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Brain-Imaging Studies of Posttraumatic Stress Disorder

Published online by Cambridge University Press:  07 November 2014

Israel Liberzon  and
K. Luan Phan
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Abstract

Brain-imaging studies of posttraumatic stress disorder (PTSD) have rapidly increased in recent years. Structural studies have identified potential smaller volumes of the hippocampus of traumatized and/or PTSD subjects. Functional activation studies have implicated hyperactive or altered functioning of brain regions, such as the amygdala and the insula, and a failure to engage emotional regulatory structures, such as the medial prefrontal and anterior cingulate cortex. Recent neurochemical investigations have suggested that neuromodulatory systems (eg, γ-aminobutyric acid, μ-opioid) may underlie these aberrant brain activation patterns. This article reviews the literature on structural, functional, and neurochemical brain-imaging studies of PTSD.

Type
Review Article
Information
CNS Spectrums , Volume 8 , Issue 9: Posttraumatic Stress Disorder , September 2003 , pp. 641 - 650
Copyright
Copyright © Cambridge University Press 2003

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References

REFERENCES

1.Kolb, LC. A neuropsychological hypothesis explaining posttraumatic stress disorders. Am J Psychiatry. 1987;144:989–995.Google ScholarPubMed
2.McEwen, BS. The neurobiology and neuroendocrinology of stress implications for post-traumatic stress disorder from a basic science perspective. Psychiatr Clin North Am. 2002;25:469–494.CrossRefGoogle ScholarPubMed
3.Southwick, SM, Bremner, D, Krystal, JH, Charney, DS. Psychobiologic research in post-traumatic stress disorder. Psychiatr Clin North Am. 1994;17:251–264.CrossRefGoogle ScholarPubMed
4.Orr, SP, Roth, WT. Psychophysiological assessment: clinical applications for PTSD. J Affect Disord. 2000;61:225–240.CrossRefGoogle ScholarPubMed
5.Silverman, JJ, Hart, RP, Garrettson, LK, et al.Posttraumatic stress disorder from pentaborane intoxication. Neuropsychiatric evaluation and short-term follow-up. JAMA. 1985;254:2603–2608.CrossRefGoogle ScholarPubMed
6.Peters, J, van Kammen, DP, van Kammen, WB, Neylan, T. Sleep disturbance and computerized axial tomographic scan findings in former prisoners of war. Compr Psychiatry. 1990;31:535–539.CrossRefGoogle ScholarPubMed
7.Canive, JM, Lewine, JD, Orrison, WW Jr, et al.MRI reveals gross structural abnormalities in PTSD. Ann N Y Acad Sci. 1997;821:512–515.CrossRefGoogle ScholarPubMed
8.Myslobodsky, MS, Glicksohn, J, Singer, J, et al.Changes of brain anatomy in patients with posttraumatic stress disorder: a pilot magnetic resonance imaging study. Psychiatry Res. 1995;58:259–264.CrossRefGoogle ScholarPubMed
9.Bremner, JD, Randall, P, Scott, TM, et al.MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry. 1995;152:973–981.Google ScholarPubMed
10.Bremner, JD, Randall, P, Vermetten, E, et al.Magnetic resonance imaging-based measurement of hippocampal volume in posttraumatic stress disorder related to childhood physical and sexual abuse—a preliminary report. Biol Psychiatry. 1997;41:23–32.CrossRefGoogle ScholarPubMed
