Neurobiology of anxiety disorders and implications for treatment

Mount Sinai Journal of Medicine

Volumn 73, Issue 7, 2006, Pages 941-949

  Garakani, Amir ^a   Mathew, Sanjay J ^a   Charney, Dennis S ^a,b  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b MOUNT SINAI MEDICAL CENTER   (United States)

Author keywords

Amygdala; Classical conditioning; Extinction; Fear; Panic; Pavlov; Phobia; Prefrontal cortex; PTSD; Reconsolidation

Indexed keywords

ANXIOLYTIC AGENT; BENZODIAZEPINE DERIVATIVE; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CALCIUM CHANNEL BLOCKING AGENT; CALCIUM CHANNEL STIMULATING AGENT; CYCLOSERINE; FLUOXETINE; LAMOTRIGINE; MEMANTINE; N (4 HYDROXYPHENYL)ARACHIDONAMIDE; N [3 [(2 AMINO 4 METHYLTHIO)BUTYLDITHIO] 2 BENZYLPROPIONYL]PHENYLALANINE BENZYL ESTER; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; NORADRENALIN UPTAKE INHIBITOR; PAROXETINE; PLACEBO; PREGABALIN; PROPRANOLOL; SEROTONIN UPTAKE INHIBITOR; SERTRALINE; VENLAFAXINE; VOLTAGE GATED CALCIUM CHANNEL; YOHIMBINE;

AMYGDALOID NUCLEUS; ANXIETY DISORDER; ARTICLE; AVERSION; BEHAVIOR THERAPY; BRAIN DAMAGE; BREATHING EXERCISE; CLINICAL TRIAL; COGNITIVE THERAPY; CONDITIONING; DRUG ABUSE; DRUG DEPENDENCE; FEAR; HUMAN; INHIBITION KINETICS; LEARNING; MEMORY CONSOLIDATION; MUSCLE RELAXATION; NEUROBIOLOGY; NONHUMAN; PANIC; PHOBIA; POSTTRAUMATIC STRESS DISORDER; PSYCHOEDUCATION; PSYCHOTHERAPY; SINGLE DRUG DOSE; STIMULUS RESPONSE; TREATMENT OUTCOME;

AMYGDALA; ANIMALS; ANXIETY DISORDERS; COGNITIVE THERAPY; CONDITIONING (PSYCHOLOGY); EXTINCTION, PSYCHOLOGICAL; FEAR; HUMANS; MEMORY; PANIC DISORDER; RECEPTORS, N-METHYL-D-ASPARTATE;

EID: 33845999929     PISSN: 00272507     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (85)

