The COMTval158met polymorphism is associated with symptom relief during exposure-based cognitive-behavioral treatment in panic disorder

Tina B Lonsdorf, Christian Rück, Jan Bergström, Gerhard Andersson, Arne Ohman, Nils Lindefors, Martin Schalling, Tina B Lonsdorf, Christian Rück, Jan Bergström, Gerhard Andersson, Arne Ohman, Nils Lindefors, Martin Schalling

Abstract

Background: Cognitive behavioral therapy (CBT) represents a learning process leading to symptom relief and resulting in long-term changes in behavior. CBT for panic disorder is based on exposure and exposure-based processes can be studied in the laboratory as extinction of experimentally acquired fear responses. We have recently demonstrated that the ability to extinguish learned fear responses is associated with a functional genetic polymorphism (COMTval158met) in the COMT gene and this study was aimed at transferring the experimental results on the COMTval158met polymorphism on extinction into a clinical setting.

Methods: We tested a possible effect of the COMTval158met polymorphism on the efficacy of CBT, in particular exposure-based treatment modules, in a sample of 69 panic disorder patients.

Results: We present evidence that panic patients with the COMTval158met met/met genotype may profit less from (exposure-based) CBT treatment methods as compared to patients carrying at least one val-allele. No association was found with the 5-HTTLPR/rs25531 genotypes which is presented as additional material.

Conclusions: We were thus able to transfer findings on the effect of the COMTval158met polymorphism from an experimental extinction study obtained using healthy subjects to a clinical setting. Furthermore patients carrying a COMT val-allele tend to report more anxiety and more depression symptoms as compared to those with the met/met genotype. Limitations of the study as well as possible clinical implications are discussed.

Trial registration: Clinical Trial Registry name: Internet-Versus Group-Administered Cognitive Behavior Therapy for Panic Disorder (IP2). Registration Identification number: NCT00845260, http://www.clinicaltrials.gov/ct2/show/NCT00845260.

Figures

Figure 1
Figure 1
Difference scores between the HADS anxiety mean scores pre-treatment and during the cognitive block as well as during the cognitive vs. the exposure block for COMT 158val-carriers (black bars) and patients with the met/met genotype (white bars).

