Amygdala and Ventrolateral Prefrontal Cortex Function During Anticipated Peer Evaluation in Pediatric Social Anxiety | Adolescent Medicine | JAMA Psychiatry | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
Nelson  EELeibenluft  EMcClure  EBPine  DS The social re-orientation of adolescence: a neuroscience perspective on the process and its relation to psychopathology.  Psychol Med 2005;35 (2) 163- 174PubMedGoogle Scholar
Pine  DSCohen  PGurley  DBrook  JMa  Y The risk for early-adulthood anxiety and depressive disorders in adolescents with anxiety and depressive disorders.  Arch Gen Psychiatry 1998;55 (1) 56- 64PubMedGoogle Scholar
Costello  EJPine  DSHammen  CMarch  JSPlotsky  PMWeissman  MMBiederman  JGoldsmith  HHKaufman  JLewinsohn  PMHellander  MHoagwood  KKoretz  DSNelson  CALeckman  JF Development and natural history of mood disorders.  Biol Psychiatry 2002;52 (6) 529- 542PubMedGoogle Scholar
Steinberg  LMorris  AS Adolescent development.  Annu Rev Psychol 2001;5283- 110PubMedGoogle Scholar
Clark  DMWells  A A cognitive model of social phobia Heimberg  RGLiebowitz  MRHope  DASchneier  FR Social Phobia Diagnosis and Treatment. New York, NY Guilford Press1995;69- 93Google Scholar
Rapee  RMHeimberg  RG A cognitive-behavioral model of anxiety in social phobia.  Behav Res Ther 1997;35 (8) 741- 756PubMedGoogle Scholar
Adolphs  R Is the human amygdala specialized for processing social information?  Ann N Y Acad Sci 2003;985326- 340PubMedGoogle Scholar
Gross  CHen  R The developmental origins of anxiety.  Nat Rev Neurosci 2004;5 (7) 545- 552PubMedGoogle Scholar
Amaral  DG The amygdala, social behavior, and danger detection.  Ann N Y Acad Sci 2003;1000337- 347PubMedGoogle Scholar
Sabatini  MJEbert  PLewis  DALevitt  PCameron  JLMirnics  K Amygdala gene expression correlates of social behavior in monkeys experiencing maternal separation.  J Neurosci 2007;27 (12) 3295- 3304PubMedGoogle Scholar
McClure  EBMonk  CSNelson  EEParrish  JMAdler  ABlair  RJFromm  SCharney  DSLeibenluft  EErnst  MPine  DS Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder.  Arch Gen Psychiatry 2007;64 (1) 97- 106PubMedGoogle Scholar
Thomas  KMDrevets  WCDahl  RERyan  NDBirmaher  BEccard  CHAxelson  DWhalen  PJCasey  BJ Amygdala response to fearful faces in anxious and depressed children.  Arch Gen Psychiatry 2001;58 (11) 1057- 1063PubMedGoogle Scholar
Monk  CSNelson  EEMcClure  EBMogg  KBradley  BPLeibenluft  EBlair  RJChen  GCharney  DSErnst  MPine  DS Ventrolateral prefrontal cortex activation and attentional bias in response to angry faces in adolescents with generalized anxiety disorder.  Am J Psychiatry 2006;163 (6) 1091- 1097PubMedGoogle Scholar
Monk  CSTelzer  EHMogg  KBradley  BPMai  XLouro  HMChen  GMcClure-Tone  EBErnst  MPine  DS Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder.  Arch Gen Psychiatry 2008;65 (5) 568- 576PubMedGoogle Scholar
Pine  DS Research review: a neuroscience framework for pediatric anxiety disorders.  J Child Psychol Psychiatry 2007;48 (7) 631- 648PubMedGoogle Scholar
Birbaumer  NGrodd  WDiedrich  OKlose  UErb  MLotze  MSchneider  FWeiss  UFlor  H fMRI reveals amygdala activation to human faces in social phobics.  Neuroreport 1998;9 (6) 1223- 1226PubMedGoogle Scholar
Lorberbaum  JPKose  SJohnson  MRArana  GWSullivan  LKHamner  MBBallenger  JCLydiard  RBBrodrick  PSBohning  DEGeorge  MS Neural correlates of speech anticipatory anxiety in generalized social phobia.  Neuroreport 2004;15 (18) 2701- 2705PubMedGoogle Scholar
Veit  RFlor  HErb  MHermann  CLotze  MGrodd  WBirbaumer  N Brain circuits involved in emotional learning in antisocial behavior and social phobia in humans.  Neurosci Lett 2002;328 (3) 233- 236PubMedGoogle Scholar
Stein  MBGoldin  PRSareen  JZorrilla  LTBrown  GG Increased amygdala activation to angry and contemptuous faces in generalized social phobia.  Arch Gen Psychiatry 2002;59 (11) 1027- 1034PubMedGoogle Scholar
Straube  TKolassa  ITGlauer  MMentzel  HJMiltner  WH Effect of task conditions on brain responses to threatening faces in social phobics: an event-related functional magnetic resonance imaging study.  Biol Psychiatry 2004;56 (12) 921- 930PubMedGoogle Scholar
Phan  KLFitzgerald  DANathan  PJTancer  ME Association between amygdala hyperactivity to harsh faces and severity of social anxiety in generalized social phobia.  Biol Psychiatry 2006;59 (5) 424- 429PubMedGoogle Scholar
Tillfors  MFurmark  TMarteinsdottir  IFischer  HPissiota  ALångström  BFredrikson  M Cerebral blood flow in subjects with social phobia during stressful speaking tasks: a PET study.  Am J Psychiatry 2001;158 (8) 1220- 1226PubMedGoogle Scholar
Blair  KShaywitz  JSmith  BWRhodes  RGeraci  MJones  MMcCaffrey  DVythilingam  MFinger  EMondillo  KJacobs  MCharney  DSBlair  RJDrevets  WCPine  DS Response to emotional expressions in generalized social phobia and generalized anxiety disorder: evidence for separate disorders [published online ahead of print May 15, 2008].  Am J Psychiatry 10.1176/appi.ajp.2008.07071060Google Scholar