11.Sheline, YI, Gado, MH, Price, JL. Amygdala core nuclei volumes are decreased in recurrent major depression [Erratum in: Neuroreport. 1998;9:2436.]. Neuroreport. 1998;9:2023–2028.CrossRefGoogle ScholarPubMed
12.Gurvits, TV, Shenton, ME, Hokama, H, et al.Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder. Biol Psychiatry. 1996;40:1091–1099.CrossRefGoogle ScholarPubMed
13.Stein, MB, Koverola, C, Hanna, C, Torchia, MG, McClarty, B. Hippocampal volume in women victimized by childhood sexual abuse. Psychol Med. 1997;27:951–959.CrossRefGoogle ScholarPubMed
14.Vythilingam, M, Heim, C, Newport, J, et al.Childhood trauma associated with smaller hippocampal volume in women with major depression. Am J Psychiatry. 2002;159:2072–2080.CrossRefGoogle ScholarPubMed
15.Villarreal, G, Hamilton, DA, Petropoulos, H, et al.Reduced hippocampal volume and total white matter volume in posttraumatic stress disorder. Biol Psychiatry. 2002;52:119–125.CrossRefGoogle ScholarPubMed
16.Bonne, O, Brandes, D, Gilboa, A, et al.Longitudinal MRI study of hippocampal volume in trauma survivors with PTSD. Am J Psychiatry. 2001;158:1248–1251.CrossRefGoogle ScholarPubMed
17.Fennema-Notestine, C, Stein, MB, Kennedy, CM, Archibald, SL, Jernigan, TL. Brain morphometry in female victims of intimate partner violence with and without posttraumatic stress disorder. Biol Psychiatry. 2002;52:1089–1101.CrossRefGoogle ScholarPubMed
18.Driessen, M, Herrmann, J, Stahl, K, et al.Magnetic resonance imaging volumes of the hippocampus and the amygdala in women with borderline personality disorder and early traumatization. Arch Gen Psychiatry. 2000;57:1115–22.CrossRefGoogle ScholarPubMed
19.De Bellis, MD, Keshavan, MS, Clark, DB, et al.A.E. Bennett Research Award. Developmental traumatology. Part II: Brain development. Biol Psychiatry. 1999;45:1271–1284.CrossRefGoogle ScholarPubMed
20.De Bellis, MD, Keshavan, MS, Frustaci, K, et al.Superior temporal gyrus volumes in maltreated children and adolescents with PTSD. Biol Psychiatry. 2002;51:544–552.CrossRefGoogle ScholarPubMed
21.Sapolsky, RM. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry. 2000;57:925–935.CrossRefGoogle ScholarPubMed
22.Starkman, MN, Gebarski, SS, Berent, S, Schteingart, DE. Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing's syndrome. Biol Psychiatry. 1992;32:756–765.CrossRefGoogle ScholarPubMed
23.Bremner, JD. Does stress damage the brain? Biol Psychiatry. 1999;45:797–805.CrossRefGoogle ScholarPubMed
24.Yehuda, R, Kahana, B, Binder-Brynes, K, Southwick, SM, Mason, JW, Giller, EL. Low urinary cortisol excretion in Holocaust survivors with posttraumatic stress disorder. Am J Psychiatry. 1995;152:982–986.Google ScholarPubMed
25.Yehuda, R, Southwick, SM, Nusshaum, G, Wahby, V, Giller, EL Jr, Mason, JW. Low urinary cortisol excretion in patients with posttraumatic stress disorder. J Nerv Ment Dis. 1990;178:366–369.CrossRefGoogle ScholarPubMed
26.Gilbertson, MW, Shenton, ME, Ciszewski, A, et al.Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nat Neurosci. 2002;5:1242–1247.CrossRefGoogle ScholarPubMed
27.LeDoux, JE. Emotion circuits in the brain. Annu Rev Neurosci. 2000;23:155–184.CrossRefGoogle ScholarPubMed
28.Bechara, A, Damasio, H, Damasio, AR. Emotion, decision making and the orbitofrontal cortex. Cereb Cortex. 2000;10:295–307.CrossRefGoogle ScholarPubMed
