Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-11-17T14:34:00.624Z Has data issue: false hasContentIssue false

21 - Molecular imaging of other anxiety disorders

from Section III - Anxiety Disorders

Published online by Cambridge University Press:  10 January 2011

By
James W. Murrough  and
Sanjay J. Mathew
Edited by
Martha E. Shenton  and
Bruce I. Turetsky
James W. Murrough
Affiliation:
Department of Psychiatry Mount Sinai School of Medicine New York, NY, USA
Sanjay J. Mathew
Affiliation:
Department of Psychiatry and Behavioral Sciences Baylor College of Medicine Houston, TX, USA
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

Neuroimaging research is beginning to define functional anatomical correlates of both normal fear and anxiety as well as the pathological anxiety symptoms found in the anxiety disorders. These studies in humans are guided by molecular biology and behavioral neuroscience research utilizing animal models of fear and anxiety. Anatomical circuits and neurochemicals that may govern normal and abnormal fear and anxiety are beginning to emerge through convergence of both animal and human data. Current research seeks to understand how normal fear systems become dysregulated in clinical anxiety disorders.

This chapter reviews the neurochemical imaging literature in the anxiety disorders, focusing on key findings in post-traumatic stress disorder (PTSD), panic disorder (PD), social anxiety disorder (SAD; also referred to as social phobia) and generalized anxiety disorder (GAD). PTSD develops in a subgroup of individuals who experience a traumatic event (for example, a life-threatening situation), and is characterized by re-experiencing phenomena and intrusive memories related to a traumatic event, hyperarousal (for example, exaggerated startle), and avoidance and emotional numbing. Panic disorder is characterized by the recurrence of discrete panic attacks with the development of anticipatory anxiety and avoidance in between attacks. Panic attacks are the unprovoked, sudden onset of a constellation of psychological and physical symptoms that include intense fear or dread, a feeling of the need to escape, rapid heart beat or palpitations, shortness of breath, dizziness and diaphoresis. Social anxiety disorder consists of excessive embarrassment or humiliation in social situations that leads to behavioral avoidance and occupational or social impairment.

Keywords

anxiety disordersCOMTGABA-BZDpost-traumatic stress disorderpanic disorderneurochemical imaginggeneralized anxiety disordermagnetic resonance spectroscopysocial anxiety disorder
Type
Chapter
Information
Understanding Neuropsychiatric Disorders
Insights from Neuroimaging
 , pp. 295 - 307
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

