL YOUTH IN OTHER MIDDLE AND LOW-INCOME NATIONS (LMIC) ARE NOT TREATED WITH QUALITY INTERVENTIONS AVAILABLE IN RICH NATIONS. MOREOVER, YOUTH IN LMIC HAVE HIGH RATES OF SB AND 75% OF ALL SUICIDES OCCUR IN THESE NATIONS. THIS IS A MENTAL HEALTH CARE INJUSTICE THAT DEMANDS URGENT RESOLUTION. THIS NIMH R34 AWARD APPLICATION PROPOSES TO CONDUCT AN ADAPTATION, IMPLEMENTATION, AND PILOT TESTING OF THE CULTURALLY CENTERED CBT PROTOCOL, THE SOCIO-COGNITIVE BEHAVIORAL THERAPY FOR SUICIDAL BEHAVIORS (SCBT- SB), AMONG SUICIDAL YOUTH IN MEXICO CITY, MEXICO. SCBT-SB IS A PSYCHOSOCIAL TREATMENT DEVELOPED WITH THE SUPPORT OF THE NIMH SPECIFICALLY FOR SUICIDAL LATINX YOUTH. SCBT-SB IS AVAILABLE IN SPANISH, HAS AN ESTABLISHED TRAINING MODEL, AND HAS YIELDED PROMISING RESULTS IN INTENT TO TREAT ANALYSES IN REDUCING SA AND DEPRESSIVE SYMPTOMS IN COMPARISON TO TREATMENT AS USUAL (TAU). FURTHERMORE, IT IS THE CBT PROTOCOL WITH THE MOST EMPIRICAL EVIDENCE FOR LATINX YOUTH WITH SB. SCBT IS ATTUNED TO THE CULTURAL NEEDS OF LATINX SUICIDAL YOUTH IN REAL-WORLD SERVICE SETTINGS. THIS WILL BE THE FIRST TIME THAT SCBT-SB, AND FOR THAT MATTER, ANY SUICIDAL IDEATION AND BEHAVIORS EVIDENCE-BASED TREATMENT, WILL BE USED IN MEXICO TO TREAT SUICIDAL YOUTH IN CONTACT WITH MENTAL HEALTH SERVICES IN THE PUBLIC HEALTH SECTOR. BY IMPLEMENTING AND PILOT TESTING SCBT-SB WITH SUICIDAL MEXICAN YOUTH, THIS PROJECT ADDRESSES PROFOUND GAPS IN SERVICES FOR THIS POPULATION AND OF TRAINING FOR CLINICIANS. THE RESEARCH PLAN WILL (A) CULTURALLY ADAPT AND CONTEXTUALIZE THE SCBT-SB FOR ITS IMPLEMENTATION IN THE MEXICAN PUBLIC HEALTH SYSTEM, (B) PILOT TEST THE PROTOCOL THROUGH AN RCT (SCBT-SB VS TAU; 60 PATIENTS AND CAREGIVERS) AND (C) EVALUATE THE IMPLEMENTATION PROCESS OF THE SCBT-SB AND ASSESS QUALITATIVELY POSSIBLE FACTORS THAT MAY PROMOTE OR HINDER ITS FUTURE UPTAKE. THE SHORT AND LONG-TERM KNOWLEDGE AND RESEARCH IMPLICATIONS INCLUDE (A) ITS POTENTIAL TO IMPROVE THE LIVES OF SUICIDAL MEXICAN YOUTH; (B) THE KNOWLEDGE ABOUT TRANSNATIONAL IMPLEMENTATION OF EBTS IN THE MEXICAN PUBLIC HEALTH SECTOR; AND (C) THE UNDERSTANDING OF THE IMPLEMENTATION AND TREATMENT EFFECT OF SCBT-SB IN MEXICO.

