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Is glutamate associated with fear extinction and cognitive behavior therapy outcome in OCD? A pilot study

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Abstract

Cognitive behavioral therapy (CBT) including exposure and response prevention is a well-established treatment for obsessive–compulsive disorder (OCD) and is based on the principles of fear extinction. Fear extinction is linked to structural and functional variability in the ventromedial prefrontal cortex (vmPFC) and has been consistently associated with glutamate neurotransmission. The relationship between vmPFC glutamate and fear extinction and its effects on CBT outcome have not yet been explored in adults with OCD. We assessed glutamate levels in the vmPFC using 3T magnetic resonance spectroscopy, and fear extinction (learning and recall) using skin conductance responses during a 2-day experimental paradigm in OCD patients (n = 17) and in healthy controls (HC; n = 13). Obsessive–compulsive patients (n = 12) then received manualized CBT. Glutamate in the vmPFC was negatively associated with fear extinction recall and positively associated with CBT outcome (with higher glutamate levels predicting a better outcome) in OCD patients. Glutamate levels in the vmPFC in OCD patients were not significantly different from those in HC, and were not associated with OCD severity. Our results suggest that glutamate in the vmPFC is associated with fear extinction recall and CBT outcome in adult OCD patients.

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References

  1. Maren S (2001) Neurobiology of Pavlovian fear conditioning. Annu Rev Neurosci 24:897–931. https://doi.org/10.1146/annurev.neuro.24.1.897

    Article  CAS  Google Scholar 

  2. Pavlov PI (1927) (2010) Conditioned reflexes: an investigation of the physiological activity of the cerebral cortex. Ann Neurosci 17:136–141. http://doi.org/10.5214/ans.0972-7531.1017309

  3. Garakani A, Mathew SJ, Charney DS (2006) Neurobiology of anxiety disorders and implications for treatment. Mt Sinai J Med 73:941–949

    Google Scholar 

  4. Graham BM, Milad MR (2011) Translational research in the neuroscience of fear extinction: implications for anxiety disorders. Am J Psychiat 168:1255–1265. https://doi.org/10.1176/appi.ajp.2011.11040557

    Article  Google Scholar 

  5. Milad MR, Rosenbaum BL, Simon NM (2014) Neuroscience of fear extinction: implications for assessment and treatment of fear-based and anxiety related disorders. Behav Res Ther 62:17–23. https://doi.org/10.1016/j.brat.2014.08.006

    Article  Google Scholar 

  6. Milad MR, Quirk GJ (2012) Fear extinction as a model for translational neuroscience: 10 years of progress. Annu Rev Psychol 63:129–151. https://doi.org/10.1146/annurev.psych.121208.131631

    Article  Google Scholar 

  7. Citri A, Malenka RC (2008) Synaptic plasticity: multiple forms, functions, and mechanisms. Neuropsychopharmacol 33:18–41. https://doi.org/10.1038/sj.npp.1301559

    Article  Google Scholar 

  8. McEntee WJ, Crook TH (1993) Glutamate: its role in learning, memory, and the aging brain. Psychopharmacology 111:391–401. https://doi.org/10.1007/BF02253527

    Article  CAS  Google Scholar 

  9. Peng S, Zhang Y, Zhang J, Wang H, Ren B (2011) Glutamate receptors and signal transduction in learning and memory. Mol Biol Rep 38:453–460. https://doi.org/10.1007/s11033-010-0128-9

    Article  CAS  Google Scholar 

  10. Richter-Levin G, Canevari L, Bliss TV (1995) Long-term potentiation and glutamate release in the dentate gyrus: links to spatial learning. Behav Brain Res 66:37–40. https://doi.org/10.1016/0166-4328(94)00121-u

    Article  CAS  Google Scholar 

  11. Riedel G, Platt B, Micheau J (2003) Glutamate receptor function in learning and memory. Behav Brain Res 140:1–47. https://doi.org/10.1016/S0166-4328(02)00272-3

    Article  CAS  Google Scholar 

  12. Myers KM, Davis M (2002) Behavioral and neural analysis of extinction. Neuron 36:567–584. https://doi.org/10.1016/S0896-6273(02)01064-4

