Advertisement

Brain Topography

, Volume 27, Issue 1, pp 12–19 | Cite as

Neuromodulation for Treatment Resistant Depression: State of the Art and Recommendations for Clinical and Scientific Conduct

  • Thomas E. Schlaepfer
  • Bettina H. Bewernick
Review

Abstract

Research of Deep Brain Stimulation as a putative treatment for resistant psychiatric disorders might very well lead to the most significant development in clinical psychiatry of the last 40 years—possibly offering a rise of hope for patients to whom medicine had hitherto little to offer. Furthermore, translational research on neuromodulation will allow us to glean something about the underlying cause of patient’s illnesses before figuring out a treatment that addresses the source of the problem. Major depression offers perhaps the best example of the rapid progress being made in understanding the biology of mental illness. Studies on the underlying neurobiology of major depression have typically focused on the description of biological differences between patients and healthy subjects such as alterations of monoaminergic or endocrine systems. Psychotropic drugs work by altering neurochemistry to a large extent in widespread regions of the brain, many of which may be unrelated to depression. We believe that more focused, targeted treatment approaches that modulate specific networks in the brain will prove a more effective approach to help treatment-resistant patients. In other words, whereas existing depression treatments approach this disease as a general brain dysfunction, a more complete and appropriate treatment will arise from thinking of depression as a dysfunction of specific brain networks that mediate mood and reward signals (Berton and Nestler, Nat Rev Neurosci 7 (2):137–151, 2006; Krishnan and Nestler, Nature 455(7215):894–902, 2008). A better understanding of defined dysfunctions in these networks will invariably lead to a better understanding of patients afflicted with depression and perhaps contribute to a de-stigmatization of psychiatric patients and the medical specialty treating them.

Keywords

Major depression Deep brain stimulation Neuromodulation Nucleus accumbens Medial forebrain bundle Subgenual cingulate gyrus Anterior limb of internal capsule 