Abadie, P, Boulenger, J P, Benali, K, Barre, L, Zarifian, E and Baron, J C. 1999. Relationships between trait and state anxiety and the central benzodiazepine receptor: A PET study. Eur J Neurosci 11, 1470–8.Google Scholar
Atack, J R. 2005. The benzodiazepine binding site of GABA(A) receptors as a target for the development of novel anxiolytics. Exp Opin Investig Drugs 14, 601–18.Google Scholar
Blair, K, Shaywitz, J, Smith, B W, et al. 2008. Response to emotional expressions in generalized social phobia and generalized anxiety disorder: Evidence for separate disorders. Am J Psychiatry 165, 1193–202.Google Scholar
Bonne, O, Bain, E, Neumeister, A, et al. 2005. No change in serotonin type 1A receptor binding in patients with posttraumatic stress disorder. Am J Psychiatry 162, 383–5.Google Scholar
Bremner, J D, Innis, R B, Southwick, S M, Staib, L, Zoghbi, S and Charney, D S. 2000a. Decreased benzodiazepine receptor binding in prefrontal cortex in combat-related posttraumatic stress disorder. Am J Psychiatry 157, 1120–6.Google Scholar
Bremner, J D, Innis, R B, White, T, et al. 2000b. SPECT [I-123]iomazenil measurement of the benzodiazepine receptor in panic disorder. Biol Psychiatry 47, 96–106.Google Scholar
Briones-Aranda, A, Rocha, L and Picazo, O. 2005. Influence of forced swimming stress on 5-HT1A receptors and serotonin levels in mouse brain. Prog Neuropsychopharmacology Biol Psychiatry 29, 275–81.Google Scholar
Cameron, O G, Huang, G C, Nichols, T, et al. 2007. Reduced gamma-aminobutyric acid(A)–benzodiazepine binding sites in insular cortex of individuals with panic disorder. Arch Gen Psychiatry 64, 793–800.Google Scholar
Caspi, A, Sugden, K, Moffitt, T E, et al. 2003. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science (New York, N.Y.) 301, 386–9.Google Scholar
Coplan, J D, Mathew, S J, Mao, X, et al. 2006. Decreased choline and creatine concentrations in centrum semiovale in patients with generalized anxiety disorder: Relationship to IQ and early trauma. Psychiatry Res 147, 27–39.Google Scholar
Win, M M, Habraken, J B, Reneman, L, Brink, W, Heeten, G J and Booij, J. 2005. Validation of [(123)I]beta-CIT SPECT to assess serotonin transporters in vivo in humans: A double-blind, placebo-controlled, crossover study with the selective serotonin reuptake inhibitor citalopram. Neuropsychopharmacology 30, 996–1005.Google Scholar
Domschke, K, Deckert, J, O'Donovan, M C and Glatt, S J. 2007. Meta-analysis of COMT val158met in panic disorder: ethnic heterogeneity and gender specificity. Am J Med Genet Part B Neuropsychiatric Genet 144B, 667–73.Google Scholar
Etkin, A and Wager, T D. 2007. Functional neuroimaging of anxiety: A meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am J Psychiatry 164, 1476–88.Google Scholar
Fox, N A, Nichols, K E, Henderson, H A, et al. 2005. Evidence for a gene–environment interaction in predicting behavioral inhibition in middle childhood. Psychol Sci 16, 921–6.Google Scholar
Fujita, M, Southwick, S M, Denucci, C C, et al. 2004. Central type benzodiazepine receptors in Gulf War veterans with posttraumatic stress disorder. Biol Psychiatry 56, 95–100.Google Scholar
Geuze, E, Berckel, B N, Lammertsma, A A, et al. 2008. Reduced GABAA benzodiazepine receptor binding in veterans with post-traumatic stress disorder. Mol Psychiatry 13, 74–83, 3.Google Scholar
Goddard, A W, Mason, G F, Almai, A, et al. 2001. Reductions in occipital cortex GABA levels in panic disorder detected with 1H-magnetic resonance spectroscopy. Arch Gen Psychiatry 58, 556–61.Google Scholar
Goddard, A W, Mason, G F, Appel, M, et al. 2004. Impaired GABA neuronal response to acute benzodiazepine administration in panic disorder. Am J Psychiatry 161, 2186–93.Google Scholar
Graeff, F G. 2004. Serotonin, the periaqueductal gray and panic. Neurosci Biobehav Rev 28, 239–59.Google Scholar
Graeff, F G. 2002. On serotonin and experimental anxiety. Psychopharmacology 163, 467–76.Google Scholar
Gross, C, Zhuang, X, Stark, K, et al. 2002. Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult. Nature 416, 396–400.Google Scholar
Hariri, A R, Drabant, E M, Munoz, K E, et al. 2005. A susceptibility gene for affective disorders and the response of the human amygdala. Arch Gen Psychiatry 62, 146–52.Google Scholar
Hasler, G, Nugent, A C, Carlson, P J, Carson, R E, Geraci, M and Drevets, W C. 2008. Altered cerebral gamma-aminobutyric acid type A–benzodiazepine receptor binding in panic disorder determined by [11C]flumazenil positron emission tomography. Arch Gen Psychiatry 65, 1166–75.Google Scholar