ASSESSING PARENTING AT THE MOMENTARY LEVEL TO UNDERSTAND PARENTING BEHAVIORS THAT CONTRIBUTE TO IMPROVED TREATMENT OUTCOMES FOR YOUTH WITH CO-OCCURRING DISORDERS - PROJECT SUMMARY/ABSTRACT. OVER 80% OF ADOLESCENTS WITH AN ALCOHOL USE DISORDER (AUD) WHO PRESENT TO TREATMENT HAVE A CO-OCCURRING PSYCHIATRIC DIAGNOSIS. ALTHOUGH THE BEST AVAILABLE TREATMENTS FOR ADOLESCENTS WITH ALCOHOL USE DISORDERS AND CO-OCCURRING DISORDERS (AUD+CODS) YIELD ONLY MODEST SHORT-TERM BENEFITS, PARENT-INVOLVED TREATMENTS RESULT IN THE BEST OUTCOMES. IN LINE WITH NIAAA’S STRATEGIC PLAN TO IMPROVE TREATMENTS FOR AUD+CODS, THIS APPLICATION SEEKS TO ADDRESS A CENTRAL, YET UNANSWERED QUESTION – WHAT PARENTING BEHAVIORS DURING PARENT-INVOLVED TREATMENT FOR AUD+CODS CONTRIBUTE TO IMPROVED OUTCOMES? PARENTING IS DYNAMIC AND VARIES FROM MOMENT TO MOMENT DEPENDING ON CONTEXT, AFFECT, AND ADOLESCENT BEHAVIOR. MOREOVER, TREATMENT MOTIVATION, ALCOHOL CRAVING, ALCOHOL AND CANNABIS USE, AND INTERNALIZING AND EXTERNALIZING SYMPTOMS — CORE ADOLESCENT AUD+CODS TREATMENT TARGETS — VARY CONSIDERABLY WITHIN AND ACROSS DAYS. UNDERSTANDING THE PARENTING BEHAVIORS DURING TREATMENT THAT ACCOUNT FOR IMPROVED TREATMENT OUTCOMES REQUIRES MOMENTARY ASSESSMENTS THAT CAN CAPTURE THE DYNAMIC NATURE OF PARENTING AND CORE ADOLESCENT TREATMENT TARGETS. THIS K99/R00 STUDY INTENDS TO LEVERAGE AN EXPERIMENTAL MEDICINE FRAMEWORK TO STUDY HOW PARENTING, CAPTURED IN REAL TIME IN DAILY LIFE, IMPACTS CORE TREATMENT TARGETS (TREATMENT MOTIVATION, ALCOHOL CRAVING, ALCOHOL, AND CANNABIS USE, AND INTERNALIZING AND EXTERNALIZING SYMPTOMS) AMONG ADOLESCENTS ENROLLED IN AN INTENSIVE OUTPATIENT FOR AUD+CODS. THE SPECIFIC AIMS FOR THE K99 ARE TO ADAPT PARENTAL COMMUNICATION, GENERAL PARENTING PRACTICES, AND ALCOHOL-SPECIFIC PARENTING MEASURES TO EMA (AIM 1), CONDUCT A PILOT FEASIBILITY AND ACCEPTABILITY STUDY OF THE EMA PROTOCOL (N=20 PARENT-ADOLESCENT DYADS; AIM 2A), AND USE MIXED METHODS TO EVALUATE AND REFINE THE EMA PARENTING MEASURES AND PROTOCOL (AIM 2B). DR. SAMUEL MEISEL’S OVERARCHING TRAINING GOALS ARE TO (1) REFINE SKILLS IN INDEPENDENTLY DESIGNING, DEVELOPING, AND EXECUTING EMA RESEARCH (DRS. ROBERT MIRANDA AND ELIZABETH MCQUAID), (2) SOLIDIFY EXPERTISE IN CONDUCTING TREATMENT RESEARCH WITH ADOLESCENTS WITH AUD+CODS (DRS. AARON HOGUE AND ROBERT MIRANDA), (3) APPLY EXPERIMENTAL MEDICINE METHODS TO ADOLESCENT AUD+COD TREATMENT MECHANISMS RESEARCH (DR. JOHN KELLY), AND (4) PROMOTE A SUCCESSFUL TRANSITION TO INDEPENDENT FACULTY RESEARCHER. THESE TRAINING OBJECTIVES BUILD ON DR. MEISEL’S F32 (AA028414), WHICH PROVIDED HIM WITH THE FOUNDATIONAL TRAINING TO BROADEN HIS RESEARCH FROM STUDYING THE INITIATION AND ESCALATION OF ADOLESCENT ALCOHOL USE TO ADOLESCENT ALCOHOL USE TREATMENT AND MECHANISMS OF BEHAVIOR CHANGE. R00 SPECIFIC AIMS INCLUDE EXAMINING MOMENTARY PARENTING-CORE TREATMENT TARGET ASSOCIATIONS (N=75 PARENT-ADOLESCENT DYADS; AIM 3A) AND EXAMINING CHANGES IN THE STRENGTH OF PARENTING-TREATMENT TARGET ASSOCIATIONS OVER THE COURSE OF AUD+COD TREATMENT (AIM 3B). FINDINGS WILL SYSTEMATICALLY IDENTIFY THE SPECIFIC PARENTING PRACTICES DURING AUD+CODS TREATMENT THAT MOST STRONGLY RELATE TO CORE TREATMENT TARGETS AND WILL SERVE AS PRELIMINARY DATA FOR FUTURE R01 AND R34 APPLICATIONS.

