title: Neurocircuitry underlying risk and resilience to social anxiety disorder.
abstract: BACKGROUND
  Almost half of children with an inhibited temperament will develop social anxiety disorder by late adolescence. Importantly, this means that half of children with an inhibited temperament will not develop social anxiety disorder. Studying adults with an inhibited temperament provides a unique opportunity to identify neural signatures of both risk and resilience to social anxiety disorder.
  
  
  METHODS
  Functional magnetic resonance imaging (fMRI) was used to measure brain activation during the anticipation of viewing fear faces in 34 young adults (17 inhibited, 17 uninhibited). To identify neural signatures of risk, we tested for group differences in functional activation and connectivity in regions implicated in social anxiety disorder, including the prefrontal cortex, amygdala, and insula. To identify neural signatures of resilience, we tested for correlations between brain activation and both emotion regulation and social anxiety scores.
  
  
  RESULTS
  Inhibited subjects had greater activation of a prefrontal network when anticipating viewing fear faces, relative to uninhibited subjects. No group differences were identified in the amygdala. Inhibited subjects had more negative connectivity between the rostral anterior cingulate cortex (ACC) and the bilateral amygdala. Within the inhibited group, those with fewer social anxiety symptoms and better emotion regulation skills had greater ACC activation and greater functional connectivity between the ACC and amygdala.
  
