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Do psychotherapies produce neurobiological effects?

Published online by Cambridge University Press:  24 June 2014

Veena Kumari
Veena Kumari*
Affiliation:
Department of Psychology, Institute of Psychiatry, King's College London, London, UK
*
Veena Kumari, PhD, PO 78, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK, Tel: +44 207 848 0233; Fax: +44 207 848 0646; E-mail: v.kumari@iop.kcl.ac.uk
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Abstract

Background:

An area of recent interest in psychiatric research is the application of neuroimaging techniques to investigate neural events associated with the development and the treatment of symptoms in a number of psychiatric disorders.

Objective:

To examine whether psychological therapies modulate brain activity and, if so, to examine whether these changes similar to those found with relevant pharmacotherapy in various mental disorders.

Methods:

Relevant data were identified from Pubmed and PsycInfo searches up to July 2005 using combinations of keywords including ‘psychological therapy’, ‘behaviour therapy’, ‘depression’, ‘panic disorder’, ‘phobia’, ‘obsessive compulsive disorder’, ‘schizophrenia’, ‘psychosis’, ‘brain activity’, ‘brain metabolism’, ‘PET’, ‘SPECT’ and ‘fMRI’.

Results:

There was ample evidence to demonstrate that psychological therapies produce changes at the neural level. The data, for example in depression, panic disorder, phobia and obsessive compulsive disorder (OCD), clearly suggested that a change in patients' symptoms and maladaptive behaviour at the mind level with psychological techniques is accompanied with functional brain changes in relevant brain circuits. In many studies, cognitive therapies and drug therapies achieved therapeutic gains through the same neural pathways although the two forms of treatment may still have different mechanisms of action.

Conclusions:

Empirical research indicates a close association between the ‘mind’ and the ‘brain’ in showing that changes made at the mind level in a psychotherapeutic context produce changes at the brain level. The investigation of changes in neural activity with psychological therapies is a novel area which is likely to enhance our understanding of the mechanisms for therapeutic changes across a range of disorders.

Keywords

behaviour therapybrainfunctional neuroimagingneural networkspsychiatric disorders
Type
Review Article
Information
Acta Neuropsychiatrica , Volume 18 , Issue 2 , April 2006 , pp. 61 - 70
Copyright
Copyright © 2006 Blackwell Munksgaard