29.Davis, M. The role of the amygdala in fear and anxiety. Annu Rev Neurosci. 1992;15:353–375.CrossRefGoogle ScholarPubMed
30.Davis, M. The role of the amygdala in fear-potentiated startle: implications for animal models of anxiety. Trends Pharmacol Sci. 1992;13:35–41.CrossRefGoogle ScholarPubMed
31.Davidson, RJ, Irwin, W. The functional neuroanatomy of emotion and affective style. Trends Cogn Sci. 1999;3:11–21.CrossRefGoogle ScholarPubMed
32.Phan, KL, Wager, T, Taylor, SF, Liberzon, I. Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI. Neuroimage. 2002;16:331–348.CrossRefGoogle ScholarPubMed
33.Breiter, HC, Etcoff, NL, Whalen, PJ, et al.Response and habituation of the human amygdala during visual processing of facial expression. Neuron. 1996;17:875–887.CrossRefGoogle ScholarPubMed
34.Taylor, SF, Liberzon, I, Koeppe, RA. The effect of graded aversive stimuli on limbic and visual activation. Neuropsychologia. 2000;38:1415–1425.CrossRefGoogle ScholarPubMed
35.Hamann, SB, Ely, TD, Grafton, ST, Kilts, CD. Amygdala activity related to enhanced memory for pleasant and aversive stimuli. Nat Neurosci. 1999;2:289–293.CrossRefGoogle ScholarPubMed
36.Liberzon, I, Phan, KL, Decker, LR, Taylor, SF. Extended amygdala and emotional salience: a PET activation study of positive and negative affect. Neuropsychopharmacology. 2003;28:726–733.CrossRefGoogle ScholarPubMed
37.Davis, M, Whalen, PJ. The amygdala: vigilance and emotion. Mol Psychiatry. 2001;6:13–34.CrossRefGoogle ScholarPubMed
38.McGaugh, JL, Cahill, L, Roozendaal, B. Involvement of the amygdala in memory storage: interaction with other brain systems. Proc Natl Acad Sci U S A. 1996;93:13508–13514.CrossRefGoogle ScholarPubMed
39.Cahill, L, Haier, RJ, Fallon, Jet al.Amygdala activity at encoding correlated with long-term, free recall of emotional information. Proc Natl Acad Sci U S A. 1996;93:8016–8021.CrossRefGoogle ScholarPubMed
40.Canli, T, Zhao, Z, Brewer, J, Gabrieli, JD, Cahill, L. Event-related activation in the human amygdala associates with later memory for individual emotional experience. J Neurosci. 2000;20:RC99.CrossRefGoogle ScholarPubMed
41.Damasio, AR, Grabowski, TJ, Bechara, Aet al.Subcortical and cortical brain activity during the feeling of self-generated emotions. Nat Neurosci. 2000;3:1049–1056.CrossRefGoogle ScholarPubMed
42.Mayberg, HS. Modulating limbic-cortical circuits in depression: targets of antidepressant treatments. Semin Clin Neuropsychiatry. 2002;7:255–268.CrossRefGoogle ScholarPubMed
43.Phan, KL, Taylor, SF, Welsh, RCet al.Activation of medial prefrontal cortex and extended amygdala by individual ratings of emotional arousal: a functional magnetic resonance imaging study. Biol Psychiatry. 2003;53:211–215.CrossRefGoogle Scholar
44.Bush, G, Luu, P, Posner, MI. Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci. 2000;4:215–222.CrossRefGoogle ScholarPubMed
45.Ochsner, KN, Bunge, SA. Emotional reappraisal modulates activity in ventromedial prefrontal cortex and amygdala. Society of Neuroscience Abstracts. 2001:317.1.Google Scholar
46.Hariri, AR, Bookheimer, SY, Mazziotta, JC. Modulating emotional responses: effects of a neocortical network on the limbic system. Neuroreport. 2000;11:43–48.CrossRefGoogle ScholarPubMed