REVERSAL LEARNING IN PEDIATRIC BIPOLAR DISORDER

CHILDREN'S HOSPITALS GRADUATE MEDICAL EDUCATION PAYMENT PROGRAM

CHILDREN'S HOSPITALS GRADUATE MEDICAL EDUCATION PAYMENT PROGRAM

CHILDREN'S HOSPITALS GRADUATE MEDICAL EDUCATION PAYMENT PROGRAM

USING EMA TO EXAMINE MINORITY STRESS MECHANISMS UNDERLYING CANNABIS USE AMONG SEXUAL MINORITIES - PROJECT SUMMARY/ABSTRACT DESPITE OFTEN BEING USED LEGALLY, CANNABIS USE IS ASSOCIATED WITH SEVERAL HARMFUL OUTCOMES (E.G., MENTAL HEALTH PROBLEMS). MOREOVER, CANNABIS USE IS DISPROPORTIONATELY HIGHER AMONG SEXUAL MINORITIES (SM) RELATIVE TO THEIR HETEROSEXUAL COUNTERPARTS. SM WHO USE CANNABIS ARE ALSO MORE LIKELY TO DEVELOP CANNABIS USE DISORDER (CUD) COMPARED TO HETEROSEXUALS. OUR UNDERSTANDING OF MECHANISMS THAT EXPLAIN DISPARITIES IN SM CANNABIS USE OUTCOMES IS NASCENT. IN LINE WITH NIDA’S FUNDING PRIORITIES TO IDENTIFY MECHANISMS UNDERLYING DIFFERENCES IN SM DRUG USE OUTCOMES, THIS K99/R00 APPLICATION AIMS TO EVALUATE MEDIATORS OF ASSOCIATIONS BETWEEN MINORITY STRESSORS, CANNABIS USE, AND USE-RELATED NEGATIVE OUTCOMES AMONG YOUNG ADULT SM. THE MINORITY STRESS PSYCHOLOGICAL MEDIATION FRAMEWORK POSITS THAT MINORITY STRESSORS RESULT IN SUBSTANCE USE OUTCOMES THROUGH IMPAIRED COPING, INTERPERSONAL, AND COGNITIVE PROCESSES. THIS MODEL HAS SUPPORT FOR SM ALCOHOL USE; HOWEVER, ONLY EIGHT STUDIES HAVE TESTED PUTATIVE MECHANISMS EXPLAINING HOW MINORITY STRESSORS RELATE TO CANNABIS USE. AMONG THESE STUDIES, MANY ARE CROSS-SECTIONAL AND MOST SOLELY TEST COPING MOTIVES MEDIATION. LONGITUDINAL RESEARCH EXAMINING HOW MINORITY STRESSORS AND THESE MECHANISMS RELATE TO USE AND NEGATIVE OUTCOMES (E.G., CUD) IS NECESSARY TO ADDRESS THESE RESEARCH GAPS AND ADVANCE UNDERSTANDING OF SM HEALTH. MOREOVER, IDENTIFYING HOW DAILY EXPERIENCES RELATE TO USE WILL PROVIDE TARGETS FOR PREVENTION AND INTERVENTION DEVELOPMENT, PARTICULARLY WHEN CERTAIN EXPERIENCES (E.G., STIGMA) MAY BE UNAVOIDABLE. THIS K99/R00 STUDY LEVERAGES ECOLOGICAL MOMENTARY ASSESSMENT (EMA) TO CAPTURE REAL-TIME MEASURES IN DAILY LIFE OF STRESSORS, CANNABIS USE, AND RELATED OUTCOMES. FOUNDATIONAL WORK DURING THE K99 PHASE WILL COLLECT DATA TO INFORM EMA ITEM DEVELOPMENT (AIM 1), THEN CONDUCT AN EMA FEASIBILITY AND ACCEPTABILITY STUDY (AIM 2). DR. PARNES’ TRAINING GOALS INCLUDE (1) REFINE SKILLS TO INDEPENDENTLY DESIGN, DEVELOP, EXECUTE, AND ANALYZE EMA RESEARCH, (2) BUILD EXPERTISE IN CONDUCTING SUBSTANCE USE RESEARCH WITH SM POPULATIONS, (3) CONTINUE TRAINING IN ADVANCED STATISTICAL MODELING OF EMA DATA, AND (4) PROMOTE A SUCCESSFUL TRANSITION FROM POSTDOCTORAL FELLOW TO INDEPENDENT FACULTY RESEARCHER. DR. PARNES’ MENTORSHIP TEAM, DRS. MIRANDA, MEREISH, AND TRELOAR PADOVANO, ARE EXPERTS IN EMA, SEXUAL MINORITY RESEARCH, AND ADVANCED STATISTICAL ANALYSIS. THESE TRAINING GOALS BUILD ON DR. PARNES’ F32 (DA054718), WHICH PROVIDED FOUNDATIONAL TRAINING IN IDENTIFYING MECHANISMS OF BEHAVIOR CHANGE IN ADOLESCENT CANNABIS TREATMENT. USING THE PROTOCOL FINALIZED THROUGH THE K00, THE R00 STUDY WILL CONDUCT A 30-DAY EMA STUDY AMONG SM WHO USE CANNABIS TO TEST PUTATIVE MECHANISMS RELATING DAILY MINORITY STRESSORS TO USE-RELATED NEGATIVE OUTCOMES (AIM 3). FINDINGS FROM THE PROPOSED STUDY WILL INFORM WHETHER AND HOW SM MINORITY STRESSORS RELATE TO HARMFUL USE-RELATED OUTCOMES. EVALUATING MECHANISMS CAN ALSO BE USED TO IDENTIFY INTERVENTION TARGETS TO COMPLEMENT OR REPLACE CANNABIS USE, THUS REDUCING LIABILITY FOR CUD OR OTHER NEGATIVE OUTCOMES, AND REDUCING KNOWN HEALTH DISPARITIES IN THIS POPULATION.

