[go: up one dir, main page]

Skip to main content
Log in

Neuroimaging Predictors and Mechanisms of Treatment Response in Social Anxiety Disorder: an Overview of the Amygdala

  • Anxiety Disorders (A Pelissolo, Section Editor)
  • Published:
Current Psychiatry Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Aberrant amygdala activity is implicated in the neurobiology of social anxiety disorder (SAD) and is, therefore, a treatment target. However, the extent to which amygdala predicts clinical improvement or is impacted by treatment has not been critically examined. This review highlights recent neuroimaging findings from clinical trials and research that test links between amygdala and mechanisms of action.

Recent Findings

Neuropredictor studies largely comprised psychotherapy where improvement was foretold by amygdala activity and regions beyond amygdala such as frontal structures (e.g., anterior cingulate cortex, medial prefrontal cortex) and areas involved in visual processes (e.g., occipital regions, superior temporal gyrus). Pre-treatment functional connectivity between amygdala and frontal areas was also shown to predict improvement signifying circuits that support emotion processing and regulation interact with treatment. Pre-to-post studies revealed decreases in amygdala response and altered functional connectivity in amygdala pathways regardless of treatment modality. In analogue studies of fear exposure, greater reduction in anxiety was predicted by less amygdala response to a speech challenge and amygdala activity decreased following exposures. Yet, studies have also failed to detect amygdala effects reporting instead treatment-related changes in regions and functional systems that support sensory, emotion, and regulation processes. An array of regions in the corticolimbic subcircuits and extrastriate cortex appear to be viable sites of action.

Summary

The amygdala and amygdala pathways predict treatment outcome and are altered following treatment. However, further study is needed to establish the role of the amygdala and other candidate regions and brain circuits as sites of action.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Kessler RC. The impairments caused by social phobia in the general population: implications for intervention. Acta Psychiatr Scand. 2003;417:19–27.

    Article  Google Scholar 

  2. Wittchen HU, Fehm L. Epidemiology and natural course of social fears and social phobia. Acta Anaesthesiol Scand. 2003;417:4–18.

    Google Scholar 

  3. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, VA: 2013.

  4. Stein MB. How shy is too shy? Lancet. 1996;347:1131–2.

    Article  CAS  PubMed  Google Scholar 

  5. Kessler RC, Petukhova M, Sampson NA, Zaslavsky AM, Wittchen H-U. Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States: anxiety and mood disorders in the United States. Int J Methods Psychiatr Res. 2012;21:169–84.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Ruscio AM, Brown TA, Chiu WT, Sareen J, Stein MB, Kessler RC. Social fears and social phobia in the United States: results from the National Comorbidity Survey Replication. Psychol Med. 2008;38:15–28.

    Article  CAS  PubMed  Google Scholar 

  7. Stein DJ, CCW L, Roest AM, de Jonge P, Aguilar-Gaxiola S, Al-Hamzawi A, et al. The cross-national epidemiology of social anxiety disorder: data from the World Mental Health Survey Initiative. BMC Med. 2017;15:143.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Davis M, Whalen PJ. The amygdala: vigilance and emotion. Mol Psychiatry. 2001;6:13–34.

    Article  CAS  PubMed  Google Scholar 

  9. LeDoux JE. Emotion circuits in the brain. Annu Rev Neurosci. 2000;23:155–84.

    Article  CAS  PubMed  Google Scholar 

  10. Marek R, Strobel C, Bredy TW, Sah P. The amygdala and medial prefrontal cortex: partners in the fear circuit. J Physiol. 2013;591:2381–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Shackman AJ, Fox AS. Contributions of the central extended amygdala to fear and anxiety. J Neurosci. 2016;36:8050–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Vuilleumier P, Pourtois G. Distributed and interactive brain mechanisms during emotion face perception: evidence from functional neuroimaging. Neuropsychologia. 2007;45:174–94.

    Article  PubMed  Google Scholar 

  13. Tso IF, Rutherford S, Fang Y, Angstadt M, Taylor SF. The “social brain” is highly sensitive to the mere presence of social information: an automated meta-analysis and an independent study. PLoS One. 2018;13:e0196503.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hayes SC, Strosahl KD, Wilson KG. Acceptance and commitment therapy: an experiential approach to behavior change. New York: Guilford Press; 1999.