  
  CONCLUSIONS
  These findings suggest that engaging regulatory prefrontal regions during anticipation may be a protective factor, or putative neural marker of resilience, in high-risk individuals. Cognitive training targeting prefrontal cortex function may provide protection against anxiety, especially in high-risk individuals, such as those with inhibited temperament.
authors.affiliation: Neuroscience Graduate Program, Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee; Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Clauss
authors.forename: Suzanne N
authors.initials: SN
authors.lastname: Avery
authors.forename: Ross M
authors.initials: RM
authors.lastname: VanDerKlok
authors.forename: Baxter P
authors.initials: BP
authors.lastname: Rogers
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Cowan
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Benningfield
authors.forename: Jennifer Urbano
authors.initials: JU
authors.lastname: Blackford
mesh_terms: D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000503:physiopathology; D059031:Anticipation, Psychological / Q000502:physiology; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000503:physiopathology; D005149:Facial Expression; D005239:Fear; D005260:Female; D059907:Functional Neuroimaging; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology*; D010698:Phobic Disorders / Q000503:physiopathology* / Q000523:psychology; D017397:Prefrontal Cortex / Q000503:physiopathology; D055500:Resilience, Psychological; D012307:Risk Factors; D013694:Temperament / Q000502:physiology*; D055815:Young Adult
keywords: anticipation; fMRI; functional connectivity; inhibited temperament; social anxiety disorder
references.citation: Arch Gen Psychiatry. 2010 Jan;67(1):78-84
references.pmid: 20048225
references.citation: Neuropsychologia. 2008 Jan 15;46(1):102-10
references.pmid: 17884110
references.citation: BMC Neurosci. 2009 Dec 10;10:145
references.pmid: 20003287
references.citation: Neuroimage. 2002 Jan;15(1):273-89
references.pmid: 11771995
references.citation: Neuroimage. 2012 Jul 16;61(4):1277-86
references.pmid: 22484411
references.citation: Int Clin Psychopharmacol. 1996 Jun;11 Suppl 3:15-23
references.pmid: 8923105
references.citation: Brain Res. 2011 Mar 10;1378:72-83
references.pmid: 21215728
references.citation: Neuroreport. 2004 Oct 5;15(14):2261-5
references.pmid: 15371746
references.citation: Psychiatry Res. 2007 Jan 15;154(1):1-12
references.pmid: 17182225
references.citation: Arch Gen Psychiatry. 2005 Jun;62(6):593-602
references.pmid: 15939837
references.citation: Arch Gen Psychiatry. 2009 Feb;66(2):170-80
references.pmid: 19188539
references.citation: Psychiatry Res. 2013 May 30;212(2):108-15
references.pmid: 23146247
references.citation: Nat Rev Neurosci. 2002 Mar;3(3):243-9
references.pmid: 11994756
references.citation: Soc Cogn Affect Neurosci. 2013 Feb;8(2):143-50
references.pmid: 22260816
references.citation: Depress Anxiety. 2014 Jan;31(1):53-62
references.pmid: 23861165
references.citation: J Cogn Neurosci. 1997 Fall;9(5):648-63
references.pmid: 23965122
references.citation: Mol Psychiatry. 2012 Oct;17(10):1042-50
references.pmid: 21894151
references.citation: Arch Gen Psychiatry. 2012 Apr;69(4):360-71
references.pmid: 22474105
references.citation: J Dev Behav Pediatr. 2007 Jun;28(3):225-33
references.pmid: 17565290
references.citation: Trends Cogn Sci. 2005 May;9(5):242-9
references.pmid: 15866151
references.citation: Am J Psychiatry. 2000 Oct;157(10):1606-13
references.pmid: 11007714
references.citation: J Clin Child Adolesc Psychol. 2004 Dec;33(4):750-9
references.pmid: 15498742
references.citation: J Pers Soc Psychol. 1989 Feb;56(2):267-83
references.pmid: 2926629
references.citation: Arch Gen Psychiatry. 2008 Nov;65(11):1275-84
references.pmid: 18981339
references.citation: J Anxiety Disord. 2009 May;23(4):469-76
references.pmid: 19028075
references.citation: Neuroimage. 2003 Jul;19(3):1233-9
references.pmid: 12880848
references.citation: Neuroimage. 2013 Jan 1;64:538-46
references.pmid: 23000783
references.citation: Arch Gen Psychiatry. 1992 Aug;49(8):624-9
references.pmid: 1637252
references.citation: J Child Psychol Psychiatry. 2009 Nov;50(11):1365-72
references.pmid: 19788588
references.citation: Science. 1988 Apr 8;240(4849):167-71
references.pmid: 3353713
references.citation: Neuroimage. 2006 Jan 1;29(1):106-16
references.pmid: 16181793
references.citation: Eur J Pharmacol. 2000 Dec 27;410(2-3):107-120
references.pmid: 11134663
references.citation: Soc Cogn Affect Neurosci. 2011 Oct;6(5):621-9
references.pmid: 20660534
references.citation: Neuroimage. 2007 May 1;35(4):1538-46
references.pmid: 17376704
references.citation: Biol Psychiatry. 2009 Dec 15;66(12):1091-9
references.pmid: 19717138
references.citation: Psychol Sci. 2007 Feb;18(2):127-9
references.pmid: 17425531
references.citation: Cereb Cortex. 2013 Aug;23(8):1874-83
references.pmid: 22763169
references.citation: J Am Acad Child Adolesc Psychiatry. 1992 Jan;31(1):103-11
references.pmid: 1537760
references.citation: Am J Psychiatry. 2007 Oct;164(10):1476-88
references.pmid: 17898336
references.citation: Hum Brain Mapp. 1994;1(3):210-20
references.pmid: 24578041
references.citation: Am J Psychiatry. 2009 Mar;166(3):302-10
references.pmid: 19122007
references.citation: Arch Gen Psychiatry. 2000 Nov;57(11):1046-52
references.pmid: 11074870
references.citation: Science. 2003 Jun 20;300(5627):1952-3
references.pmid: 12817151
references.citation: J Consult Clin Psychol. 2004 Jun;72(3):392-399
references.pmid: 15279523
references.citation: Am J Psychiatry. 2001 Oct;158(10):1673-9
references.pmid: 11579001
references.citation: J Anxiety Disord. 2002;16(6):585-98
references.pmid: 12405519
references.citation: Depress Anxiety. 2013 Mar;30(3):234-41
references.pmid: 23184639
references.citation: J Pers Soc Psychol. 1994 Mar;66(3):549-58
references.pmid: 8169764
references.citation: Am J Psychiatry. 2010 Jan;167(1):40-6
references.pmid: 19917594
references.citation: Cereb Cortex. 2010 Apr;20(4):929-40
references.pmid: 19679543
references.citation: J Am Acad Child Adolesc Psychiatry. 2012 Oct;51(10):1066-1075.e1
references.pmid: 23021481
references.citation: Cogn Affect Behav Neurosci. 2011 Mar;11(1):13-21
references.pmid: 21264642
references.citation: Biol Psychiatry. 2009 Mar 1;65(5):445-8
references.pmid: 19108817
references.citation: Behav Res Ther. 2003 Feb;41(2):209-21
references.pmid: 12547381