Baxter  MGParker  ALindner  CCIzquierdo  ADMurray  EA Control of response selection by reinforcer value requires interaction of amygdala and orbital prefrontal cortex.  J Neurosci 2000;20 (11) 4311- 4319PubMedGoogle Scholar
Hariri  ARMattay  VSTessitore  AFera  FWeinberger  DR Neocortical modulation of the amygdala response to fearful stimuli.  Biol Psychiatry 2003;53 (6) 494- 501PubMedGoogle Scholar
Pérez-Edgar  KRoberson-Nay  RHardin  MGPoeth  KGuyer  AENelson  EEMcClure  EBHenderson  HAFox  NAPine  DSErnst  M Attention alters neural responses to evocative faces in behaviorally inhibited adolescents.  Neuroimage 2007;35 (4) 1538- 1546PubMedGoogle Scholar
Yang  TTMenon  VEliez  SBlasey  CWhite  CDReid  AJGotlib  IHReiss  AL Amygdalar activation associated with positive and negative facial expressions.  Neuroreport 2002;13 (14) 1737- 1741PubMedGoogle Scholar
Breiter  HCEtcoff  NLWhalen  PJKennedy  WARauch  SLBuckner  RLStrauss  MMHyman  SERosen  BR Response and habituation of the human amygdala during visual processing of facial expression.  Neuron 1996;17 (5) 875- 887PubMedGoogle Scholar
Pezawas  LMeyer-Lindenberg  ADrabant  EMVerchinski  BAMunoz  KEKolachana  BSEgan  MFMattay  VSHariri  ARWeinberger  DR 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression.  Nat Neurosci 2005;8 (6) 828- 834PubMedGoogle Scholar
La Greca  AMStone  WL Social Anxiety Scale for Children–Revised: factor structure and concurrent validity.  J Clin Child Psychol 1993;22 (1) 117- 127Google Scholar
Nomura  MOhira  HHaneda  KIidaka  TSadato  NOkada  TYonekura  Y Functional association of the amygdala and ventral prefrontal cortex during cognitive evaluation of facial expressions primed by masked angry faces: an event-related fMRI study.  Neuroimage 2004;21 (1) 352- 363PubMedGoogle Scholar
La Greca  AMLopez  N Social anxiety among adolescents: linkages with peer relations and friendships.  J Abnorm Child Psychol 1998;26 (2) 83- 94PubMedGoogle Scholar
Kaufman  JBirmaher  BBrent  DRao  UFlynn  CMoreci  PWilliamson  DRyan  N Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data.  J Am Acad Child Adolesc Psychiatry 1997;36 (7) 980- 988PubMedGoogle Scholar
 The Pediatric Anxiety Rating Scale (PARS): development and psychometric properties.  J Am Acad Child Adolesc Psychiatry 2002;41 (9) 1061- 1069PubMedGoogle Scholar
Birmaher  BKhetarpal  SBrent  DCully  MBalach  LKaufman  JNeer  SM The Screen for Child Anxiety Related Emotional Disorders (SCARED): scale construction and psychometric characteristics.  J Am Acad Child Adolesc Psychiatry 1997;36 (4) 545- 553PubMedGoogle Scholar
Nelson  EE Adolescent Facial Expressions Stimuli Database: Section on Development and Affective Neuroscience.  Bethesda, MD National Institute of Mental Health2004;
Cox  RW AFNI: software for analysis and visualization of functional magnetic resonance neuroimages.  Comput Biomed Res 1996;29 (3) 162- 173PubMedGoogle Scholar
Talairach  JTournoux  P Co-planar Stereotaxic Altas of the Human Brain.  Stuttgart, Germany Georg Thieme Verlag1988;
Clark  A Creating Regions of Interest (ROI) in AFNI.  AFNI and NIfTI Server at the NIMH in Bethesda, MD USA Web site. Updated August 11, 2005. Accessed February 27, 2008Google Scholar
Friston  KJBuechel  CFink  GRMorris  JRolls  EDolan  RJ Psychophysiological and modulatory interactions in neuroimaging.  Neuroimage 1997;6 (3) 218- 229PubMedGoogle Scholar
Gitelman  DRPenny  WDAshburner  JFriston  KJ Modeling regional and psychophysiologic interactions in fMRI: the importance of hemodynamic deconvolution.  Neuroimage 2003;19 (1) 200- 207PubMedGoogle Scholar
Miller  EKCohen  JD An integrative theory of prefrontal cortex function.  Annu Rev Neurosci 2001;24167- 202PubMedGoogle Scholar
Budhani  SMarsh  AAPine  DSBlair  RJ Neural correlates of response reversal: considering acquisition.  Neuroimage 2007;34 (4) 1754- 1765PubMedGoogle Scholar
Phelps  EADelgado  MRNearing  KILeDoux  JE Extinction learning in humans: role of the amygdala and vmPFC.  Neuron 2004;43 (6) 897- 905PubMedGoogle Scholar
Phelps  EALeDoux  JE Contributions of the amygdala to emotion processing: from animal models to human behavior.  Neuron 2005;48 (2) 175- 187PubMedGoogle Scholar
Milad  MRQuirk  GJ Neurons in medial prefrontal cortex signal memory for fear extinction.  Nature 2002;420 (6911) 70- 74PubMedGoogle Scholar
Ongür  DPrice  JL The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans.  Cereb Cortex 2000;10 (3) 206- 219PubMedGoogle Scholar
Bystritsky  APontillo  DPowers  MSabb  FWCraske  MGBookheimer  SY Functional MRI changes during panic anticipation and imagery exposure.  Neuroreport 2001;12 (18) 3953- 3957PubMedGoogle Scholar
Rauch  SLSavage  CRAlpert  NMFischman  AJJenike  MA The functional neuroanatomy of anxiety: a study of three disorders using positron emission tomography and symptom provocation.  Biol Psychiatry 1997;42 (6) 446- 452PubMedGoogle Scholar
Original Article
November 3, 2008

