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D-cycloserine Inhibits Amygdala Responses During Repeated Presentations of Faces

Published online by Cambridge University Press:  07 November 2014

Jennifer C. Britton ,
Andrea L. Gold ,
Eric J. Feczko ,
Scott L. Rauch ,
Danielle Williams  and
Christopher I. Wright
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Abstract

Introduction: Recently, human studies using exposure therapy to treat anxiety have demonstrated that pretreatment with D-cycloserine (DCS) enhances fear reduction in anxiety disorders. However, the underlying brain mechanisms mediating this fear reduction have yet to be determined.

Methods: The effects of orally administered DCS on amygdala activity during the processing of repeated facial expressions were examined in this double-blind study. Fourteen healthy males (30.0±8.7 years of age) randomly received DCS 500 mg or placebo prior to 3.0 Tesla functional magnetic resonance imaging acquisition. All participants viewed four separate runs, consisting of a single block of a repeated facial expression (happy or fearful) bracketed by fixation blocks.

Results: Anatomic region-of-interest analyses showed that the placebo group exhibited amygdala activation and response habituation, while the DCS group displayed blunted amygdala responses to emotional faces across the experiment, whereby habituation was not detected.

Conclusion: This finding may have relevance for testing treatments of anxiety and depression.

Type
Original Research
Information
CNS Spectrums , Volume 12 , Issue 8 , August 2007 , pp. 600 - 605
Copyright
Copyright © Cambridge University Press 2007