References

  1. Argyropoulos SV, Nutt DJ (1997) Anhedonia and chronic mild stress model in depression. Psychopharmacology (Berl) 134(4):333–336 discussion 371–7CrossRefGoogle Scholar
  2. Axmacher N, Cohen MX, Fell J, Haupt S, Dumpelmann M, Elger CE, Schlaepfer TE, Lenartz D, Sturm V, Ranganath C (2010) Intracranial EEG correlates of expectancy and memory formation in the human hippocampus and nucleus accumbens. Neuron 65(4):541–549PubMedCrossRefGoogle Scholar
  3. Berton O, Nestler EJ (2006) New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci 7(2):137–151PubMedCrossRefGoogle Scholar
  4. Bewernick BH, Hurlemann R, Matusch A, Kayser S, Grubert C, Hadrysiewicz B, Axmacher N, Lemke M, Cooper-Mahkorn D, Cohen MX, Brockmann H, Lenartz D, Sturm V, Schlaepfer TE (2010) Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression. Biol Psychiatry 67(2):110–116PubMedCrossRefGoogle Scholar
  5. Bewernick B, Kayser S, Sturm V, Schlaepfer TE (2012) Long-term effects of nucleus accumbens deep brain stimulation in treatment-resistant depression: evidence for sustained efficacy. Neuropschopharmacology 37(9):1975–1985CrossRefGoogle Scholar
  6. Bourne SK, Eckhardt CA, Sheth SA, Eskandar EN (2012) Mechanisms of deep brain stimulation for obsessive compulsive disorder: effects upon cells and circuits. Front Integr Neurosci 6:29PubMedCrossRefGoogle Scholar
  7. Coenen VA, Schlaepfer TE, Maedler B, Panksepp J (2010) Cross-species affective functions of the medial forebrain bundle-implications for the treatment of affective pain and depression in humans. Neurosci Biobehav Rev 35(9):1971–1981PubMedCrossRefGoogle Scholar
  8. Coenen VA, Panksepp J, Hurwitz TA, Urbach H, Madler B (2012) Human medial forebrain bundle (MFB) and anterior thalamic radiation (ATR): imaging of two major subcortical pathways and the dynamic balance of opposite affects in understanding depression. J Neuropsychiatry Clin Neurosci 24(2):223–236PubMedCrossRefGoogle Scholar
  9. Coenen VA, Madler B, Schlaepfer TE (2013) Reply to: medial forebrain bundle stimulation-speed access to an old or entry into a new depression neurocircuit? Biol Psychiatry 73(12):1204–1212PubMedCrossRefGoogle Scholar
  10. Cohen MX, Axmacher N, Lenartz D, Elger CE, Sturm V, Schlaepfer TE (2009a) Good vibrations: cross-frequency coupling in the human nucleus accumbens during reward processing. J Cogn Neurosci 21(5):875–889PubMedCrossRefGoogle Scholar
  11. Cohen MX, Axmacher N, Lenartz D, Elger CE, Sturm V, Schlaepfer TE (2009b) Neuroelectric signatures of reward learning and decision-making in the human nucleus accumbens. Neuropsychopharmacology 34(7):1649–1658PubMedCrossRefGoogle Scholar
  12. Cohen MX, Axmacher N, Lenartz D, Elger CE, Sturm V, Schlaepfer TE (2009c) Nuclei accumbens phase synchrony predicts decision-making reversals following negative feedback. J Neurosci 29(23):7591–7598PubMedCentralPubMedCrossRefGoogle Scholar
  13. Davison K (2006) Historicalaspects of mood disorders. Psychiatry 5(4):115–118CrossRefGoogle Scholar
  14. Delgado JMR (1965) Physical control of the mind: toward a psychocivilized society. Harper and Row, New YorkGoogle Scholar
  15. Doshi PK (2011) Long-term surgical and hardware-related complications of deep brain stimulation. Stereotact Funct Neurosurg 89(2):89–95PubMedCrossRefGoogle Scholar
  16. Farah MJ, Illes J, Cook-Deegan R, Gardner H, Kandel E, King P, Parens E, Sahakian B, Wolpe PR (2004) Neurocognitive enhancement: what can we do and what should we do? Nat Rev Neurosci 5(5):421–425PubMedCrossRefGoogle Scholar
  17. Fily F, Haegelen C, Tattevin P, Buffet-Bataillon S, Revest M, Cady A, Michelet C (2011) Deep brain stimulation hardware-related infections: a report of 12 cases and review of the literature. Clin Infect Dis 52(8):1020–1023PubMedCrossRefGoogle Scholar
