Skip to main content
SpringerLink
Log in

Localized gray matter volume abnormalities in generalized anxiety disorder

  • Original Paper
  • Published:
European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

Generalized anxiety disorder (GAD) is characterized by excessive and persistent worrying. Neural substrates of this disorder are insufficiently understood, which relates to functional as well as to structural brain abnormalities. Especially, findings on the neuroanatomy of GAD have been inconsistent and were predominantly derived from pediatric samples. Therefore, we studied adult patients. Thirty-one women (16 patients with GAD and 15 healthy control participants) underwent structural MRI scanning. Gray matter volumes for specific brain regions involved in worrying, anticipatory anxiety, and emotion regulation were analyzed by means of voxel-based morphometry. Relative to controls, patients with GAD had larger volumes of the amygdala and the dorsomedial prefrontal cortex (DMPFC). Moreover, patients’ self-reports on symptom severity were positively correlated with volumes of the DMPFC and the anterior cingulate cortex. Patients with GAD show localized gray matter volume differences in brain regions associated with anticipatory anxiety and emotion regulation. This abnormality may represent either a predisposition for GAD or a consequence of disorder-specific behavior, such as chronic worrying. This issue should be addressed in future MRI studies.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Press, Washington, DC

    Google Scholar 

  2. Borkovec TD, Alcaine O, Behar E (2004) Avoidance theory of worry and generalized anxiety disorder. In: Heimberg RG, Turk C, Mennin DS (eds) General anxiety disorder: advances in research and practice. Guilford Press, New York, pp 77–108

    Google Scholar 

  3. Mennin DS, Heimberg RG, Turk CL, Fresco DM (2005) Preliminary evidence for an emotion dysregulation model of generalized anxiety disorder. Behav Res Ther 43:1281–1310

    Article  PubMed  Google Scholar 

  4. Nitschke JB, Sarinopoulos I, Oathes DJ, Johnstone T, Whalen PJ, Davidson RJ, Kalin NH (2009) Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment reponse. Am J Psychiatry 166:302–310

    Article  PubMed  Google Scholar 

  5. Monk CS, Telzer EH, Mogg K, Bradley BP, Mai X, Louro HM, Chen G, McClure-Tone EB, Ernst M, Pine DS (2008) Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder. Arch Gen Psychiatry 65:568–576

    Article  PubMed  Google Scholar 

  6. McClure EB, Monk CS, Nelson EE, Parrish JM, Adler A, Blair RJ, Fromm S, Charney DS, Leibenluft E, Ernst M, Pine DS (2007) Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder. Arch Gen Psychiatry 64:97–106

    Article  PubMed  Google Scholar 

  7. Blair K, Shaywitz J, Smith BW, Rhodes R, Geraci M, Jones M, McCaffrey D, Vythilingam M, Finger E, Mondillo K, Jacobs M, Charney DS, Blair RJ, Drevets WC, Pine DS (2008) Response to emotional expressions in generalized social phobia and generalized anxiety disorder: evidence for separate disorders. Am J Psychiatry 165:1193–1202

    Article  PubMed  Google Scholar 

  8. Whalen PJ, Johnstone T, Somerville LH, Nitschke JB, Polis S, Alexander AL, Davidson RJ, Kalin NH (2007) A functional magnetic resonance imaging predictor of treatment response to venlafaxine in generalized anxiety disorder. Biol Psychiatry 63:858–863

    Article  PubMed  Google Scholar 

  9. Etkin A, Prater KE, Schatzberg AF, Menon V, Greicius MD (2009) Disrupted amygdalar subregion functional connectivity and evidence for a compensatory network in generalized anxiety disorder. Arch Gen Psychiatry 66:1361–1372

    Article  PubMed  Google Scholar 

  10. Hoehn-Saric R, Schlund MW, Wong SSY (2004) Effects of citalopram on worry and brain activation in patients with generalized anxiety disorder. Psychiat Res Neuroim 13:111–121

    Google Scholar 

  11. Monk CS, Nelson EE, McClure EB, Mogg K, Bradley BP, Leibenluft E (2006) Ventrolateral prefrontal cortex activation and attentional bias in response to angry faces in adolescents with generalized anxiety disorder. Am J Psychiatry 163:1091–1097

    Article  PubMed  Google Scholar 

  12. Paulesu E, Sambugaro E, Torti T, Danelli L, Ferri F, Scialfa G, Sberna M, Ruggiero GM, Bottini G, Sassaroli S (2009) Neural correlates of worry in generalized anxiety disorder and in normal controls: a functional MRI study. Psychol Med 7:1–8