1. Kessler RC, Chiu WT, Demler O, et al. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005; 62(6):617-627.
2. Kessler RC, Berglund P, Demler O, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005; 62(6):593-602.
3. Greenberg PE, Sisitsky T, Kessler RC, et al. The economic burden of anxiety disorders in the 1990s. J Clin Psychiatry 1999; 60(7):427-435.
4. Wang PS, Lane M, Olfson M, et al. Twelve-month use of mental health services in the United States: results from the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005; 62(6):629-640.
5. Gorman JM. Comorbid depression and anxiety spectrum disorders. Depress Anxiety 1996-97; 4(4):160-168.
6. Diagnostic and statistical manual of mental disorders. 4th ed., Washington (DC): American Psychiatric Association; 2000.
7. American Psychiatric Association Practice guidelines for the treatment of psychiatric disorders: compendium 2006. Washington (DC): American Psychiatric Publishing; 2006.
8. Barlow DH, Craske MG. Mastery of your anxiety and panic. 3rd ed. New York: Graywind Publications, Inc.; 2000.
9. Davidson JR, Foa EB, Huppert JD, et al. Fluoxetine, comprehensive cognitive behavioral therapy, and placebo in generalized social phobia. Arch Gen Psychiatry 2004; 61(10):1005-1013.
10. Phelps EA, LeDoux JE. Contributions of the amygdala to emotion processing: from animal models to behavior. Neuron 2005; 48(2):175-187.
11. Pavlov IP. Conditioned reflexes. London: Oxford University Press; 1927. p. 246.
12. Watson JB, Raynor R. Conditioned emotional reactions. J Exp Psychol 1920; 3:1-14.
13. Pare D, Quirk GJ, Ledoux JE. New vistas on amygdala networks in conditioned fear. J Neurophysiol 2004; 92(1):1-9.
14. Rosen JB. The neurobiology of conditioned and unconditioned fear: a neurobehavioral system analysis of the amygdala. Behav Cogn Neurosci Rev 2004; 3(1):23-41.
15. LeDoux JE. Emotion circuits in the brain. Annu Rev Neurosci 2000; 23:155-184.
16. Cahill L, McGaugh JL. Mechanisms of emotional arousal and lasting declarative memory. Trends Neurosci 1998; 21:294-299.
17. Blair HT, Schafe GE, Bauer EP, et al. Synaptic plasticity in the lateral amygdala: a cellular hypothesis of fear conditioning. Learn Mem 2001; 8(5):229-242.
18. Shumyatsky G, Tsvetkov E, Malleret G, et al. Identification of a signaling network in lateral nucleus of amygdala important for inhibiting memory specifically related to learned fear. Cell 2002; 111:905-918.
19. Wallace KJ, Rosen JB. Neurotoxic lesions of the lateral nucleus of the amygdala decrease conditioned fear but not unconditioned fear of a predator odor: comparison with electrolytic lesions. J Neurosci 2001; 21(10):3619-3627.
20. Blair HT, Sotres-Bayon F, Moita MA, Ledoux JE. The lateral amygdala processes the value of conditioned and unconditioned aversive stimuli. Neuroscience 2005; 133(2):561-569.
21. Goosens KA, Maren S. Contextual and auditory fear conditioning are mediated by the lateral, basal, and central amygdaloid nuclei in rats. Learn Mem 2001; 8(3):148-155.
22. Anglada-Figueroa D, Quirk GJ. Lesions of the basal amygdala block expression of conditioned fear but not extinction. J Neurosci 2005; 25(42):9680-9685.
23. Chapman PF, Kairiss EW, Keenan CL, Brown TH. Long-term synaptic potentiation in the amygdala. Synapse 1990; 6(3):271-278.
24. Bauer EP, Schafe GE, LeDoux JE. NMDA receptors and L-type voltage-gated calcium channels contribute to long-term potentiation and different components of fear memory formation in the lateral amygdala. J Neurosci 2002; 22(12):5239-5249.
25. Rodrigues SM, Schafe GE, LeDoux JE. Intra-amygdala blockade of the NR2B subunit of the NMDA receptor disrupts the acquisition but not the expression of fear conditioning. J Neurosci 2001; 21:6889-6896.
26. Walker DL, Davis M. Involvement of NMDA receptors within the amygdala in short-versus long-term memory for fear conditioning as assessed with fear-potentiated startle. Behav Neurosci 2000; 114:1019-1033.
27. Cain CK, Blouin AM, Barad M. L-type voltage-gated calcium channels are required for extinction, but not for acquisition or expression, of conditional fear in mice. J Neurosci 2002; 22(20):9113-9121.
28. Roesler R, Vianna MR, De-Paris F, et al. Infusions of AP5 into the basolateral amygdala impair the formation, but not the expression, of step-down inhibitory avoidance. Braz J Med Biol Res 2000; 33(7):829-834.
29. Fendt M. Injections of the NMDA receptor antagonist aminophosphonopentanoic acid into the lateral nucleus of the amygdala block the expression of fear-potentiated startle and freezing. J Neurosci 2001; 21(11):4111-4115.