    Article  CAS  Google Scholar 

  13. Davis M (2011) NMDA receptors and fear extinction: implications for cognitive behavioral therapy. Dialogues Clin Neurosci 13:463–474

    Google Scholar 

  14. Myers KM, Carlezon WA Jr, Davis M (2010) Glutamate receptors in extinction and extinction-based therapies for psychiatric illness. Neuropsychopharmacol 36:274. https://doi.org/10.1038/npp.2010.88

    Article  CAS  Google Scholar 

  15. Hugues S, Garcia R, Léna I (2007) Time course of extracellular catecholamine and glutamate levels in the rat medial prefrontal cortex during and after extinction of conditioned fear. Synapse 61:933–937. https://doi.org/10.1002/syn.20448

    Article  CAS  Google Scholar 

  16. Burgos-Robles A, Vidal-Gonzalez I, Santini E, Quirk GJ (2007) Consolidation of fear extinction requires NMDA receptor-dependent bursting in the ventromedial prefrontal cortex. Neuron 53:871–880. https://doi.org/10.1016/j.neuron.2007.02.021

    Article  CAS  Google Scholar 

  17. Milad MR, Quirk GJ (2002) Neurons in medial prefrontal cortex signal memory for fear extinction. Nature 420:70–74. https://doi.org/10.1038/nature01138

    Article  CAS  Google Scholar 

  18. Morgan MA, LeDoux JE (1995) Differential contribution of dorsal and ventral medial prefrontal cortex to the acquisition and extinction of conditioned fear in rats. Behav Neurosci 109:681–688. https://doi.org/10.1037/0735-7044.109.4.681

    Article  CAS  Google Scholar 

  19. Morgan MA, Romanski LM, LeDoux JE (1993) Extinction of emotional learning: contribution of medial prefrontal cortex. Neurosci Lett 163:109–113. https://doi.org/10.1016/0304-3940(93)90241-C

    Article  CAS  Google Scholar 

  20. Morgan MA, Schulkin J, LeDoux JE (2003) Ventral medial prefrontal cortex and emotional perseveration: the memory for prior extinction training. Behav Brain Res 146:121–130. https://doi.org/10.1016/j.bbr.2003.09.021

    Article  Google Scholar 

  21. Quirk GJ, Russo GK, Barron JL, Lebron K (2000) The role of ventromedial prefrontal cortex in the recovery of extinguished fear. J Neurosci 20:6225–6231. https://doi.org/10.1523/JNEUROSCI.20-16-06225.2000

    Article  CAS  Google Scholar 

  22. Milad MR, Vidal-Gonzalez I, Quirk GJ (2004) Electrical stimulation of medial prefrontal cortex reduces conditioned fear in a temporally specific manner. Behav Neurosci 118:389–394. https://doi.org/10.1037/0735-7044.118.2.389

    Article  CAS  Google Scholar 

  23. Quirk GJ, Likhtik E, Pelletier JG, Paré D (2003) Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons. J Neurosci 23:8800–8807. https://doi.org/10.1523/JNEUROSCI.23-25-08800.2003

    Article  CAS  Google Scholar 

  24. Vidal-Gonzalez I, Vidal-Gonzalez B, Rauch SL, Quirk GJ (2006) Microstimulation reveals opposing influences of prelimbic and infralimbic cortex on the expression of conditioned fear. Learn Mem 13:728–733. https://doi.org/10.1101/lm.306106

    Article  Google Scholar 

  25. Phelps EA, Delgado MR, Nearing KI, LeDoux JE (2004) Extinction learning in humans: role of the amygdala and vmPFC. Neuron 43:897–905. https://doi.org/10.1016/j.neuron.2004.08.042

    Article  CAS  Google Scholar 

  26. Kalisch R, Korenfeld E, Stephan KE, Weiskopf N, Seymour B, Dolan RJ (2006) Context-dependent human extinction memory is mediated by a ventromedial prefrontal and hippocampal network. J Neurosci 26:9503–9511. https://doi.org/10.1523/JNEUROSCI.2021-06.2006

    Article  CAS  Google Scholar 

  27. Milad MR, Quinn BT, Pitman RK, Orr SP, Fischl B, Rauch SL (2005) Thickness of ventromedial prefrontal cortex in humans is correlated with extinction memory. PNAS (USA) 102:10706–10711. https://doi.org/10.1073/pnas.0502441102