    Google Scholar 

  13. Etkin A, Prater KE, Hoeft F, Menon V, Schatzberg AF (2010) Failure of anterior cingulate activation and connectivity with the amygdala during implicit regulation of emotional processing in Generalized Anxiety Disorder. Am J Psychiatry 167:545–554

    Google Scholar 

  14. De Bellis MD, Casey BJ, Dahl R, Birmaher B, Williamson D, Thomas KM, Axelson DA, Frustaci K, Boring AM, Hall J, Ryan ND (2000) A pilot study of amygdala volumes in pediatric generalized anxiety disorder. Biol Psychiatry 48:51–57

    Article  PubMed  Google Scholar 

  15. De Bellis MD, Keshavan MS, Shifflett H, Iyengar S, Dahl RE, Axelson DA (2002) Superior temporal gyrus volumes in pediatric generalized anxiety disorder. Biol Psychiatry 51:553–562

    Article  PubMed  Google Scholar 

  16. Milham MP, Nugent AC, Drevets WC, Dickstein DP, Leibenluft E, Ernst M, Charney D, Pine DS (2005) Selective reduction in amygdala volume in pediatric anxiety disorders: a voxel-based morphometry investigation. Biol Psychiatry 57:961–966

    Article  PubMed  Google Scholar 

  17. Margraf J (1994) Diagnostisches kurz-interview bei psychischen Störungen (Mini-DIPS). Springer, Berlin

    Google Scholar 

  18. Stoeber J (1995) Penn state worry questionnaire–German version. Z Diff Diagn Psychol 16:50–63

    Google Scholar 

  19. Möbius J, Hoyer J (2003) Metacogntion questionnaire (MKF). In: Hoyer J, Margraf J (eds) Angst-diagnostik. Grundlagen und Testverfahren. Berlin, Springer, pp 220–223

    Google Scholar 

  20. Hautzinger M, Bailer M, Worall H, Keller F (1993) Beck-depressions-inventar (BDI). Bern, Huber

    Google Scholar 

  21. Ashburner J, Friston K (2006) Unified segmentation. NeuroImage 26:839–851

    Article  Google Scholar 

  22. Maldjian JA, Laurienti PJ, Burdette JB, Kraft RA (2003) An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. NeuroImage 19:1233–1239

    Article  PubMed  Google Scholar 

  23. Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N (2002) Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 15:273–289

    Article  PubMed  CAS  Google Scholar 

  24. Draganski B, Gaser C, Busch V, Schuierer G, Bogdahn U (2004) Neuroplasticity: changes in gray matter induced by training. Nature 427:311–312

    Article  PubMed  CAS  Google Scholar 

  25. Maguire EA, Gadian DG, Johnsrude IS, Good CD, Ashburner J (2000) Navigation-related structural change in the hippocampi of taxi drivers. Proc Natl Acad Sci USA 97:4398–4403

    Article  PubMed  CAS  Google Scholar 

  26. Nitschke JB, Sarinopoulos I, Mackiewicz KL, Schaefer HS, Davidson RJ (2006) Functional neuroanatomy of aversion and its anticipation. NeuroImage 29:106–116

    Article  PubMed  Google Scholar 

  27. Critchely H, Mathias C, Dolan R (2001) Neural activity in the human brain relating to uncertainty and arousal during anticipation. Neuron 29:537–545

    Article  Google Scholar 

  28. Angst J, Gamma A, Baldwin DS, Ajdacic-Gross V, Rösler W (2009) The generalized anxiety spectrum: prevalence, onset, course and outcome. Eur Arch Psychiatry Clin Neurosci 259:37–45

    Article  PubMed  Google Scholar 

  29. Schienle A, Schäfer A, Hermann A, Rohrmann S, Vaitl D (2007) Symptom provocation and symptom reduction in spider phobia. Eur Arch Psychiatry Clin Neurosci 257:486–493

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

The authors have no conflict of interest to declare.

Author information

Authors and Affiliations

  1. Department of Clinical Psychology, University of Graz, Universitätsplatz 2/III, 8010, Graz, Austria

    Anne Schienle & Axel Schäfer

  2. Department of Radiology, Medical University of Graz, Graz, Austria

    Franz Ebner

Authors
  1. Anne Schienle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Franz Ebner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Axel Schäfer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anne Schienle.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schienle, A., Ebner, F. & Schäfer, A. Localized gray matter volume abnormalities in generalized anxiety disorder. Eur Arch Psychiatry Clin Neurosci 261, 303–307 (2011). https://doi.org/10.1007/s00406-010-0147-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00406-010-0147-5

Keywords

Search

Navigation