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References

Andreasen, NC. Linking mind with the brain in the study of mental illnesses: a project for scientific psychopathology. Science 1997;275: 1568–1593. CrossRefGoogle Scholar
Konradi, C, Heckers, S. Antipsychotic drugs and neuroplasticity: insights into the treatment and neurobiology of schizophrenia. Biol Psychiatry 2001;50: 729–942. CrossRefGoogle ScholarPubMed
Mayberg, HS. Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment. Br Med Bull 2003;65: 193–207. CrossRefGoogle ScholarPubMed
Lahti, AC, Holcomb, HH, Weiler, MAet al. Clozapine but not haloperidol re-establishes normal task-activated rCBF patterns in schizophrenia within the anterior cingulate cortex. Neuropsychopharmacol 2004;29 (2):171–178. CrossRefGoogle Scholar
Davis, CE, Jeste, DV, Eyler, LT. Review of longitudinal neuroimaging studies of drug treatments in patients with schizophrenia. Schizophr Res 2005;78(1):45–60.CrossRefGoogle ScholarPubMed
Hollon, SD, Derubeis, RJ, Evans, MDet al. Cognitive therapy and pharmacotherapy for depression: singly and in combination. Arch Gen Psychiatry 1992;49: 774–781. CrossRefGoogle ScholarPubMed
Derubeis, RJ, Gelfand, LA, Tang, TZ, Simons, AD. Medications versus cognitive behavior therapy for severely depressed outpatients: mega-analysis of four randomized comparisons. Am J Psychiatry 1999;156: 1007–1013. CrossRefGoogle ScholarPubMed
Öst, LG. One-session treatment for specific phobias. Behav Res Ther 1989;27: 1–7. CrossRefGoogle ScholarPubMed
Öst, LG. One-session group treatment of spider phobia. Behav Res Ther 1996;34: 707–715. CrossRefGoogle ScholarPubMed
Antony, MM, Swinson, RP, Specific Phobia. In: Antony, MM and Swinson, RP, eds. Phobic disorders and panic in adults: a guide to assessment and treatment. Washington, DC: American Psychological Association, 2000: 79–104. Google Scholar
Perani, D, Colombo, C, Bressi, Set al. [18F]FDGPET study in obsessive-compulsive disorder. A clinical/metabolic correlation study after treatment. Br J Psychiatry 1995;166 (2):244–250. CrossRefGoogle Scholar
Otto, MW, Pollack, MH, Maki, KM. Empirically supported treatments for panic disorder: costs, benefits, and stepped care. J Consult Clin Psychol 2000;68 (4):556–563. CrossRefGoogle ScholarPubMed
Gorman, JM, Shear, K, Cowley, Det al. Practice guideline for the treatment of patients with panic disorder. In: American Psychiatric Association guidelines for the treatment of psychiatric disorders. Compendium 2002: 635–696, American Psychiatric Publishing, Inc., Arlington, VA.Google Scholar
Kjaer, TW, Bertelsen, C, Piccini, P, Brooks, D, Alving, J, Lou, HC. Increased dopamine tone during meditation-induced change of consciousness. Brain Res Cogn Brain Res 2002;13 (2):255–259. CrossRefGoogle ScholarPubMed
Davidson, RJ, Ekman, P, Saron, C, Senulis, J, Friesen, WV. Approach/withdrawal and cerebral asymmetry: emotional expression and brain physiology. I. J Pers Soc Psychol 1990;58: 330–341. CrossRefGoogle ScholarPubMed
Davidson, RJ. Emotion and affective style: hemispheric substrates. Psychol Sci 1992;3: 39–43. CrossRefGoogle Scholar
Davidson, RJ, Kabat-Zinn, J, Schumacher, Jet al. Alterations in brain and immune function produced by mindfulness meditation. Psychosom Med 2003;65 (4):564–570. CrossRefGoogle ScholarPubMed
Baxter, LR JR, Schwartz, JM, Bergman, KSet al. Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch Gen Psychiatry 1992;49 (9):681–689. CrossRefGoogle ScholarPubMed
Wolpe, J. The practice of behavior therapy. New York: Pergamon Press, 1982. Google Scholar
Montarolo, PG, Goelet, P, Castellucci, VF, Morgan, J, Kandel, ER, Schacher, S. A critical period for macromolecular synthesis in long-term heterosynaptic facilitation in Aplysia. Science 1986;234 (4781):1249–1254. CrossRefGoogle ScholarPubMed