  18. Fins JJ, Schlaepfer TE, Nuttin B, Kubu CS, Galert T, Sturm V, Merkel R, Mayberg HS (2011) Ethical guidance for the management of conflicts of interest for researchers, engineers and clinicians engaged in the development of therapeutic deep brain stimulation. J Neural Eng 8(3):033001PubMedCrossRefGoogle Scholar
  19. Goodman WK, Foote KD, Greenberg BD, Ricciuti N, Bauer R, Ward H, Shapira NA, Wu SS, Hill CL, Rasmussen SA, Okun MS (2010) Deep brain stimulation for intractable obsessive compulsive disorder: pilot study using a blinded, staggered-onset design. Biol Psychiatry 67(6):535–542PubMedCrossRefGoogle Scholar
  20. Gradinaru V, Mogri M, Thompson KR, Henderson JM, Deisseroth K (2009) Optical deconstruction of parkinsonian neural circuitry. Science 324(5925):354–359PubMedCrossRefGoogle Scholar
  21. Greenberg BD, Askland KD, Carpenter LL (2008) The evolution of deep brain stimulation for neuropsychiatric disorders. Front Biosci 13:4638–4648PubMedCrossRefGoogle Scholar
  22. Hariz MI, Hariz GM (2012) Hyping deep brain stimulation in psychiatry could lead to its demise. BMJ 345:e5447PubMedCrossRefGoogle Scholar
  23. Hariz MI, Blomstedt P, Zrinzo L (2010) Deep brain stimulation between 1947 and 1987: the untold story. Neurosurg Focus 29(2):E1PubMedCrossRefGoogle Scholar
  24. Heath RG (1972) Pleasure and brain activity in man. Deep and surface electroencephalograms during orgasm. J Nerv Ment Dis 154(1):3–18PubMedCrossRefGoogle Scholar
  25. Holtzheimer PE, Kelley ME, Gross RE, Filkowski MM, Garlow SJ, Barrocas A, Wint D, Craighead MC, Kozarsky J, Chismar R, Moreines JL, Mewes K, Posse PR, Gutman DA, Mayberg HS (2012) Subcallosal cingulate deep brain stimulation for treatment-resistant unipolar and bipolar depression. Arch Gen Psychiatry 69(2):150–158PubMedCrossRefGoogle Scholar
  26. Isometsa ET, Henriksson MM, Aro HM, Heikkinen ME, Kuoppasalmi KI, Lonnqvist JK (1994) Suicide in major depression. Am J Psychiatry 151(4):530–536PubMedGoogle Scholar
  27. Kennedy SH, Giacobbe P, Rizvi SJ, Placenza FM, Nishikawa Y, Mayberg HS, Lozano AM (2011) Deep brain stimulation for treatment-resistant depression: follow-up after 3–6 years. Am J Psychiatry 168(5):502–510PubMedCrossRefGoogle Scholar
  28. Krishnan V, Nestler EJ (2008) The molecular neurobiology of depression. Nature 455(7215):894–902PubMedCentralPubMedCrossRefGoogle Scholar
  29. Lozano AM, Mayberg HS, Giacobbe P, Hamani C, Craddock RC, Kennedy SH (2008) Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression. Biol Psychiatry 64(6):461–467PubMedCrossRefGoogle Scholar
  30. Lozano AM, Giacobbe P, Hamani C, Rizvi SJ, Kennedy SH, Kolivakis TT, Debonnel G, Sadikot AF, Lam RW, Howard AK, Ilcewicz-Klimek M, Honey CR, Mayberg HS (2012) A multicenter pilot study of subcallosal cingulate area deep brain stimulation for treatment-resistant depression. J Neurosurg 116(2):315–322PubMedCrossRefGoogle Scholar
  31. Malone DA Jr, Dougherty DD, Rezai AR, Carpenter LL, Friehs GM, Eskandar EN, Rauch SL, Rasmussen SA, Machado AG, Kubu CS, Tyrka AR, Price LH, Stypulkowski PH, Giftakis JE, Rise MT, Malloy PF, Salloway SP, Greenberg BD (2009) Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression. Biol Psychiatry 65(4):267–275PubMedCentralPubMedCrossRefGoogle Scholar
  32. Mayberg HS (1997) Limbic-cortical dysregulation: a proposed model of depression. J Neuropsychiatry Clin Neurosci 9(3):471–481PubMedGoogle Scholar
  33. Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH (2005) Deep brain stimulation for treatment-resistant depression. Neuron 45(5):651–660PubMedCrossRefGoogle Scholar
  34. Millon T (2004) Masters of the mind: exploring the story of mental illness from ancient times to the new millennium. Hoboken, New JerseyGoogle Scholar