    Google Scholar 

  15. Schmidt NB, Richey JA, Buckner JD, Timpano KR. Attention training for generalized social anxiety disorder. J Abnorm Psychol. 2009;118:5–14.

    Article  PubMed  Google Scholar 

  16. Gingnell M, Frick A, Engman J, Alaie I, Björkstrand J, Faria V, et al. Combining escitalopram and cognitive–behavioural therapy for social anxiety disorder: randomised controlled fMRI trial. Br J Psychiatry. 2016;209:229–35.

    Article  PubMed  Google Scholar 

  17. Grund T, Goyon S, Li Y, Eliava M, Liu H, Charlet A, et al. Neuropeptide S activates paraventricular oxytocin neurons to induce anxiolysis. J Neurosci. 2017;37:12214–25.

    Article  CAS  PubMed  Google Scholar 

  18. Grace SA, Rossell SL, Heinrichs M, Kordsachia C, Labuschagne I. Oxytocin and brain activity in humans: a systematic review and coordinate-based meta-analysis of functional MRI studies. Psychoneuroendocrinology. 2018;96:6–24.

    Article  CAS  PubMed  Google Scholar 

  19. Stein MB, Goldin P, Sareen J, Eyler-Zorrilla LT, Brown GG. Increased amygdala activation to angry and contemptuous faces in generalized social phobia. Arch Gen Psychiatry. 2002;59:107–1034.

    Google Scholar 

  20. Davidson RJ, Irwin W. The functional neuroanatomy of emotion and affective style. Trends Cogn Sci. 1999;3:11–21.

    Article  CAS  PubMed  Google Scholar 

  21. Brühl AB, Delsignore A, Komossa K, Weidt S. Neuroimaging in social anxiety disorder—a meta-analytic review resulting in a new neurofunctional model. Neurosci Biobehav Rev. 2014;47:260–80.

    Article  PubMed  Google Scholar 

  22. Cremers HR, Roelofs K. Social anxiety disorder: a critical overview of neurocognitive research: social anxiety disorder. Wiley Interdiscip Rev Cogn Sci. 2016;7:218–32.

    Article  PubMed  Google Scholar 

  23. Schulz C, Mothes-Lasch M, Straube T. Automatic neural processing of disorder-related stimuli in social anxiety disorder: faces and more. Front Psychol. 2013;4

  24. Simon D, Becker M, Mothes-Lasch M, Miltner WHR, Straube T. Loud and angry: sound intensity modulates amygdala activation to angry voices in social anxiety disorder. Soc Cogn Affect Neurosci 2017;409–416.

  25. Blair K, Shaywitz J, Smith BW, Rhodes R, Geraci M, Jones M, et al. Response to emotional expressions in generalized social phobia and generalized anxiety disorder: evidence for separate disorders. Am J Psychiatry. 2008;165:1193–202.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Schmidt S, Mohr A, Miltner WHR, Straube T. Task-dependent neural correlates of the processing of verbal threat-related stimuli in social phobia. Biol Psychol. 2010;84:304–12.

    Article  PubMed  Google Scholar 

  27. Davies CD, Young K, Torre JB, Burklund LJ, Goldin PR, Brown LA, et al. Altered time course of amygdala activation during speech anticipation in social anxiety disorder. J Affect Disord. 2017;209:23–9.

    Article  PubMed  Google Scholar 

  28. Lorberbaum JP, Kose S, Johnson MR, Arana GW, Sullivan LK, Hamner MB, et al. Neural correlates of speech anticipatory anxiety in generalized social phobia. Neuroreport. 2004;15:2701–5.

    PubMed  Google Scholar 

  29. A Richey J, Ghane M, Valdespino A, Coffman MC, Strege MV, White SW, Ollendick TH. Spatiotemporal dissociation of brain activity underlying threat and reward in social anxiety disorder. Soc Cogn Affect Neurosci 2017;81–9.

  30. Gentili C, Cristea IA, Angstadt M, Klumpp H, Tozzi L, Phan KL, et al. Beyond emotions: a meta-analysis of neural response within face processing system in social anxiety. Exp Biol Med. 2016;241:225–37.

    Article  CAS  Google Scholar 

  31. Balderston NL, Schultz DH, Hopkins L, Helmstetter FJ. Functionally distinct amygdala subregions identified using DTI and high-resolution fMRI. Soc Cogn Affect Neurosci. 2015;10:1615–22.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Roy AK, Shehzad Z, Margulies DS, Kelly AMC, Uddin LQ, Gotimer K, et al. Functional connectivity of the human amygdala using resting state fMRI. NeuroImage. 2009;45:614–26.