30. Miserendino MJ, Sananes CB, Melia KR, Davis M. Blocking of acquisition but not expression of conditioned fear-potentiated startle by NMDA antagonists in the amygdala. Nature 1990; 345(6277):716-718.
31. Jasnow AM, Cooper MA, Huhman KL. N-methyt-D-aspartate receptors in the amygdala are necessary for the acquisition and expression of conditioned defeat. Neuroscience 2004; 123(3):625-634.
32. Maren S, Aharonov G, Stote DL, Fanselow MS. N-methyl-D-aspartate receptors in the basolateral amygdala are required for both acquisition and expression of conditional fear in rats. Behav Neurosci 1996; 110(6):1365-1374.
33. Lee HJ, Choi JS, Brown TH, Kim JJ. Amygdalar NMDA receptors are critical for the expression of multiple conditioned fear responses. J Neurosci 2001; 21(11):4116-4124.
34. Mei B, Li C, Dong S, et al. Distinct gene expression profiles in hippocampus and amygdala after fear conditioning. Brain Res Bull 2005; 67(1-2):1-12.
35. Zhao MG, Toyoda H, Lee YS, et al. Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory. Neuron 2005; 47(6):859-872.
36. Melik E, Babar E, Ozen E, Ozgunen T. Hypofunction of the dorsal hippocampal NMDA receptors impairs retrieval of memory to partially presented foreground context in a single-trial fear conditioning in rats. Eur Neuropsychopharmacol 2006; 16(4):241-247.
37. Parsons CG, Danysz W, Quack G. Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist - a review of preclinical data. Neuropharmacology 1999; 38(6):735-767.
38. Bertoglio LJ, Carobrez AP. Anxiolytic-like effects of NMDA/glycine-B receptor ligands are abolished during the elevated plus-maze trial 2 in rats. Psychopharmacology (Berl) 2003; 170(4):335-342.
39. Bertoglio LJ, Carobrez AP. Scopolamine given pre-Trial 1 prevents the one-trial tolerance phenomenon in the elevated plus-maze Trial 2. Behav Pharmacol 2004; 15(1):45-54.
40. Karcz-Kubicha M, Jessa M, Nazar M, et al. Anxiolytic activity of glycine-B antagonists and partial agonists - no relation to intrinsic activity in the patch clamp. Neuropharmacology 1997; 36(10):1355-1367.
41. Harvey BH, Bothma T, Nel A, et al. Involvement of the NMDA receptor, NO-cyclic GMP and nuclear factor K-beta in an animal model of repeated trauma. Hum Psychopharmacol 2005; 20(5):367-373.
42. Zarate CA Jr, Singh JB, Quiroz JA, et al. A double-blind, placebo-controlled study of memantine in the treatment of major depression. Am J Psychiatry 2006; 163(1):153-155.
43. Mirza NR, Bright JL, Stanhope KJ, et al. Lamotrigine has an anxiolytic-like profile in the rat conditioned emotional response test of anxiety: a potential role for sodium channels? Psychopharmacology (Berl) 2005; 180(1):159-168.
44. Hertzberg MA, Butterfield MI, Feldman ME, et al. A preliminary study of lamotrigine for the treatment of posttraumatic stress disorder. Biol Psychiatry 1999; 45(9):1226-1229.
45. Rickels K, Pollack MH, Feltner DE, et al. Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam. Arch Gen Psychiatry 2005; 62(9):1022-1030.
46. McGaugh JL. Memory - a century of consolidation. Science 2000; 287(5451):248-251.
47. Davis HP, Squire LR. Protein synthesis and memory: a review. Psychol Bull 1984; 96(3):518-559.
48. Dudai Y. The neurobiology of consolidations, or, how stable is the engram? Annu Rev Psychol 2004; 55:51-86.
49. Nader K, Schafe GE, LeDoux JE. The labile nature of consolidation theory. Nat Rev Neurosci 2000; 1(3):216-219.
50. Debiec J, LeDoux JE, Nader K. Cellular and systems reconsolidation in the hippocampus. Neuron 2002; 36(3):527-538.
51. Anderson JR, Bower GH. Human associative memory. 1st ed. Washington (DC): VH Winston & Sons: 1973.
52. Debiec J, Doyere V, Nader K, Ledoux JE. Directly reactivated, but not indirectly reactivated, memories undergo reconsolidation in the amygdala. Proc Natl Acad Sci U S A 2006; 103(9):3428-3433.
53. Gewirtz JC, Davis M. Using pavlovian higher-order conditioning paradigms to investigate the neural substrates of emotional learning and memory. Learn Mem 2000; 7(5):257-266.
54. Kida S, Josselyn SA, de Ortiz SP, et al. CREB required for the stability of new and reactivated fear memories. Nat Neurosci 2002; 5(4):348-355.
55. Sara SJ. Retrieval and reconsolidation: toward a neurobiology of remembering. Learn Mem 2000; 7:73-784.
56. Kern RP, Libkuman TM, Otani H, Holmes K. Emotional stimuli, divided attention, and memory. Emotion 2005; 5(4):408-417.
