Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-26T07:10:01.324Z Has data issue: false hasContentIssue false

Brain regions related to fear extinction in obsessive-compulsive disorder and its relation to exposure therapy outcome: a morphometric study

Published online by Cambridge University Press:  18 June 2013

M. A. Fullana*
Affiliation:
Institute of Neuropsychiatry and Addictions (INAD), Hospital del Mar and Department of Psychiatry, Autonomous University of Barcelona, Barcelona, Spain King's College London, Institute of Psychiatry, London, UK
N. Cardoner
Affiliation:
Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain CIBERSAM, Carlos III Health Institute, Spain Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain
P. Alonso
Affiliation:
Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain CIBERSAM, Carlos III Health Institute, Spain Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain
M. Subirà
Affiliation:
Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain
C. López-Solà
Affiliation:
Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain CIBERSAM, Carlos III Health Institute, Spain Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain
J. Pujol
Affiliation:
CRC Mar, Hospital del Mar, Barcelona, Spain
C. Segalàs
Affiliation:
Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain CIBERSAM, Carlos III Health Institute, Spain
E. Real
Affiliation:
Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain CIBERSAM, Carlos III Health Institute, Spain
M. Bossa
Affiliation:
Aragon Institute of Engineering Research, University of Zaragoza, Zaragoza, Spain
E. Zacur
Affiliation:
Aragon Institute of Engineering Research, University of Zaragoza, Zaragoza, Spain
I. Martínez-Zalacaín
Affiliation:
Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain
A. Bulbena
Affiliation:
Institute of Neuropsychiatry and Addictions (INAD), Hospital del Mar and Department of Psychiatry, Autonomous University of Barcelona, Barcelona, Spain
J. M. Menchón
Affiliation:
Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain CIBERSAM, Carlos III Health Institute, Spain Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain
S. Olmos
Affiliation:
Aragon Institute of Engineering Research, University of Zaragoza, Zaragoza, Spain
C. Soriano-Mas
Affiliation:
Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain CIBERSAM, Carlos III Health Institute, Spain
*
* Address for correspondence: M. A. Fullana, Ph.D., Institute of Neuropsychiatry and Addictions (INAD), Hospital del Mar, Passeig Marítim, 25/29, 08003 Barcelona, Spain. (Email: Miguel.Fullana@kcl.ac.uk)

Abstract

Background

The size of particular sub-regions within the ventromedial prefrontal cortex (vmPFC) has been associated with fear extinction in humans. Exposure therapy is a form of extinction learning widely used in the treatment of obsessive-compulsive disorder (OCD). Here we investigated the relationship between morphometric measurements of different sub-regions of the vmPFC and exposure therapy outcome in OCD.

Method

A total of 74 OCD patients and 86 healthy controls underwent magnetic resonance imaging (MRI). Cortical thickness and volumetric measurements were obtained for the rostral anterior cingulate cortex (rACC), the medial orbital frontal cortex and the subcallosal cortex. After MRI acquisition, patients were enrolled in an exposure therapy protocol, and we assessed the relationship between MRI-derived measurements and treatment outcome. Baseline between-group differences for such measurements were also assessed.

Results

Compared with healthy controls, OCD patients showed a thinner left rACC (p = 0.008). Also, left rACC thickness was inversely associated with exposure therapy outcome (r – 0.32, p = 0.008), and this region was significantly thinner in OCD patients who responded to exposure therapy than in those who did not (p = 0.006). Analyses based on regional volumetry did not yield any significant results.