47.Phan, KL, Taylor, SF, Decker, LR, Liberzon, I. Emotional appraisal modulates amygdaloid activity to aversive pictures. Society of Neuroscience Abstracts. 2000:775.17.Google Scholar
48.Morgan, MA, Romanski, LM, LeDoux, JE. Extinction of emotional learning: contribution of medial prefrontal cortex. Neurosci Lett. 1993;163:109–113.CrossRefGoogle ScholarPubMed
49.Davidson, RJ, Putnam, KM, Larson, CL. Dysfunction in the neural circuitry of emotion regulation—a possible prelude to violence. Science. 2000;289:591–594.CrossRefGoogle ScholarPubMed
50.Shalev, AY, Peri, T, Gelpin, E, Orr, SP, Pitman, RK. Psychophysiologic assessment of mental imagery of stressful events in Israeli civilian posttraumatic stress disorder patients. Compr Psychiatry. 1997;38:269–273.CrossRefGoogle ScholarPubMed
51.Liberzon, I, Abelson, JL, Flagel, SB, Raz, J, Young, EA. Neuroendocrine and psychophysiologic responses in PTSD: a symptom provocation study. Neuropsychopharmacology. 1999;21:40–50.CrossRefGoogle ScholarPubMed
52.Pitman, RK, Orr, SP, Forgue, DF, Altman, B, de Jong, JB, Herz, LR. Psychophysiologic responses to combat imagery of Vietnam veterans with posttraumatic stress disorder versus other anxiety disorders. J Abnorm Psychol. 1990;99:49–54.CrossRefGoogle ScholarPubMed
53.Rauch, SL, van der Kolk, BA, Fisler, RE, et al.A symptom provocation study of posttraumatic stress disorder using positron emission tomography and script-driven imagery. Arch Gen Psychiatry. 1996;53:380–387.CrossRefGoogle ScholarPubMed
54.Bystritsky, A, Pontillo, D, Powers, M, Sabb, FW, Craske, MG, Bookheimer, SY. Functional MRI changes during panic anticipation and imagery exposure. Neuroreport. 2001;12:3953–3957.CrossRefGoogle ScholarPubMed
55.Chua, P, Krams, M, Toni, I, Passingham, R, Dolan, R. A functional anatomy of anticipatory anxiety. Neuroimage. 1999;9:563–571.CrossRefGoogle ScholarPubMed
56.Shin, LM, Kosslyn, SM, McNally, RJ, et al.Visual imagery and perception in posttraumatic stress disorder. A positron emission tomographic investigation. Arch Gen Psychiatry. 1997;54:233–241.CrossRefGoogle ScholarPubMed
57.Liberzon, I, Taylor, SF, Amdur, R, et al.Brain activation in PTSD in response to trauma-related stimuli. Biol Psychiatry. 1999;45:817–826.CrossRefGoogle ScholarPubMed
58.Woods, SW, Koster, K, Krystal, JK, et al.Yohimbine alters regional cerebral blood flow in panic disorder. Lancet. 1988;2:678.CrossRefGoogle ScholarPubMed
59.Bremner, JD, Staib, LH, Kaloupek, D, Southwick, SM, Soufer, R, Charney, DS. Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: a positron emission tomography study. Biol Psychiatry. 1999;45:806–816.CrossRefGoogle ScholarPubMed
60.Bremner, JD, Narayan, M, Staib, LH, Southwick, SM, McGlashan, T, Charney, DS. Neural correlates of memories of childhood sexual abuse in women with and without posttraumatic stress disorder. Am J Psychiatry. 1999;156:1787–1795.CrossRefGoogle ScholarPubMed
61.Shin, LM, McNally, RJ, Kosslyn, SM, et al.Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: a PET investigation. Am J Psychiatry. 1999;156:575–584.CrossRefGoogle ScholarPubMed
62.Lanius, RA, Williamson, PC, Densmore, M, et al.Neural correlates of traumatic memories in posttraumatic stress disorder: a functional MRI investigation. Am J Psychiatry. 2001;158:1920–1922.CrossRefGoogle ScholarPubMed