Kandel, ER. Genes, nerve cells, and the remembrance of things past. J Neuropsychiatry Clin Neurosci 1989;1 (2):103–125. Google ScholarPubMed
Mayberg, H. Limbic-cortical dysregulation: a proposed model of depression. J Neuropsychiatry Clin Neurosci 1997;9: 471–481. Google ScholarPubMed
Byrun, CE, Ahearn, EP, Krishan, KRR. A neuroanatomic model for depression. Prog Neuro-Psychopharmacol Biol Psychiat 1999;23: 175–193. CrossRefGoogle Scholar
Brody, AL, Barsom, MW, Bota, RG, Saxena, S. Prefrontal-subcortical and limbic circuit mediation of major depressive disorder. Semin Clin Neuropsychiatry 2001;6: 102–112. CrossRefGoogle ScholarPubMed
Drevets, WC. Functional neuroimaging studies of depression: the anatomy of melancholia. Annu Rev Med 1998;49: 341–361. CrossRefGoogle ScholarPubMed
Drevets, WC. Prefrontal cortical-amygdalar metabolism in major depression. In: Mcginty, JF, ed. Advancing from the ventral striatum to the extended amygdala: implications for neuropsychiatry and drug use: in honor of Lennart Heimer. New York: New York Academy of Sciences, 1999: 614–637. Google Scholar
Mayberg, HS, Liotti, M, Brannan, SKet al. Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiatry 1999;156 (5):675–682. CrossRefGoogle ScholarPubMed
Brody, AL, Saxena, S, Silverman, DHet al. Brain metabolic changes in major depressive disorder from pre- to post-treatment with paroxetine. Psychiatry Res 1999;91 (3):127–139. CrossRefGoogle ScholarPubMed
Brody, AL, Saxena, S, Stoessel, Pet al. Brain metabolic changes associated with symptom factor improvement in major depressive disorder. Biol Psychiatry 2001;50 (3):171–178. CrossRefGoogle ScholarPubMed
Mayberg, H, Brannan, SK, Mahrin, RKet al. Cingulate function in depression: a potential predictor of treatment response. Neuroreport 1997;8: 1957–1961. CrossRefGoogle ScholarPubMed
Pizzagalli, D, Pascual-Marqui, RD, Nitschke, JBet al. Anterior cingulate activity as a predictor of degree of treatment response in major depression: evidence from brain electrical tomography analysis. Am J Psychiatry 2001;158 (3):405–415. CrossRefGoogle ScholarPubMed
Brody, AL, Saxena, S, Stoessel, Pet al. Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy. Arch Gen Psychiatry 2001;58: 631–640. CrossRefGoogle ScholarPubMed
Martin, SD, Martin, E, Rai, SS, Richardson, MA, Royall, R. Brain blood flow changes in depressed patients treated with interpersonal psychotherapy or venlafaxine hydrochloride: preliminary findings. Arch Gen Psychiatry 2001;58: 641–648. CrossRefGoogle ScholarPubMed
Goldapple, K, Segal, Z, Garson, Cet al. Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy. Arch Gen Psychiatry 2004;61 (1):34–41. CrossRefGoogle ScholarPubMed
Clark, D, Beck, AT, Alford, B. Scientific foundations of cognitive theory and therapy of depression. New York: John Wiley, 1999. Google Scholar
Seminowicz, DA, Mayberg, HS, McIntosh, ARet al. Limbic-frontal circuitry in major depression: a path modeling metanalysis. Neuroimage 2004;22 (1): 409–418. CrossRefGoogle ScholarPubMed
Gorman, JM, Liebowitz, MR, Fyer, AJ, Stein, J. A neuroanatomical hypothesis for panic disorder. Am J Psychiatry 1989;146 (2):148–161. Google ScholarPubMed
Prasko, J, Horacek, J, Zalesky, Ret al. The change of regional brain metabolism (18FDG PET) in panic disorder during the treatment with cognitive behavioral therapy or antidepressants. Neuro Endocrinol Lett 2004;25 (5):340–348. Google ScholarPubMed
Fredrikson, M, Wik, G, Greitz, Tet al. Regional cerebral blood flow during experimental phobic fear. Psychophysiology 1993;30: 126–130. CrossRefGoogle ScholarPubMed
