Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic

Abstract

Recent decades have witnessed tremendous advances in the neuroscience of emotion, learning and memory, and in animal models for understanding depression and anxiety. This review focuses on new rationally designed psychiatric treatments derived from preclinical human and animal studies. Nonpharmacological treatments that affect disrupted emotion circuits include vagal nerve stimulation, rapid transcranial magnetic stimulation and deep brain stimulation, all borrowed from neurological interventions that attempt to target known pathological foci. Other approaches include drugs that are given in relation to specific learning events to enhance or disrupt endogenous emotional learning processes. Imaging data suggest that common regions of brain activation are targeted with pharmacological and somatic treatments as well as with the emotional learning in psychotherapy. Although many of these approaches are experimental, the rapidly developing understanding of emotional circuit regulation is likely to provide exciting and powerful future treatments for debilitating mood and anxiety disorders.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Subgenual cingulate cortex activation across studies.
Figure 2: Amygdala activation across studies.
Figure 3: Ascending projections from vagus–nucleus solitarius pathways with VNS.
Figure 4: Deep brain stimulation.
Figure 5: Emotional learning processes related to fear.

Similar content being viewed by others

References

  1. Kessler, R.C., Chiu, W.T., Demler, O., Merikangas, K.R. & Walters, E.E. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch. Gen. Psychiatry 62, 617–627 (2005).

    PubMed  PubMed Central  Google Scholar 

  2. Keller, M.B. et al. Time to recovery, chronicity, and levels of psychopathology in major depression. A 5-year prospective follow-up of 431 subjects. Arch. Gen. Psychiatry 49, 809–816 (1992).

    CAS  PubMed  Google Scholar 

  3. Greenberg, P. et al. The economic burden of anxiety disorders in the 1990s. J. Clin. Psychiatry 60, 427–435 (1999).

    CAS  PubMed  Google Scholar 

  4. Gorman, J.M. Comorbid depression and anxiety spectrum disorders. Depress. Anxiety 4, 160–168 (1996).

    PubMed  Google Scholar 

  5. Ressler, K.J. & Nemeroff, C.B. Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress. Anxiety 12, 2–19 (2000).

    PubMed  Google Scholar 

  6. Berton, O. et al. Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 311, 864–868 (2006).

    Article  CAS  PubMed  Google Scholar 

  7. Bornstein, S.R., Schuppenies, A., Wong, M.L. & Licinio, J. Approaching the shared biology of obesity and depression: the stress axis as the locus of gene-environment interactions. Mol. Psychiatry 11, 892–902 (2006).

    CAS  PubMed  Google Scholar 

  8. Nestler, E.J. & Carlezon, W.A., Jr. The mesolimbic dopamine reward circuit in depression. Biol. Psychiatry 59, 1151–1159 (2006).

    CAS  PubMed  Google Scholar 

  9. Tremblay, L.K. et al. Functional neuroanatomical substrates of altered reward processing in major depressive disorder revealed by a dopaminergic probe. Arch. Gen. Psychiatry 62, 1228–1236 (2005).

    PubMed  Google Scholar 

  10. Schlaepfer, T.E. et al. Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression. Neuropsychopharmacology, advance online publication 11 April 2007 (doi: 10.1038/sj.npp.1301408).

    PubMed  Google Scholar 

  11. Mayberg, H.S. Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment. Br. Med. Bull. 65, 193–207 (2003).

    PubMed  Google Scholar 

  12. Mayberg, H.S. et al. Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am. J. Psychiatry 156, 675–682 (1999).

    CAS  PubMed  Google Scholar 

  13. Drevets, W.C. Functional anatomical abnormalities in limbic and prefrontal cortical structures in major depression. Prog. Brain Res. 126, 413–431 (2000).

    CAS  PubMed  Google Scholar 

  14. Milad, M.R. et al. Recall of fear extinction in humans activates the ventromedial prefrontal cortex and hippocampus in concert. Biol. Psychiatry, published online 9 January 2007 (doi:10.1016/j.biopsych.2006.10.011).