    Article  PubMed  Google Scholar 

  33. Phelps EA. Emotion and cognition: insights from studies of the human amygdala. Annu Rev Psychol. 2006;57:27–53.

    Article  PubMed  Google Scholar 

  34. Kemppainen S, Jolkkonen E, Pitkänen A. Projections from the posterior cortical nucleus of the amygdala to the hippocampal formation and parahippocampal region in rat: amygdalohippocampal connections. Hippocampus. 2002;12:735–55.

    Article  PubMed  Google Scholar 

  35. Feldker K, Heitmann CY, Neumeister P, Tupak SV, Schrammen E, Moeck R, et al. Transdiagnostic brain responses to disorder-related threat across four psychiatric disorders. Psychol Med. 2017;47:730–743.

    Article  CAS  PubMed  Google Scholar 

  36. Phillips ML, Drevets WC, Rauch SL, Lane R. Neurobiology of emotion perception I: the neural basis of normal emotion perception. Biol Psychiatry. 2003;54:504–14.

    Article  PubMed  Google Scholar 

  37. Cremers HR, Veer IM, Spinhoven P, Rombouts SARB, Yarkoni T, Wager TD, et al. Altered cortical-amygdala coupling in social anxiety disorder during the anticipation of giving a public speech. Psychol Med. 2015;45:1521–9.

    Article  CAS  PubMed  Google Scholar 

  38. Geiger MJ, Domschke K, Ipser J, Hattingh C, Baldwin DS, Lochner C, et al. Altered executive control network resting-state connectivity in social anxiety disorder. World J Biol Psychiatry. 2016;17:47–57.

    Article  PubMed  Google Scholar 

  39. Heitmann CY, Feldker K, Neumeister P, Brinkmann L, Schrammen E, Zwitserlood P, et al. Brain activation to task-irrelevant disorder-related threat in social anxiety disorder: the impact of symptom severity. Neuroimage Clin. 2017;14:323–33.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Jung Y-H, Shin JE, Lee YI, Jang JH, Jo HJ, Choi S-H. Altered amygdala resting-state functional connectivity and hemispheric asymmetry in patients with social anxiety disorder. Front Psychiatry. 2018;9

  41. Laeger I, Dobel C, Radenz B, Kugel H, Keuper K, Eden A, et al. Of “disgrace” and “pain”—corticolimbic interaction patterns for disorder-relevant and emotional words in social phobia. PLoS One. 2014;9:e109949.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Minkova L, Sladky R, Kranz GS, Woletz M, Geissberger N, Kraus C, et al. Task-dependent modulation of amygdala connectivity in social anxiety disorder. Psychiatry Res Neuroimaging. 2017;262:39–46.

    Article  PubMed  Google Scholar 

  43. Prater KE, Hosanagar A, Klumpp H, Angstadt M, Luan Phan K. Aberrant amygdala-frontal cortex connectivity during perception of fearful faces and at rest in generalized social anxiety disorder: research article: amygdala-frontal connectivity in gSAD. Depress Anxiety. 2013;30:234–41.

    Article  PubMed  Google Scholar 

  44. Sladky R, Höflich A, Küblböck M, Kraus C, Baldinger P, Moser E, et al. Disrupted effective connectivity between the amygdala and orbitofrontal cortex in social anxiety disorder during emotion discrimination revealed by dynamic causal modeling for fMRI. Cereb Cortex. 2015;25:895–903.

    Article  PubMed  Google Scholar 

  45. Yoon H-J, Kim JS, Shin Y-B, Choi S-H, Lee S-K, Kim J-J. Neural activity during self-referential working memory and the underlying role of the amygdala in social anxiety disorder. Neurosci Lett. 2016;627:139–47.

    Article  CAS  PubMed  Google Scholar 

  46. Anteraper AS, Triantafyliou C, Sawyer AT, Hofmann SG, Gabrieli JD, Whitfield-Gabrieli S. Hyper-connectivity of subcortical resting-state networks in social anxiety disorder. Brain Connect. 2014;4:81–90.

    Article  Google Scholar 

  47. Pannekoek JN, Veer IM, van Tol M-J, van der Werff SJ, Demenescu LR, Aleman A, et al. Resting-state functional connectivity abnormalities in limbic and salience networks in social anxiety disorder without comorbidity. Eur Neuropsychopharmacol. 2013;23:186–95.

