Skip to main content Accessibility help
×
Hostname: page-component-586b7cd67f-t7czq Total loading time: 0 Render date: 2024-11-28T03:23:04.914Z Has data issue: false hasContentIssue false

18 - Molecular imaging of obsessive–compulsive disorder

from Section III - Anxiety Disorders

Published online by Cambridge University Press:  10 January 2011

Martijn Figee
Affiliation:
Department of Psychiatry University of Amsterdam Amsterdam, The Netherlands
Jan Booij
Affiliation:
Department of Nuclear Medicine University of Amsterdam Amsterdam, The Netherlands
Damiaan Denys
Affiliation:
Department of Psychiatry University of Amsterdam Amsterdam, The Netherlands
Martha E. Shenton
Affiliation:
VA Boston Healthcare System and Brigham and Women's Hospital, Harvard Medical School
Bruce I. Turetsky
Affiliation:
University of Pennsylvania
Get access

Summary

Introduction

Obsessive–compulsive disorder (OCD) is a chronic psychiatric disorder that is characterized by the presence of recurrent and anxiety-provoking thoughts, images or impulses (obsessions), typically followed by repetitive ritualistic behaviors (compulsions) to relieve anxiety. The prevalence of OCD is estimated to be between 1 and 3% (Ruscio et al.,2010; Fullana et al., 2009). Without adequate treatment, obsessions and compulsions can become extremely time-consuming, causing significant impairments in social and occupational functioning. Effective treatment options for OCD are cognitive behavioral therapy, pharmacotherapy or psychosurgical interventions.

Approximately 40–60% of OCD patients respond to pharmacotherapy with drugs that increase intrasynaptic serotonin (Denys 2006; Soomro et al., 2008). Hence, it is often suggested that OCD is related to a dysfunction of brain serotonin systems. Central dopaminergic systems are likely to be involved as well, since patients who do not respond to treatment with serotonin reuptake inhibitors (SRIs) can be successfully augmented with dopamine receptor antagonists (Fineberg et al., 2006; Bloch et al., 2006). Finally, the potential efficacy of glutamate modulating drugs in OCD (Denys, 2006) suggests glutaminergic abnormalities in OCD.

Functional imaging studies indicate involvement of the cortico-striatal–thalamic–cortical circuit in OCD pathophysiology (Saxena and Rauch, 2000; Menzies et al., 2008) and within this circuitry, the neurotransmitters serotonin, dopamine and glutamate are important regulators of neuronal activity. The exact function of these neurotransmitters in OCD is still unclear, however. They may be directly implicated in the pathophysiology of OCD, or only related to treatment effects.

Type
Chapter
Information
Understanding Neuropsychiatric Disorders
Insights from Neuroimaging
, pp. 260 - 273
Publisher: Cambridge University Press
Print publication year: 2010