    PubMed  Google Scholar 

  15. Siegle, G.J., Carter, C.S. & Thase, M.E. Use of FMRI to predict recovery from unipolar depression with cognitive behavior therapy. Am. J. Psychiatry 163, 735–738 (2006).

    PubMed  Google Scholar 

  16. Furmark, T. et al. Common changes in cerebral blood flow in patients with social phobia treated with citalopram or cognitive-behavioral therapy. Arch. Gen. Psychiatry 59, 425–433 (2002).

    PubMed  Google Scholar 

  17. Drevets, W.C. Neuroimaging studies of mood disorders. Biol. Psychiatry 48, 813–829 (2000).

    CAS  PubMed  Google Scholar 

  18. Canli, T. & Lesch, K.-P. Long story short: the serotonin transporter in emotion regulation and social cognition. Nat. Neurosci. 10, 1103–1109 (2007).

    CAS  PubMed  Google Scholar 

  19. Pezawas, L. et al. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat. Neurosci. 8, 828–834 (2005).

    CAS  PubMed  Google Scholar 

  20. George, M.S. et al. Vagus nerve stimulation for the treatment of depression and other neuropsychiatric disorders. Expert Rev. Neurother. 7, 63–74 (2007).

    PubMed  Google Scholar 

  21. Henry, T.R. et al. Brain blood flow alterations induced by therapeutic vagus nerve stimulation in partial epilepsy: I. Acute effects at high and low levels of stimulation. Epilepsia 39, 983–990 (1998).

    CAS  PubMed  Google Scholar 

  22. Ben-Menachem, E. et al. Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures. Epilepsy Res. 20, 221–227 (1995).

    CAS  PubMed  Google Scholar 

  23. Krahl, S.E., Senanayake, S.S. & Handforth, A. Seizure suppression by systemic epinephrine is mediated by the vagus nerve. Epilepsy Res. 38, 171–175 (2000).

    CAS  PubMed  Google Scholar 

  24. Walker, B.R., Easton, A. & Gale, K. Regulation of limbic motor seizures by GABA and glutamate transmission in nucleus tractus solitarius. Epilepsia 40, 1051–1057 (1999).

    CAS  PubMed  Google Scholar 

  25. Craig, A.D. How do you feel? Interoception: the sense of the physiological condition of the body. Nat. Rev. Neurosci. 3, 655–666 (2002).

    CAS  PubMed  Google Scholar 

  26. Henry, T.R. Therapeutic mechanisms of vagus nerve stimulation. Neurology 59, S3–S14 (2002).

    PubMed  Google Scholar 

  27. Cox, C.L., Huguenard, J.R. & Prince, D.A. Nucleus reticularis neurons mediate diverse inhibitory effects in thalamus. Proc. Natl. Acad. Sci. USA 94, 8854–8859 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Malow, B.A. et al. Vagus nerve stimulation reduces daytime sleepiness in epilepsy patients. Neurology 57, 879–884 (2001).

    CAS  PubMed  Google Scholar 

  29. Zobel, A. et al. Changes in regional cerebral blood flow by therapeutic vagus nerve stimulation in depression: an exploratory approach. Psychiatry Res. 139, 165–179 (2005).

    PubMed  Google Scholar 

  30. Bohning, D.E. et al. Feasibility of vagus nerve stimulation-synchronized blood oxygenation level-dependent functional MRI. Invest. Radiol. 36, 470–479 (2001).

    CAS  PubMed  Google Scholar 

  31. Nahas, Z. et al. Serial vagus nerve stimulation functional MRI in treatment-resistant depression. Neuropsychopharmacology, 32, 1649–1660 (2007).

    CAS  Google Scholar 

  32. Sackeim, H.A. et al. Durability of antidepressant response to vagus nerve stimulation (VNSTM). Int. J. Neuropsychopharmacol., published online 9 February 2007 (doi:10.1017/S1461145706007425).

  33. Lisanby, S.H. et al. New developments in electroconvulsive therapy and magnetic seizure therapy. CNS Spectr. 8, 529–536 (2003).

    PubMed  Google Scholar 

  34. Sackeim, H.A. et al. Cognitive consequences of low-dosage electroconvulsive therapy. Ann. NY Acad. Sci. 462, 326–340 (1986).