    Article  CAS  PubMed  Google Scholar 

  48. Frick A, Howner K, Fischer H, Kristiansson M, Furmark T. Altered fusiform connectivity during processing of fearful faces in social anxiety disorder. Transl Psychiatry. 2013;3:e312.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Danti S, Ricciardi E, Gentili C, Gobbini MI, Pietrini P, Guazzelli M. Is social phobia a “mis-communication” disorder? Brain functional connectivity during face perception differs between patients with social phobia and healthy control subjects. Front Syst Neurosci. 2010;4

  50. Goldin PR, Manber-Ball T, Werner K, Heimberg R, Gross JJ. Neural mechanisms of cognitive reappraisal of negative self-beliefs in social anxiety disorder. Biol Psychiatry. 2009;66:1091–9.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Carpenter JK, Andrews LA, Witcraft SM, Powers MB, Smits JAJ, Hofmann SG. Cognitive behavioral therapy for anxiety and related disorders: a meta-analysis of randomized placebo-controlled trials. Depress Anxiety. 2018;35:502–14.

    Article  CAS  PubMed  Google Scholar 

  52. Curtiss J, Andrews L, Davis M, Smits J, Hofmann SG. A meta-analysis of pharmacotherapy for social anxiety disorder: an examination of efficacy, moderators, and mediators. Expert Opin Pharmacother. 2017;18:243–51.

    Article  CAS  PubMed  Google Scholar 

  53. Arch JJ, Craske MG. First-line treatment: a critical appraisal of cognitive behavioral therapy developments and alternatives. Psychiatr Clin N Am. 2009;32:525–47.

    Article  Google Scholar 

  54. Goldapple K, Segal Z, Garson C, Lau M, Bieling P, Kennedy S, et al. Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy. Arch Gen Psychiatry. 2004;61:34–41.

    Article  PubMed  Google Scholar 

  55. Yang Y, Kircher T, Straube B. The neural correlates of cognitive behavioral therapy: recent progress in the investigation of patients with panic disorder. Behav Res Ther. 2014;62:88–96.

    Article  PubMed  Google Scholar 

  56. Rhodes RA, Murthy NV, Dresner MA, Selvaraj S, Stavrakakis N, Babar S, et al. Human 5-HT transporter availability predicts amygdala reactivity in vivo. J Neurosci. 2007;27:9233–7.

    Article  CAS  PubMed  Google Scholar 

  57. Maron E, Wall M, Norbury R, Godlewska B, Terbeck S, Cowen P, et al. Effect of short-term escitalopram treatment on neural activation during emotional processing. J Psychopharmacol. 2016;30:33–9.

    Article  CAS  PubMed  Google Scholar 

  58. Faria V, Appel L, Åhs F, Linnman C, Pissiota A, Frans Ö, et al. Amygdala subregions tied to SSRI and placebo response in patients with social anxiety disorder. Neuropsychopharmacology. 2012;37:2222–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Frick A, Åhs F, Appel L, Jonasson M, Wahlstedt K, Bani M, et al. Reduced serotonin synthesis and regional cerebral blood flow after anxiolytic treatment of social anxiety disorder. Eur Neuropsychopharmacol. 2016;26:1775–83.

    Article  CAS  PubMed  Google Scholar 

  60. Giménez M, Ortiz H, Soriano-Mas C, López-Solà M, Farré M, Deus J, et al. Functional effects of chronic paroxetine versus placebo on the fear, stress and anxiety brain circuit in social anxiety disorder: initial validation of an imaging protocol for drug discovery. Eur Neuropsychopharmacol. 2014;24:105–16.

    Article  CAS  PubMed  Google Scholar 

  61. Farabaugh A, Fisher L, Nyer M, Holt D, Cohen M, Baer L, et al. Similar changes in cognitions following cognitive-behavioral therapy or escitalopram for major depressive disorder: implications for mechanisms of change. Ann Clin Psychiatry. 2015;27:118–26.

    PubMed  Google Scholar 

  62. Szentagotai A, David D, Lupu V, Cosman D. Rational emotive behavior therapy versus cognitive therapy versus pharmacotherapy in the treatment of major depressive disorder: mechanisms of change analysis. Psychotherapy. 2008;45:523–38.