    Article  CAS  Google Scholar 

  28. Lewin AB, Wu MS, McGuire JF, Storch EA (2014) Cognitive behavior therapy for obsessive-compulsive and related disorders. Psychiatr Clin North Am 37:415–445. https://doi.org/10.1016/j.psc.2014.05.002

    Article  Google Scholar 

  29. McKay D, Sookman D, Neziroglu F, Wilhelm S, Stein DJ, Kyrios M, Matthews K, Veale D, Accreditation Task Force of The Canadian Institute for Obsessive Compulsive Disorders (2015) Efficacy of cognitive-behavioral therapy for obsessive-compulsive disorder. Psychiatry Res 227:104–113. https://doi.org/10.1016/j.psychres.2015.02.004

    Article  Google Scholar 

  30. Öst LG, Havnen A, Hansen B, Kvale G (2015) Cognitive behavioral treatments of obsessive-compulsive disorder. A systematic review and meta-analysis of studies published 1993–2014. Clin Psychol Rev 40:156–169. https://doi.org/10.1016/j.cpr.2015.06.003

    Article  Google Scholar 

  31. Wenzel A (2017) Basic strategies of cognitive behavioral therapy. Psychiatr Clin North Am 40:597–609. https://doi.org/10.1016/j.psc.2017.07.001

    Article  Google Scholar 

  32. Fullana MA, Cardoner N, Alonso P, Subirà M, López-Solà C, Pujol J, Segalàs C, Real E, Bossa M, Zacur E, Martínez-Zalacaín I, Bulbena A, Menchón JM, Olmos S, Soriano-Mas C (2014) Brain regions related to fear extinction in obsessive-compulsive disorder and its relation to exposure therapy outcome: a morphometric study. Psychol Med 44:845–856. https://doi.org/10.1017/S0033291713001128

    Article  CAS  Google Scholar 

  33. Fullana MA, Zhu X, Alonso P, Cardoner N, Real E, López-Solà C, Segalàs C, Subirà M, Galfalvy H, Menchón JM, Simpson HB, Marsh R, Soriano-Mas C (2017) Basolateral amygdala-ventromedial prefrontal cortex connectivity predicts cognitive behavioural therapy outcome in adults with obsessive-compulsive disorder. J Psychiatry Neurosci 42:378–385. https://doi.org/10.1503/jpn.160215

    Article  Google Scholar 

  34. Hofmann SG, Otto MW, Pollack MH, Smits JA (2015) D-cycloserine augmentation of cognitive behavioral therapy for anxiety disorders: an update. Curr Psychiatry Rep 17:532. https://doi.org/10.1007/s11920-014-0532-2

    Article  Google Scholar 

  35. Klass A, Glaubitz B, Tegenthoff M, Lissek S (2017) d-Cycloserine facilitates extinction learning and enhances extinction-related brain activation. Neurobiol Learn Mem 144:235–247. https://doi.org/10.1016/j.nlm.2017.08.003

    Article  CAS  Google Scholar 

  36. Kushner MG, Kim SW, Donahue C, Thuras P, Adson D, Kotlyar M, McCabe J, Peterson J, Foa EB (2007) D-cycloserine augmented exposure therapy for obsessive-compulsive disorder. Biol Psychiatry 62:835–838. https://doi.org/10.1016/j.biopsych.2006.12.020

    Article  CAS  Google Scholar 

  37. Otto MW, Kredlow MA, Smits JAJ, Hofmann SG, Tolin DF, de Kleine RA, van Minnen A, Evins AE, Pollack MH (2016) Enhancement of psychosocial treatment with d-cycloserine: models, moderators, and future directions. Biol Psychiatry 80:274–283. https://doi.org/10.1016/j.biopsych.2015.09.007

    Article  CAS  Google Scholar 

  38. Rodrigues H, Figueira I, Lopes A, Gonçalves R, Mendlowicz MV, Coutinho ESF, Ventura P (2014) Does d-cycloserine enhance exposure therapy for anxiety disorders in humans? A meta-analysis. PLoS One 9:e93519. https://doi.org/10.1371/journal.pone.0093519

