ThisExploratoryClinicalTrialsofNovelInterventionsforMentalDisorders(RFA-MH- 16-406)grantapplicationproposesastudyofeffectsinadolescents/youngadultsofanovelpsychobehavioral intervention,BrainEmotionSelf-MonitoringandRegulationTherapy(BE-SMART),designedtotargetbrain circuitryunderlyingimpairedemotionalregulation.Emotionaldysregulationiscommon,causessuffering, disabilityandincreasinglyshowsimportanceinsuicide.Convergingresearch,includingfromourgroup, demonstratesemotionaldysregulationanditsunderlyingbraincircuitryascentralinBipolarDisorder(BD).Yet, previouspsychobehavioraltreatmentshavenottranslatedtheneuroscientificfindingsintotargeted interventions.Itisespeciallypressingtostudytargetingofthiscircuitryduringadolescenceandyoung adulthood,thetypicalperiodoftransitionfromsubsyndromalemotionaldysregulationtoBD,asdatasupport underlyingalteredcircuitrydevelopmentduringthistime.Interventionsthatsteertrajectoriesbackontrack couldimprovesymptomsandprognosis.Moreover,BDprovidesamodeltostudydysregulationinvolving excessivepositive,negativeandmixedemotionalstates.Currenttreatmentsoftenaddressoneemotional state,buttreatmentsdesignedtoaddressbothemotionalextremesareneeded.Datasupportbottom-updaily circadianrhythm(DR),andtop-downexecutivecontrol(ER),mechanismsinregulatingemotions.Pilotstudyof theBE-SMART,whichincludedDRandERcomponents,providedpromisinginitialdataofimprovedemotional brainandbehaviorregulation,includingfindingsthatsuggestDRandERcomponentsbothaffectemotional circuitryandmayaffectdifferentaspectsofcircuitry,behaviorsandsymptoms.However,thesecomponents havenotbeenstudiedseparately.IntheR61phase,wewillseparatelyassessengagementofemotional regulationbraincircuitry(functionalmagneticresonanceimaging)andbehaviorbyDRorERcomponents (N=26withBDpergroup),at6-and12-weekdoses.Ifsuccessfulindemonstratingtargetengagement,wewill useR61datatogenerateanoptimized,revisedBE-SMART-Rversion.IntheR33,wewillperforma preliminaryrandomizedcontrolledtrialofadolescentsandyoungadultswithBDtotestfeasibility,acceptability, signalsofefficacyandassociationsbetweentargetengagementandmoodsymptomimprovementofBE- SMART-R(N=64),comparedtoapsychoeducationalcontrolintervention(N=32).Thiswillbethebasisfor subsequentstudiespoweredtoestablishBE-SMART-Refficacyandinterventionmediatorsandmoderators, producinganeasilydisseminablenewinterventionthatmaybepersonalized.Alongtermgoalistotarget neurodevelopmentaltrajectoriesearlierinthediseasecoursetopreventprogression.Thisstudyhaspotential fortremendousscientificandpublichealthbenefitinrevealingnovelinsightsintobehavioralchangesthat influencebraincircuitrymechanismsinpositiveandnegativevalenceandarousalsystems,anddevelopingBD andtransdiagnosticcircuitry-targetedpsychobehavioralinterventions.

Public Health Relevance

Non-medication therapies are critically-needed to treat impaired emotional regulation, which affects millions of individuals worldwide, causes immeasurable suffering, disability and can be central to suicide. Emotional dysregulation is extreme in bipolar disorder for which the treatment need is pressing, especially in adolescents and young adults, as improving emotional regulation may not only reduce acute symptoms, but prevent disease progression, improve prognosis, and decrease risk of suicide, saving lives. This study tests a promising novel psychobehavioral intervention, Brain Emotion Self-Monitoring and Regulation Therapy (BE- SMART), that is based on advances in neuroscience and the first designed specifically to target emotional regulation problems and their underlying brain circuitry, that could have tremendous, wide-ranging public health benefits, especially in adolescents/young adults.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Project #
1R61MH111929-01A1
Application #
9372707
Study Section
Special Emphasis Panel (ZMH1)
Program Officer
Garvey, Marjorie A
Project Start
2017-08-01
Project End
2019-06-30
Budget Start
2017-08-01
Budget End
2018-06-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520