CHILDREN'S HOSPITALS GRADUATE MEDICAL EDUCATION PAYMENT PROGRAM

EXAMINATION OF EMOTION REGULATION STRATEGY USE IN AN OUTPATIENT TREATMENT PROGRAM FOR ADOLESCENTS WITH CO-OCCURRING DISORDERS - PROJECT SUMMARY/ABSTRACT MOST ADOLESCENTS (61-88%) WHO PRESENT TO TREATMENT WITH ALCOHOL USE DISORDER (AUD) HAVE A CO-OCCURRING PSYCHIATRIC DIAGNOSIS. YOUTH WITH AUD AND A CO-OCCURRING DIAGNOSIS EXHIBIT POORER GENERAL FUNCTIONING AND WORSE TREATMENT OUTCOMES COMPARED TO THOSE WITH AUD ALONE. UNFORTUNATELY, TREATMENTS FOR ADOLESCENT AUD LAG BEHIND THOSE FOR ADULTS AND SHOW SMALL EFFECT SIZES. TO IMPROVE INTERVENTIONS FOR THIS POPULATION, THERE IS A NEED TO UNDERSTAND HOW AND WHY ADOLESCENT AUD TREATMENTS WORK AND TO IDENTIFY TRANSDIAGNOSTIC TREATMENT MECHANISMS THAT CAN TARGET SYMPTOMS OF MULTIPLE DISORDERS SIMULTANEOUSLY. EMOTION REGULATION SKILL USE IS ONE SUCH MECHANISM. THIS PROPOSAL LEVERAGES ECOLOGICAL MOMENTARY ASSESSMENT (EMA) TO STUDY THE CHANGE IN EMOTION REGULATION SKILL USE WITHIN A TREATMENT CONTEXT AS WELL AS EXAMINE ITS INFLUENCE ON RELEVANT AUD AND CO-OCCURRING DISORDER TREATMENT OUTCOMES. THE PROPOSED RESEARCH WILL EXAMINE THESE PROCESSES WITHIN A COMMUNITY SAMPLE OF ADOLESCENTS (AGED 13-18) UNDERGOING AN INTENSIVE OUTPATIENT PROGRAM FOR AUD AND CO- OCCURRING DISORDERS. GIVEN THE COST AND LABOR-INTENSIVE RESOURCES REQUIRED FOR EMA RESEARCH AND THE LITTLE WORK USING EMA WITH THIS POPULATION, THE K99 PROJECT WILL CONSIST OF A PILOT STUDY TO TEST THE FEASIBILITY AND ACCEPTABILITY OF THE EMA PROTOCOL, WILL IDENTIFY BARRIERS TO COMPLIANCE, AND WILL REFINE THE PROTOCOL. (AIMS 1A-1C). THE R00 PROJECT (N = 80 ADOLESCENTS) WILL CONSIST OF A 10-WEEK STUDY DURING WHICH PARTICIPANTS WILL COMPLETE TWO 3-WEEK BURSTS OF EMA REPORTS. AIMS OF THE R00 PROJECT ARE TO EXAMINE PROSPECTIVE MOMENTARY ASSOCIATIONS BETWEEN EMOTION REGULATION SKILL USE AND MOMENTARY TREATMENT OUTCOMES (AIM 2), TO CHARACTERIZE THE EXTENT OF CHANGE IN EMOTION REGULATION SKILL USE ACROSS TREATMENT (AIM 3A) AND EXAMINE WHETHER CHANGES IN EMOTION REGULATION SKILL USE COINCIDE WITH CHANGES IN TREATMENT OUTCOMES ACROSS TREATMENT (AIM 3B). FINDINGS WILL SERVE AS PILOT DATA TO A LARGER NIAAA R01 GRANT SUBMISSION IN THIS AREA OF WORK. IMPORTANTLY, THIS K99/R00 APPLICATION WILL SERVE AS FOUNDATIONAL TRAINING FOR DR. JENZER'S DEVELOPMENT AS AN INDEPENDENT SCIENTIST. MENTORS (DRS. MIRANDA, MAGILL, WEISS, LITT) ARE COMMITTED TO THE CANDIDATE'S TRAINING AND EACH WILL PROVIDE UNIQUE EXPERTISE TO THE RESEARCH AND TRAINING PLAN.