    Article  CAS  Google Scholar 

  39. Mataix-Cols D, Fernández de la Cruz L, Monzani B et al (2017) d-Cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data. JAMA Psychiatry 74:501–510. https://doi.org/10.1001/jamapsychiatry.2016.3955

    Article  Google Scholar 

  40. Ori R, Amos T, Bergman H, Soares-Weiser K, Ipser JC, Stein DJ (2015) Augmentation of cognitive and behavioural therapies (CBT) with d-cycloserine for anxiety and related disorders. Cochrane Database Sys Rev. https://doi.org/10.1002/14651858.cd007803.pub2

    Article  Google Scholar 

  41. O’Neill J, Piacentini J, Chang S et al (2017) Glutamate in pediatric obsessive-compulsive disorder and response to cognitive-behavioral therapy: randomized clinical trial. Neuropsychopharmacology 42:2414–2422. https://doi.org/10.1038/npp.2017.77

    Article  CAS  Google Scholar 

  42. O’Neill J, Piacentini JC, Chang S, Levitt JG, Rozenman M, Bergman L, Salamon N, Alger JR, McCracken JT (2012) MRSI correlates of cognitive-behavioral therapy in pediatric obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry 36:161–168. https://doi.org/10.1016/j.pnpbp.2011.09.007

    Article  Google Scholar 

  43. O’Neill J, Gorbis E, Feusner JD, Yip JC, Chang S, Maidment KM, Levitt JG, Salamon N, Ringman JM, Saxena S (2013) Effects of intensive cognitive-behavioral therapy on cingulate neurochemistry in obsessive-compulsive disorder. J Psychiatr Res 47:494–504. https://doi.org/10.1016/j.jpsychires.2012.11.010

    Article  Google Scholar 

  44. Zurowski B, Weber-Fahr W, Freyer T, Wahli K, Büchert M, Kuel A et al (2007). Neurochemical abnormalities in patients with obsessive–compulsive disorder diminish in the course of behavior therapy. Poster session presentation at the meeting of the Society for Neuroscience 37th Annual Meeting, San Diego

  45. Milad MR, Furtak SC, Greenberg JL, Keshaviah A, Im JJ, Falkenstein MJ, Jenike M, Rauch SL, Wilhelm S (2013) Deficits in conditioned fear extinction in obsessive-compulsive disorder and neurobiological changes in the fear circuit. JAMA Psychiatry 70:608–618. https://doi.org/10.1001/jamapsychiatry.2013.914

    Article  Google Scholar 

  46. First M, Spitzer R, Gibbon M, Williams J (1996) Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV). American Psychiatric Press Inc, Washington (DC)

    Google Scholar 

  47. Pallanti S, Hollander E, Bienstock C, Koran L, Leckman J, Marazziti D et al (2002) Treatment non-response in OCD: methodological issues and operational definitions. Int J Neuropsychopharmacol 5:181–191. https://doi.org/10.1017/S1461145702002900

    Article  Google Scholar 

  48. Koran LM, Simpson HB (2013) Guideline watch (2013): practice guideline for the treatment of patients with obsessive-compulsive disorder. APA practice guidelines. American Psychiatric Association, Arlington, pp 1–22

    Google Scholar 

  49. First M, Gibbon M, Spitzer R, Williams J, Benjamin LS (1997) Structured clinical interview for DSM-IV Axis II personality disorders (SCID-II). American Psychiatric Press Inc, Washington (DC)

    Google Scholar 

  50. Bobes J (1998) A Spanish validation study of the mini international neuropsychiatric interview. Eur Psychiat 13:198s–199s. https://doi.org/10.1016/S0924-9338(99)80240-5

    Article  Google Scholar 

  51. Milad MR, Wright CI, Orr SP, Pitman RK, Quirk GJ, Rauch SL (2007) Recall of fear extinction in humans activates the ventromedial prefrontal cortex and hippocampus in concert. Biol Psychiatry 62:446–454. https://doi.org/10.1016/j.biopsych.2006.10.011

    Article  Google Scholar 

  52. Choi C, Coupland NJ, Bhardwaj PP, Malykhin N, Gheorghiu D, Allen PS (2006) Measurement of brain glutamate and glutamine by spectrally-selective refocusing at 3 Tesla. Magn Reson Med 55:997–1005. https://doi.org/10.1002/mrm.20875