Fredrikson, M, Wik, G, Annas, P, Ericson, K, Stone-Elander, S. Functional neuroanatomy of visually elicited simple phobic fear: additional data and theoretical analysis. Psychophysiology 1995;32: 43–48. CrossRefGoogle ScholarPubMed
Rauch, SL, Savage, CR, Alpert, NMet al. A positron emission tomographic study of simple phobic symptom provocation. Arch Gen Psychiatry 1995;52 (1):20–28. CrossRefGoogle ScholarPubMed
Johanson, A, Gustafson, L, Passant, Uet al. Brain function in spider phobia. Psychiatry Res 1998;84: 101–111. CrossRefGoogle ScholarPubMed
Paquette, V, Levesque, J, Mensour, Bet al. ‘Change the mind and you change the brain’: effects of cognitive-behavioral therapy on the neural correlates of spider phobia. Neuroimage 2003;18 (2):401–419. CrossRefGoogle ScholarPubMed
Gorman, JM, Kent, JM, Sullivan, GM, Coplan, JD. Neuroanatomical hypothesis of panic disorder, revised. Am J Psychiatry 2000;157 (4):493–505. CrossRefGoogle ScholarPubMed
Baxter, Lr JR, Phelps, ME, Mazziotta, JC, Guze, BH, Schwartz, JM, Selin, CE. Local cerebral glucose metabolic rates in obsessive-compulsive disorder. A comparison with rates in unipolar depression and in normal controls. Arch Gen Psychiatry 1987;44 (3):211–218. CrossRefGoogle ScholarPubMed
Insel, TR. Obsessive-compulsive disorder: a neuroethological perspective. Psychopharmacol Bull 1988;24 (3):365–369. Google ScholarPubMed
Modell, JG, Mountz, JM, Curtis, GC, Greden, JF. Neurophysiologic dysfunction in basal ganglia/limbic striatal and thalamocortical circuits as a pathogenetic mechanism of obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci 1989;1 (1):27–36. Google ScholarPubMed
Rapoport, JL. Recent advances in obsessive-compulsive disorder. Neuropsychopharmacology 1991;5 (1):1–10. Google ScholarPubMed
Jenike, MA. An update on obsessive-compulsive disorder. Bull Menninger Clin 2000;65: 4–25. CrossRefGoogle Scholar
Schwartz, JM, Stoessel, PW, Baxter, Lr JR, Martin, KM, Phelps, ME. Systematic changes in cerebral glucose metabolic rate after successful behavior modification treatment of obsessive-compulsive disorder. Arch Gen Psychiatry 1996;53 (2):109–113. CrossRefGoogle ScholarPubMed
Benes, FM. Emerging principles of altered neural circuitry in schizophrenia. Brain Research Reviews 2000;3: 251–269. Google Scholar
Arnt, J, Skarsfeldt, T. Do novel antipsychotics have similar pharmacological characteristics? A review. Neuropsychopharmacology 1998;18: 63–101. CrossRefGoogle ScholarPubMed
Honey, GD, Bullmore, ET, Soni, W, Varatheesan, M, Williams, SCR, Sharma, T. Differences in frontal cortical activation by a working memory task following substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia. Proc Nat Acad Sci USA 1999;96 (23):13432–13437. CrossRefGoogle Scholar
Stip, E, Fahim, C, Mancini-Marie, Aet al. Restoration of frontal activation during a treatment with quetiapine: an fmri study of blunted affect in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2005;29 (1):21–26. CrossRefGoogle ScholarPubMed
Dickerson, FB. Cognitive behavioral psychotherapy for schizophrenia: a review of recent empirical studies. Schizophr Res 2000;43 (2–3):71–90. CrossRefGoogle ScholarPubMed
Jones, C, Cormac, I, Mota, J, Campbell, C. Cognitive behaviour therapy for schizophrenia. Cochrane Database Syst Rev 2000;2: cd000524. Google Scholar
Gould, RA, Mueser, KT, Bolton, E, Mays, V, Goff, D. Cognitive therapy for psychosis in schizophrenia: an effect size analysis. Schizophr Res 2001;48 (2–3):335–342. CrossRefGoogle ScholarPubMed
Pilling, S, Bebbington, P, Kuipers, Eet al. Psychological treatments in schizophrenia. I. Meta-analysis of family intervention and cognitive behaviour therapy. Psychol Med 2002;32 (5):763–782. CrossRefGoogle ScholarPubMed
