Abstract

Anxietydisorders,asagroup,arethemostcommonmentalillnessesintheUS,affectingabout25%ofado- lescentsand18%ofadults.Symptomstypicallybegininchildhoodoradolescence.Acrucialgapinstudiesof anxietyisthelackofempiricaldatalinkingpediatricanxietytoabnormalbraindevelopment.Thisfour-yearK01 applicationpresentsaprogramforresearchandtrainingthatwillsupporttheapplicantonapathtowards becominganNIH-fundedindependentinvestigator,focusedonstudyingtheneuralcorrelatesoffeargenerali- zationinyouthwithpathologicalanxietyusinginterdisciplinaryapproaches(affectiveneuroscience,multimodal neuroimaging,andcomputationalmethods).Thetrainingplanbuildsonthecandidate?sprevioustrainingand experience,andcapitalizesonamentorshipteamandaresearchenvironmenttofosterdevelopmentofthe candidate?sexpertisein(1)thephenomenologyofanxietydisorders;?(2)patient-oriented,translationaland developmentalneuroscienceofanxiety;?(3)advancedcomputationalneuroimaging;?and(4)responsibleand ethicalconductinscientificresearchinvulnerableindividuals.Theresearchprojectwillinvestigatefeargener- alizationbehavioranditsrelationshipwithvmPFC(ventromedialprefrontalcortex)functionandcorticolimbic connectivityinhealthyyouth(Aim#1),andinvestigatefearover-generalizationbehavioranditsrelationship withvmPFCfunctionandcorticolimbicconnectivityinyouthwithpathologicalanxiety(Aim#2).Wehypothesize thatchildhoodanxietyinvolvesfearover-generalizationandthatfearover-generalizationinvolvesabnormal functionandconnectivityofthecorticolimbicsystem.Totestthesehypotheses,wewilluseafeargeneraliza- tionfMRItaskandmultimodalMRI(structural,diffusion,andfunctionalMRI)inhealthyyouthwithoutanxiety (n=25)aswellasinyouthwithpathologicalanxietyacrossaspectrumofseverity(i.e.,thosewithsubthreshold anxiety[n=25]andthosewithanyDSM-5anxietydisorder[n=25]).Successfulcompletionofthisstudywill providecross-sectionalevidenceoftheassociationofpediatricanxietywithfeargeneralizationbehavior, vmPFCfunction,andcorticolimbicsystemconnectivity.Themultipleunitsofanalysiswillhelpelucidatebrain- behaviorrelationshipsunderlyingfeargeneralization.Thesedataalongwiththeresearchexpertisedeveloped throughthisK01awardwillsupportafutureR01applicationtotrackovertimethedevelopmentaltrajectoriesof feargeneralizationandpathologicalanxietyinyouth.Theultimategoalofthislineofresearchistodevelop neurobehavioralmarkerstodeterminewhenandwheretointerveneinanxietydisorders(NIMHStrategic Objective2)andtopromotepreventivetherapeuticinterventionstoyouthwithpathologicalanxiety(NIMH StrategicObjective3).

Public Health Relevance

Anxietydisordersinyouthareverycommonandpresagethedevelopmentofotherdebilitatingdiseases,such asdepressionandsubstanceabuse.Inthisproposal,wewilltestwhetheranxiousyouthshowover- generalizationtostimuliconditionedtofear,andtoexaminetherelatedneuralcircuitry.Resultsfromthisstudy couldleadtothedevelopmentofnewtargetsfortreatmentdevelopmentaswellasstrategiestopreventthe onsetofanxietydisorders.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01MH109836-04
Application #
9767861
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Bechtholt, Anita J
Project Start
2016-09-20
Project End
2020-02-14
Budget Start
2019-09-01
Budget End
2020-02-14
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost

  Institution

Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032

  Publications

Cha, Jiook; Guffanti, Guia; Gingrich, Jay et al. (2018) Effects of Serotonin Transporter Gene Variation on Impulsivity Mediated by Default Mode Network: A Family Study of Depression. Cereb Cortex 28:1911-1921
Lugo-Candelas, Claudia; Cha, Jiook; Hong, Susie et al. (2018) Associations Between Brain Structure and Connectivity in Infants and Exposure to Selective Serotonin Reuptake Inhibitors During Pregnancy. JAMA Pediatr 172:525-533
Mujica-Parodi, Lilianne R; Cha, Jiook; Gao, Jonathan (2017) From Anxious to Reckless: A Control Systems Approach Unifies Prefrontal-Limbic Regulation Across the Spectrum of Threat Detection. Front Syst Neurosci 11:18
Cha, Jiook; Zea-Hernandez, Johanna A; Sin, Sanghun et al. (2017) The Effects of Obstructive Sleep Apnea Syndrome on the Dentate Gyrus and Learning and Memory in Children. J Neurosci 37:4280-4288
Cha, Jiook; Ide, Jaime S; Bowman, F Dubois et al. (2016) Abnormal reward circuitry in anorexia nervosa: A longitudinal, multimodal MRI study. Hum Brain Mapp 37:3835-3846
Posner, J; Cha, J; Roy, A K et al. (2016) Alterations in amygdala-prefrontal circuits in infants exposed to prenatal maternal depression. Transl Psychiatry 6:e935