Hasler, G, Veen, J W, Geraci, M, Shen, J, Pine, D and Drevets, W C. 2009. Prefrontal cortical gamma-aminobutyric acid levels in panic disorder determined by proton magnetic resonance spectroscopy. Biol Psychiatry 65, 273–5.Google Scholar
Kalueff, A V and Nutt, D J. 2007. Role of GABA in anxiety and depression. Depress Anxiety 24, 495–517.Google Scholar
Kaschka, W, Feistel, H and Ebert, D. 1995. Reduced benzodiazepine receptor binding in panic disorders measured by iomazenil SPECT. J Psychiatric Res 29, 427–34.Google Scholar
Kent, J M, Coplan, J D, Lombardo, I, et al. 2002a. Occupancy of brain serotonin transporters during treatment with paroxetine in patients with social phobia: A positron emission tomography study with 11C McN 5652. Psychopharmacology 164, 341–8.Google Scholar
Kent, J M, Mathew, S J and Gorman, J M. 2002b. Molecular targets in the treatment of anxiety. Biol Psychiatry 52, 1008–30.Google Scholar
Klemenhagen, K C, Gordon, J A, David, D J, Hen, R and Gross, C T. 2006. Increased fear response to contextual cues in mice lacking the 5-HT1A receptor. Neuropsychopharmacology 31, 101–11.Google Scholar
Kuikka, J T, Pitkanen, A, Lepola, U, et al. 1995. Abnormal regional benzodiazepine receptor uptake in the prefrontal cortex in patients with panic disorder. Nucl Med Commun 16, 273–80.Google Scholar
Kusserow, H, Davies, B, Hortnagl, H, et al. 2004. Reduced anxiety-related behaviour in transgenic mice overexpressing serotonin 1A receptors. Brain Res Mol Brain Res 129, 104–16.Google Scholar
Lanzenberger, R R, Mitterhauser, M, Spindelegger, C, et al. 2007. Reduced serotonin-1A receptor binding in social anxiety disorder. Biol Psychiatry 61, 1081–9.Google Scholar
LeDoux, J E. 2000. Emotion circuits in the brain. Annu Rev Neurosci 23, 155–84.Google Scholar
Lemonde, S, Turecki, G, Bakish, D, et al. 2003. Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. J Neurosci 23, 8788–99.Google Scholar
Lesch, K P, Bengel, D, Heils, A, et al. 1996. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science (New York, N.Y.) 274, 1527–31.Google Scholar
Malizia, A L, Cunningham, V J, Bell, C J, Liddle, P F, Jones, T and Nutt, D J. 1998. Decreased brain GABA(A)–benzodiazepine receptor binding in panic disorder: Preliminary results from a quantitative PET study. Arch Gen Psychiatry 55, 715–20.Google Scholar
Maron, E, Kuikka, J T, Ulst, K, Tiihonen, J, Vasa, V and Shlik, J. 2004. SPECT imaging of serotonin transporter binding in patients with generalized anxiety disorder. Eur Arch Psychiatry Clin Neurosci 254, 392–6.Google Scholar
Mathew, S J, Coplan, J D and Gorman, J M. 2001. Neurobiological mechanisms of social anxiety disorder. Am J Psychiatry 158, 1558–67.Google Scholar
Mathew, S J, Mao, X, Coplan, J D, et al. 2004. Dorsolateral prefrontal cortical pathology in generalized anxiety disorder: A proton magnetic resonance spectroscopic imaging study. Am J Psychiatry 161, 1119–21.Google Scholar
Mathew, S J, Price, R B, Mao, X, et al. 2008. Hippocampal N-acetylaspartate concentration and response to riluzole in generalized anxiety disorder. Biol Psychiatry 63, 891–8.Google Scholar
McClure, E B, Monk, C S, Nelson, E E, et al. 2007. Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder. Arch Gen Psychiatry 64, 97–106.Google Scholar
Monk, C S, Nelson, E E, McClure, E B, et al. 2006. Ventrolateral prefrontal cortex activation and attentional bias in response to angry faces in adolescents with generalized anxiety disorder. Am J Psychiatry 163, 1091–7.Google Scholar
Monk, C S, Telzer, E H, Mogg, K, et al. 2008. Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder. Arch Gen Psychiatry 65, 568–76.Google Scholar
Morris, H V, Dawson, G R, Reynolds, D S, Atack, J R and Stephens, D N. 2006. Both alpha2 and alpha3 GABAA receptor subtypes mediate the anxiolytic properties of benzodiazepine site ligands in the conditioned emotional response paradigm. Eur J Neurosci 23, 2495–504.Google Scholar
Morrow, B A, Elsworth, J D, Rasmusson, A M and Roth, R H. 1999. The role of mesoprefrontal dopamine neurons in the acquisition and expression of conditioned fear in the rat. Neuroscience 92, 553–64.Google Scholar
Neumeister, A, Bain, E, Nugent, A C, et al. 2004a. Reduced serotonin type 1A receptor binding in panic disorder. J Neurosci 24, 589–91.Google Scholar
Neumeister, A, Nugent, A C, Waldeck, T, et al. 2004b. Neural and behavioral responses to tryptophan depletion in unmedicated patients with remitted major depressive disorder and controls. Arch Gen Psychiatry 61, 765–73.Google Scholar