    Article  PubMed  Google Scholar 

  63. Bhar SS, Gelfand LA, Schmid SP, Gallop R, DeRubeis RJ, Hollon SD, et al. Sequence of improvement in depressive symptoms across cognitive therapy and pharmacotherapy. J Affect Disord. 2008;110:161–6.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Furmark T, Tillfors M, Marteinsdottir I, Fischer H, Pissiota A, Langstrom B, et al. Common changes in cerebral blood flow in patients with social phobia treated with citalopram or cognitive-behavioral therapy. Arch Gen Psychiatry. 2002;59:425–33.

    Article  PubMed  Google Scholar 

  65. Burklund LJ, Torre JB, Lieberman MD, Taylor SE, Craske MG. Neural responses to social threat and predictors of cognitive behavioral therapy and acceptance and commitment therapy in social anxiety disorder. Psychiatry Res Neuroimaging. 2017;261:52–64.

    Article  PubMed  Google Scholar 

  66. Klumpp H, Fitzgerald JM, Kinney KL, Kennedy AE, Shankman SA, Langenecker SA, et al. Predicting cognitive behavioral therapy response in social anxiety disorder with anterior cingulate cortex and amygdala during emotion regulation. Neuroimage Clin. 2017;15:25–34.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Klumpp H, Fitzgerald DA, Angstadt M, Post D, Phan KL. Neural response during attentional control and emotion processing predicts improvement after cognitive behavioral therapy in generalized social anxiety disorder. Psychol Med. 2014;44:3109–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Månsson KNT, Frick A, Boraxbekk C-J, Marquand AF, Williams SCR, Carlbring P, et al. Predicting long-term outcome of internet-delivered cognitive behavior therapy for social anxiety disorder using fMRI and support vector machine learning. Transl Psychiatry. 2015;5:e530.

    Article  PubMed  PubMed Central  Google Scholar 

  69. • Whitfield-Gabrieli S, Ghosh SS, Nieto-Castanon A, Saygin Z, Doehrmann O, Chai XJ, et al. Brain connectomics predict response to treatment in social anxiety disorder. Mol Psychiatry. 2016;21:680–5. This study demonstrates a state-of-science approach to identify brain-based predictors of treatment response in social anxiety disorder.

    Article  CAS  PubMed  Google Scholar 

  70. Doehrmann O, Ghosh SS, Polli FE, Reynolds GO, Horn F, Keshavan A, et al. Predicting treatment response in social anxiety disorder from functional magnetic resonance imaging. JAMA Psychiatry. 2013;70:87–97.

    Article  PubMed  Google Scholar 

  71. Ball TM, Stein MB, Ramsawh HJ, Campbell-Sills L, Paulus MP. Single-subject anxiety treatment outcome prediction using functional neuroimaging. Neuropsychopharmacology. 2014;39:1254–61.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Thompson DG, Kesler SR, Sudheimer K, Mehta KM, Thompson LW, Marquett RM, et al. fMRI activation during executive function predicts response to cognitive behavioral therapy in older, depressed adults. Am J Geriatr Psychiatry. 2015;23:13–22.

    Article  PubMed  Google Scholar 

  73. Klumpp H, Keutmann MK, Fitzgerald DA, Shankman SA, Phan KL. Resting state amygdala-prefrontal connectivity predicts symptom change after cognitive behavioral therapy in generalized social anxiety disorder. Biol Mood Anxiety Disord. 2014;4:14.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Furini C, Myskiw J, Izquierdo I. The learning of fear extinction. Neurosci Biobehav Rev. 2014;47:670–83.

    Article  PubMed  Google Scholar 

  75. Ball TM, Knapp SE, Paulus MP, Stein MB. Brain activation during fear extinction predicts exposure success. Depress Anxiety. 2017;34:257–66.

    Article  CAS  PubMed  Google Scholar 

  76. Klumpp H, Fitzgerald DA, Phan KL. Neural predictors and mechanisms of cognitive behavioral therapy on threat processing in social anxiety disorder. Prog Neuro-Psychopharmacol Biol Psychiatry. 2013;45:83–91.

    Article  Google Scholar 

  77. Klumpp H, Fitzgerald DA, Piejko K, Roberts J, Kennedy AE, Phan KL. Prefrontal control and predictors of cognitive behavioral therapy response in social anxiety disorder. Soc Cogn Affect Neurosci. 2016;11:630–40.