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References

REFERENCES

1.Wright, Cl, Fischer, H, Whalen, PJ, McInerney, SC, Shin, LM, Rauch, SL. Differential prefrontal cortex and amygdala habituation to repeatedly presented emotional stimuli. Neuroreport. 2001;12:379–383.CrossRefGoogle ScholarPubMed
2.Falls, WA, Miserendino, MJ, Davis, M, et al.Extinction of fear-potentiated startle: blockade by infusion of an NMDA antagonist into the amygdala. J Neurosci. 1992;12:854–863.CrossRefGoogle ScholarPubMed
3.Lu, KT, Walker, DL, Davis, M. Mitogen-activated protein kinase cascade in the basolateral nucleus of amygdala is involved in extinction of fear-potentiated startle. J Neurosci. 2001;21:RC162.CrossRefGoogle ScholarPubMed
4.Walker, DL, Ressler, KJ, Lu, KT, Davis, M. Facilitation of conditioned fear extinction by systemic administration or intra-amygdala infusions of D-cycloserine as assessed with fear-potentiated startle in rats. J Neurosci. 2002;22:2343–2351.CrossRefGoogle ScholarPubMed
5.Myers, KM, Davis, M. Behavioral and neural analysis of extinction. Neuron. 2002;36:567–584.CrossRefGoogle ScholarPubMed
6.Ledgerwood, L, Richardson, R, Cranney, J. Effects of D-cycloserine on extinction of conditioned freezing. Behav Neurosci. 2003;117:341–349.CrossRefGoogle ScholarPubMed
7.Richardson, R, Ledgerwood, L, Cranney, J. Facilitation of fear extinction by D-cycloserine: theoretical and clinical implications. Learn Mem. 2004;11:510–516.CrossRefGoogle ScholarPubMed
8.Hofmann, SG, Meuret, AE, Smits, JA, et al.Augmentation of exposure therapy with D-cycloserine for social anxiety disorder. Arch Gen Psychiatry. 2006;63:298–304.CrossRefGoogle ScholarPubMed
9.Ressler, KJ, Rothbaum, BO, Tannenbaum, L, et al.Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear. Arch Gen Psychiatry. 2004;61:1136–1144.CrossRefGoogle ScholarPubMed
10.First, MB, Spitzer, RL, Gibbon, M, Williams, JB. Structured Clinical Interview for DSM-IV Axis I Disorders (SCID). New York, NY: Psychiatric Institute, Biometrics Research; 1995.Google Scholar
11.Beck, AT, Epstein, N, Brown, G, Steer, RA. An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol. 1988;56:893–897.CrossRefGoogle ScholarPubMed
12.Beck, AT, Steer, RA. Beck Anxiety Inventory Manual. San Antonio, Tex: The Psychological Corporation, Harcourt Brace and Company; 1990.Google Scholar
13.Beck, AT, Ward, CH, Mendelson, M, Mock, J, Erbaugh, J. An inventory for measuring depression. Arch Gen Psychiatry. 196;4:561–571.CrossRefGoogle Scholar
14.Spielberger, CD, Gorsuch, RL, Lushene, RD. STAI: Manual for the State-Trait Anxiety Inventory. Palo Alto, Calif: Consulting Psychologists Press; 1970.Google Scholar
15.Ekman, P, Friesen, WV. Pictures of Facial Affect. Palo Alto, Calif: Consulting Psychologists Press; 1976.Google Scholar
16.Crane, GE. Cyloserine as an antidepressant agent. Am J Psychiatry. 1959;115:1025–1026.CrossRefGoogle ScholarPubMed
17.van Berckel, BN, Lipsch, C, Timp, S, et al.Behavioral and neuroendocrine effects of the partial NMDA agonist D-cycloserine in healthy subjects. Neuropsychopharmacology. 1997;16:317–324.CrossRefGoogle ScholarPubMed
18.Wedig, MM, Rauch, SL, Albert, MS, Wright, CI. Differential amygdala habituation to neutral faces in young and elderly adults. Neurosci Lett. 2005;385:114–119.CrossRefGoogle Scholar
19.Fischer, H, Wright, Cl, Whalen, PJ, McInerney, SC, Shin, LM, Rauch, SL. Brain habituation during repeated exposure to fearful and neutral faces: a functional MRI study. Brain Res Bull. 2003;59:387–392.CrossRefGoogle ScholarPubMed
20.Holt, DJ, Weiss, AP, Rauch, SL, et al.Sustained activation of the hippocampus in response to fearful faces in schizophrenia. Biol Psychiatry. 2005;57:1011–1019.CrossRefGoogle ScholarPubMed
21.Wright, Cl, Martis, B, Schwartz, CE. Novelty responses and differential effects of order in the amygdala, substantia innominata, and inferior temporal cortex. Neuroimage. 2003;18:660–669.CrossRefGoogle ScholarPubMed
22.Cox, RW. AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput Biomed Res. 1996;29:162–173.CrossRefGoogle ScholarPubMed
23.Wright, CI, Williams, D, Feczko, E, et al.Neuroanatomical correlates of extraversion and neuroticism. Cereb Cortex. 2006;16:1809–1819.CrossRefGoogle ScholarPubMed