    CAS  PubMed  Google Scholar 

  35. Carpenter, L.L. Neurostimulation in resistant depression. J. Psychopharmacol. 20, 35–40 (2006).

    PubMed  Google Scholar 

  36. Epstein, C.M., Schwartzberg, D.G., Davey, K.R. & Sudderth, D.B. Localizing the site of magnetic brain stimulation in humans. Neurology 40, 666–670 (1990).

    CAS  PubMed  Google Scholar 

  37. Barker, A.T., Jalinous, R. & Freeston, I.L. Non-invasive magnetic stimulation of human motor cortex. Lancet 1, 1106–1107 (1985).

    CAS  PubMed  Google Scholar 

  38. Paus, T. & Barrett, J. Transcranial magnetic stimulation (TMS) of the human frontal cortex: implications for repetitive TMS treatment of depression. J. Psychiatry Neurosci. 29, 268–279 (2004).

    PubMed  PubMed Central  Google Scholar 

  39. Pascual-Leone, A., Rubio, B., Pallardo, F. & Catala, M.D. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet 348, 233–237 (1996).

    CAS  PubMed  Google Scholar 

  40. George, M.S. et al. Mood improvement following daily left prefrontal repetitive transcranial magnetic stimulation in patients with depression: a placebo-controlled crossover trial. Am. J. Psychiatry 154, 1752–1756 (1997).

    CAS  PubMed  Google Scholar 

  41. Herrmann, L.L. & Ebmeier, K.P. Factors modifying the efficacy of transcranial magnetic stimulation in the treatment of depression: a review. J. Clin. Psychiatry 67, 1870–1876 (2006).

    PubMed  Google Scholar 

  42. Couturier, J.L. Efficacy of rapid-rate repetitive transcranial magnetic stimulation in the treatment of depression: a systematic review and meta-analysis. J. Psychiatry Neurosci. 30, 83–90 (2005).

    PubMed  PubMed Central  Google Scholar 

  43. O'Reardon, J.P. et al. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol. Psychiatry, published online 14 June 2007 (doi:10.1016/j.biopsych.2007.01.018).

    PubMed  Google Scholar 

  44. Bohning, D.E. et al. Mapping transcranial magnetic stimulation (TMS) fields in vivo with MRI. Neuroreport 8, 2535–2538 (1997).

    CAS  PubMed  Google Scholar 

  45. Kimbrell, T.A. et al. Frequency dependence of antidepressant response to left prefrontal repetitive transcranial magnetic stimulation (rTMS) as a function of baseline cerebral glucose metabolism. Biol. Psychiatry 46, 1603–1613 (1999).

    CAS  PubMed  Google Scholar 

  46. Speer, A.M. et al. Opposite effects of high and low frequency rTMS on regional brain activity in depressed patients. Biol. Psychiatry 48, 1133–1141 (2000).

    CAS  PubMed  Google Scholar 

  47. Kim, E.J. et al. Repetitive transcranial magnetic stimulation protects hippocampal plasticity in an animal model of depression. Neurosci. Lett. 405, 79–83 (2006).

    CAS  PubMed  Google Scholar 

  48. Kosel, M., Frick, C., Lisanby, S.H., Fisch, H.U. & Schlaepfer, T.E. Magnetic seizure therapy improves mood in refractory major depression. Neuropsychopharmacology 28, 2045–2048 (2003).

    PubMed  Google Scholar 

  49. Benabid, A.L. Deep brain stimulation for Parkinson's disease. Curr. Opin. Neurobiol. 13, 696–706 (2003).

    CAS  PubMed  Google Scholar 

  50. Bejjani, B.P. et al. Transient acute depression induced by high-frequency deep-brain stimulation. N. Engl. J. Med. 340, 1476–1480 (1999).

    CAS  PubMed  Google Scholar 

  51. Kopell, B.H., Greenberg, B. & Rezai, A.R. Deep brain stimulation for psychiatric disorders. J. Clin. Neurophysiol. 21, 51–67 (2004).

    PubMed  Google Scholar 

  52. Aouizerate, B. et al. Deep brain stimulation of the ventral caudate nucleus in the treatment of obsessive-compulsive disorder and major depression. Case report. J. Neurosurg. 101, 682–686 (2004).