Conclusions

OCD patients showed cortical thickness reductions in the left rACC, and these alterations were related to exposure therapy outcome. The precise characterization of neuroimaging predictors of treatment response derived from the study of the brain areas involved in fear extinction may optimize exposure therapy planning in OCD and other anxiety disorders.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abramowitz, JS (2006). The psychological treatment of obsessive-compulsive disorder. Canadian Journal of Psychiatry 51, 407416.CrossRefGoogle ScholarPubMed
APA (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Association: Washington, DC.Google Scholar
Arango, C, Breier, A, McMahon, R, Carpenter, WT Jr., Buchanan, RW (2003). The relationship of clozapine and haloperidol treatment response to prefrontal, hippocampal, and caudate brain volumes. American Journal of Psychiatry 160, 14211427.CrossRefGoogle ScholarPubMed
Baek, K, Chae, JH, Jeong, J (2012). The effect of repetitive transcranial magnetic stimulation on fear extinction in rats. Neuroscience 200, 159165.Google Scholar
Berry, AC, Rosenfield, D, Smits, JA (2009). Extinction retention predicts improvement in social anxiety symptoms following exposure therapy. Depression Anxiety 26, 2227.CrossRefGoogle ScholarPubMed
Boschen, MJ, Drummond, LM (2012).Community treatment of severe, refractory obsessive-compulsive disorder. Behaviour Research and Therapy 50, 203209.Google Scholar
Bouton, ME (2004). Context and behavioral processes in extinction. Learning and Memory 11, 485494.Google Scholar
Bryant, RA, Felmingham, K, Whitford, TJ, Kemp, A, Hughes, G, Peduto, A, Williams, LM (2008). Rostral anterior cingulate volume predicts treatment response to cognitive-behavioural therapy for posttraumatic stress disorder. Journal of Psychiatry and Neuroscience 33, 142146.Google ScholarPubMed
Cardoner, N, Soriano-Mas, C, Pujol, J, Alonso, P, Harrison, BJ, Deus, J, Hernandez-Ribas, R, Menchon, JM, Vallejo, J (2007). Brain structural correlates of depressive comorbidity in obsessive-compulsive disorder. Neuroimage 38, 413421.Google Scholar
Chen, CH, Ridler, K, Suckling, J, Williams, S, Fu, CH, Merlo-Pich, E, Bullmore, E (2007). Brain imaging correlates of depressive symptom severity and predictors of symptom improvement after antidepressant treatment. Biological Psychiatry 62, 407414.CrossRefGoogle ScholarPubMed
Destrieux, C, Fischl, B, Dale, A, Halgren, E (2010). Automatic parcellation of human cortical gyri and sulci using standard anatomical nomenclature. Neuroimage 53, 115.Google Scholar
First, MB, Spitzer, RL, Gibbon, M, Williams, JBW (1996). Structured Clinical Inteview for DSM-IV Axis I Disorders-Clinician Version (SCID-CV). American Psychiatric Press, Inc.: Washington, DC.Google Scholar
First, MB, Spitzer, RL, Gibbon, M, Williams, JBW (2002). Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition (SCID-I/NP). Biometrics Research, New York State Psychiatric Institute: New York.Google Scholar
Fischl, B, Salat, DH, Busa, E, Albert, M, Dieterich, M, Haselgrove, C, van der Kouwe, A, Killiany, R, Kennedy, D, Klaveness, S, Montillo, A, Makris, N, Rosen, B, Dale, AM (2002). Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 33, 341355.Google Scholar
Fischl, B, Salat, DH, van der Kouwe, AJ, Makris, N, Segonne, F, Quinn, BT, Dale, AM (2004). Sequence-independent segmentation of magnetic resonance images. Neuroimage 23 (Suppl. 1), S69S84.Google Scholar
Fu, CH, Steiner, H, Costafreda, SG (2013). Predictive neural biomarkers of clinical response in depression: a meta-analysis of functional and structural neuroimaging studies of pharmacological and psychological therapies. Neurobiology of Disease 52, 7583.CrossRefGoogle ScholarPubMed
Goodman, WK, Price, LH, Rasmussen, SA, Mazure, C, Fleischmann, RL, Hill, CL, Heninger, GR, Charney, DS (1989). The Yale–Brown Obsessive Compulsive Scale: I. Development, use, and reliability. Archives of General Psychiatry 46, 10061011.Google Scholar