    Article  CAS  Google Scholar 

  53. Hurd R, Sailasuta N, Srinivasan R, Vigneron DB, Pelletier D, Nelson SJ (2004) Measurement of brain glutamate using TE-averaged PRESS at 3T. Magn Reson Med 51:435–440. https://doi.org/10.1002/mrm.20007

    Article  CAS  Google Scholar 

  54. Kanowski M, Kaufmann J, Braun J, Bernanding J, Tempelmann C (2004) Quantitation of simulated short echo time 1H human brain spectra by LCModel and AMARES. Magn Reson Med 51:904–912. https://doi.org/10.1002/mrm.20063

    Article  CAS  Google Scholar 

  55. Schubert F, Gallinat J, Seifert F, Rinneberg H (2004) Glutamate concentrations in human brain using single voxel proton magnetic resonance spectroscopy at 3 Tesla. Neuroimage 21:1762–1771. https://doi.org/10.1016/j.neuroimage.2003.11.014

    Article  Google Scholar 

  56. Yahya A, Mädler B, Fallone BG (2008) Exploiting the chemical shift displacement effect in the detection of glutamate and glutamine (Glx) with PRESS. J Magn Reson 191:120–127. https://doi.org/10.1016/j.jmr.2007.12.007

    Article  CAS  Google Scholar 

  57. Provencher SW (1993) Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 30:672–679. https://doi.org/10.1002/mrm.1910300604

    Article  CAS  Google Scholar 

  58. Provencher SW (2001) Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed 14:260–264. https://doi.org/10.1002/nbm.698

    Article  CAS  Google Scholar 

  59. Pozza A, Dèttore D (2017) Drop-out and efficacy of group versus individual cognitive behavioural therapy: what works best for Obsessive-Compulsive Disorder? A systematic review and meta-analysis of direct comparisons. Psychiatry Res 258:24–36. https://doi.org/10.1016/j.psychres.2017.09.056

    Article  Google Scholar 

  60. Kozak MJ, Foa EB (1997) Mastery of obsessive-compulsive disorder. A cognitive-behavioral approach. The Psychological Corporation, San Antonio

    Google Scholar 

  61. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62. https://doi.org/10.1136/jnnp.23.1.56

    Article  CAS  Google Scholar 

  62. Holt DJ, Coombs G, Zeidan MA, Goff DC, Milad MR (2012) Failure of neural responses to safety cues in schizophrenia. Arch Gen Psychiatry 69:893–903. https://doi.org/10.1001/archgenpsychiatry.2011.2310

    Article  Google Scholar 

  63. Cliff N (1996) Answering ordinal questions with ordinal data using ordinal statistics. Multivariate Behav Res 31:331–350. https://doi.org/10.1207/s15327906mbr3103_4

    Article  CAS  Google Scholar 

  64. Romano J, Kromrey J, Coraggio J, Skowronek J (2006) Appropriate statistics for ordinal level data: Should we really be using t test and Cohen’s d for evaluating group differences on the NSSE and other surveys? Poster session presentation at the meeting of the Florida Association of Institutional Research, Cocoa Beach

  65. Bédard MJ, Chantal S (2011) Brain magnetic resonance spectroscopy in obsessive-compulsive disorder: the importance of considering subclinical symptoms of anxiety and depression. Psychiatry Res 192:45–54. https://doi.org/10.1016/j.pscychresns.2010.10.008

    Article  Google Scholar 

  66. Simpson HB, Shungu DC, Bender J, Mao X, Xu X, Slifstein M, Kegeles LS (2012) Investigation of cortical glutamate-glutamine and γ-aminobutyric acid in obsessive-compulsive disorder by proton magnetic resonance spectroscopy. Neuropsychopharmacology 37:2684–2692. https://doi.org/10.1038/npp.2012.132

    Article  CAS  Google Scholar 

  67. Rosenberg DR, Mirza Y, Russell A, Tang J, Smith JM, Banerjee SP, Bhandari R, Rose M, Ivey J, Boyd C, Moore GJ (2004) Reduced anterior cingulate glutamatergic concentrations in childhood OCD and major depression versus healthy controls. J Am Acad Child Adolesc Psychiatry 43:1146–1153. https://doi.org/10.1097/01.chi.0000132812.44664.2d