63.Shin, LM, Whalen, PJ, Pitman, RK, et al.An fMRI study of anterior cingulate function in posttraumatic stress disorder. Biol Psychiatry. 2001;50:932–942.CrossRefGoogle ScholarPubMed
64.Hendler, T, Rotshtein, P, Hadar, U. Emotion-perception interplay in the visual cortex: “the eyes follow the heart.” Cell Mol Neurobiol. 2001;21:733–752.CrossRefGoogle Scholar
65.Pissiota, A, Frans, O, Fernandez, M, von Knorring, L, Fischer, H, Fredrikson, M. Neurofunctional correlates of posttraumatic stress disorder: a PET symptom provocation study. Eur Arch Psychiatry Clin Neurosci. 2002;252:68–75.CrossRefGoogle ScholarPubMed
66.Rauch, SL, Whalen, PJ, Shin, LM, et al.Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder: a functional MRI study. Biol Psychiatry. 2000;47:769–776.CrossRefGoogle ScholarPubMed
67.Liberzon, I, Taylor, SF, Fig, LM, Decker, LR, Koeppe, RA, Minoshima, S. Limbic activation and psychophysiologic responses to aversive visual stimuli. Interaction with cognitive task. Neuropsychopharmacology. 2000;23:508–516.CrossRefGoogle ScholarPubMed
68.Phan, KL, Taylor, SF, Welsh, RC, et al.Activation of the medial prefrontal cortex and extended amygdala by individual ratings of emotional arousal: a functional magnetic resonance imaging study. Biol Psychiatry. 2003;53:211–215.CrossRefGoogle Scholar
69.Bremner, JD, Southwick, S, Brett, E, Fontana, A, Rosenheck, R, Charney, DS. Dissociation and posttraumatic stress disorder in Vietnam combat veterans. Am J Psychiatry. 1992;149:328–332.Google ScholarPubMed
70.Liberzon, I, Taylor, SF, Fig, LM, Koeppe, RA. Alteration of corticothalamic perfusion ratios during a PTSD flashback. Depress Anxiety. 1996;4:146–150.3.0.CO;2-E>CrossRefGoogle ScholarPubMed
71.Krystal, JH, Bennett, AL, Bremner, JD, Southwick, SM, Charney, DS. Toward a cognitive neuroscience of dissociation and altered memory functions in post-traumatio stress disorder. In: Friedman, MJ, Chamey, DS, Deutsch, AY, eds. Neurobiobgical and Clinical Consequences of Stress: From Normal Adaptations to PTSD. New York, NY: Raven Press; 1995:239–268.Google Scholar
72.Osuch, EA, Benson, B, Geraci, M, et al.Regional cerebral blood flow correlated with flashback intensity in patients with posttraumatic stress disorder. Biol Psychiatry. 2001;50:246–253.CrossRefGoogle ScholarPubMed
73.Lanius, RA, Williamson, PC, Boksman, K, et al.Brain activation during script-driven imagery induced dissociative responses in PTSD: a functional magnetic resonance imaging investigation. Biol Psychiatry. 2002;52:305–311.CrossRefGoogle ScholarPubMed
74.Semple, WE, Goyer, P, McCormick, R, et al.Preliminary report: brain blood flow using PET in patients with posttraumatic stress disorder and substance-abuse histories. Biol Psychiatry. 1993;34:115–118.CrossRefGoogle ScholarPubMed
75.Semple, WE, Goyer, PF, McCormick, R, et al.Attention and regional cerebral blood flow in posttraumatic stress disorder patients with substance abuse histories. Psychiatry Res. 1996;67:17–28.CrossRefGoogle ScholarPubMed
76.Bremner, JD, Scott, TM, Delaney, RC, et al.Deficits in short-term memory in posttraumatic stress disorder. Am J Psychiatry. 1993;150:1015–1019.Google ScholarPubMed
77.Shaw, ME, Strother, SC, McFarlane, AC, et al.Abnormal functional connectivity in posttraumatic stress disorder. Neuroimage. 2002;15:661–674.CrossRefGoogle ScholarPubMed