24.Fischl, B, van der Kouwe, A, Destrieux, C, et al.Automatically parcellating the human cerebral cortex. Cereb Cortex. 2004;14:11–22.CrossRefGoogle ScholarPubMed
25.Rauch, SL, Shin, LM, Wright, CI, et al.Neuroimaging studies of amygdala function in anxiety disorders. Ann N Y Acad Sci. 2003;985:389–410.CrossRefGoogle ScholarPubMed
26.Shin, LM, Wright, Cl, Cannistraro, PA. A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder. Arch Gen Psychiatry. 2005;62:273–281.CrossRefGoogle ScholarPubMed
27.Birbaumer, N, Grodd, W, Diedrich, O. fMRI reveals amygdala activation to human faces in social phobics. Neuroreport. 1998;9:1223–1226.CrossRefGoogle ScholarPubMed
28.Furmark, T, Tillfors, M, Marteinsdottir, I, et al.Common changes in cerebral blood flow in patients with social phobia treated with citalopram or cognitive-behavioral therapy. Arch Gen Psychiatry. 2002;59:425–433.CrossRefGoogle ScholarPubMed
29.Regier, DA, Boyd, JH, Burke, JD, et al.One-month prevalence of mental disorders in the United States. Based on five Epidemiologic Catchment Area sites. Arch Gen Psychiatry. 1988;45:977–986.CrossRefGoogle ScholarPubMed
30.Drevets, WC, Videen, TO, Price, JL, et al.A functional anatomical study of unipolar depression. J Neurosci. 1992;12:3628–3641.CrossRefGoogle ScholarPubMed
31.Drevets, WC, Price, JL, Bardgett, ME, Reich, T, Todd, RD, Raichle, ME. Glucose metabolism in the amygdala in depression: relationship to diagnostic subtype and plasma cortisol levels. Pharmacol Biochem Behav. 2002;71:431–447.CrossRefGoogle ScholarPubMed
32.Yurgelun-Todd, DA, Gruber, SA, Kanayama, G. fMRI during affect discrimination in bipolar affective disorder. Bipolar Disord. 2000;2:237–248.CrossRefGoogle ScholarPubMed
33.Drevets, WC, Bogers, W, Raichle, ME. Functional anatomical correlates of antidepressant drug treatment assessed using PET measures of regional glucose metabolism. Eur Neuropsychopharmacol. 2002;12:527–544.CrossRefGoogle ScholarPubMed
34.Sheline, YI, Barch, DM, Donnelly, JM, Ollinger, JM, Snyder, AZ, Mintun, MA. Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biol Psychiatry. 2001;50:651–658.CrossRefGoogle ScholarPubMed
35.Abel, KM, Allin, MP, Kucharska-Pietura, K. Ketamine alters neural processing of facial emotion recognition in healthy men: an fMRI study. Neuroreport. 2003;14:387–391.CrossRefGoogle ScholarPubMed
36.Millan, MJ. N-methyl-D-aspartate receptor-coupled glycineB receptors in the pathogenesis and treatment of schizophrenia: a critical review. Curr Drug Targets CNS Neurol Disord. 2002;1:191–213.CrossRefGoogle ScholarPubMed
37.Zarate, CA, Singh, JB, Carlson, PJ, et al.A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63:856–864.CrossRefGoogle ScholarPubMed
38.Parnas, AS, Weber, M, Richardson, R, et al.Effects of multiple exposures to D-cycloserine on extinction of conditioned fear in rats. Neurobiol Learn Mem. 2005;83:224–231.CrossRefGoogle ScholarPubMed
39.Quartermain, D, Mower, J, Rafferty, MF, Herting, RL, Lanthorn, TH. Acute but not chronic activation of the NMDA-coupled glycine receptor with D-cycloserine facilitates learning and retention. Eur J Pharmacol. 1994;257:7–12.CrossRefGoogle Scholar
40.Cammarota, M, Barros, DM, Vianna, MR, et al.The transition from memory retrieval to extinction. An Acad Bras Cienc. 2004;76:573–582.CrossRefGoogle ScholarPubMed
41.Krystal, JH, Sanacora, G, Blumberg, H, et al.Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments. Mol Psychiatry. 2002;7(suppl 1):S71–S80.CrossRefGoogle ScholarPubMed
42.Inanobe, A, Furukawa, H, Gouaux, E, et al.Mechanism of partial agonist action at the NR1 subunit of NMDA receptors. Neuron. 2005;47:71–84.CrossRefGoogle ScholarPubMed
43.Fitzgerald, DA, Angstadt, M, Jelsone, LM, Nathan, PJ, Phan, KL. Beyond threat: amygdala reactivity across multiple expressions of facial affect. Neuroimage. 2006;30:1441–1448.CrossRefGoogle ScholarPubMed
44.Breiter, HC, Etcoff, NL, Whalen, PJ. Response and habituation of the human amygdala during visual processing of facial expression. Neuron. 1996;17:875–887.CrossRefGoogle ScholarPubMed
45.van Berckel, BN, Lipsch, C, Gispen-de Wied, C. The partial NMDA agonist D-cycloserine stimulates LH secretion in healthy volunteers. Psychopharmacology (Berl). 1998;138:190–197.CrossRefGoogle ScholarPubMed