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Vol. 82, No. 3, 2013
Issue release date: April 2013
Psychother Psychosom 2013;82:142-151

Using Neurobiological Measures to Predict and Assess Treatment Outcome of Psychotherapy in Posttraumatic Stress Disorder: Systematic Review

Zantvoord J.B. · Diehle J. · Lindauer R.J.L.
Department of Child and Adolescent Psychiatry, Academic Medical Centre, University of Amsterdam and the Bascule Academic Centre for Child and Adolescent Psychiatry, Amsterdam, The Netherlands

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Background: Trauma-focused cognitive-behavioral therapy (TF-CBT) and eye movement desensitization and reprocessing (EMDR) are effective treatments for posttraumatic stress disorder. However, little is known about their neurobiological effects. The usefulness of neurobiological measures to predict the treatment outcome of psychotherapy also has yet to be determined. Methods: Systematic review of randomized controlled trials (RCTs) focused on neurobiological treatment effects of TF-CBT or EMDR and trials with neurobiological measures as predictors of treatment response. Results: We included 23 publications reporting on 16 separate trials. TF-CBT was compared with a waitlist in most trials. TF-CBT was associated with a decrease in heart rate and blood pressure and changes in activity but not in volume of frontal brain structures and the amygdala. Neurobiological changes correlated with changes in symptom severity. EMDR was only tested against other active treatments in included trials. We did not find a difference in neurobiological treatment effects between EMDR and other treatments. Publications on neurobiological predictors of treatment response showed ambiguous results. Conclusion: TF-CBT was associated with a reduction of physiological reactivity. There is some preliminary evidence that TF-CBT influences brain regions involved in fear conditioning, extinction learning and possibly working memory and attention regulation; however, these effects could be nonspecific psychotherapeutic effects. Future trials should use paradigms aimed specifically at these brain regions and physiological reactivity. There are concerns regarding the risk of bias in some of the RCTs, indicating that methodologically more rigorous trials are required. Trials with neurobiological measures as predictors of treatment outcome render insufficient results to be useful in clinical practice.

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  1. Kessler RC: Posttraumatic stress disorder: the burden to the individual and to society. J Clin Psychiatry 2000;61(suppl 5):4-12.

    External Resources

  2. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE: Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62:617-627.
  3. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4. Text revision (DSM-IV-TR). Washington, American Psychiatric Publishing, 2000.
  4. Yehuda R, LeDoux J: Response variation following trauma: a translational neuroscience approach to understanding PTSD. Neuron 2007;56:19-32.
  5. Francati V, Vermetten E, Bremner JD: Functional neuroimaging studies in posttraumatic stress disorder: review of current methods and findings. Depress Anxiety 2007;24:202-218.
  6. Karl A, Schaefer M, Malta LS, Dorfel D, Rohleder N, Werner A: A meta-analysis of structural brain abnormalities in PTSD. Neurosci Biobehav Rev 2006;30:1004-1031.
  7. Charney DS: Psychobiological mechanisms of resilience and vulnerability: implications for successful adaptation to extreme stress. Am J Psychiatry 2004;161:195-216.
  8. Carrion VG, Weems CF, Richert K, Hoffman BC, Reiss AL: Decreased prefrontal cortical volume associated with increased bedtime cortisol in traumatized youth. Biol Psychiatry 2010;68:491-493.
  9. Rodrigues SM, LeDoux JE, Sapolsky RM: The influence of stress hormones on fear circuitry. Annu Rev Neurosci 2009;32:289-313.
  10. Koenen KC, Amstadter AB, Nugent NR: Gene-environment interaction in posttraumatic stress disorder: an update. J Trauma Stress 2009;22:416-426.
  11. Foa EB, Keane TM, Friedman MJ, Cohen JA: Effective treatments for PTSD: Practice Guidelines from the International Society for Traumatic Stress Studies. New York, The Guilford Press, 2008, p 139.
  12. Bisson J, Andrew M: Psychological treatment of post-traumatic stress disorder (PTSD). Cochrane Database Syst Rev 2007;CD003388.
  13. Roffman JL, Marci CD, Glick DM, Dougherty DD, Rauch SL: Neuroimaging and the functional neuroanatomy of psychotherapy. Psychol Med 2005;35:1385-1398.
  14. Linden DE: How psychotherapy changes the brain - the contribution of functional neuroimaging. Mol Psychiatry 2006;11:528-538.
  15. Siegle GJ, Carter CS, Thase ME: Use of fMRI to predict recovery from unipolar depression with cognitive behavior therapy. Am J Psychiatry 2006;163:735-738.
  16. Knaup C, Koesters M, Schoefer D, Becker T, Puschner B: Effect of feedback of treatment outcome in specialist mental healthcare: meta-analysis. Br J Psychiatry 2009;195:15-22.
  17. Moher D, Liberati A, Tetzlaff J, Altman DG: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009;339:b2535.
  18. Higgins JPT, Green S: Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. The Cochrane Collaboration (available from, 2011).
  19. Stein MB, Walker JR, Hazen AL, Forde DR: Full and partial posttraumatic stress disorder: findings from a community survey. Am J Psychiatry 1997;154:1114-1119.
  20. Foa EB: Prolonged exposure therapy: past, present, and future. Depress Anxiety 2011;28:1043-1047.
  21. Lindauer RJ, Gersons BP, van Meijel EP, Blom K, Carlier IV, Vrijlandt I, Olff M: Effects of brief eclectic psychotherapy in patients with posttraumatic stress disorder: randomized clinical trial. J Trauma Stress 2005;18:205-212.
  22. Lindauer RT, van Meijel EP, Jalink M, Olff M, Carlier IV, Gersons BP: Heart rate responsivity to script-driven imagery in posttraumatic stress disorder: specificity of response and effects of psychotherapy. Psychosom Med 2006;68:33-40.
  23. Hinton DE, Hofmann SG, Pollack MH, Otto MW: Mechanisms of efficacy of CBT for Cambodian refugees with PTSD: improvement in emotion regulation and orthostatic blood pressure response. CNS Neurosci Ther 2009;15:255-263.
  24. Rabe S, Dorfel D, Zollner T, Maercker A, Karl A: Cardiovascular correlates of motor vehicle accident-related posttraumatic stress disorder and its successful treatment. Appl Psychophysiol Biofeedback 2006;31:315-330.
  25. Karl A, Malta LS, Alexander J, Blanchard EB: Startle responses in motor vehicle accident survivors: a pilot study. Appl Psychophysiol Biofeedback 2004;29:223-231.
  26. Blanchard EB, Hickling EJ, Veazey CH, Buckley TC, Freidenberg BM, Walsh JD, Keefer L: Treatment-related changes in cardiovascular reactivity to trauma cues in motor vehicle accident-related PTSD. Behav Ther 2002;33:417-426.

