Functional Neuroimaging in Social Anxiety Disorder

  • James M. Warwick
  • D. J. Stein
  • P. Carey


The amygdala-based fear circuit involved in mediating fear conditioning and anxiety symptoms appears to also be implicated in social anxiety disorder (SAD). Imaging literature in SAD using PET and SPECT provides encouraging support for this model. The provocation of anxiety in SAD sufferers by a variety of substances may point to nonspecific activation of such a circuit, though to a lesser degree than in panic disorder. Differences in the particular anxiety symptoms experienced by subjects may, however, point to more specific circuits being involved in SAD, although this suggestion is not yet substantiated by the imaging literature. Convincing evidence now implicates limbic structures in fear conditioning that play a role in mediating social anxiety, and that effective pharmacotherapy and cognitive behavioural therapy alter activity in these areas and perhaps also in circuits related to fear extinction. Future work to determine the functioning of specific neurotransmitter and neurochemical systems in general fear circuits using novel ligands provides hope for the translation of such work to the clinic.


Social Anxiety Social Phobia Fear Conditioning Social Anxiety Disorder Panic Disorder 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adolphs R, Baron-Cohen S, Tranel D (2002) Impaired recognition of social emotions following amygdala damage. J Cogn Neurosci 14:1264–1274PubMedCrossRefGoogle Scholar
  2. Beidel DC (1998) Social anxiety disorder: etiology and early clinical presentation. J Clin Psychiatry 59[Suppl 17]:27–31PubMedGoogle Scholar
  3. Bell CM, Malizia AL, Nutt DJ (1999) The neurobiology of social phobia. Eur Arch Psychiatry Clin Neurosci 249[Suppl 1]:S11–S18PubMedCrossRefGoogle Scholar
  4. Benjamin J, Li L, Patterson C et al (1996) Population and familial association between the D4 dopamine receptor gene and measures of novelty seeking. Nat Genet 12:81–84PubMedCrossRefGoogle Scholar
  5. Bonne O, Krausz Y, Ahron Y et al (1999) Clinical doses of fluoxetine and cerebral blood flow in healthy volunteers. Psychopharmacology 143:24–28PubMedCrossRefGoogle Scholar
  6. Cloninger CR (ed) (1994) The Temperament and Character Inventory (TCI): a guide to its development and use. Center for Psychobiology of Personality, St LouisGoogle Scholar
  7. Davis M, Shi C (1999) The extended amygdala: are the central nucleus of the amygdala and the bed nucleus of the stria terminalis differentially involved in fear versus anxiety? Ann N Y Acad Sei 877:281–291CrossRefGoogle Scholar
  8. De Paulis T (2003) The discovery of epidepride and its analogs as high-affinity radioligands for imaging extrastriatal dopamine D(2) receptors in human brain. Curr Pharm Des 9:673–696PubMedCrossRefGoogle Scholar
  9. Ebstein RP, Novick O, Umansky R et al (1996) Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of novelty seeking. Nat Genet 12:78–80PubMedCrossRefGoogle Scholar
  10. Furmark T, Tillfors M, Marteinsdottir I et al (2002) Common changes in cerebral blood flow in patients with social phobia treated with Citalopram or cognitive behavioural therapy. Arch Gen Psychiatry 59:425–433PubMedCrossRefGoogle Scholar
  11. Gorman JM, Kent JM, Sullivan GM et al (2000) Neuro anatomical hypothesis of panic disorder, revised. Am J Psychiatry 157:493–505PubMedCrossRefGoogle Scholar
  12. Graeff FG, Guimeras TS, de Andrade TG et al (1996) The role of 5-HT in stress, anxiety and depression. Pharmacol Biochem Behav 54:129–141PubMedCrossRefGoogle Scholar
  13. Grant KA, Shively CA, Nader MA et al (1998) Effect of social status on striatal DA D2 receptor binding characteristics in cynomolgus monkeys assessed with positron emission tomography. Synapse 29:80–83PubMedCrossRefGoogle Scholar
  14. Higley JD, King ST Jr, Hasert MF et al (1996) Stability of interindividual differences in serotonin function and its relationship to severe aggression and competent social behaviour in rhesus macaque females. Neuropsychopharmacology 14:67–76PubMedCrossRefGoogle Scholar
  15. Johnson MR, Lydiard RB, Zealberg JJ et al (1994) Plasma and CSF levels in panic patients with co-morbid social phobia. Biol Psychiatry 36:426–427CrossRefGoogle Scholar
  16. Kendler KS, Neale MC, Kessler RC et al (1992) The genetic epidemiology of phobias in women: the interrelationship of agoraphobia, social phobia, situational phobia and simple phobia. Arch Gen Psychiatry 49:273–281PubMedCrossRefGoogle Scholar
  17. Kent JM, Coplan JD, Lombardo I et al (2002) Occupancy of brain serotonin transporters during treatment with paroxetine in patients with social phobia: a positron emission tomography study with [11C]McN 5652 Psychopharmacology 164:341–348PubMedCrossRefGoogle Scholar
  18. LeDoux J (1998) Fear and the brain: where have we been, and where are we going? Biol Psychiatry 44:1229–1238PubMedCrossRefGoogle Scholar
  19. Liebowitz MR, Campeas R, Hollander E(1987) Possible dopamine dysregulation in social phobia and atypical depression. Psychiatry Res 22:89–90PubMedCrossRefGoogle Scholar