    Article  PubMed  Google Scholar 

  78. Klumpp H, Roberts J, Kennedy AE, Shankman SA, Langenecker SA, Gross JJ, et al. Emotion regulation related neural predictors of cognitive behavioral therapy response in social anxiety disorder. Prog Neuro-Psychopharmacol Biol Psychiatry. 2017;75:106–12.

    Article  Google Scholar 

  79. Yuan M, Meng Y, Zhang Y, Nie X, Ren Z, Zhu H, et al. Cerebellar neural circuits involving executive control network predict response to group cognitive behavior therapy in social anxiety disorder. Cerebellum. 2017;16:673–82.

    Article  Google Scholar 

  80. Evans KC, Simon NM, Dougherty DD, Hoge EA, Worthington JJ, Chow C, et al. A PET study of tiagabine treatment implicates ventral medial prefrontal cortex in generalized social anxiety disorder. Neuropsychopharmacology. 2009;34:390–8.

    Article  CAS  PubMed  Google Scholar 

  81. Månsson KNT, Carlbring P, Frick A, Engman J, Olsson C-J, Bodlund O, et al. Altered neural correlates of affective processing after internet-delivered cognitive behavior therapy for social anxiety disorder. Psychiatry Res Neuroimaging. 2013;214:229–37.

    Article  Google Scholar 

  82. Phan KL, Coccaro EF, Angstadt M, Kreger KJ, Mayberg HS, Liberzon I, et al. Corticolimbic brain reactivity to social signals of threat before and after sertraline treatment in generalized social phobia. Biol Psychiatry. 2013;73:329–36.

    Article  CAS  PubMed  Google Scholar 

  83. Yuan M, Zhu H, Qiu C, Meng Y, Zhang Y, Shang J, et al. Group cognitive behavioral therapy modulates the resting-state functional connectivity of amygdala-related network in patients with generalized social anxiety disorder. BMC Psychiatry. 2016;16:198.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Åhs F, Gingnell M, Furmark T, Fredrikson M. Within-session effect of repeated stress exposure on extinction circuitry function in social anxiety disorder. Psychiatry Res Neuroimaging. 2017;261:85–90.

    Article  PubMed  Google Scholar 

  85. Barton DA, Esler MD, Dawood T, Lambert EA, Haikerwal D, Brenchley C, et al. Elevated brain serotonin turnover in patients with depression: effect of genotype and therapy. Arch Gen Psychiatry. 2008;65:38–46.

    Article  CAS  PubMed  Google Scholar 

  86. Esler M, Lambert E, Alvarenga M, Socratous F, Richards J, Esler M, et al. Increased brain serotonin turnover in panic disorder patients in the absence of a panic attack: reduction by a selective serotonin reuptake inhibitor: research report. Stress. 2007;10:295–304.

    Article  CAS  PubMed  Google Scholar 

  87. Honig G, Jongsma ME, van der Hart MCG, Tecott LH. Chronic citalopram administration causes a sustained suppression of serotonin synthesis in the mouse forebrain. PLoS One. 2009;4:e6797.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Xu Y-L, Reinscheid RK, Huitron-Resendiz S, Clark SD, Wang Z, Lin SH, et al. Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects. Neuron. 2004;43:487–97.

    Article  CAS  PubMed  Google Scholar 

  89. Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E. Oxytocin increases trust in humans. Nature. 2005;435:673–6.

    Article  CAS  PubMed  Google Scholar 

  90. Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U. Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol Psychiatry. 2003;54:1389–98.

    Article  CAS  PubMed  Google Scholar 

  91. Dodhia S, Hosanagar A, Fitzgerald DA, Labuschagne I, Wood AG, Nathan PJ, et al. Modulation of resting-state amygdala-frontal functional connectivity by oxytocin in generalized social anxiety disorder. Neuropsychopharmacology. 2014;39:2061–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Gorka SM, Fitzgerald DA, Labuschagne I, Hosanagar A, Wood AG, Nathan PJ, et al. Oxytocin modulation of amygdala functional connectivity to fearful faces in generalized social anxiety disorder. Neuropsychopharmacology. 2015;40:278–86.

    Article  CAS  PubMed  Google Scholar 

  93. Guastella AJ, Howard AL, Dadds MR, Mitchell P, Carson DS. A randomized controlled trial of intranasal oxytocin as an adjunct to exposure therapy for social anxiety disorder. Psychoneuroendocrinology. 2009;34:917–23.