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

Adams, K H, Hansen, E S, Pinborg, L H, et al. 2005. Patients with obsessive–compulsive disorder have increased 5-HT2A receptor binding in the caudate nuclei. Int. J. Neuropsychopharmacol 8, 391–401.Google Scholar
Becquet, D, Faudon, M and Hery, F. 1990. In vivo evidence for an inhibitory glutamatergic control of serotonin release in the cat caudate nucleus: Involvement of GABA neurons. Brain Res 519, 82–8.Google Scholar
Benmansour, S, Owens, W A, Cecchi, M, Morilak, D A and Frazer, A. 2002. Serotonin clearance in vivo is altered to a greater extent by antidepressant-induced downregulation of the serotonin transporter than by acute blockade of this transporter. J Neurosci 22, 6766–72.Google Scholar
Bloch, M H, Landeros-Weisenberger, A, Kelmendi, B, Coric, V, Bracken, M B and Leckman, J F. 2006. A systematic review: Antipsychotic augmentation with treatment refractory obsessive–compulsive disorder. Mol Psychiatry 11, 622–32.Google Scholar
Booij, J, Jong, J, Bruin, K, Knol, R J J, Win, M M and Eck-Smit, B L F. 2007. Quantification of striatal dopamine transporters with [123I] beta-CIT SPECT is influenced by the selective serotonin reuptake inhibitor paroxetine: A double-blind, placebo-controlled, crossover study in healthy controls. J Nucl Med 48, 359–66.Google Scholar
Denys, D. 2006. Pharmacotherapy of obsessive–compulsive disorder and obsessive–compulsive spectrum disorders. Psychiatr Clin North Am 29, 553–84, xi.Google Scholar
Denys, D, Klompmakers, A A and Westenberg, H G. 2004. Synergistic dopamine increase in the rat prefrontal cortex with the combination of quetiapine and fluvoxamine. Psychopharmacology (Berl) 176, 195–203.Google Scholar
Dewey, S L, Smith, G S, Logan, J, et al. 1995. Serotonergic modulation of striatal dopamine measured with positron emission tomography (PET) and in vivo microdialysis. J Neurosci 15, 821–9.Google Scholar
Fineberg, N A, Gale, T M and Sivakumaran, T. 2006. A review of antipsychotics in the treatment of obsessive compulsive disorder. J Psychopharmacol 20, 97–103.Google Scholar
Fletcher, P J, Korth, K M and Chambers, J W. 1999. Selective destruction of brain serotonin neurons by 5,7-dihydroxytryptamine increases responding for a conditioned reward. Psychopharmacology (Berl) 147, 291–9.Google Scholar
Fowler, J S, Wang, G J, Volkow, N D, et al. 1999. PET studies of the effect of the antidepressant drugs nefazodone or paroxetine on [11C]raclopride binding in human brain. Clin Positron Imaging 2, 205–09.Google Scholar
Fullana, M A, Mataix-Cols, D, Caspi, A, et al. 2009. Obsessions and compulsions in the community: Prevalence, interference, help-seeking, developmental stability, and co-occurring psychiatric conditions. Am J Psychiatry 166, 329–36.Google Scholar
Gray, J A and Roth, B L. 2001. Paradoxical trafficking and regulation of 5-HT(2A) receptors by agonists and antagonists. Brain Res Bull 56, 441–51.Google Scholar
Hasselbalch, S G, Hansen, E S, Jacobsen, T B, Pinborg, L H, Lønborg, J H and Bolwig, T G. 2007. Reduced midbrain-pons serotonin transporter binding in patients with obsessive–compulsive disorder. Acta Psychiatr Scand 115, 388–94.Google Scholar
Hesse, S, Muller, U, Lincke, T, et al. 2005. Serotonin and dopamine transporter imaging in patients with obsessive–compulsive disorder. Psychiatry Res 140, 63–72.Google Scholar
Kapur, S and Remington, G. 1996. Serotonin–dopamine interaction and its relevance to schizophrenia. Am J Psychiatry 153, 466–76.Google Scholar
Kim, C H, Cheon, K A, Koo, M S, et al. 2007. Dopamine transporter density in the basal ganglia in obsessive–compulsive disorder, measured with [123I]IPT SPECT before and after treatment with serotonin reuptake inhibitors. Neuropsychobiology 55, 156–62.Google Scholar
Kim, C H, Koo, M S, Cheon, K A, Ryu, Y H, Lee, J D, Lee, H S. 2003. Dopamine transporter density of basal ganglia assessed with [123I]IPT SPET in obsessive–compulsive disorder. Eur J Nucl Med Mol Imaging 30, 1637–43.Google Scholar