  35. Puigdemont D, Perez-Egea R, Portella MJ, Molet J, de Diego-Adelino J, Gironell A, Radua J, Gomez-Anson B, Rodriguez R, Serra M, de Quintana C, Artigas F, Alvarez E, Perez V (2011) Deep brain stimulation of the subcallosal cingulate gyrus: further evidence in treatment-resistant major depression. Int J Neuropsychopharmacol 15:1–13Google Scholar
  36. Rush AJ, Weissenburger JE (1994) Melancholic symptom features and DSM-IV. Am J Psychiatry 151(4):489–498PubMedGoogle Scholar
  37. Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M (2006) Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 163(11):1905–1917PubMedCrossRefGoogle Scholar
  38. Schlaepfer TE, Fins JJ (2010) Deep brain stimulation and the neuroethics of responsible publishing: when one is not enough. JAMA 303(8):775–776PubMedCrossRefGoogle Scholar
  39. Schlaepfer TE, Cohen MX, Frick C, Kosel M, Brodesser D, Axmacher N, Joe AY, Kreft M, Lenartz D, Sturm V (2008) Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression. Neuropsychopharmacology 33(2):368–377PubMedCrossRefGoogle Scholar
  40. Schlaepfer TE, Agren H, Monteleone P, Gasto C, Pitchot W, Rouillon F, Nutt DJ, Kasper S (2012a) The hidden third: improving outcome in treatment-resistant depression. J Psychopharmacol 26(5):587–602PubMedCrossRefGoogle Scholar
  41. Schlaepfer TE, Bewernick BH, Kayser S, Mädler B, Coenen VA (2012b) Rapid effects of deep brain stimulation for treatment resistant major depression. Biol Psychiatry 15(73):1204–1212Google Scholar
  42. Schoene-Bake JC, Parpaley Y, Weber B, Panksepp J, Hurwitz TA, Coenen VA (2010) Tractographic analysis of historical lesion surgery for depression. Neuropsychopharmacology 35(13):2553–2563PubMedCrossRefGoogle Scholar
  43. Schuepbach WM, Rau J, Knudsen K, Volkmann J, Krack P, Timmermann L, Halbig TD, Hesekamp H, Navarro SM, Meier N, Falk D, Mehdorn M, Paschen S, Maarouf M, Barbe MT, Fink GR, Kupsch A, Gruber D, Schneider GH, Seigneuret E, Kistner A, Chaynes P, Ory-Magne F, Brefel Courbon C, Vesper J, Schnitzler A, Wojtecki L, Houeto JL, Bataille B, Maltete D, Damier P, Raoul S, Sixel-Doering F, Hellwig D, Gharabaghi A, Kruger R, Pinsker MO, Amtage F, Regis JM, Witjas T, Thobois S, Mertens P, Kloss M, Hartmann A, Oertel WH, Post B, Speelman H, Agid Y, Schade-Brittinger C, Deuschl G, Earlystim Study Group (2013) Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med 368(7):610–622PubMedCrossRefGoogle Scholar
  44. Shorter E, Healy D (2007) Shock therapy: a history of electroconvulsive treatment in mental illness. University of Toronto Press, TorontoGoogle Scholar
  45. Stephen JH, Halpern CH, Barrios CJ, Balmuri U, Pisapia JM, Wolf JA, Kampman KM, Baltuch GH, Caplan AL, Stein SC (2012) Deep brain stimulation compared with methadone maintenance for the treatment of heroin dependence: a threshold and cost-effectiveness analysis. Addiction 107(3):624–634PubMedCrossRefGoogle Scholar
  46. Tremblay LK, Naranjo CA, Graham SJ, Herrmann N, Mayberg HS, Hevenor S, Busto UE (2005) Functional neuroanatomical substrates of altered reward processing in major depressive disorder revealed by a dopaminergic probe. Arch Gen Psychiatry 62(11):1228–1236PubMedCrossRefGoogle Scholar
  47. van Dijk A, Klompmakers AA, Feenstra MG, Denys D (2012) Deep brain stimulation of the accumbens increases dopamine, serotonin and noradrenaline in the prefrontal cortex. J Neurochem 123(6):897–903PubMedCrossRefGoogle Scholar
  48. Wulsin LR, Vaillant GE, Wells VE (1999) A systematic review of the mortality of depression. Psychosom Med 61(1):6–17PubMedGoogle Scholar
  49. Zrinzo L, Foltynie T, Limousin P, Hariz MI (2012) Reducing hemorrhagic complications in functional neurosurgery: a large case series and systematic literature review. J Neurosurg 116(1):84–94PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Psychiatry and PsychotherapyUniversity HospitalBonnGermany
  2. 2.Departments of Psychiatry and Mental HealthThe Johns Hopkins UniversityBaltimoreUSA

Personalised recommendations