References

    1. Linden DEJ. How psychotherapy changes the brain - the contribution of functional neuroimaging. Molecular Psychiatry. 2006;11:528–538. doi: 10.1038/sj.mp.4001816.
    1. Kandel ER. Biology and the future of psychoanalysis: A new intellectual framework for psychiatry revisited. American Journal of Psychiatry. 1999;156:505–524.
    1. Lonsdorf TB, Weike AI, Nikamo P, Schalling M, Hamm AO, Ohman A. Genetic Gating of Human Fear Learning and Extinction: Possible Implications for Gene-Environment Interaction in Anxiety Disorder. Psychological Science. 2009;20:198–206. doi: 10.1111/j.1467-9280.2009.02280.x.
    1. Weinshilboum RM, Otterness DM, Szumlanski CL. Methylation pharmacogenetics: Catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase. Annual Review of Pharmacology and Toxicology. 1999;39:19–52. doi: 10.1146/annurev.pharmtox.39.1.19.
    1. Chen JS, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S, Kolachana BS, Hyde TM, Herman MM, Apud J. et al.Functional analysis of genetic variation in catechol-o-methyltransferase (COMT): Effects on mRNA, protein, and enzyme activity in postmortem human brain. Am J Hum Genet. 2004;75:807–821. doi: 10.1086/425589.
    1. Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL, Weinshilboum RM. Human catechol-O-methyltransferase pharmacogenetics: Description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics. 1996;6:243–250. doi: 10.1097/00008571-199606000-00007.
    1. Kolassa IT, Kolassa S, Ertl V, Papassotiropoulos A, De Quervain DJF. The Risk of Posttraumatic Stress Disorder After Trauma Depends on Traumatic Load and the Catechol-O-Methyltransferase Val(158)Met Polymorphism. Biological Psychiatry. pp. 304–308.
    1. Heinz A, Smolka MN. The effects of catechol O-methyltransferase genotype on brain activation elicited by affective stimuli and cognitive tasks. Reviews in the Neurosciences. 2006;17:359–367.
    1. Bilder RM, Volavka J, Lachman HM, Grace AA. The catechol-O-methyltransferase polymorphism: Relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes. Neuropsychopharmacology. 2004;29:1943–1961. doi: 10.1038/sj.npp.1300542.
    1. Domschke K, Freitag CM, Kuhlenbaumer G, Schirmacher A, Sand P, Nyhuis P, Jacob C, Fritze J, Franke P, Rietschel M. et al.Association of the functional V158 M catechol-O-methyl-transferase polymorphism with panic disorder in women. International Journal of Neuropsychopharmacology. 2004;7:183–188. doi: 10.1017/S146114570400416X.
    1. Rothe C, Koszycki D, Bradwejn J, King N, Deluca V, Tharmalingam S, Macciardi F, Deckert J, Kennedy JL. Association of the Val158Met catechol O-methyltransferase genetic polymorphism with panic disorder. Neuropsychopharmacology. 2006;31:2237–2242.
    1. Domschke K, Deckert J, O'Donovan MC, Glatt SJ. Meta-analysis of COMT val158met in panic disorder: Ethnic heterogeneity and gender specificity. American Journal of Medical Genetics Part B-Neuropsychiatric Genetics. 2007;144B:667–673. doi: 10.1002/ajmg.b.30494.
    1. Bergstrom J, Andersson G, Ljotsson B, Ruck C, Andreewitch S, Karlsson A, Carlbring P, Andersson E, Lindefors N. Internet-versus group-administered cognitive behaviour therapy for panic disorder in a psychiatric setting: a randomised trial. Bmc Psychiatry. 2010;10 doi: 10.1186/1471-244X-10-54.
    1. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59(Suppl 20):22–33. quiz 34-57.
    1. Zigmond AS, Snaith RP. THE HOSPITAL ANXIETY AND DEPRESSION SCALE. Acta Psychiatrica Scandinavica. 1983;67:361–370. doi: 10.1111/j.1600-0447.1983.tb09716.x.
    1. Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the Hospital Anxiety and Depression Scale - An updated literature review. Journal of Psychosomatic Research. 2002;52:69–77. doi: 10.1016/S0022-3999(01)00296-3.
    1. Bergstrom J, Andersson G, Karlsson A, Andreewitch S, Ruck C, Carlbring P, Lindefors N. An open study of the effectiveness of Internet treatment for panic disorder delivered in a psychiatric setting. Nordic Journal of Psychiatry. 2009;63:44–50. doi: 10.1080/08039480802191132.
    1. Geijer T, Neiman J, Rydberg U, Gyllander A, Jonsson E, Sedvall G, Valverius P, Terenius L. DOPAMINE D2-RECEPTOR GENE POLYMORPHISMS IN SCANDINAVIAN CHRONIC-ALCOHOLICS. European Archives of Psychiatry and Clinical Neuroscience. 1994;244:26–32. doi: 10.1007/BF02279808.
    1. Livak KJ. Allelic discrimination using fluorogenic probes and the 5 ' nuclease assay. Genetic Analysis-Biomolecular Engineering. 1999;14:143–149. doi: 10.1016/S1050-3862(98)00019-9.
    1. Enoch MA, Xu K, Ferro E, Harris CR, Goldman D. Genetic origins of anxiety in women: a role for a functional catechol-O-methyltransferase polymorphism. Psychiatric Genetics. 2003;13:33–41. doi: 10.1097/00041444-200303000-00006.
    1. Bouton ME, Mineka S, Barlow DH. A modern learning theory perspective on the etiology of panic disorder. Psychological Review. 2001;108:4–32. doi: 10.1037/0033-295X.108.1.4.
    1. Myers KM, Davis M. Mechanisms of fear extinction. Molecular Psychiatry. 2007;12:120–150. doi: 10.1038/sj.mp.4001939.
    1. Kim W, Choi YH, Yoon KS, Cho DY, Pae CU, Woo JM. Tryptophan hydroxylase and serotonin transporter gene polymorphism does not affect the diagnosis, clinical features and treatment outcome of panic disorder in the Korean population. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2006;30:1413–1418.
    1. Roffman JL, Marci CD, Glick DM, Dougherty DD, Rauch SL. Neuroimaging and the functional neuroanatomy of psychotherapy. Psychological Medicine. 2005;35:1385–1398. doi: 10.1017/S0033291705005064.
    1. Bryant RA, Felmingham KL, Falconer EM, Benito LP, 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. Biological Psychiatry. 2010;67:1217–1219. doi: 10.1016/j.biopsych.2010.03.016.
    1. Gorman JM, Kent JM, Sullivan GM, Coplan JD. Neuroanatomical hypothesis of panic disorder, revised. American Journal of Psychiatry. 2000;157:493–505. doi: 10.1176/appi.ajp.157.4.493.
    1. Kiropoulos LA, Klein B, Austin DW, Gilson K, Pier C, Mitchell J, Ciechomski L. Is internet-based CBT for panic disorder and agoraphobia as effective as face-to-face CBT? Journal of Anxiety Disorders. 2008;22:1273–1284. doi: 10.1016/j.janxdis.2008.01.008.
    1. Carlbring P, Nilsson-Ihrfelt E, Waara J, Kollenstam C, Buhrman M, Kaldo V, Soderberg M, Ekselius L, Andersson G. Treatment of panic disorder: live therapy vs. self-help via the Internet. Behaviour Research and Therapy. 2005;43:1321–1333. doi: 10.1016/j.brat.2004.10.002.
    1. Reger MA, Gahm GA. A Meta-Analysis of the Effects of Internet- and Computer-Based Cognitive-Behavioral Treatments for Anxiety. Journal of Clinical Psychology. 2009;65:53–75. doi: 10.1002/jclp.20536.
    1. Anttila S, Huuhka K, Huuhka M, Illi A, Rontu R, Leinonen E, Lehtimaki T. Catechol-O-methyltransferase (COMT) polymorphisms predict treatment response in electroconvulsive therapy. Pharmacogenomics Journal. 2008;8:113–116. doi: 10.1038/sj.tpj.6500468.
    1. Domschke K, Zavorotnyy M, Diemer J, Nitsche S, Hohoff C, Baune BT, Deckert J, Arolt V, Zwanzger P. COMT val158met Influence on Electroconvulsive Therapy Response in Major Depression. American Journal of Medical Genetics Part B-Neuropsychiatric Genetics. 2010;153B:286–290.
    1. Huuhka K, Anttila S, Huuhka M, Hietala J, Huhtala H, Mononen N, Lehtimaki T, Leinonen E. Dopamine 2 receptor C957T and catechol-o-methyltransferase Val158Met polymorphisms are associated with treatment response in electroconvulsive therapy. Neuroscience Letters. 2008;448:79–83. doi: 10.1016/j.neulet.2008.10.015.
    1. Szegedi A, Rujescu D, Tadic A, Muller MJ, Kohnen R, Stassen HH, Dahmen N. The catechol-O-methyltransferase Val(108/158)Met polymorphism affects short-term treatment response to mirtazapine, but not to paroxetine in major depression. Pharmacogenomics Journal. 2005;5:49–53. doi: 10.1038/sj.tpj.6500289.
    1. Arias B, Serretti A, Lorenzi C, Gasto C, Catalan R, Fananas L. Analysis of COMT gene (Val 158 Met polymorphism) in the clinical response to SSRIs in depressive patients of European origin. Journal of Affective Disorders. 2006;90:251–256. doi: 10.1016/j.jad.2005.11.008.
    1. Baune BT, Hohoff C, Berger K, Neumann A, Mortensen S, Roehrs T, Deckert J, Arolt V, Domschke K. Association of the COMT val158met variant with antidepressant treatment response in major depression. Neuropsychopharmacology. 2008;33:924–932. doi: 10.1038/sj.npp.1301462.
    1. Inada T, Nakamura A, Iijima Y. Relationship between catechol-O-methyltransferase polymorphism and treatment-resistant schizophrenia. American Journal of Medical Genetics Part B-Neuropsychiatric Genetics. 2003;120B:35–39. doi: 10.1002/ajmg.b.20023.
    1. Bryant RA, Felmingham KL, Falconer EM, Pe Benito L, 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. Biological Psychiatry. in press Corrected Proof.
    1. Hofmann SG, Pollack MH, Otto MW. Augmentation treatment of psychotherapy for anxiety disorders with D-cycloserine. Cns Drug Reviews. 2006;12:208–217. doi: 10.1111/j.1527-3458.2006.00208.x.
    1. Kandel ER. A new intellectual framework for psychiatry. American Journal of Psychiatry. 1998;155:457–469.

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