DEVELOPMENT AND IMPLEMENTATION OF A DIGITAL SLEEP INTERVENTION FOR PRESCHOOLERS IN FOSTER CARE - PROJECT SUMMARY CHILDREN IN FOSTER CARE (FC) ARE AT RISK FOR CHRONIC HEALTH CONDITIONS, IN PART DUE TO EXPOSURE TO ADVERSE CHILDHOOD EXPERIENCES (ACES). EARLY INTERVENTION MAY AMELIORATE HEALTH DISPARITIES AND ECONOMIC BURDEN ASSOCIATED WITH ACES, WITH THE PRESCHOOL PERIOD YIELDING A SUBSTANTIALLY LARGER RETURN ON INVESTMENT COMPARED TO INTERVENTIONS LATER IN DEVELOPMENT. CHILDREN IN FC ARE AT HIGH RISK FOR SLEEP DISTURBANCES, WHICH ARE A MAJOR CONTRIBUTOR TO THE DEVELOPMENT AND EXACERBATION OF CHRONIC HEALTH CONDITIONS, YET BEHAVIORAL SLEEP INTERVENTIONS FOR THIS POPULATION ARE NONEXISTENT. THIS K01 PROPOSAL SEEKS TO ADDRESS THIS CRITICAL GAP IN CARE AND PROMOTE HEALTH EQUITY IN THIS UNDERSERVED POPULATION BY DEVELOPING AND IMPLEMENTING A TRAUMA-INFORMED DIGITAL PUBLIC-HEALTH-LEVEL SLEEP INTERVENTION CALLED SLEEP WIZARD, WHICH WE WILL ADMINISTER TO FOSTER CAREGIVERS OF PRESCHOOLERS. OUR INNOVATIVE APPROACH INVOLVES COLLABORATION WITH A PLANNING GROUP OF KEY STAKEHOLDERS INCLUDING FC WORKERS AND PARENTS, AND EXPERTS IN SLEEP, TRAUMA, HEALTH, AND INTERVENTIONS IN THE CONTEXT OF FC. THE GOAL OF AIM 1 IS TO DEVELOP AND DIGITIZE INITIAL SLEEP WIZARD INTERVENTION CONTENT WITH THE PLANNING GROUP, INFORMED BY THE LITERATURE ON TRAUMA-INFORMED CARE, EVIDENCE-BASED STRATEGIES TO SUPPORT HEALTHY SLEEP, FC LICENSING REGULATIONS, AND FOSTER PARENT NEEDS AND EXPERIENCES. IN AIM 2, SLEEP WIZARD WILL BE PRETESTED BY FOSTER CAREGIVERS WHO WILL PROVIDE QUANTITATIVE AND QUALITATIVE DATA ON ACCEPTABILITY, FEASIBILITY, AND APPROPRIATENESS OF THE INTERVENTION, WHICH WILL BE USED TO MAKE FINAL INTERVENTION MODIFICATIONS. AIM 3 WILL EVALUATE WHETHER SLEEP WIZARD IS ASSOCIATED WITH IMPROVEMENTS IN FOSTER CAREGIVER BEHAVIORS AROUND SLEEP, AND IN CHILD SLEEP FROM PRE TO POST INTERVENTION, AND AT A 3-MONTH FOLLOW-UP. THIS WILL BE THE FIRST LARGE SCALE SLEEP INTERVENTION DEVELOPED AND TESTED IN THIS POPULATION. LOCAL AND NATIONAL STAKEHOLDERS HAVE EXPRESSED ENTHUSIASM AND HAVE COMMITTED TO INVOLVEMENT IN THE DEVELOPMENT, IMPLEMENTATION, AND EVALUATION OF SLEEP WIZARD. TO ACHIEVE THE RESEARCH PLAN, THE PI WILL EXECUTE A STRUCTURED COMPREHENSIVE TRAINING PLAN TO GAIN SPECIALIZED SKILLS IN (1) SLEEP, MENTAL HEALTH, AND ACES IN EARLY CHILDHOOD IN THE CONTEXT OF FOSTER CARE, (2) DEVELOPING PARTNERSHIPS WITH THE CHILD WELFARE COMMUNITY, (3) INTERVENTION DEVELOPMENT AND IMPLEMENTATION SCIENCE, (4) IMPLEMENTATION AND DISSEMINATION OF DIGITAL INTERVENTIONS, AND (5) CONDUCTING CLINICAL TRIALS. TRAINING WILL BE OVERSEEN BY AN OUTSTANDING MENTORSHIP TEAM WITH CROSS-CUTTING EXPERTISE IN THESE AREAS AND A TRACK RECORD OF SUCCESSFUL MENTORSHIP EXPERIENCES AND COLLABORATIONS. IMPLEMENTATION OF THE RESEARCH AND TRAINING PLAN WILL ALSO BE BOLSTERED BY SUPPORT FROM THE INSTITUTIONAL ENVIRONMENT, NAMELY BROWN MEDICAL SCHOOL, BRADLEY HOSPITAL, AND TWO NEW MAJOR CENTER GRANTS FOCUSED ON PROMOTING THE CAREER DEVELOPMENT OF EARLY-STAGE INVESTIGATORS IN 1) CHILDHOOD STRESS, TRAUMA, AND RESILIENCE, AND 2) SLEEP AND CIRCADIAN RHYTHMS IN CHILD AND ADOLESCENT MENTAL HEALTH. THIS AWARD WILL CATAPULT MY TRANSITION TO AN INDEPENDENT TRANSLATIONAL SCIENTIST WITH A CAREER HIGH IN SCIENTIFIC AND PUBLIC HEALTH IMPACT IN EARLY LIFE ADVERSITY, SLEEP, AND HEALTH.