    Article  Google Scholar 

  68. Berry AC, Rosenfield D, Smits JAJ (2009) Extinction retention predicts improvement in social anxiety symptoms following exposure therapy. Depress Anxiety 26:22–27. https://doi.org/10.1002/da.20511

    Article  Google Scholar 

  69. Ball TM, Knapp SE, Paulus MP, Stein MB (2017) Brain activation during fear extinction predicts exposure success. Depress Anxiety 34:257–266. https://doi.org/10.1002/da.22583

    Article  CAS  Google Scholar 

  70. Forcadell E, Torrents-Rodas D, Vervliet B, Leiva D, Tortella-Feliu M, Fullana MA (2017) Does fear extinction in the laboratory predict outcomes of exposure therapy? A treatment analog study. Int J Psychophysiol 121:63–71. https://doi.org/10.1016/j.ijpsycho.2017.09.001

    Article  Google Scholar 

  71. Quirk GJ, Mueller D (2008) Neural mechanisms of extinction learning and retrieval. Neuropsychopharmacology 33:56–72. https://doi.org/10.1038/sj.npp.1301555

    Article  Google Scholar 

  72. Yücel M, Wood SJ, Wellard RM, Harrison BJ, Fornito A, Pujol J, Velakoulis D, Pantelis C (2008) Anterior cingulate glutamate-glutamine levels predict symptom severity in women with obsessive-compulsive disorder. Aust N Z J Psychiatry 42:467–477. https://doi.org/10.1080/00048670802050546

    Article  Google Scholar 

  73. Mussazi L, Treccani G, Mallei A, Popoli M (2013) The action of antidepressants on the glutamate system: regulation of glutamate release and glutamate receptors. Biol Pychiatry 73:1180–1188. https://doi.org/10.1016/j.biopsych.2012.11.009

    Article  CAS  Google Scholar 

  74. Fitzgerald PJ, Seemann JR, Maren S (2014) Can fear extinction be enhanced? A review of pharmacological and behavioral findings. Brain Res Bull 105:46–60. https://doi.org/10.1016/j.brainresbull.2013.12.007

    Article  CAS  Google Scholar 

  75. Burghardt NS, Sigurdsson T, Gorman JM, McEwen BS, LeDoux JE (2013) Chronic antidepressant treatment impairs the acquisition of fear extinction. Biol Psychiatry 73:1078–1086. https://doi.org/10.1016/j.biopsych.2012.10.012

    Article  CAS  Google Scholar 

  76. Lázaro L, Bargalló N, Andrés S, Falcón C, Morer A, Junqué C, Castro-Fornieles J (2012) Proton magnetic resonance spectroscopy in pediatric obsessive-compulsive disorder: longitudinal study before and after treatment. Psychiatry Res 201:17–24. https://doi.org/10.1016/j.pscychresns.2011.01.017

    Article  CAS  Google Scholar 

  77. Boschen MJ, Drummond LM (2012) Community treatment of severe, refractory obsessive-compulsive disorder. Behav Res Ther 50:203–209. https://doi.org/10.1016/j.brat.2012.01.002

    Article  Google Scholar 

  78. Koran LM, Hanna GL, Hollander E, Nestadt G, Simpson HB, Association American Psychiatric (2007) Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry 164:5–53

    Google Scholar 

  79. Hájek M, Burian M, Dezortová M (2000) Application of LCModel for quality control and quantitative in vivo 1H MR spectroscopy by short echo time STEAM sequence. MAGMA 10:6–17. https://doi.org/10.1007/BF02613107

    Article  Google Scholar 

  80. Ramadan S, Lin A, Stanwell P (2013) Glutamate and glutamine: a review of In Vivo MRS in the human brain. NMR in Biomed 26:1630–1646. https://doi.org/10.1002/nbm.3045

    Article  CAS  Google Scholar 

  81. Wijtenburg SA, Knight-Scott J (2011) Very short echo time improves the precision of glutamate detection at 3T in 1H magnetic resonance spectroscopy. J Magn Reson Imaging 34:645–652. https://doi.org/10.1002/jmri.22638

    Article  Google Scholar 

  82. Maddock RJ, Casazza GA, Fernandez DH, Maddock MI (2016) Acute modulation of cortical glutamate and GABA content by physical activity. J Neurosci 36:2449–2457. https://doi.org/10.1523/JNEUROSCI.3455-15.2016