    PubMed  Google Scholar 

  53. Brody, A.L. et al. Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: preliminary findings. Arch. Gen. Psychiatry 58, 631–640 (2001).

    CAS  PubMed  Google Scholar 

  54. Seminowicz, D.A. et al. Limbic-frontal circuitry in major depression: a path modeling metanalysis. Neuroimage 22, 409–418 (2004).

    CAS  PubMed  Google Scholar 

  55. Dougherty, D.D. et al. Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for treatment of major depression. J. Neurosurg. 99, 1010–1017 (2003).

    PubMed  Google Scholar 

  56. Goldapple, K. et al. Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy. Arch. Gen. Psychiatry 61, 34–41 (2004).

    PubMed  Google Scholar 

  57. Nobler, M.S. et al. Structural and functional neuroimaging of electroconvulsive therapy and transcranial magnetic stimulation. Depress. Anxiety 12, 144–156 (2000).

    CAS  PubMed  Google Scholar 

  58. Mayberg, H.S. et al. Deep brain stimulation for treatment-resistant depression. Neuron 45, 651–660 (2005).

    CAS  PubMed  Google Scholar 

  59. Davis, K.D. et al. Globus pallidus stimulation activates the cortical motor system during alleviation of parkinsonian symptoms. Nat. Med. 3, 671–674 (1997).

    CAS  PubMed  Google Scholar 

  60. Lozano, A.M., Dostrovsky, J., Chen, R. & Ashby, P. Deep brain stimulation for Parkinson's disease: disrupting the disruption. Lancet Neurol. 1, 225–231 (2002).

    PubMed  Google Scholar 

  61. McIntyre, C.C., Savasta, M., Kerkerian-Le Goff, L. & Vitek, J.L. Uncovering the mechanism(s) of action of deep brain stimulation: activation, inhibition, or both. Clin. Neurophysiol. 115, 1239–1248 (2004).

    PubMed  Google Scholar 

  62. Harbishettar, V., Pal, P.K., Janardhan Reddy, Y.C. & Thennarasu, K. Is there a relationship between Parkinson's disease and obsessive-compulsive disorder? Parkinsonism Relat. Disord. 11, 85–88 (2005).

    PubMed  Google Scholar 

  63. Nuttin, B., Cosyns, P., Demeulemeester, H., Gybels, J. & Meyerson, B. Electrical stimulation in anterior limbs of internal capsules in patients with obsessive-compulsive disorder. Lancet 354, 1526 (1999).

    CAS  PubMed  Google Scholar 

  64. Greenberg, B.D. et al. Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. Neuropsychopharmacology 31, 2384–2393 (2006).

    PubMed  Google Scholar 

  65. Pitman, R.K. & Delahanty, D.L. Conceptually driven pharmacologic approaches to acute trauma. CNS Spectr. 10, 99–106 (2005).

    PubMed  Google Scholar 

  66. Rothbaum, B.O. & Davis, M. Applying learning principles to the treatment of post-trauma reactions. Ann. NY Acad. Sci. 1008, 112–121 (2003).

    PubMed  Google Scholar 

  67. Myers, K.M. & Davis, M. Behavioral and neural analysis of extinction. Neuron 36, 567–584 (2002).

    CAS  PubMed  Google Scholar 

  68. Walker, D.L., Ressler, K.J., Lu, K.T. & 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. 22, 2343–2351 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Monahan, J.B., Handelmann, G.E., Hood, W.F. & Cordi, A.A. D-cycloserine, a positive modulator of the N-methyl-D-aspartate receptor, enhances performance of learning tasks in rats. Pharmacol. Biochem. Behav. 34, 649–653 (1989).

    CAS  PubMed  Google Scholar 

  70. Lee, J.L., Milton, A.L. & Everitt, B.J. Reconsolidation and extinction of conditioned fear: inhibition and potentiation. J. Neurosci. 26, 10051–10056 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Botreau, F., Paolone, G. & Stewart, J. D-Cycloserine facilitates extinction of a cocaine-induced conditioned place preference. Behav. Brain Res. 172, 173–178 (2006).