DEVELOPMENTAL NEURAL ALTERATIONS IN YOUTHS AND ADULTS WITH BIPOLAR DISORDER

IDENTIFYING TREATMENT EFFECTS, MECHANISMS, AND MODERATORS IN YOUTH CANNABIS USE TREATMENT USING ECOLOGICAL MOMENTARY ASSESSMENT - PROJECT SUMMARY/ABSTRACT BACKGROUND. ADOLESCENT CANNABIS USE DISORDER (CUD) INTERVENTIONS HAVE DEMONSTRATED MIXED EFFICACY, UNDERSCORING THE NEED FOR IMPROVED TREATMENT. IDENTIFYING TREATMENT MODERATORS (I.E., INDIVIDUAL DIFFERENCES), AS WELL AS THE MECHANISMS LEADING TO BEHAVIOR CHANGE, CAN INCREASE TREATMENT SUCCESS. VIRTUALLY ALL EVIDENCE- BASED PSYCHOSOCIAL INTERVENTIONS LEVERAGE ASPECTS OF SOCIAL LEARNING THEORY (SLT), INCLUDING SOCIAL, BEHAVIORAL, AND COGNITIVE FACTORS. ONE UNDERSTUDIED ASPECT OF SLT IN THE CONTEXT OF TREATMENT IS OUTCOME EXPECTANCIES, WHICH ARE KNOWN TO INFLUENCE CANNABIS USE AND SUBJECTIVE EFFECTS. RESEARCH HAS SUGGESTED THAT OUTCOME EXPECTANCIES CAN SERVE AS MODERATORS AND MEDIATORS OF TREATMENT OUTCOMES; HOWEVER, FINE-GRAINED APPROACHES HAVE YET TO ELUCIDATE THEIR ROLE IN ADOLESCENT CUD INTERVENTIONS. SPECIFIC AIMS. THIS F32 SUPPORTS INTEGRATED RESEARCH AND TRAINING AIMS FOR APPLYING ECOLOGICAL MOMENTARY ASSESSMENT (EMA) TO EXAMINE HOW SLT FACTORS, E.G., OUTCOME EXPECTANCIES, MAY MODERATE ADOLESCENT CUD TREATMENT OUTCOMES AND RELATE TO MECHANISMS OF BEHAVIOR CHANGE. METHODS. THE PROPOSED PROJECT WILL USE AN EXISTING DATASET FROM A CLINICAL TRIAL EXAMINING THE EFFECTS OF PHARMACOTHERAPY (TOPIRAMATE) AND PSYCHOSOCIAL INTERVENTION (MOTIVATIONAL ENHANCEMENT AND COGNITIVE BEHAVIORAL THERAPY), RELATIVE TO PLACEBO AND PSYCHOSOCIAL INTERVENTION (N = 66, AGES 15-24). THE PROPOSED STUDY AIMS TO UNDERSTAND 1) HOW OUTCOME EXPECTANCIES AND CORRESPONDING SUBJECTIVE EFFECTS SHIFT OVER THE COURSE OF TREATMENT, 2) IF TOPIRAMATE INFLUENCES GREATER CHANGES IN SUBJECTIVE EFFECTS AND EXPECTANCIES THROUGHOUT TREATMENT, RELATIVE TO PLACEBO, AND 3) HOW BASELINE EXPECTANCIES MAY MODERATE TOPIRAMATE’S EFFECTS ON SUBJECTIVE EFFECTS AND QUANTITY OF CANNABIS USED. LONG- TERM GOAL. THIS RESEARCH PLAN PROVIDES AN OPPORTUNITY FOR MENTORED TRAINING IN IDENTIFYING MODERATED MECHANISMS OF BEHAVIOR CHANGE FOR YOUTH CUD TREATMENTS AND ADVANCED TRAINING IN CLEANING AND ANALYZING COMPLEX EMA DATA. THE SELECTED MENTORSHIP TEAM INCLUDES EXPERTS IN THE FIELDS OF ADOLESCENT CUD TREATMENT, MECHANISMS OF BEHAVIOR CHANGE RESEARCH, CLINICAL TRIALS RESEARCH, AND EMA DATA COLLECTION AND ANALYSIS. MOREOVER, THE TRAINING ENVIRONMENT INCLUDES AN INTERNATIONALLY RECOGNIZED SUBSTANCE DEPENDENCE RESEARCH CENTER AND A NATIONALLY LEADING CHILD PSYCHIATRIC HOSPITAL. TRAINING GAINED THROUGH THIS F32 WILL PROVIDE NECESSARY EXPERIENCES TO FACILITATE THE TRANSITION TO BECOMING AN INDEPENDENT CLINICAL SCIENTIST. ADDITIONALLY, IT WILL LEVERAGE EMA DATA TO RESEARCH THE INFLUENCE OF SOCIAL, COGNITIVE, AND BEHAVIORAL INDIVIDUAL DIFFERENCES ON ADOLESCENT CUD TREATMENT, THUS SUPPORTING FUTURE GRANT APPLICATIONS. THUS, THIS F32 AIDS IN NIDA’S RESEARCH PRIORITIES OF IDENTIFYING PSYCHOSOCIAL FACTORS IMPLICATED IN SUBSTANCE USE DISORDERS.