Amygdala and Ventrolateral Prefrontal Cortex Function During Anticipated Peer Evaluation in Pediatric Social Anxiety

Author Affiliations

Author Affiliations: Mood and Anxiety Program (Drs Guyer, Lau, Blair, Leibenluft, Ernst, Pine, and Nelson and Ms Shiffrin) and Scientific and Statistical Computing Core (Dr Chen and Mr Reyonlds), National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland; Department of Psychology, Georgia State University, Atlanta, Georgia (Dr McClure-Tone); Department of Psychology, Catholic University, Washington, DC (Ms Parrish); and Department of Human Development, University of Maryland, College Park, Maryland (Dr Fox).

Arch Gen Psychiatry. 2008;65(11):1303-1312. doi:10.1001/archpsyc.65.11.1303

Context  Amygdala and ventrolateral prefrontal cortex (vlPFC) dysfunction manifests in adolescents with anxiety disorders when they view negatively valenced stimuli in threatening contexts. Such fear-circuitry dysfunction may also manifest when anticipated social evaluation leads socially anxious adolescents to misperceive peers as threatening.

Objective  To determine whether photographs of negatively evaluated smiling peers viewed during anticipated social evaluation engage the amygdala and vlPFC differentially in adolescents with and without social anxiety.

Design  Case-control study.

Setting  Government clinical research institute.

Participants  Fourteen adolescents with anxiety disorders associated with marked concerns of social evaluation and 14 adolescents without a psychiatric diagnosis matched on sex, age, intelligence quotient, and socioeconomic status.

Main Outcome Measures  Blood oxygenation level–dependent signal measured with event-related functional magnetic resonance imaging. Before and during neuroimaging scans, participants anticipating social evaluation completed peer- and self-appraisals. Event-related analyses were tailored to participants' ratings of specific peers.

Results  Participants classified 40 pictures of same-age peers as ones with whom they did or did not want to engage in a social interaction. Anxious adolescents showed greater amygdala activation than healthy adolescents when anticipating evaluation from peers previously rated as undesired for an interaction. Psychophysiological interaction connectivity analyses also revealed a significant positive association between amygdala and vlPFC activation in anxious vs healthy adolescents in response to these stimuli.

Conclusions  Anticipating social evaluation from negatively perceived peers modulates amygdala and vlPFC engagement differentially in anxious and healthy adolescents. Amygdala and vlPFC dysfunction manifests in adolescent anxiety disorders in specific contexts of anticipated peer evaluation.