Koch, S, Perry, K W, Nelson, D L, Conway, R G, Threlkeld, P G and Bymaster, F P. 2002. R-fluoxetine increases extracellular DA, NE, as well as 5-HT in rat prefrontal cortex and hypothalamus: An in vivo microdialysis and receptor binding study. Neuropsychopharmacology 27, 949–59.Google Scholar
Laruelle, M, Baldwin, R M, Malison, R T, et al. 1993. SPECT imaging of dopamine and serotonin transporters with [123I]β-CIT: Pharmacological characterization of brain uptake in nonhuman primates. Synapse 13, 295–309.Google Scholar
Laruelle, M, Wallace, E, Seibyl, J P, et al. 1994. Graphical, kinetic, and equilibrium analyses of in vivo [123I]β-CIT binding to dopamine transporters in healthy human subjects. J Cereb Blood Flow Metab 14, 982–94.Google Scholar
Malison, R T, Price, L H, Berman, R, et al. 1998. Reduced brain serotonin transporter availability in major depression as measured by [123I]-2bcarbomethoxy-3b-(4-iodophenyl)tropane and single photon emission computed tomography. Biol Psychiatry 44, 1090–8.Google Scholar
Menzies, L, Chamberlain, S R, Laird, A R, Thelen, S M, Sahakian, B J and Bullmore, E T. 2008. Integrating evidence from neuroimaging and neuropsychological studies of obsessive compulsive disorder: The orbitofronto-striatal model revisited. Neurosci Biobehav Rev 32, 525–49.Google Scholar
Moore, G J, MacMaster, F P, Stewart, C and Rosenberg, D R. 1998. Case study: Caudate glutamatergic changes with paroxetine therapy for paediatric obsessive–compulsive disorder. J Am Acad Child Adolesc Psychiatry 37, 663–7.Google Scholar
Moresco, R M, Pietra, L, Henin, M, et al. 2007. Fluvoxamine treatment and D2 receptors: A PET study on OCD drug-naïve patients. Neuropsychopharmacology 32, 197–205.Google Scholar
Olver, J S, O'Keefe, G, Jones, G R, et al. 2009. Dopamine D(1) receptor binding in the striatum of patients with obsessive–compulsive disorder. J Affect Disord 114, 321–6.Google Scholar
Olvera-Cortés, M E, Anguiano-Rodríguez, P, López-Vázquez, M A and Alfaro, J M. 2008. Serotonin/dopamine interaction in learning. Prog Brain Res 172, 567–602.Google Scholar
Perani, D, Garibotto, V, Gorini, A, et al. 2008. In vivo PET study of 5HT(2A) serotonin and D(2) dopamine dysfunction in drug-naïve obsessive–compulsive disorder. Neuroimage 42, 306–14.Google Scholar
Pfund, Z, Chugani, D C, Juhasz, C, et al. 2000. Evidence for coupling between glucose metabolism and glutamate cycling using FDG PET and 1H magnetic resonance spectroscopy in patients with epilepsy. J Cerebr Blood Flow Metab 20, 871–8.Google Scholar
Pirker, W, Asenbaum, S, Hauk, M, et al. 2000. Imaging serotonin and dopamine transporters with 123I-β-CIT SPECT: Binding kinetics and effects of normal aging. J Nucl Med 41, 36–44.Google Scholar
Pogarell, O, Hamann, C, Popperl, G, et al. 2003. Elevated brain serotonin transporter availability in patients with obsessive–compulsive disorder. Biol Psychiatry 54, 1406–13.Google Scholar
Pogarell, O, Poepperl, G, Mulert, C, et al. 2005. SERT and DAT availabilities under citalopram treatment in obsessive–compulsive disorder (OCD). Eur Neuropsychopharmacol 15, 521–4.Google Scholar
Reimold, M, Smolka, M N, Zimmer, A, et al. 2007. Reduced availability of serotonin transporters in obsessive–compulsive disorder correlates with symptom severity – A [11C]DASB PET study. J Neural Transm 114, 1603–09.Google Scholar
Rosario-Campos, M C, Leckman, J F, Mercadante, M T, et al. 2001. Adults with early-onset obsessive–compulsive disorder. Am J Psychiatry 158, 1899–903.Google Scholar
Rosenberg, D R, MacMaster, F P, Keshavan, M S, Fitzgerald, K D and Stewart, C M. 2000. Decrease in caudate glutamatergic concentrations in paediatric obsessive–compulsive disorder patients taking paroxetine. J Am Acad Child Adolesc Psychiatry 39, 1096–103.Google Scholar
Rosenberg, D R, Mirza, Y, Russell, A, et al. 2004. Reduced anterior cingulate glutamatergic concentrations in childhood OCD and major depression versus healthy controls. J Am Acad Child Adolesc Psychiatry 43, 1146–53.Google Scholar