    External Resources

  27. Fecteau G, Nicki R: Cognitive behavioural treatment of post traumatic stress disorder after motor vehicle accident. Behav Cogn Psychother 1999;27:201-214.
  28. Lindauer RJ, Vlieger EJ, Jalink M, Olff M, Carlier IV, Majoie CB, den Heeten GJ, Gersons BP: Effects of psychotherapy on hippocampal volume in out-patients with post-traumatic stress disorder: a MRI investigation. Psychol Med 2005;35:1421-1431.
  29. Lindauer RJ, Booij J, Habraken JB, van Meijel EP, Uylings HB, Olff M, Carlier IV, den Heeten GJ, van Eck-Smit BL, Gersons BP: Effects of psychotherapy on regional cerebral blood flow during trauma imagery in patients with post-traumatic stress disorder: a randomized clinical trial. Psychol Med 2008;38:543-554.
  30. Rabe S, Zoellner T, Beauducel A, Maercker A, Karl A: Changes in brain electrical activity after cognitive behavioral therapy for posttraumatic stress disorder in patients injured in motor vehicle accidents. Psychosom Med 2008;70:13-19.
  31. Peres JF, Newberg AB, Mercante JP, Simao M, Albuquerque VE, Peres MJ, Nasello AG: Cerebral blood flow changes during retrieval of traumatic memories before and after psychotherapy: a SPECT study. Psychol Med 2007;37:1481-1491.
  32. Gerardi M, Rothbaum BO, Astin MC, Kelley M: Cortisol response following exposure treatment for PTSD in rape victims. J Aggression Maltreat Trauma 2010;19:349-356.
  33. Rogers S, Silver SM, Goss J, Obenchain J, Willis A, Whitney RL: A single session, group study of exposure and eye movement desensitization and reprocessing in treating posttraumatic stress disorder among Vietnam War veterans: preliminary data. J Anxiety Disord 1999;13:119-130.
  34. Carlson JG, Chemtob CM, Rusnak K, Hedlund NL, Muraoka MY: Eye movement desensitization and reprocessing (EDMR) treatment for combat-related posttraumatic stress disorder. J Trauma Stress 1998;11:3-24.
  35. Renfrey G, Spates CR: Eye movement desensitization: a partial dismantling study. J Behav Ther Exp Psychiatry 1994;25:231-239.
  36. Peres JFP, Foerster B, Santana LG, Domin-gues Fereira M, Nasello AG, Savoia MN, Moreira-Almeida A, Lederman H: Police officers under attack: resilience implications of an fMRI study. J Psychiatric Res 2011;45:727-734.
  37. Adenauer H, Catani C, Gola H, Keil J, Ruf M, Schauer M, Neuner F: Narrative exposure therapy for PTSD increases top-down processing of aversive stimuli - evidence from a randomized controlled treatment trial. BMC Neurosci 2011;12:127.
  38. Yehuda R, Bierer LM, Sarapas C, Makotkine I, Andrew R, Seckl JR: Cortisol metabolic predictors of response to psychotherapy for symptoms of PTSD in survivors of the World Trade Center attacks on September 11, 2001. Psychoneuroendocrinology 2009;34:1304-1313.
  39. Bryant RA, Felmingham KL, Falconer EM, Pe BL, Dobson-Stone C, Pierce KD, Schofield PR: Preliminary evidence of the short allele of the serotonin transporter gene predicting poor response to cognitive behavior therapy in posttraumatic stress disorder. Biol Psychiatry 2010;67:1217-1219.
  40. Bryant RA, Felmingham K, Kemp A, Das P, Hughes G, Peduto A, Williams L: Amygdala and ventral anterior cingulate activation predicts treatment response to cognitive behaviour therapy for post-traumatic stress disorder. Psychol Med 2008;38:555-561.
  41. Bryant RA, Felmingham K, Whitford TJ, Kemp A, Hughes G, Peduto A, Williams LM: Rostral anterior cingulate volume predicts treatment response to cognitive-behavioural therapy for posttraumatic stress disorder. J Psychiatry Neurosci 2008;33:142-146.