    Article  CAS  PubMed  Google Scholar 

  94. Blomhoff S, Haug TT, Hellström K, Holme I, Humble M, Madsbu HP, et al. Randomised controlled general practice trial of sertraline, exposure therapy and combined treatment in generalised social phobia. Br J Psychiatry. 2001;179:23–30.

    Article  CAS  PubMed  Google Scholar 

  95. • Gingnell M, Frick A, Engman J, Alaie I, Björkstrand J, Faria V, et al. Combining escitalopram and cognitive–behavioural therapy for social anxiety disorder: randomised controlled fMRI trial. Br J Psychiatry. 2016;209:229–35. Pharmacotherapy is frequently combined with psychotherapy in clinical practice; findings show comparable reductions in amygdala response to emotional faces in patients who demonstrate clinical improvement regardless of combined treatment or monotherapy.

    Article  PubMed  Google Scholar 

  96. Young KS, Burklund LJ, Torre JB, Saxbe D, Lieberman MD, Craske MG. Treatment for social anxiety disorder alters functional connectivity in emotion regulation neural circuitry. Psychiatry Res Neuroimaging. 2017;261:44–51.

    Article  PubMed  Google Scholar 

  97. Månsson KNT, Salami A, Frick A, Carlbring P, Andersson G, Furmark T, et al. Neuroplasticity in response to cognitive behavior therapy for social anxiety disorder. Transl Psychiatry. 2016;6:e727.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Månsson KNT, Salami A, Carlbring P, Boraxbekk C-J, Andersson G, Furmark T. Structural but not functional neuroplasticity one year after effective cognitive behaviour therapy for social anxiety disorder. Behav Brain Res. 2017;318:45–51.

    Article  PubMed  Google Scholar 

  99. Bandelow B, Sagebiel A, Belz M, Görlich Y, Michaelis S, Wedekind D. Enduring effects of psychological treatments for anxiety disorders: meta-analysis of follow-up studies. Br J Psychiatry. 2018;212:333–8.

    Article  PubMed  Google Scholar 

  100. Goldin PR, Ziv M, Jazaieri H, Hahn K, Heimberg R, Gross JJ. Impact of cognitive behavioral therapy for social anxiety disorder on the neural dynamics of cognitive reappraisal of negative self-beliefs: randomized clinical trial. JAMA Psychiatry. 2013;70:1048–56.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Goldin PR, Ziv M, Jazaieri H, Weeks J, Heimberg RG, Gross JJ. Impact of cognitive-behavioral therapy for social anxiety disorder on the neural bases of emotional reactivity to and regulation of social evaluation. Behav Res Ther. 2014;62:97–106.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Doruyter A, Lochner C, Jordaan GP, Stein DJ, Dupont P, Warwick JM. Resting functional connectivity in social anxiety disorder and the effect of pharmacotherapy. Psychiatry Res Neuroimaging. 2016;251:34–44.

    Article  PubMed  Google Scholar 

  103. • Li Y, Meng Y, Yuan M, Zhang Y, Ren Z, Zhang Y, et al. Therapy for adult social anxiety disorder: a meta-analysis of functional neuroimaging studies. J Clin Psychiatry. 2016;77:e1429–38. This meta-analysis of pre-to-post treatment neuroimaging studies of social anxiety disorder reports treatment-dependent and treatment-independent effects in brain activity and associations between brain response and illness severity following treatment.

    Article  PubMed  Google Scholar 

  104. Sladky R, Höflich A, Atanelov J, Kraus C, Baldinger P, Moser E, et al. Increased neural habituation in the amygdala and orbitofrontal cortex in social anxiety disorder revealed by fMRI. PLoS One. 2012;7:e50050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Cui Q, Vanman EJ, Long Z, Pang Y, Chen Y, Wang Y, et al. Social anxiety disorder exhibit impaired networks involved in self and theory of mind processing. Soc Cogn Affect Neurosci. 2017;12:1284–95.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by NIMH MH112705 (HK).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Heide Klumpp.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Anxiety Disorders

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Klumpp, H., Fitzgerald, J.M. Neuroimaging Predictors and Mechanisms of Treatment Response in Social Anxiety Disorder: an Overview of the Amygdala. Curr Psychiatry Rep 20, 89 (2018). https://doi.org/10.1007/s11920-018-0948-1

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11920-018-0948-1

Keywords

Navigation