78.Southwick, SM, Bremner, JD, Rasmusson, A, Morgan, CA 3rd, Arnsten, A, Charney, DS. Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder. Biol Psychiatry. 1999;46:1192–1204.CrossRefGoogle ScholarPubMed
79.Bremner, JD, Innis, RB, Ng, CK, et al.Positron emission tomography measurement of cerebral metabolic correlates of yohimbine administration in combat-related posttraumatic stress disorder. Arch Gen Psychiatry. 1997;54:246–254.CrossRefGoogle ScholarPubMed
80.Sachinvala, N, Kling, A, Suffin, S, Lake, R, Cohen, M. Increased regional cerebral perfusion by 99mTc hexamethyl propylene amine oxime single photon emission computed tomography in post-traumatic stress disorder. Mil Med. 2000;165:473–479.CrossRefGoogle ScholarPubMed
81.De Bellis, MD, Keshavan, MS, Harenski, KA. Anterior cingulate N-acetylaspartate/creatine ratios during clonidine treatment in a maltreated child with posttraumatic stress disorder. J Child Adolesc Psychopharmacol. 2001;11:311–316.CrossRefGoogle Scholar
82.Steingard, RJ, Yurgelun-Todd, DA, Hennen, J, et al.Increased orbitofrontal cortex levels of choline in depressed adolescents as detected by in vivo proton magnetic resonance spectroscopy. Biol Psychiatry. 2000;48:1053–1061.CrossRefGoogle ScholarPubMed
83.De Bellis, MD, Keshavan, MS, Spencer, S, Hall, J. N-Acetylaspartate concentration in the anterior cingulate of maltreated children and adolescents with PTSD. Am J Psychiatry. 2000;157:1175–1177.CrossRefGoogle ScholarPubMed
84.Freeman, TW, Cardwell, D, Karson, CN, Komoroski, RA. In vivo proton magnetic resonance spectroscopy of the medial temporal lobes of subjects with combat-related posttraumatic stress disorder. Magn Reson Med. 1998;40:66–71.CrossRefGoogle ScholarPubMed
85.Schuff, N, Neylan, TC, Lenoci, MA, et al.Decreased hippocampal N-acetylaspartate in the absence of atrophy in posttraumatic stress disorder. Biol Psychiatry. 2001;50:952–959.CrossRefGoogle ScholarPubMed
86.Villarreal, G, Petropoulos, H, Hamilton, DA, et al.Proton magnetic resonance spectroscopy of the hippocampus and occipital white matter in PTSD: preliminary results. Can J Psychiatry. 2002;47:666–760.CrossRefGoogle ScholarPubMed
87.Fields, HL, Heinricher, MM, Mason, P. Neurotransmitters in nociceptive modulatory circuits. Annu Rev Neurosci. 1991;14:219–245.CrossRefGoogle ScholarPubMed
88.Nutt, DJ, Malizia, AL. New insights into the role of the GABA(A)-benzodiazepine receptor in psychiatric disorder. Br J Psychiatry. 2001;179:390–396.CrossRefGoogle ScholarPubMed
89.Belzung, C, Griebel, G. Measuring normal and pathological anxiety-like behaviour in mice: a review. Behav Brain Res. 2001;125:141–149.CrossRefGoogle ScholarPubMed
90.Menard, J, Treit, D. Effects of centrally administered anxiolytic compounds in animal models of anxiety. Neurosci Biobehav Rev. 1999;23:591–613.CrossRefGoogle ScholarPubMed
91.Argyropoulos, SV, Nutt, DJ. The use of benzodiazepines in anxiety and other disorders. Eur Neuropsychopharmacol. 1999;9(suppl 6):S407–S412.CrossRefGoogle ScholarPubMed
92.Niehoff, DL, Kuhar, MJ. Benzodiazepine receptors: localization in rat amygdala. J Neurosci. 1983;3:2091–2097.CrossRefGoogle ScholarPubMed