    CAS  PubMed  Google Scholar 

  72. Ledgerwood, L., Richardson, R. & Cranney, J. Effects of D-cycloserine on extinction of conditioned freezing. Behav. Neurosci. 117, 341–349 (2003).

    CAS  PubMed  Google Scholar 

  73. Yang, Y.L. & Lu, K.T. Facilitation of conditioned fear extinction by D-cycloserine is mediated by mitogen-activated protein kinase and phosphatidylinositol 3-kinase cascades and requires de novo protein synthesis in basolateral nucleus of amygdala. Neuroscience 134, 247–260 (2005).

    CAS  PubMed  Google Scholar 

  74. Otto, M. Learning and “unlearning” fears: preparedness, neural pathways, and patients. Biol. Psychiatry 52, 917–920 (2002).

    PubMed  Google Scholar 

  75. Ressler, K.J. et al. Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear. Arch. Gen. Psychiatry 61, 1136–1144 (2004).

    PubMed  Google Scholar 

  76. Hofmann, S.G. et al. Augmentation of exposure therapy with D-cycloserine for social anxiety disorder. Arch. Gen. Psychiatry 63, 298–304 (2006).

    CAS  PubMed  Google Scholar 

  77. Kushner, M.G. et al. D-Cycloserine augmented exposure therapy for obsessive compulsive disorder. Biol. Psychiatry, published online 22 June 2007 (doi:10.1016/j.biopsych.2006.12.020).

    CAS  PubMed  Google Scholar 

  78. Guastella, A.J., Dadds, M.R., Lovibond, P.F., Mitchell, P. & Richardson, R. A randomized controlled trial of the effect of D-cycloserine on exposure therapy for spider fear. J. Psychiatr. Res. 41, 466–471 (2007).

    PubMed  Google Scholar 

  79. Guastella, A.J., Lovibond, P.F., Dadds, M.R., Mitchell, P. & Richardson, R. A randomized controlled trial of the effect of D-cycloserine on extinction and fear conditioning in humans. Behav. Res. Ther. 45, 663–672 (2007).

    PubMed  Google Scholar 

  80. McGaugh, J.L. Memory–a century of consolidation. Science 287, 248–251 (2000).

    CAS  PubMed  Google Scholar 

  81. Ferry, B., Roozendaal, B. & McGaugh, J.L. Basolateral amygdala noradrenergic influences on memory storage are mediated by an interaction between β- and α1-adrenoceptors. J. Neurosci. 19, 5119–5123 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Quirarte, G.L., Roozendaal, B. & McGaugh, J.L. Glucocorticoid enhancement of memory storage involves noradrenergic activation in the basolateral amygdala. Proc. Natl. Acad. Sci. USA 94, 14048–14053 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Pitman, R.K. et al. Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol. Psychiatry 51, 189–192 (2002).

    CAS  PubMed  Google Scholar 

  84. Vaiva, G. et al. Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma. Biol. Psychiatry 54, 947–949 (2003).

    CAS  PubMed  Google Scholar 

  85. Yehuda, R. et al. Low urinary cortisol excretion in Holocaust survivors with posttraumatic stress disorder. Am. J. Psychiatry 152, 982–986 (1995).

    CAS  PubMed  Google Scholar 

  86. Yehuda, R., Golier, J.A., Yang, R.K. & Tischler, L. Enhanced sensitivity to glucocorticoids in peripheral mononuclear leukocytes in posttraumatic stress disorder. Biol. Psychiatry 55, 1110–1116 (2004).

    CAS  PubMed  Google Scholar 

  87. Borrell, J., De Kloet, E.R., Versteeg, D.H. & Bohus, B. Inhibitory avoidance deficit following short-term adrenalectomy in the rat: the role of adrenal catecholamines. Behav. Neural Biol. 39, 241–258 (1983).

    CAS  PubMed  Google Scholar 

  88. Schelling, G. et al. The effect of stress doses of hydrocortisone during septic shock on posttraumatic stress disorder in survivors. Biol. Psychiatry 50, 978–985 (2001).