Ruscio, A M, Stein, D J, Chiu, W T and Kessler, R C. 2010. The epidemiology of obsessive–compulsive disorder in the National Comorbidity Survey Replication Mol Psychiatry 15, 53–63.Google Scholar
Saiz, P A, Garcia-Portilla, M P, Arango, C, et al. 2008. Association study between obsessive–compulsive disorder and serotonergic candidate genes. Prog Neuropsychopharmacol Biol Psychiatry 32, 765–70.Google Scholar
Saxena, S and Rauch, S L. 2000. Functional neuroimaging and the neuroanatomy of obsessive–compulsive disorder. Psychiatr Clin North Am 23, 563–86.Google Scholar
Schneier, F R, Liebowitz, M R, Abi-Dargham, A, Zea-Ponce, Y, Lin, S H and Laruelle, M. 2000. Low dopamine D(2) receptor binding potential in social phobia. Am J Psychiatry 157, 457–9.Google Scholar
Schneier, F R, Martinez, D, Abi-Dargham, A, et al. 2008. Striatal dopamine D(2) receptor availability in OCD with and without comorbid social anxiety disorder: preliminary findings. Depress Anxiety 25, 1–7.Google Scholar
Schultz, W. 1998. Predictive reward signal of dopamine neurons. J Neurophysiol 80, 1–27.Google Scholar
Simpson, H B, Lombardo, I, Slifstein, M, et al. 2003. Serotonin transporters in obsessive–compulsive disorder: A positron emission tomography study with [11C]McN 5652. Biol Psychiatry 54, 1414–21.Google Scholar
Smith, G S, Dewey, S L, Brodie, J D, et al. 1997. Serotonergic modulation of dopamine measured with [11C]raclopride and PET in normal human subjects. Am J Psychiatry 154, 490–6.Google Scholar
Soomro, G M, Altman, D, Rajagopal, S and Oakley-Browne, M. 2008. Selective serotonin re-uptake inhibitors (SSRIs) versus placebo for obsessive compulsive disorder (OCD). Cochrane Database Syst Rev 1, CD001765.
Starck, G, Ljungberg, M, Nilsson, M, et al. 2008. A 1H magnetic resonance spectroscopy study in adults with obsessive compulsive disorder: relationship between metabolite concentrations and symptom severity. J Neural Transm 115, 1051–62.Google Scholar
Stengler-Wenzke, K, Müller, U, Angermeyer, M C, Sabri, O and Hesse, S. 2004. Reduced serotonin transporter availability in obsessive–compulsive disorder (OCD). Eur Arch Psychiatry Clin Neurosci 254, 252–5.Google Scholar
Stengler-Wenzke, K, Müller, U, Barthel, H, Angermeyer, M C, Sabri, O and Hesse, S. 2006. Serotonin transporter imaging with [123I]beta-CIT SPECT before and after one year of citalopram treatment of obsessive–compulsive disorder. Neuropsychobiology 53, 40–5.Google Scholar
Wee, N J, Stevens, H, Hardeman, J A, et al. 2004. Enhanced dopamine transporter density in psychotropic-naïve patients with obsessive–compulsive disorder shown by [123I]{beta}-CIT SPECT. Am J Psychiatry 161, 2201–06.Google Scholar
Whiteside, S P, Port, J D, Deacon, B J and Abramowitz, J S. 2006. A magnetic resonance spectroscopy investigation of obsessive–compulsive disorder and anxiety. Psychiatry Res. 146, 137–47.Google Scholar
Wong, D F, Brašic, J R, Singer, H S, et al. 2008. Mechanisms of dopaminergic and serotonergic neurotransmission in Tourette Syndrome: Clues from an in vivo neurochemistry study with PET. Neuropsychopharmacology 33, 1239–51.Google Scholar
Yücel, M, Wood, S J, Wellard, R M, et al. 2008. Anterior cingulate glutamate–glutamine levels predict symptom severity in women with obsessive–compulsive disorder. Aust N Z J Psychiatry 42, 467–77.Google Scholar
Zhou, F M, Liang, Y, Salas, R, Zhang, L, Biasi, M and Dani, J A. 2005. Corelease of dopamine and serotonin from striatal dopamine terminals. Neuron 46, 65–74.Google Scholar
Zitterl, W, Aigner, M, Stompe, T, et al. 2007. [123I]-beta-CIT SPECT imaging shows reduced thalamus–hypothalamus serotonin transporter availability in 24 drugfree obsessive–compulsive checkers. Neuropsychopharmacology 32, 1661–8.Google Scholar
Zitterl, W, Aigner, M, Stompe, T, et al. 2008. Changes in thalamus–hypothalamus serotonin transporter availability during clomipramine administration in patients with obsessive–compulsive disorder. Neuropsychopharmacology 33, 3126–34.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×