Turkington, D, Dudley, R, Warman, DM, Beck, AT. Cognitive-behavioral therapy for schizophrenia: a review. J Psychiatr Pract 2004;10 (1):5–16. CrossRefGoogle ScholarPubMed
Kuipers, E, Garety, P, Fowler, Det al. London-east anglia randomised controlled trial of cognitive-behavioural therapy for psychosis. I: effects of the treatment phase. Br J Psychiatry 1997;171: 319–327. CrossRefGoogle ScholarPubMed
Kuipers, E, Fowler, D, Garety, Pet al. London-east anglia randomised controlled trial of cognitive-behavioural therapy for psychosis. III: follow-up and economic evaluation at 18 months. Br J Psychiatry 1998;173: 61–68. CrossRefGoogle ScholarPubMed
Tarrier, N, Yusupoff, L, Kinney, Cet al. Randomised controlled trial of intensive cognitive behaviour therapy for patients with chronic schizophrenia. BMJ 1998;317: 303–307. CrossRefGoogle ScholarPubMed
Garety, PA, Fowler, D, Kuipers, E. Cognitive-behavioral therapy for medication-resistant symptoms. Schizophr Bull 2000;26: 73–86. CrossRefGoogle ScholarPubMed
Pinto, A, La Pia, S, Mennella, R, Giorgio, D, Desimone, L. Cognitive-behavioral therapy and clozapine for clients with treatment-refractory schizophrenia. Psychiatr Serv 1999;50 (7):91–904. CrossRefGoogle ScholarPubMed
Sensky, T, Turkington, D, Kingdon, Det al. A randomized controlled trial of cognitive-behavioral therapy for persistent symptoms in schizophrenia resistant to medication. Arch Gen Psychiatry 2000;57 (2): 165–172. CrossRefGoogle ScholarPubMed
Gumley, A, O'Grady, M, McNay, L, Reilly, J, Power, K, Norrie, J. Early intervention for relapse in schizophrenia: results of a 12-month randomized controlled trial of cognitive behavioural therapy. Psychol Med 2003;33 (3):419–431. CrossRefGoogle ScholarPubMed
Rector, NA, Seeman, MV, Segal, ZV. Cognitive therapy for schizophrenia: a preliminary randomized controlled trial. Schizophr Res 2003;63 (1–2):1–11. CrossRefGoogle ScholarPubMed
Rector, N, Beck, AT. Cognitive behavioral therapy for schizophrenia: an empirical review. J Nerv Ment Dis 2001;189: 278–287. CrossRefGoogle ScholarPubMed
Startup, M, Jackson, MC, Bendix, S. North Wales randomized controlled trial of cognitive behaviour therapy for acute schizophrenia spectrum disorders: outcomes at 6 and 12 months. Psychol Med 2004;34 (3):413–422. CrossRefGoogle ScholarPubMed
Zimmermann, G, Favrod, J, Trieu, VH, Pomini, V. The effect of cognitive behavioral treatment on the positive symptoms of schizophrenia spectrum disorders: a meta-analysis. Schizophr Res 2005;77 (1):1–9. CrossRefGoogle ScholarPubMed
Wykes, T, Brammer, M, Mellers, Jet al. Effects on the brain of a psychological treatment: cognitive remediation therapy: functional magnetic resonance imaging in schizophrenia. Br J Psychiatry 2002;181: 144–152. Google ScholarPubMed
Frith, CD. The cognitive neuropsychology of schizophrenia. Lea: Hove, 1992. Google Scholar
Frith, CD, Friston, K, Liddle, PF, Frackowiak, RS. Willed action and the prefrontal cortex in man: a study with PET. Proc Biol Sci 1991;244: 241–246. Google Scholar
Blakemore, SJ, Smith, J, Steel, R, Johnstone, CE, Frith, CD. The perception of self-produced sensory stimuli in patients with auditory hallucinations and passivity experiences: evidence for a breakdown in self-monitoring. Psychol Med 2000;30 (5):1131–1319. CrossRefGoogle ScholarPubMed
Johns, LC, Rossell, S, Frith, Cet al. Verbal self-monitoring and auditory verbal hallucinations in patients with schizophrenia. Psychol Med 2001;31: 705–715. CrossRefGoogle ScholarPubMed
Allen, PP, Johns, LC, Fu, CH, Broome, MR, Vythelingum, GN, McGuire, PK. Misattribution of external speech in patients with hallucinations and delusions. Schizophr Res 2004;69 (2–3):277–287. CrossRefGoogle ScholarPubMed