Goto, M, Abe, O, Miyati, T, Inano, S, Hayashi, N, Aoki, S, Mori, H, Kabasawa, H, Ino, K, Yano, K, Iida, K, Mima, K, Ohtomo, K (2011). 3 Tesla MRI detects accelerated hippocampal volume reduction in postmenopausal women. Journal of Magnetic Resonance Imaging 33, 4853.Google Scholar
Graham, BM, Milad, MR (2011). The study of fear extinction: implications for anxiety disorders. American Journal of Psychiatry 168, 12551265.Google Scholar
Greenberg, BD, Rauch, SL, Haber, SN (2010). Invasive circuitry-based neurotherapeutics: stereotactic ablation and deep brain stimulation for OCD. Neuropsychopharmacology 35, 317336.Google Scholar
Hamilton, M (1960). A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry 23, 5662.Google Scholar
Hartley, CA, Fischl, B, Phelps, EA (2011). Brain structure correlates of individual differences in the acquisition and inhibition of conditioned fear. Cerebral Cortex 21, 19541962.Google Scholar
Hoexter, MQ, Dougherty, DD, Shavitt, RG, D'Alcante, CC, Duran, FL, Lopes, AC, Diniz, JB, Batistuzzo, MC, Evans, KC, Bressan, RA, Busatto, GF, Miguel, EC (2012). Differential prefrontal gray matter correlates of treatment response to fluoxetine or cognitive-behavioral therapy in obsessive-compulsive disorder. European Neuropsychopharmacology. Published online 26 July 2012 . doi:10.1016/j.euroneuro.2012.06.014.Google Scholar
Hofmann, SG (2007). Enhancing exposure-based therapy from a translational research perspective. Behaviour Research and Therapy 45, 19872001.CrossRefGoogle ScholarPubMed
Hutton, C, Draganski, B, Ashburner, J, Weiskopf, N (2009). A comparison between voxel-based cortical thickness and voxel-based morphometry in normal aging. Neuroimage 48, 371380.Google Scholar
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. Journal of Neuroscience 26, 95039511.Google Scholar
Konradi, C, Heckers, S (2001). Antipsychotic drugs and neuroplasticity: insights into the treatment and neurobiology of schizophrenia. Biological Psychiatry 50, 729742.Google Scholar
Koran, LM, Hanna, GL, Hollander, E, Nestadt, G, Simpson, HB; American Psychiatric Association (2007). Practice guideline for the treatment of patients with obsessive-compulsive disorder. American Journal of Psychiatry 164, 553.Google Scholar
Kozak, M, Foa, EB (1997). Mastery of your Obsessive-Compulsive Disorder. Psychological Corp.: San Antonio, TX.Google Scholar
Labate, A, Cerasa, A, Mula, M, Mumoli, L, Gioia, MC, Aguglia, U, Quattrone, A, Gambardella, A (2012). Neuroanatomic correlates of psychogenic nonepileptic seizures: a cortical thickness and VBM study. Epilepsia 53, 377385.Google Scholar
Linden, DE (2008). Brain imaging and psychotherapy: methodological considerations and practical implications. European Archives of Psychiatry and Clinical Neurosciences 258 (Suppl. 5), 7175.Google Scholar
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 correlate to neurobiological changes in the fear circuit. Journal of the American Medical Association. Published online 17 April 2013 . doi:10:1001/jama.2010.920.Google Scholar
Milad, MR, Orr, SP, Lasko, NB, Chang, Y, Rauch, SL, Pitman, RK (2008). Presence and acquired origin of reduced recall for fear extinction in PTSD: results of a twin study. Journal of Psychiatric Research 42, 515520.CrossRefGoogle ScholarPubMed
Milad, MR, Pitman, RK, Ellis, CB, Gold, AL, Shin, LM, Lasko, NB, Zeidan, MA, Handwerger, K, Orr, SP, Rauch, SL (2009). Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biological Psychiatry 66, 10751082.CrossRefGoogle ScholarPubMed
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. Procedings of the National Academy of Sciences USA 102, 1070610711.Google Scholar
Milad, MR, Quirk, GJ (2012). Fear extinction as a model for translational neuroscience: ten years of progress. Annual Review of Psychology 63, 129151.Google Scholar