THE LONGITUDINAL AND PROXIMAL ROLES OF REJECTION AND REJECTION SENSITIVITY IN SUICIDALITY AND NON-SUICIDAL SELF-INJURY AMONG SEXUAL MINORITY ADOLESCENTS. - PROJECT SUMMARY SUICIDE IS THE SECOND LEADING CAUSE OF DEATH AMONG YOUTH AGES 10-24, CONSTITUTING A MAJOR PUBLIC HEALTH CRISIS. ADOLESCENCE IS ALSO ASSOCIATED WITH THE ONSET OF NON-SUICIDAL SELF-INJURY (NSSI), WHICH OFTEN CO-OCCURS WITH SUICIDAL THOUGHTS AND BEHAVIORS (STBS). IMPORTANTLY, SEXUAL MINORITY (E.G., GAY, LESBIAN, BISEXUAL) ADOLESCENTS ARE AT INCREASED RISK FOR STBS/NSSI COMPARED TO THEIR HETEROSEXUAL PEERS. AS SUCH, THERE IS A CRITICAL NEED TO IDENTIFY RISK FACTORS FOR STBS/NSSI AMONG SEXUAL MINORITY ADOLESCENTS. INTERPERSONAL STRESS, PARTICULARLY REJECTION, CAN HAVE MAJOR CONSEQUENCES FOR MENTAL HEALTH DURING ADOLESCENCE GIVEN THE INCREASED SALIENCE OF INTERPERSONAL RELATIONSHIPS DURING THIS DEVELOPMENTAL PERIOD. DESPITE SUPPORT FOR REJECTION AS A RISK FACTOR FOR STBS/NSSI AMONG ADOLESCENTS, THERE ARE CRITICAL GAPS IN OUR UNDERSTANDING OF THESE ASSOCIATIONS INCLUDING: 1) MOST RESEARCH IN THIS AREA HAS BEEN CROSS-SECTIONAL, LIMITING OUR UNDERSTANDING OF THE EXTENT TO WHICH REJECTION IS ASSOCIATED WITH CHANGES IN STBS/NSSI OVER TIME; 2) IN ADDITION TO EXPERIENCES OF REJECTION, THE EXTENT TO WHICH AN INDIVIDUAL ANTICIPATES AND WORRIES ABOUT FUTURE REJECTION (REJECTION SENSITIVITY [RS]) MAY ALSO CONTRIBUTE TO STBS/NSSI, BUT RESEARCH HAS YET TO EXAMINE RS IN RELATION TO STBS/NSSI; AND 3) SEXUAL MINORITY YOUTH ARE EXPOSED TO UNIQUE FORMS OF INTERPERSONAL STRESS RELATED TO THEIR STIGMATIZED IDENTITIES, INCLUDING BEING REJECTED BY THEIR PEERS AND PARENTS, BUT NO STUDIES TO DATE HAVE EXAMINED IDENTITY-SPECIFIC REJECTION AND RS IN RELATION TO STBS/NSSI AMONG SEXUAL MINORITY ADOLESCENTS. TO ADDRESS THESE LIMITATIONS, THE GOALS OF THE CURRENT STUDY ARE TO EXAMINE SEXUAL MINORITY STATUS AS A MODERATOR OF THE LONGITUDINAL ASSOCIATIONS BETWEEN REJECTION/RS AND STBS/NSSI AMONG ADOLESCENTS, AND TO EXAMINE THE ASSOCIATIONS BETWEEN DAILY EXPERIENCES OF SEXUAL ORIENTATION-RELATED REJECTION/RS AND STBS/NSSI AMONG SEXUAL MINORITY ADOLESCENTS. THESE GOALS WILL BE ACCOMPLISHED BY LEVERAGING DATA FROM TWO NIMH-FUNDED R01S (PI: LIU; CO- SPONSOR). AS PART OF THE PARENT STUDIES, PSYCHIATRICALLY-HOSPITALIZED ADOLESCENTS WILL COMPLETE MEASURES OF REJECTION, RS, STBS, AND NSSI AT BASELINE AND SIX-MONTHS POST-HOSPITALIZATION. THEY WILL ALSO COMPLETE MEASURES OF STBS AND NSSI ON A DAILY BASIS FOR ONE-MONTH BEGINNING UPON DISCHARGE FROM THE HOSPITAL. CONSISTENT WITH NIMHD’S PRIORITIES TO ELUCIDATE INTERPERSONAL AND SOCIOCULTURAL INFLUENCES ON BEHAVIORAL DISPARITIES AMONG MINORITIES, THIS PROJECT WILL LEVERAGE LONGITUDINAL DATA AND REAL-TIME MONITORING OF DAILY EXPERIENCES TO ADVANCE OUR UNDERSTANDING OF RISK FOR STBS/NSSI AMONG SEXUAL MINORITY ADOLESCENTS AND TO INFORM TAILORED SUICIDE PREVENTION EFFORTS. THIS AWARD WILL ALSO SUPPORT THE APPLICANT’S TRAINING IN ADOLESCENT STBS/NSSI, SEXUAL MINORITY HEALTH, AND INTENSIVE LONGITUDINAL METHODS. FINDINGS FROM THE CURRENT STUDY WILL BE USED TO INFORM A PROPOSAL FOR A K-AWARD FOCUSED ON DEVELOPING AN INTERVENTION TO REDUCE STBS/NSSI AMONG SEXUAL MINORITY ADOLESCENTS.

LEVERAGING ECOLOGICAL MOMENTARY ASSESSMENT TO EXAMINE PEER AFFILIATIONS AS A MECHANISM OF BEHAVIOR CHANGE IN YOUTH ALCOHOL USE TREATMENT