    CAS  PubMed  Google Scholar 

  89. Cai, W.H., Blundell, J., Han, J., Greene, R.W. & Powell, C.M. Postreactivation glucocorticoids impair recall of established fear memory. J. Neurosci. 26, 9560–9566 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Tronel, S. & Alberini, C.M. Persistent disruption of a traumatic memory by postretrieval inactivation of glucocorticoid receptors in the amygdala. Biol. Psychiatry 62, 33–39 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Schafe, G.E., Nader, K., Blair, H.T. & LeDoux, J.E. Memory consolidation of Pavlovian fear conditioning: a cellular and molecular perspective. Trends Neurosci. 24, 540–546 (2001).

    CAS  PubMed  Google Scholar 

  92. Guarraci, F.A., Frohardt, R.J., Falls, W.A. & Kapp, B.S. The effects of intra-amygdaloid infusions of a D2 dopamine receptor antagonist on Pavlovian fear conditioning. Behav. Neurosci. 114, 647–651 (2000).

    CAS  PubMed  Google Scholar 

  93. Shimizu, E., Tang, Y.P., Rampon, C. & Tsien, J.Z. NMDA receptor-dependent synaptic reinforcement as a crucial process for memory consolidation. Science 290, 1170–1174 (2000).

    CAS  PubMed  Google Scholar 

  94. Nader, K., Schafe, G.E. & Le Doux, J.E. Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature 406, 722–726 (2000).

    CAS  PubMed  Google Scholar 

  95. Przybyslawski, J., Roullet, P. & Sara, S.J. Attenuation of emotional and nonemotional memories after their reactivation: role of beta adrenergic receptors. J. Neurosci. 19, 6623–6628 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Przybyslawski, J. & Sara, S.J. Reconsolidation of memory after its reactivation. Behav. Brain Res. 84, 241–246 (1997).

    CAS  PubMed  Google Scholar 

  97. Debiec, J. & Ledoux, J.E. Disruption of reconsolidation but not consolidation of auditory fear conditioning by noradrenergic blockade in the amygdala. Neuroscience 129, 267–272 (2004).

    CAS  PubMed  Google Scholar 

  98. Eisenberg, M. & Dudai, Y. Reconsolidation of fresh, remote, and extinguished fear memory in medaka: old fears don't die. Eur. J. Neurosci. 20, 3397–3403 (2004).

    PubMed  Google Scholar 

  99. Paulus, M.P., Feinstein, J.S., Castillo, G., Simmons, A.N. & Stein, M.B. Dose-dependent decrease of activation in bilateral amygdala and insula by lorazepam during emotion processing. Arch. Gen. Psychiatry 62, 282–288 (2005).

    CAS  PubMed  Google Scholar 

  100. Dostrovsky, J.O. et al. Microstimulation-induced inhibition of neuronal firing in human globus pallidus. J. Neurophysiol. 84, 570–574 (2000).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This authors are supported by grants from the US National Institutes of Mental Health (K.J.R., MH071537 and MH069884; H.S.M., P50 MH58922, P50 MH077083 and 1R01MH073719), US National Institute on Drug Abuse (K.J.R., DA-019624), NARSAD, Burroughs Wellcome Fund, Stanley Medical Research Foundation, Woodruff Fund and The Dana Foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kerry J Ressler.

Ethics declarations

Competing interests

K.J.R. has a consulting agreement with and is on the Scientific Advisory Board of Tikvah Therapeutics, LLC, which has licensed a use-patent for D-cycloserine for the specific enhancement of learning during psychotherapy. K.J.R. is also entitled to sales royalty from future sales of D-cycloserine for this purpose. H.S.M. has served on the Cyberonics Scientific Advisory Board for Mechanisms of Action and has a consulting agreement with Advanced Neuromodulation Systems, Inc, which has licensed her intellectual property to develop Deep Brain Stimulation for the treatment of severe depression. K.J.R. also receives unrelated research support from Lundbeck, Inc. The terms of these arrangements have been reviewed and approved by Emory University in accordance with their conflict of interest policies.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ressler, K., Mayberg, H. Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic. Nat Neurosci 10, 1116–1124 (2007). https://doi.org/10.1038/nn1944

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn1944

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing