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Variation in the BDNF Val66Met polymorphism and response to cognitive-behavior therapy in obsessive-compulsive disorder

Published online by Cambridge University Press:  15 April 2020

M.A. Fullana ,
P. Alonso ,
M. Gratacòs ,
N. Jaurrieta ,
S. Jiménez-Murcia ,
C. Segalàs ,
E. Real ,
X. Estivill  and
J.M. Menchón
M.A. Fullana*
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, United Kingdom Department of Psychiatry, Autonomous University of Barcelona & Anxiety Unit, INAD, Parc de Salut Mar, Barcelona, Spain
P. Alonso
Affiliation:
OCD Clinical and Research Unit, Psychiatry Department, Hospital Universitari de Bellvitge, Barcelona, Spain CIBERSAM (Centro de Investigación en Red de Salud Mental), Instituto de Salud Carlos III., Spain Department of Clinical Sciences, Bellvitge Campus, University of Barcelona, Barcelona, Spain
M. Gratacòs
Affiliation:
CIBERESP en Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III., Spain Genes and Disease Program, Center for Genomic Regulation (CRG), Barcelona Biomedical Research Park, Barcelona, Spain
N. Jaurrieta
Affiliation:
OCD Clinical and Research Unit, Psychiatry Department, Hospital Universitari de Bellvitge, Barcelona, Spain
S. Jiménez-Murcia
Affiliation:
OCD Clinical and Research Unit, Psychiatry Department, Hospital Universitari de Bellvitge, Barcelona, Spain Department of Clinical Sciences, Bellvitge Campus, University of Barcelona, Barcelona, Spain
C. Segalàs
Affiliation:
OCD Clinical and Research Unit, Psychiatry Department, Hospital Universitari de Bellvitge, Barcelona, Spain
E. Real
Affiliation:
Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
X. Estivill
Affiliation:
CIBERESP en Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III., Spain Genes and Disease Program, Center for Genomic Regulation (CRG), Barcelona Biomedical Research Park, Barcelona, Spain Genomics Core Facility and Centro Nacional de Genotipado (CeGen), Center for Genomic Regulation (CRG), Barcelona, Spain Experimental and Health Sciences Department, Pompeu Fabra University, Barcelona, Spain
J.M. Menchón
Affiliation:
OCD Clinical and Research Unit, Psychiatry Department, Hospital Universitari de Bellvitge, Barcelona, Spain CIBERSAM (Centro de Investigación en Red de Salud Mental), Instituto de Salud Carlos III., Spain Department of Clinical Sciences, Bellvitge Campus, University of Barcelona, Barcelona, Spain
*
*Corresponding author. King's College London, Institute of Psychiatry, PO69 De Crespigny Park Road, SE5 8AF, London, United Kingdom. Tel.: +44 2078 480 543; fax: +44 2078 480 379. E-mail address: Miguel.Fullana@kcl.ac.uk (M.A. Fullana).
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Abstract

Background

Recent research suggests that the brain-derived neurotrophic factor (BDNF) may play a role in extinction learning. The goal of this study was to test whether variation in the BDNF Val66Met polymorphism is related to treatment response to exposure-based cognitive-behavior therapy (CBT), a form of extinction learning, in obsessive-compulsive disorder (OCD).

Methods

One hundred and six OCD patients from a specialized clinic, who underwent a standardized CBT treatment after partial or non-response to a 12-week pharmacological trial, were genotyped for the BDNF Val66Met and the relationship between genotype and treatment response was analyzed.

Results

Among 98 CBT completers, 36% of those carrying the BDNF Met allele were rated as CBT responders compared to 60% of nonMet allele carriers (P = 0.027). When analyzing the different obsessive-compulsive symptom dimensions, in patients with contamination/cleaning symptoms, the Met allele was associated with a significantly worse CBT response (P<0.0001) and a lower obsessions severity decrease from pre- to posttreatment (P = 0.046).

Conclusion

Genetic variation in BDNF may be associated with treatment response in exposure-based CBT in OCD, especially in those patients exhibiting contamination/cleaning symptoms.

Keywords

Obsessive-compulsive disorderExtinctionCognitive-behavior therapyGeneticsBDNFVal66Met
Type
Original articles
Information
European Psychiatry , Volume 27 , Issue 5 , July 2012 , pp. 386 - 390
Copyright
Copyright © Elsevier Masson SAS 2012

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References

Abramowitz, J.S., Taylor, S., McKay, D.Obsessive-compulsive disorder. Lancet. 2009; 374: 491–499.CrossRefGoogle ScholarPubMed
Alonso, P., Gratacos, M., Menchon, J.M., Saiz-Ruiz, J., Segalas, C., Baca-Garcia, E.et al.Extensive genotyping of the BDNF and NTRK2 genes define protective haplotypes against obsessive-compulsive disorder. Biol Psychiatry. 2008; 63: 619–628.CrossRefGoogle ScholarPubMed
Alonso, M., Gratacos, M., Segalas, C., Escaramis, G., Real, E., Bayes, M.et al.Association of glutamate receptor gene GRIN2B and phenotypical expresion of obsessive-compulsive disorder. Athens, Greece: XVIIIth World Congress on Psychiatric Genetics; 2010.Google Scholar
Alonso, P., Gratacos, M., Segalas, C., Escaramis, G., Real, E., Bayes, M.et al.Variants in estrogen receptor alpha gene are associated with phenotypical expression of obsessive-compulsive disorder. Psychoneuroendocrinology. 2011; 36: 473–483.CrossRefGoogle ScholarPubMed
American Psychiatric Association Diagnostic and statistical manual of mental disorders. Washington, D.C: American Psychiatric Association; 1994.Google Scholar
Barlow, D.Anxiety and its disorders: the nature and treatment of anxiety and panic. New York: Guilford Press; 2002.Google Scholar
Bryant, R.A., Felmingham, K.L., Falconer, E.M., Pe Benito, L., Dobson-Stone, C., Pierce, K.D.et al.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: 1217–1219.10.1016/j.biopsych.2010.03.016CrossRefGoogle ScholarPubMed
Casey, B.J., Glatt, C.E., Tottenham, N., Soliman, F., Bath, K., Amso, D.et al.Brain-derived neurotrophic factor as a model system for examining gene by environment interactions across development. Neuroscience. 2009; 164: 108–120.CrossRefGoogle ScholarPubMed
Chen, Z.Y., Jing, D., Bath, K.G., Ieraci, A., Khan, T., Siao, C.J.et al.Genetic variant bdnf (Val66Met) polymorphism alters anxiety-related behavior. Science. 2006; 314: 140–143.CrossRefGoogle ScholarPubMed
Fineberg, N.A., Pampaloni, I., Pallanti, S., Ipser, J., Stein, D.J.Sustained response versus relapse: the pharmacotherapeutic goal for obsessive-compulsive disorder. Int Clin Psychopharmacol. 2007; 22: 313–322.CrossRefGoogle ScholarPubMed
Goodman, W.K., Price, L.H., Rasmussen, S.A., Mazure, C., Fleischmann, R.L., Hill, C.L.et al.The Yale-Brown Obsessive Compulsive Scale. I. Development, use and reliability. Arch Gen Psychiatry. 1989; 46: 1006–1011.CrossRefGoogle ScholarPubMed
Goodman, W.K., Price, L.H., Rasmussen, S.A., Mazure, C., Delgado, P., Heninger, G.R.et al.The Yale-Brown Obsessive Compulsive Scale. II. Validity. Arch Gen Psychiatry. 1989; 46: 1012–1016.CrossRefGoogle ScholarPubMed
Hajcak, G., Castille, C., Olvet, D.M., Dunning, J.P., Roohi, J., Hatchwell, E.Genetic variation in brain-derived neurotrophic factor and human fear conditioning. Genes Brain Behav. 2009; 8: 80–85.10.1111/j.1601-183X.2008.00447.xCrossRefGoogle ScholarPubMed
Hamilton, M.A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960; 23: 56–62.CrossRefGoogle ScholarPubMed
Koran, L.M., Hanna, G.L., Hollander, E., Nestadt, G., Simpson, H.B.Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007; 164: 5–53.Google ScholarPubMed
Kozak, M., Foa, E.Mastery of your obsessive-compulsive disorder: a cognitive behavioral approach. San Antonio, TX: The Psychological Corporation; 1997.Google Scholar
Lonsdorf, T.B., Weike, A.I., Golkar, A., Schalling, M., Hamm, A.O., Ohman, A.Amygdala-dependent fear conditioning in humans is modulated by the BDNF Val66Met polymorphism. Behav Neurosci. 2010; 124: 9–15.CrossRefGoogle Scholar
Mataix-Cols, D., Wooderson, S., Lawrence, N., Brammer, M.J., Speckens, A., Phillips, M.L.Distinct neural correlates of washing, checking, and hoarding symptom dimensions in obsessive-compulsive disorder. Arch Gen Psychiatry. 2004; 61: 564–576.CrossRefGoogle ScholarPubMed
Mataix-Cols, D., Rosario-Campos, M.C., Leckman, J.F.A multidimensional model of obsessive-compulsive disorder. Am J Psychiatry. 2005; 162: 228–238.CrossRefGoogle ScholarPubMed
Milad, M.R., Quirk, G.J.Neurons in medial prefrontal cortex signal memory for fear extinction. Nature. 2002; 420: 70–74.CrossRefGoogle ScholarPubMed
Myers KM, Carlezon WA, Jr., Davis M. Glutamate receptors in extinction and extinction-based therapies for psychiatric illness. Neuropsychopharmacology 2010.CrossRefGoogle Scholar
Pallanti, S., Hollander, E., Bienstock, C., Koran, L., Leckman, J., Marazziti, D.et al.Treatment non-response in OCD: methodological issues and operational definitions. Int J Neuropsychopharmacol. 2002; 5: 181–191.CrossRefGoogle ScholarPubMed
Peters, J., Dieppa-Perea, L.M., Melendez, L.M., Quirk, G.J.Induction of fear extinction with hippocampal-infralimbic BDNF. Science. 2010; 328: 1288–1290.CrossRefGoogle ScholarPubMed
Petryshen, T.L., Sabeti, P.C., Aldinger, K.A., Fry, B., Fan, J.B., Schaffner, S.F.et al.Population genetic study of the brain-derived neurotrophic factor (BDNF) gene. Mol Psychiatry. 2010; 15: 810–815.CrossRefGoogle ScholarPubMed
Real, E., Gratacos, M., Soria, V., Escaramis, G., Alonso, P., Segalas, C.et al.A brain-derived neurotrophic factor haplotype is associated with therapeutic response in obsessive-compulsive disorder. Biol Psychiatry. 2009; 66: 674–680.CrossRefGoogle ScholarPubMed
Sohrabji, F., Lewis, D.K.Estrogen-BDNF interactions: implications for neurodegenerative diseases. Front Neuroendocrinol. 2006; 27: 404–414.CrossRefGoogle ScholarPubMed
Soliman, F., Glatt, C.E., Bath, K.G., Levita, L., Jones, R.M., Pattwell, S.S.et al.A genetic variant bdnf polymorphism alters extinction learning in both mouse and human. Science. 2010; 327: 863–866.CrossRefGoogle ScholarPubMed
Tolin, D.F., Abramowitz, J.S., Diefenbach, G.J.Defining response in clinical trials for obsessive-compulsive disorder: a signal detection analysis of the yale-brown obsessive compulsive scale. J Clin Psychiatry. 2005; 66: 1549–1557.CrossRefGoogle ScholarPubMed
van Grootheest, D.S., Bartels, M., van Beijsterveldt, C.E., Cath, D.C., Beekman, A.T., Hudziak, J.J.et al.Genetic and environmental contributions to self-report obsessive-compulsive symptoms in dutch adolescents at ages 12, 14 and 16. J Am Acad Child Adolesc Psychiatry. 2008; 47: 1182–1188.CrossRefGoogle ScholarPubMed
Wellman, C.L., Izquierdo, A., Garrett, J.E., Martin, K.P., Carroll, J., Millstein, R.et al.Impaired stress-coping and fear extinction and abnormal corticolimbic morphology in serotonin transporter knock-out mice. J Neurosci. 2007; 27: 684–691.CrossRefGoogle ScholarPubMed
Yu, H., Wang, Y., Pattwell, S., Jing, D., Liu, T., Zhang, Y.et al.Variant BDNF Val66Met polymorphism affects extinction of conditioned aversive memory. J Neurosci. 2009; 29: 4056–4064.CrossRefGoogle ScholarPubMed
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