Nutt, D J and Malizia, A L. 2001. New insights into the role of the GABA(A)–benzodiazepine receptor in psychiatric disorder. Br J Psychiatry 179, 390–6.Google Scholar
Ongur, D, Ferry, A T and Price, J L. 2003. Architectonic subdivision of the human orbital and medial prefrontal cortex. J Comp Neurol 460, 425–49.Google Scholar
Paulus, M P and Stein, M B. 2006. An insular view of anxiety. Biol Psychiatry 60, 383–7.Google Scholar
Phan, K L, Fitzgerald, D A, Nathan, P J and Tancer, M E. 2006. Association between amygdala hyperactivity to harsh faces and severity of social anxiety in generalized social phobia. Biol Psychiatry 59, 424–9.Google Scholar
Phan, K L, Wager, T, Taylor, S F and Liberzon, I. 2002. Functional neuroanatomy of emotion: A meta-analysis of emotion activation studies in PET and fMRI. Neuroimage 16, 331–48.Google Scholar
Pollack, M H, Jensen, J E, Simon, N M, Kaufman, R E and Renshaw, P F. 2008. High-field MRS study of GABA, glutamate and glutamine in social anxiety disorder: response to treatment with levetiracetam. Prog Neuropsychopharmacol Biol Psychiatry 32, 739–43.Google Scholar
Quirk, G J, Garcia, R and Gonzalez-Lima, F. 2006. Prefrontal mechanisms in extinction of conditioned fear. Biol Psychiatry 60, 337–43.Google Scholar
Rauch, S L, Shin, L M and Phelps, E A. 2006. Neurocircuitry models of posttraumatic stress disorder and extinction: Human neuroimaging research – Past, present, and future. Biol Psychiatry 60, 376–82.Google Scholar
Schlegel, S, Steinert, H, Bockisch, A, Hahn, K, Schloesser, R and Benkert, O. 1994. Decreased benzodiazepine receptor binding in panic disorder measured by IOMAZENIL-SPECT. A preliminary report. Eur Arch Psychiatry Clin Neurosci 244, 49–51.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
Shin, L M, Orr, S P, Carson, M A, et al. 2004. Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD. Arch Gen Psychiatry 61, 168–76.Google Scholar
Shin, L M, Wright, C I, Cannistraro, P A, et al. 2005. A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder. Arch Gen Psych 62, 273–81.Google Scholar
Smith, T A. 2001. Type A gamma-aminobutyric acid (GABAA) receptor subunits and benzodiazepine binding: Significance to clinical syndromes and their treatment. Br J Biomed Sci 58, 111–21.Google Scholar
Stein, M B, Goldin, P R, Sareen, J, Zorrilla, L T and Brown, G G. 2002. Increased amygdala activation to angry and contemptuous faces in generalized social phobia. Arch Gen Psychiatry 59, 1027–34.Google Scholar
Straube, T, Mentzel, H J and Miltner, W H. 2006. Neural mechanisms of automatic and direct processing of phobogenic stimuli in specific phobia. Biol Psychiatry 59, 162–70.Google Scholar
Sullivan, G M, Oquendo, M A, Simpson, N, Heertum, R L, Mann, J J and Parsey, R V. 2005. Brain serotonin1A receptor binding in major depression is related to psychic and somatic anxiety. Biol Psychiatry 58, 947–54.Google Scholar
Tiihonen, J, Kuikka, J, Bergstrom, K, Lepola, U, Koponen, H and Leinonen, E. 1997a. Dopamine reuptake site densities in patients with social phobia. Am J Psychiatry 154, 239–42.Google Scholar
Tiihonen, J, Kuikka, J, Rasanen, P, et al. 1997b. Cerebral benzodiazepine receptor binding and distribution in generalized anxiety disorder: A fractal analysis. Mol Psychiatry 2, 463–71.Google Scholar
Vaiva, G, Thomas, P, Ducrocq, F, et al. 2004. Low posttrauma GABA plasma levels as a predictive factor in the development of acute posttraumatic stress disorder. Biol Psychiatry 55, 250–4.Google Scholar
Heuvel, O A, Veltman, D J, Groenewegen, H J, et al. 2005. Disorder-specific neuroanatomical correlates of attentional bias in obsessive–compulsive disorder, panic disorder, and hypochondriasis. Arch Gen Psychiatry 62, 922–33.Google Scholar
Wee, N J, Veen, J F, Stevens, H, Vliet, I M, Rijk, P P and Westenberg, H G. 2008. Increased serotonin and dopamine transporter binding in psychotropic medication-naive patients with generalized social anxiety disorder shown by 123I-beta-(4-iodophenyl)-tropane SPECT. J Nucl Med 49, 757–63.Google Scholar
Ventura, R, Cabib, S and Puglisi-Allegra, S. 2002. Genetic susceptibility of mesocortical dopamine to stress determines liability to inhibition of mesoaccumbens dopamine and to behavioral “despair” in a mouse model of depression. Neuroscience 115, 999–1007.Google Scholar
Zhang, W, Connor, K M and Davidson, J R. 2005. Levetiracetam in social phobia: A placebo controlled pilot study. J Psychopharmacol (Oxford, England) 19, 551–3.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org 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
×