EMOTIONAL AND PHYSIOLOGICAL REGULATION LINKING CHILD MALTREATMENT TO HEALTH RISK

MCH RESEARCH

UNDERSTANDING AND ASSESSING PEDIATRIC IRRITABILITY: DEVELOPMENTAL TRAJECTORIES, CONVERGENT VALIDITY, AND MULTI-LEVEL RISKS - PROJECT SUMMARY/ABSTRACT IRRITABILITY IS A SIGNIFICANT AND WIDESPREAD ISSUE AMONG YOUTH, AFFECTING UP TO 20% AND PROMPTING TREATMENT- SEEKING IN 58% OF CASES. IT DISRUPTS DAILY FUNCTIONING AND PREDICTS LONG-TERM PROBLEMS SUCH AS ACADEMIC DIFFICULTIES, POVERTY, AND SUICIDALITY. TRANSDIAGNOSTIC IN PSYCHIATRIC CLASSIFICATION, IRRITABILITY SPANS MULTIPLE DISORDERS INCLUDING DEPRESSION, ANXIETY, AND OPPOSITIONAL DEFIANT DISORDER. DESPITE THE PROFOUND PUBLIC HEALTH IMPLICATIONS OF IRRITABILITY, NO RESEARCH TRACKS IRRITABILITY FROM EARLY CHILDHOOD TO LATE ADOLESCENCE, A TIME OF PROFOUND CHANGES. EXISTING STUDIES FOCUS ON NARROW AGE RANGES AND DON’T OFTEN INCLUDE DIVERSE POPULATIONS. MOREOVER, THE FIELD RELIES SOLELY ON CAREGIVER REPORTS, NEGLECTING A MULTI-METHOD APPROACH. WHILE INITIAL DATA SHOWS PROMISE IN CAREGIVER REPORTED, OBSERVATIONAL, AND PHYSIOLOGICAL INDICATORS OF IRRITABILITY, NO RESEARCH HAS TESTED THE CONVERGENT VALIDITY OF THESE METHODS FOR A MORE COMPREHENSIVE ASSESSMENT OF IRRITABILITY IN YOUTH. FINALLY, DESPITE A WIDE RANGE OF RISK FACTORS LINKED TO YOUTH MENTAL HEALTH, SEVERAL FACTORS THAT MAY INFLUENCE IRRITABILITY REMAIN POORLY UNDERSTOOD AND UNDEREXPLORED. THIS APPLICATION WILL ANALYZE SECONDARY DATA AND CONDUCT A BRIEF ONLINE FOLLOW-UP SURVEY FROM THE KIDS MARKERS STUDY (KMS), A SAMPLE OF 245 CHILDREN EXPOSED TO MALTREATMENT AND MATCHED CONTROLS. KMS PROVIDES DATA ON IRRITABILITY ACROSS DEVELOPMENT AND RELEVANT EARLY CHILDHOOD RISK FACTORS. THE NEW COMPONENT IN THIS F32 PROPOSAL IS CAREGIVER-REPORTED IRRITABILITY IN LATE ADOLESCENCE (N=100; AGES 16-19). THE OVERALL AIMS OF THIS STUDY ARE TO INVESTIGATE DEVELOPMENTAL TRAJECTORIES OF IRRITABILITY FROM EARLY CHILDHOOD THROUGH LATE ADOLESCENCE, ESTABLISH THE CONVERGENT VALIDITY OF VARIOUS INDICATORS (CAREGIVER, OBSERVATIONAL AND PHYSIOLOGICAL AROUSAL) OF IRRITABILITY, AND EXPLORE MULTILEVEL (CHILD, FAMILY, AND ENVIRONMENTAL) RISK FACTORS OF IRRITABILITY. THIS INNOVATIVE STUDY WILL CONTRIBUTE TO UNDERSTANDING THE DYNAMIC NATURE OF IRRITABILITY, AIMING TO PAVE THE WAY FOR MORE EFFECTIVE INTERVENTIONS AND POLICIES. THIS STUDY UTILIZES COMPREHENSIVE ASSESSMENTS OF EARLY CHILDHOOD CHILD, FAMILY, AND ENVIRONMENTAL RISK FACTORS, ALONG WITH NOVEL APPROACHES TO MEASURING IRRITABILITY, SUCH AS RESPIRATORY SINUS ARRHYTHMIA (RSA) AND A CAREGIVER-CHILD INTERACTION TASK. THIS HIGHLY STRUCTURED TRAINING PLAN WILL ALLOW THE APPLICANT TO 1) DEVELOP EXPERTISE IN CONDUCTING TRANSLATIONAL, DEVELOPMENTALLY INFORMED RESEARCH ON CHILD, FAMILY, AND ENVIRONMENTAL RISK FACTORS IMPACTING IRRITABILITY; 2) GAIN EXPERTISE IN OBSERVATIONAL CODING OF CAREGIVER-CHILD INTERACTIONS, FOCUSING ON IRRITABILITY-RELATED BEHAVIORS; 3) MASTER ADVANCED PHYSIOLOGICAL DATA PROCESSING AND ANALYSIS TECHNIQUES; 4) LEARN ADVANCED STATISTICAL METHODS FOR TESTING DEVELOPMENTAL AND BIOPSYCHOSOCIAL RESEARCH QUESTIONS; AND 5) ENHANCE AUTONOMY IN PRESENTING SCIENTIFIC WORK, PREPARING MANUSCRIPTS, AND WRITING GRANT PROPOSALS. GUIDED BY AN OUTSTANDING MENTORSHIP TEAM WITH RELEVANT EXPERTISE AND A HISTORY OF COLLABORATION, THE TRAINING AND RESEARCH PLANS AT THE DEPARTMENT OF PSYCHIATRY AND HUMAN BEHAVIOR OF THE WARREN ALPERT MEDICAL SCHOOL OF BROWN UNIVERSITY OFFER A TAILORED ENVIRONMENT TO SUPPORT THE APPLICANT IN BECOMING AN INDEPENDENT INVESTIGATOR.