93.Bremner, JD, Innis, RB, Southwick, SM, Staib, L, Zoghbi, S, Charney, DS. Decreased benzodiazepine receptor binding in prefrontal cortex in combat-related posttraumatic stress disorder. Am J Psychiatry. 2000;157:1120–1126.CrossRefGoogle ScholarPubMed
94.Caldji, C, Francis, D, Sharma, S, Plotsky, PM, Meaney, MJ. The effects of early rearing environment on the development of GABAA and central benzodiazepine receptor levels and novelty-induced fearfulness in the rat. Neuropsychopharmacology. 2000;22:219–229.CrossRefGoogle ScholarPubMed
95.Weizman, R, Weizman, A, Kook, KA, Vocci, F, Deutsch, SI, Paul, SM. Repeated swim stress alters brain benzodiazepine receptors measured in vivo. J Pharmacol Exp Ther. 1989;249:701–707.Google ScholarPubMed
96.Malizia, AL, Cunningham, VJ, Bell, CJ, Liddle, PF, Jones, T, Nutt, DJ. Decreased brain GABA(A)-benzodiazepine receptor binding in panic disorder: preliminary results from a quantitative PET study. Arch Gen Psychiatry. 1998;55:715–720.CrossRefGoogle ScholarPubMed
97.Bremner, JD, Innis, RB, White, T, et al.SPECT [I-123]iomazenil measurement of the benzodiazepine receptor in panic disorder. Biol Psychiatry. 2000;47:96–106.CrossRefGoogle ScholarPubMed
98.Liberzon, I, Phan, KL, Koeppe, RA, Britton, JC, Frey, KA. GABA-A benzodiazepine receptors in PTSD. Paper presented at: Annual Meeting of the American College of Neuropsychopharmacology; December 8-12, 2002; San Juan, PR.Google Scholar
99.Good, AJ, Westbrook, RF. Effects of a microinjection of morphine into the amygdala on the acquisition and expression of conditioned fear and hypoalgesia in rats. Behav Neurosci. 1995;109:631–641.CrossRefGoogle ScholarPubMed
100.Shaikh, MB, Lu, CL, Siegel, A. An enkephalinergic mechanism involved in amygdaloid suppression of affective defence behavior elicited from the midbrain periaqueductal gray in the cat. Brain Res. 1991;559:109–117.CrossRefGoogle ScholarPubMed
101.Graeff, FG. Neuroanatomy and neurotransmitter regulation of defensive behaviors and related emotions in mammals. Brat J Med Biol Res. 1994;27:811–829.Google ScholarPubMed
102.Zubieta, JK, Bueller, JA, Xu, Y, Koeppe, RA, Ketter, TA. Anterior cingulate and limbic mu opioid receptors regulate affective states. Biol Psychiatry. 2002:50S.Google Scholar
103.Zubieta, JK, Smith, YR, Bueller, JA, et al.Regional μ opioid receptor regulation of sensory and affective dimensions of pain. Science. 2001;293:311–315.CrossRefGoogle ScholarPubMed
104.Pitman, RK, van der Kolk, BA, Orr, SP, Greenberg, MS. Naloxone-reversible analgesic response to combat-related stimuli in posttraumatic stress disorder. A pilot study. Arch Gen Psychiatry. 1990;47:541–544.CrossRefGoogle ScholarPubMed
105.Liberzon, I, Zubieta, JK, Fig, LM, Phan, KL, Koeppe, RA, Taylor, SF. μ-Opioid receptors and limbic responses to aversive emotional stimuli. Proc Natl Acad Sci U S A. 2002;99:7084–7089.CrossRefGoogle ScholarPubMed
106.Liberzon, I, Taylor, SF, Fig, LM, et al.μ-Opioid receptors in amygdala in PTSD. Biol Psychiatry. 2002:14S.Google Scholar
107.Fields, HL. Pain modulation: expectation, opioid analgesia and virtual pain. Prog Brain Res. 2000;122:245–253.CrossRefGoogle ScholarPubMed
108.Oertel, WH, Riethmuller, G, Mugnaini, E, et al.Opioid peptide-like immunoreactivity localized in GABAErgic neurons of rat neostriatum and central amygdaloid nucleus. Life Sci. 1983;33(suppl 1):73–76.CrossRefGoogle ScholarPubMed