Rushworth, MF, Walton, ME, Kennerley, SW, Bannerman, DM. Action sets and decisions in the medial frontal cortex. Trends Cogn Sci 2004;8 (9):410–417. CrossRefGoogle ScholarPubMed
Carter, CS, MacDonald, AW, Ross, LL, Stenger, VA. Anterior cingulate cortex activity and impaired self-monitoring of performance in patients with schizophrenia: an event-related fMRI study. Am J Psychiatry 2001;158: 1423–1428. CrossRefGoogle ScholarPubMed
Garety, P, Fowler, D, Kuipers, Eet al. London-East Anglia randomised controlled trial of cognitive-behavioural therapy for psychosis. II. Predictors of outcome. Br J Psychiatry 1997;171: 420–426. CrossRefGoogle ScholarPubMed
Lackner, JM, Lou Coad, M, Mertz, HRet al. Cognitive therapy for irritable bowel syndrome is associated with reduced limbic activity, GI symptoms, and anxiety. Behav Res Ther 2006;44(5):621–638.CrossRefGoogle ScholarPubMed
Mayer, EA, Berman, S, Derbyshire, SWet al. The effect of the 5-HT3 receptor antagonist, alosetron, on brain responses to visceral stimulation in irritable bowel syndrome patients. Aliment Pharmacol Ther 2002;16 (7):1357–1366. CrossRefGoogle ScholarPubMed
Sykes, MA, Blanchard, EB, Lackner, J, Keefer, L, Krasner, S. Psychopathology in irritable bowel syndrome: support for a psychophysiological model. J Behav Med 2003;26 (4):361–372. CrossRefGoogle ScholarPubMed
Kumar, D, Thompson, PD, Wingate, DL, Vesselinova-Jenkins, CK, Libby, G. Abnormal REM sleep in the irritable bowel syndrome. Gastroenterology 1992;103 (1):12–17. CrossRefGoogle ScholarPubMed
Whitehead, WE, Palsson, O, Jones, KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders. What are the causes and implications? Gastroenterology 2002;122: 1140–1156. CrossRefGoogle ScholarPubMed
Silverman, D, Munakata, J, Ennes, H, Mandelkern, M, Hoh, C, Mayer, E. Regional cerebral activity in normal and pathological perception of visceral pain. Gastroenterology 1997;112: 64–72. CrossRefGoogle ScholarPubMed
Drossman, DA, Li, Z, Leserman, J, Keefe, FJ, Hu, YJ, Toomey, TC. Effects of coping on health outcome among female patients with gastrointestinal disorders. Psychosom Med 2000;62: 309–317. CrossRefGoogle ScholarPubMed
Lackner, JM, Quigley, BM, Blanchard, EB. Depression and abdominal pain in IBS patients: the mediating role of catastrophizing. Psychosom Med 2004;66 (3):435–441. Google Scholar
Lackner, JM, Morley, S, Dowzer, C, Mesmer, C, Hamilton, S. Psychological treatments for irritable bowel syndrome. A systematic review and meta-analysis. J Consult Clin Psychol 2004;72 (6):1100–1113. CrossRefGoogle ScholarPubMed
Pissiota, A, Frans, O, Michelgard, Aet al. Amygdala and anterior cingulate cortex activation during affective startle modulation: a PET study of fear. Eur J Neurosci 2003;18 (5):1325–1331. CrossRefGoogle ScholarPubMed
Berman, SM, Chang, L, Suyenobu, Bet al. Condition-specific deactivation of brain regions by 5-HT3 receptor antagonist Alosetron. Gastroenterology 2002;123 (4):969–977. CrossRefGoogle ScholarPubMed
Mayer, EA, Naliboff, BD, Chang, L, Coutinho, SVV. Stress and irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 2001;280 (4):G519–G524. CrossRefGoogle ScholarPubMed
Kraemer, HC, Wilson, GT, Fairburn, CG, Agras, WS. Mediators and moderators of treatment effects in randomized clinical trials. Arch Gen Psychiatry 2002;59 (10):877–883. CrossRefGoogle ScholarPubMed
Beck, AT, Rush, AJ, Shaw, BF. Cognitive therapy of depression. New York: Guilford Press, 1979. Google Scholar
Bandura, A. Clinical functioning. In: Bandura, A, ed. Self-efficacy: the exercise of control. New York: Freeman, 1997: 319–368. Google Scholar
Blanchard, EB. Irritable bowel syndrome: psychosocial assessment and treatment. Washington, DC: APA, 2001. CrossRefGoogle Scholar