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Mohammed R. Milad, Ph.D., for providing the stimuli used in the present study and for his general advice on implementing the paradigm in our laboratory. We thank Dr. Neus Aymamí, Dr. Isabel Sánchez, and Dr. Nadine Riesgo for their help and collaboration in dispensing the CBT to the study patients. This study was funded by Instituto de Salud Carlos III (ISCIII) [PI13/01958, PI14/00413, PI16/00889, PI16/00950], FEDER funds/European Regional Development Fund (ERDF)—a way to build Europe, a PERIS award from the Ministry of Health of the Generalitat de Catalunya (SLT006/17/249), and AGAUR [2017 SGR 1247]. MC is supported by a grant from the Spanish Ministry for Education, Culture and Sport [FPU13/02141]. IM-Z is supported by a P-FIS grant [FI17/00294] and CS-M is supported by a ‘Miguel Servet’ contract [CPII16/00048] from the ISCIII.

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Authors and Affiliations

  1. Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, Feixa Llarga s/n, Hospitalet de Llobregat, 08907, Barcelona, Spain

    M. Giménez, M. Cano, I. Martínez-Zalacaín, E. Real, P. Alonso, C. Segalàs, J. M. Menchón & C. Soriano-Mas

  2. Carlos III Health Institute, Centro de Investigación Biomédica en Red de Salud Mental-CIBERSAM, Av. de Monforte de Lemos 5, 28029, Madrid, Spain

    M. Giménez, M. Cano, E. Real, P. Alonso, C. Segalàs, J. M. Menchón, C. Soriano-Mas & M. A. Fullana

  3. Department of Clinical Sciences, School of Medicine, University of Barcelona, Casanova 143, 08036, Barcelona, Spain

    M. Cano, I. Martínez-Zalacaín, P. Alonso & J. M. Menchón

  4. Diagnostic Imaging Department, Fundació de Recerca Hospital Sant Joan de Déu, Passeig Sant Joan de Déu, 2, Esplugues de Llobregat, 08950, Barcelona, Spain

    J. Munuera

  5. Department of Psychiatry and Radiology, Columbia University, 622 W 168th St, New York, 10032, USA

    L. S. Kegeles, J. J. Weinstein & X. Xu

  6. New York State Psychiatric Institute, 1051 Riverside Dr, New York, 10032, USA

    L. S. Kegeles, J. J. Weinstein & X. Xu

  7. Department of Psychiatry, Stony Brook University, Stony Brook, 101 Nicolls Rd, Stony Brook, New York, 11794, USA

    J. J. Weinstein

  8. Depression and Anxiety Program, Department of Mental Health, Parc Taulí Sabadell, Hospital Universitari, Parc Taulí 1, 08208, Sabadell, Spain

    N. Cardoner

  9. Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Av. de Can Domènech, 737, 08193, Cerdanyola Del Vallès Barcelona, Barcelona, Spain

    N. Cardoner & M. A. Fullana

  10. Department of Psychobiology and Methodology of Health Sciences, Universitat Autònoma de Barcelona, Building B1, Ca n’Altayó, s/n, Bellaterra, 08193, Barcelona, Spain

    C. Soriano-Mas

  11. Psychiatry Department, Hospital Clínic-Institute of Neurosciences, CIBERSAM, C/Rosselló 140, 08036, Barcelona, Spain

    M. A. Fullana

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  1. M. Giménez
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  2. M. Cano
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  3. I. Martínez-Zalacaín
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Corresponding author

Correspondence to M. A. Fullana.

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The authors declare that they have no conflict of interest.

Ethical standards

The study has been approved by the Institutional Review Board of University Hospital of Bellvitge and it has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki ad its later amendments. All participants gave written informed consent to participate.

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Giménez, M., Cano, M., Martínez-Zalacaín, I. et al. Is glutamate associated with fear extinction and cognitive behavior therapy outcome in OCD? A pilot study. Eur Arch Psychiatry Clin Neurosci 270, 1003–1014 (2020). https://doi.org/10.1007/s00406-019-01056-3

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  • DOI: https://doi.org/10.1007/s00406-019-01056-3

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