57. Przybyslawski J, Roullet P, Sara SJ. Attenuation of emotional and nonemotional memories after their reactivation: role of beta adrenergic receptors. J Neurosci 1999; 19(15):6623-6628.
58. Cahill L, Prins B, Weber M, McGaugh JL. Beta-adrenergic activation and memory for emotional events. Nature 1994; 371(6499):702-704.
59. Strange BA, Hurlemann R, Dolan RJ. An emotion-induced retrograde amnesia in humans is amygdala- and beta-adrenergic-dependent. Proc Natl Acad Sci U S A 2003; 100:13626-13631.
60. van Stegeren AH, Goekoop R, Everaerd W, et al. Noradrenaline mediates amygdala activation in men and women during encoding of emotional material. NeuroImage 2005; 24:898-909.
61. Hurlemann R, Hawellek B, Matusch A, et al. Noradrenergic modulation of emotion-induced forgetting and remembering. J Neurosci 2005; 25(27):6343-6439.
62. Dbiec J, Ledoux JE. Disruption of reconsolidation but not consolidation of auditory fear conditioning by noradrenergic blockade in the amygdala. Neuroscience 2004; 129(2):267-272.
63. Reist C, Duffy JG, Fujimoto K, Cahill L. beta-Adrenergic blockade and emotional memory in PTSD. Int J Neuropsychopharmacol 2001; 4(4):377-383.
64. Pitman RK, Sanders KM, Zusman RM, et al. Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol Psychiatry 2002; 51:183-188.
65. Bouton ME. Context and behavioral processes in extinction. Learn Mem 2004; 11(5):485-494.
66. Sotres-Bayon F, Cain CK, LeDoux JE. Brain mechanisms of fear extinction: historical perspectives on the contribution of prefrontal cortex. Biol Psychiatry 2006; 60(4):329-336.
67. Quirk GJ, Russo GK, Barron JL, Lebron K. The role of ventro-medial prefrontal cortex in the recovery of extinguished fear. J Neurosci 2000; 20(16):6225-6231.
68. Milad MR, Quirk GJ. Neurons in medial prefrontal cortex signal memory for fear extinction. Nature 2002; 420(6911):70-74.
69. Santini E, Ge H, Ren K, et al. Consolidation of fear extinction requires protein synthesis in the medial prefrontal cortex. J Neurosci 2004 Jun 23; 24(25):5704-5710.
70. Cook SC, Wellman CL. Chronic stress alters dendritic morphology in rat medial prefrontal cortex. J Neurobiol 2004; 60(2):236-248.
71. Radley JJ, Sisti HM, Hao J, et al. Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex. Neuroscience 2004; 125(1):1-6.
72. Miracle AD, Brace MF, Huyck KD, et al. Chronic stress impairs recall of extinction of conditioned fear. Neurobiol Learn 2006; 85(3):213-218.
73. Falls WA, Miserendino MJ, Davis M. Extinction of fear-potentiated startle: blockade by infusion of an NMDA antagonist into the amygdala. J Neurosci 1992; 12(3):854-863.
74. 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(6):2343-2351.
75. Ledgerwood L, Richardson R, Cranney J. D-cycloserine facilitates extinction of learned fear: effects on reacquisition and generalized extinction. Biol Psychiatry 2005; 57(8):841-847.
76. Heresco-Levy U, Kremer I, Javitt DC, et al. Pilot-controlled trial of D-cycloserine for the treatment of post-traumatic stress disorder. Int J Neuropsychopharmacol 2002; 5(4):301-307.
77. 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(11):1136-1144.
78. Hofmann SG, Meuret AE, Smits JA, et al. Augmentation of exposure therapy with D-cycloserine for social anxiety disorder. Arch Gen Psychiatry 2006, 63(3):298-304.
79. Cain CK, Blouin AM, Barad M. Adrenergic transmission facilitates extinction of conditioned fear in mice. Learn Mem 2004; 11(2):179-187.
80. Cain CK, Godsil BP, Jami S, Barad M. The L-type calcium channel nifedipine impairs extinction, but not reduced contingency effects, in mice. Learn Mem 2005; 12(3):277-284.
81. Chhatwal JP, Davis M, Maguschak KA, Ressler JK. Enhancing cannabinoid neurotransmission augments the extinction of conditioned fear. Neuropsychopharmacology 2005; 30(3):516-524.
82. Marsicano G, Wotjak CT, Azad SC, et al. The endogenous cannabinoid system controls extinction of aversive memories. Nature 2002; 418:530-534.
83. McNally GP, Lee BW, Chiem JY, Choi EA. The midbrain periaque-ductal gray and fear extinction: opioid receptor subtype and roles of cyclic AMP, protein kinase A, and mitogen-activated protein kinase. Behav Neurosci 2005; 119(4):1023-1033.
84. McNally GP. Faciliation of fear extinction by midbrain periacque-ductal gray infusions of RB101 (S), an inhibitor of enkephalin-degrading enzymes. Behav Neurosci 2005; 119(6):1672-1677.
85. First MB. Stress-induced and fear circuitry disorders. http://dsm5.org/ conference7.cfm [accessed Sept 15, 2006].