Milad, MR, Rauch, SL (2012). Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways. Trends in Cognitive Sciences 16, 4351.Google Scholar
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. Biological Psychiatry 62, 446454.Google Scholar
Norberg, MM, Krystal, JH, Tolin, DF (2008). A meta-analysis of d-cycloserine and the facilitation of fear extinction and exposure therapy. Biological Psychiatry 63, 11181126.Google Scholar
Osuch, EA, Benson, BE, Luckenbaugh, DA, Geraci, M, Post, RM, McCann, U (2009). Repetitive TMS combined with exposure therapy for PTSD: a preliminary study. Journal of Anxiety Disorders 23, 5459.Google Scholar
Pallanti, S, Hollander, E, Bienstock, C, Koran, L, Leckman, J, Marazziti, D, Pato, M, Stein, D, Zohar, J; International Treatment Refractory OCD Consortium (2002). Treatment non-response in OCD: methodological issues and operational definitions. International Journal of Neuropsychopharmacology 5, 181191.Google Scholar
Phelps, EA, Delgado, MR, Nearing, KI, LeDoux, JE (2004). Extinction learning in humans: role of the amygdala and vmPFC. Neuron 43, 897905.Google Scholar
Polli, FE, Wright, CI, Milad, MR, Dickerson, BC, Vangel, M, Barton, JJ, Rauch, SL, Manoach, DS (2009). Hemispheric differences in amygdala contributions to response monitoring. Neuroreport 20, 398402.Google Scholar
Pujol, J, Soriano-Mas, C, Alonso, P, Cardoner, N, Menchon, JM, Deus, J, Vallejo, J (2004). Mapping structural brain alterations in obsessive-compulsive disorder. Archives of General Psychiatry 61, 720730.Google Scholar
Quirk, GJ, Mueller, D (2008). Neural mechanisms of extinction learning and retrieval. Neuropsychopharmacology 33, 5672.Google Scholar
Radua, J, Mataix-Cols, D (2009). Voxel-wise meta-analysis of grey matter changes in obsessive-compulsive disorder. British Journal of Psychiatry 195, 393402.Google Scholar
Rauch, SL, Shin, LM, Phelps, EA (2006). Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research – past, present, and future. Biological Psychiatry 60, 376382.Google Scholar
Rotge, JY, Guehl, D, Dilharreguy, B, Tignol, J, Bioulac, B, Allard, M, Burbaud, P, Aouizerate, B (2009). Meta-analysis of brain volume changes in obsessive-compulsive disorder. Biological Psychiatry 65, 7583.Google Scholar
Rotge, JY, Langbour, N, Guehl, D, Bioulac, B, Jaafari, N, Allard, M, Aouizerate, B, Burbaud, P (2010). Gray matter alterations in obsessive-compulsive disorder: an anatomic likelihood estimation meta-analysis. Neuropsychopharmacology 35, 686691.Google Scholar
Shin, YW, Yoo, SY, Lee, JK, Ha, TH, Lee, KJ, Lee, JM, Kim, IY, Kim, SI, Kwon, JS (2007). Cortical thinning in obsessive compulsive disorder. Human Brain Mapping 28, 11281135.Google Scholar
Siegle, GJ, Thompson, WK, Collier, A, Berman, SR, Feldmiller, J, Thase, ME, Friedman, ES (2012). Toward clinically useful neuroimaging in depression treatment: prognostic utility of subgenual cingulate activity for determining depression outcome in cognitive therapy across studies, scanners, and patient characteristics. Archives of General Psychiatry 69, 913924.Google Scholar
Sotres-Bayon, F, Cain, CK, LeDoux, JE (2006). Brain mechanisms of fear extinction: historical perspectives on the contribution of prefrontal cortex. Biological Psychiatry 60, 329336.CrossRefGoogle ScholarPubMed
Venkatasubramanian, G, Zutshi, A, Jindal, S, Srikanth, SG, Kovoor, JM, Kumar, JK, Janardhan Reddy, YC (2012). Comprehensive evaluation of cortical structure abnormalities in drug-naive, adult patients with obsessive-compulsive disorder: a surface-based morphometry study. Journal of Psychiatric Research 46, 11611168.CrossRefGoogle ScholarPubMed
Zeidan, MA, Igoe, SA, Linnman, C, Vitalo, A, Levine, JB, Klibanski, A, Goldstein, JM, Milad, MR (2011). Estradiol modulates medial prefrontal cortex and amygdala activity during fear extinction in women and female rats. Biological Psychiatry 70, 920927.Google Scholar