    External Resources

  42. Nardo D, Hogberg G, Looi JC, Larsson S, Hallstrom T, Pagani M: Gray matter density in limbic and paralimbic cortices is associated with trauma load and EMDR outcome in PTSD patients. J Psychiatr Res 2010;44:477-485.
  43. Tarrier N, Pilgrim H, Sommerfield C, Faragher B, Reynolds M, Graham E, Barrowclough C: A randomized trial of cognitive therapy and imaginal exposure in the treatment of chronic posttraumatic stress disorder. J Consult Clin Psychol 1999;67:13-18.
  44. Blanchard EB, Hickling EJ, Malta LS, Jaccard J, Devineni T, Veazey CH, Galovski TE: Prediction of response to psychological treatment among motor vehicle accident survivors with PTSD. Behav Ther 2003;34:351-363.
  45. Blake DD, Weathers FW, Nagy LM, Kaloupek DG, Gusman FD, Charney DS, Keane TM: The development of a clinician-administered PTSD scale. J Trauma Stress 1995;8:75-90.
  46. Davidson JRT, Kudler HS, Smith RD: Assessment and pharmacotherapy of posttraumatic stress disorder; in Giller JEL (ed): Biological Assessment and Treatment of Posttraumatic Stress Disorder. Washington, American Psychiatric Press, 1990, pp 205-221.
  47. LeDoux JE: Emotion circuits in the brain. Annu Rev Neurosci 2000;23:155-184.
  48. Shaw ME, Moores KA, Clark RC, McFarlane AC, Strother SC, Bryant RA, Brown GC, Taylor JD: Functional connectivity reveals inefficient working memory systems in post-traumatic stress disorder. Psychiatry Res 2009;172:235-241.
  49. Veltman DJ, Rombouts SA, Dolan RJ: Maintenance versus manipulation in verbal working memory revisited: an fMRI study. Neuroimage 2003;18:247-256.
  50. Lanius RA, Williamson PC, Hopper J, Densmore M, Boksman K, Gupta MA, Neufeld RW, Gati JS, Menon RS: Recall of emotional states in posttraumatic stress disorder: an fMRI investigation. Biol Psychiatry 2003;53:204-210.
  51. Lanius RA, Williamson PC, Densmore M, Boksman K, Neufeld RW, Gati JS, Menon RS: The nature of traumatic memories: a 4-T fMRI functional connectivity analysis. Am J Psychiatry 2004;161:36-44.
  52. Bremner JD, Vythilingam M, Vermetten E, Southwick SM, McGlashan T, Nazeer A, Khan S, Vaccarino LV, Soufer R, Garg PK, Ng CK, Staib LH, Duncan JS, Charney DS: MRI and PET study of deficits in hippocampal structure and function in women with childhood sexual abuse and posttraumatic stress disorder. Am J Psychiatry 2003;160:924-932.
  53. Lindauer RJ, Vlieger EJ, Jalink M, Olff M, Carlier IV, Majoie CB, den Heeten GJ, Gersons BP: Smaller hippocampal volume in Dutch police officers with posttraumatic stress disorder. Biol Psychiatry 2004;56:356-363.
  54. Orr SP, Metzger LJ, Pitman RK: Psychophysiology of post-traumatic stress disorder. Psychiatr Clin North Am 2002;25:271-293.
  55. Phelps EA, LeDoux JE: Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron 2005;48:175-187.
  56. Wessa M, Flor H: Failure of extinction of fear responses in posttraumatic stress disorder: evidence from second-order conditioning. Am J Psychiatry 2007;164:1684-1692.
  57. Oei NY, Tollenaar MS, Spinhoven P, Elzinga BM: Hydrocortisone reduces emotional distracter interference in working memory. Psychoneuroendocrinology 2009;34:1284-1293.
  58. McLaughlin KA, Green JG, Gruber MJ, Sampson NA, Zaslavsky AM, Kessler RC: Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication II: associations with persistence of DSM-IV disorders. Arch Gen Psychiatry 2010;67:124-132.
  59. Pynoos RS, Steinberg AM, Layne CM, Briggs EC, Ostrowski SA, Fairbank JA: DSM-V PTSD diagnostic criteria for children and adolescents: a developmental perspective and recommendations. J Trauma Stress 2009;22:391-398.

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