  20. Magee WJ, Eaton WW, Wittchen HU et al (1996) Agoraphobia, simple phobia and social phobia in the National Comorbidity Survey. Arch Gen Psychiatry 53:159–168PubMedCrossRefGoogle Scholar
  21. Martinez D, Slifstein M, Broft A et al (2003) Imaging human mesolimbic dopamine transmission with positron emission tomography, part II: amphetamine-induced dopamine release in the functional subdivisions of the striatum. J Cereb Blood Flow Metab 23:285–300PubMedCrossRefGoogle Scholar
  22. Mattay VS, Goldberg TE, Fera F et al (2003) Catechol O-methyltransferase vall58-met genotype and individual variation in the brain response to amphetamine. Neuroscience 100:6186–6191Google Scholar
  23. Mayleben M, Gariepy J, Tancer M et al (1992) Genetic differences in social behaviour: neurobiological mechanisms in a mouse model (abstract). Biol Psychiatry 31S:216AGoogle Scholar
  24. Mikkelsen EJ, Deltor J, Cohen DJ (1981) School avoidance and social phobia triggered by haloperidol in patients with Tourette’s syndrome. Am J Psychiatry 138:1572–1576PubMedGoogle Scholar
  25. Potts NL, Davidson JR, Krishnan KR et al (1994) Magnetic resonance imaging in social phobia. Psychiatry Res 52:35–42PubMedCrossRefGoogle Scholar
  26. Raleigh MJ, Brammer GL, McGuire MT et al (1985) Dominant social status facilitates behavioural effects of serotoninergic agonists. Brain Res 348:274–282PubMedCrossRefGoogle Scholar
  27. Raleigh MJ, McGuire MT, Brammer GL et al (1991) Serotoninergic mechanisms promote dominance acquisition in adult male vervet monkeys. Brain Res 559:181–190PubMedCrossRefGoogle Scholar
  28. Schneier FR, Liebowitz MR, Abi-Dargam A et al (2000) Low dopamine D2 receptor binding potential in social phobia. Am J Psychiatry 157:457–459PubMedCrossRefGoogle Scholar
  29. Stein DJ, Westenberg HGM, Liebowitz MD (2001) Social anxiety disorder and generalised anxiety disorder: serotoninergic and dopaminergic neurocircuitry. J Clin Psychiatry 63 [Suppl 6]:12–19Google Scholar
  30. Stein MB (1998) Neurobiological perspectives on social phobia: an affiliation to zoology. Biol Psychiatry 44:1277–1285PubMedCrossRefGoogle Scholar
  31. Stein MB, Leslie WD (1996) A brain single photon-emission computed tomography (SPECT) study of generalised social phobia. Biol Psychiatry 39:825–828PubMedCrossRefGoogle Scholar
  32. Stein MB, Heuser IJ, Juncos JL et al (1990) Anxiety disorders in patients with Parkinson’s disease. Am J Psychiatry 147:217–220PubMedGoogle Scholar
  33. Stein MB, Chartier MJ, Hazen AL et al (1998) A direct-interview family study of generalized social phobia. Am J Psychiatry 155:90–97PubMedGoogle Scholar
  34. Sutton SK, Davidson RJ (1997) Prefrontal brain asymmetry: a biological substrate of the behavioural approach and inhibition systems. Psychol Sci 8:204–209CrossRefGoogle Scholar
  35. Tancer ME, Mailman RB, Stein MB et al (1994) Neuroendocrine sensitivity to monoaminergic system probes in generalised social phobia. Anxiety 1:216–223PubMedGoogle Scholar
  36. Tiihonen J, Kuikka J, Bergstrom K et al (1997) Dopamine reuptake site densities in patients with social phobia. Am J Psychiatry 154:239–242PubMedGoogle Scholar
  37. Tillfors M, Furmark T, Marteinsdottir I et al (2001) Cerebral blood flow in subjects with social phobia during stressful speaking tasks: a PET study. Am J Psychiatry 158:1220–1226PubMedCrossRefGoogle Scholar
  38. Tillfors M, Furmark T, Marteinsdottir I et al (2002) Cerebral blood flow during anticipation of public speaking in social phobia: a PET study. Biol Psychiatry 52:1113–1119PubMedCrossRefGoogle Scholar
  39. Tupler LA, Davidson JRT, Smith R et al (1997) A repeated proton magnetic resonance spectroscopy study in social phobia. Biol Psychiatry 42:419–424PubMedCrossRefGoogle Scholar
  40. Van der Linden G, Van Heerden B, Warwick J et al (2000a) Functional brain imaging and pharmacotherapy in social phobia: single photon emission computed tomography before and after treatment with the selective serotonin reuptake inhibitor Citalopram. Prog Neuropsychop-harmacol Biol Psychiat 24:419–438CrossRefGoogle Scholar
  41. Van der Linden GJ, Stein DJ, Van Balkom AJ (2000b) The efficacy of the selective serotonin reuptake inhibitors for social anxiety disorder (social phobia): a meta-analysis of randomised controlled trials. Int Clin Psychopharmacol 15[Suppl 2]:S15–S23PubMedGoogle Scholar
  42. Weiller E, Bisserbe J-C, Boyer P et al (1996) Social phobia in general health care: an unrecognised undertreated disabling disorder. Br J Psychiatry 168:169–174PubMedCrossRefGoogle Scholar
  43. Wittchen HU, Beloch E (1996) The impact of social phobia on quality of life. Int Clin Psychopharmacol 11[Suppl 3]:15–23PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2004

Authors and Affiliations

  • James M. Warwick
    • 1
  • D. J. Stein
    • 1
  • P. Carey
    • 1
  1. 1.Department of PsychiatryUniversity of Stellenbosch and TygerbergCape TownSouth Africa

Personalised recommendations