Current Psychiatry Reports

, Volume 14, Issue 6, pp 634–642 | Cite as

Where in the Brain Is Depression?

  • Mayur Pandya
  • Murat Altinay
  • Donald A. MaloneJr.
  • Amit Anand
Mood Disorders (SM Strakowski, Section Editor)


Major depressive disorder is a serious medical illness which is responsible for considerable morbidity and disability. Despite decades of research, the neural basis for depression is still incompletely understood. In this review, evidence from neuroimaging, neuropsychiatric and brain stimulations studies are explored to answer the question regarding the localization of depression in the brain. Neuroimaging studies indicate that although many regions of the brain have been repeatedly implicated in the pathophysiology of depression, not many consistent findings have been found until present. In recent times, the focus of neuroimaging has shifted from regional brain abnormalities to circuit level connectivity abnormalities. However, connectivity models are inherently more complicated, and the validity of these models remains to be tested. Neuropsychiatric studies of illnesses such as Parkinson’s disease and stroke provide promising clues regarding areas involved in depression, but again consistent findings are rare. Similarly, stimulation of a variety of brain regions and circuits has been reported as being effective in depression. Therefore, the current knowledge indicates that the pathophysiology of depression may be distributed across many brain regions and circuits. In future studies, this distributed nature of depression needs to be further investigated, primary and secondary areas affected need to be identified, and new paradigms to explain complex mental functions need to be explored.


Depression Major depressive disorder MDD Unipolar depression Limbic system Resting state connectivity Neuroimaging fMRI MRI PET Parkinson’s disease Stroke Deep brain stimulation DBS Transcranial magnetic stimulation TMS Vagus nerve stimulation VNS Mood disorders Psychiatry 



No potential conflicts of interest relevant to this article were reported.


Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    First MB. Diagnostic and Statsitical Manual 4th Edition - Text Revision (DSM-IV-TR). Washington DC: American Psychiatric Publishing; 2000.Google Scholar
  2. 2.
    Maclean PD. Evolutionary psychiatry and the triune brain. Psychol Med. 1985;15(02):219–21.PubMedCrossRefGoogle Scholar
  3. 3.
    Rigucci S, Serafini G, Pompili M, Kotzalidis GD, Tatarelli R. Anatomical and functional correlates in major depressive disorder: the contribution of neuroimaging studies. World J Biol Psychiatr. 2009;11(2 Pt 2):165–80.Google Scholar
  4. 4.
    Kimbrell TA, Ketter TA, George MS, Little JT, Benson BE, Willis MW, et al. Regional cerebral glucose utilization in patients with a range of severities of unipolar depression. Biol Psychiatry. 2002;51(3):237–52.PubMedCrossRefGoogle Scholar
  5. 5.
    Desmyter S, van Heeringen C, Audenaert K. Structural and functional neuroimaging studies of the suicidal brain. Prog Neuropsychopharmacol Biol Psychiatr. 2011;35(4):796–808.CrossRefGoogle Scholar
  6. 6.
    George MS. Transcranial magnetic stimulation for the treatment of depression. Expert Rev Neurother. 2010;10(11):1761–72.PubMedCrossRefGoogle Scholar
  7. 7.
    Mayberg HS, Brannan SK, Tekell JL, Silva JA, Mahurin RK, McGinnis S, et al. Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biol Psychiatry. 2000;48(8):830–43.PubMedCrossRefGoogle Scholar
  8. 8.
    Coffey CE, Wilkinson WE, Weiner RD, Parashos IA, Djang WT, Webb MC, et al. Quantitative cerebral anatomy in depression. A controlled magnetic resonance imaging study. Arch Gen Psychiatry. 1993;50(1):7–16.PubMedCrossRefGoogle Scholar
  9. 9.
    Kumar A, Bilker W, Jin Z, Udupa J. Atrophy and high intensity lesions: complementary neurobiological mechanisms in late-life major depression. Neuropsychopharmacology. 2000;22(3):264–74.PubMedCrossRefGoogle Scholar
  10. 10.
    Schweitzer I, Tuckwell V, Ames D, O'Brien J. Structural neuroimaging studies in late-life depression: a review. World J Biol Psychiatr. 2001;2(2):83–8.CrossRefGoogle Scholar
  11. 11.
    Bremner JD, Vythilingam M, Vermetten E, Nazeer A, Adil J, Khan S, et al. Reduced volume of orbitofrontal cortex in major depression. Biol Psychiatry. 2002;51(4):273–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Drevets WC, Price JL, Simpson Jr JR, Todd RD, Reich T, Vannier M, et al. Subgenual prefrontal cortex abnormalities in mood disorders. Nature. 1997;386(6627):824–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Mayberg HS, Liotti M, Brannan SK, McGinnis S, Mahurin RK, Jerabek PA, et al. Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiatry. 1999;156(5):675–82.PubMedGoogle Scholar
  14. 14.
    Vogt BA, Finch DM, Olson CR. Functional heterogeneity in cingulate cortex: the anterior executive and posterior evaluative regions. Cerebr Cortex. 1992;2(6):435–43.Google Scholar
  15. 15.
    Critchley HD. The human cortex responds to an interoceptive challenge. Proc Natl Acad Sci U S A. 2004;101(17):6333–4.PubMedCrossRefGoogle Scholar
  16. 16.
    Etkin A, Egner T, Peraza DM, Kandel ER, Hirsch J. Resolving emotional conflict: a role for the rostral anterior cingulate cortex in modulating activity in the Amygdala. Neuron. 2006;51(6):871–82.PubMedCrossRefGoogle Scholar
  17. 17.
    Deen B, Pitskel NB, Pelphrey KA. Three systems of insular functional connectivity identified with cluster analysis. Cerebr Cortex. 2010.Google Scholar
  18. 18.
    Phillips ML, Young AW, Senior C, Brammer M, Andrew C, Calder AJ, et al. A specific neural substrate for perceiving facial expressions of disgust. Nature. 1997;389(6650):495–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Modinos G, Ormel J, Aleman A. Activation of anterior insula during self-reflection. PLoS One. 2009;4(2):e4618.PubMedCrossRefGoogle Scholar
  20. 20.
    Critchley HD, Wiens S, Rotshtein P, Ohman A, Dolan RJ. Neural systems supporting interoceptive awareness. Nat Neurosci. 2004;7(2):189–95.PubMedCrossRefGoogle Scholar
  21. 21.
    Surguladze SA, El-Hage W, Dalgleish T, Radua J, Gohier B, Phillips ML. Depression is associated with increased sensitivity to signals of disgust: a functional magnetic resonance imaging study. J Psychiatr Res. 2010;44(14):894–902.PubMedCrossRefGoogle Scholar
  22. 22.
    Anand A, Li Y, Wang Y, Wu J, Gao S, Kalnin A, et al. Activity and connectivity of mood regulating circuit in depression: a functional magnetic resonance study. Biol Psychiatry. 2005;15(10):1079–88.CrossRefGoogle Scholar
  23. 23.
    Sprengelmeyer R, Steele JD, Mwangi B, Kumar P, Christmas D, Milders M, et al. The insular cortex and the neuroanatomy of major depression. J Affect Disord. 2011;133(1–2):120–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Davidson RJ, Irwin W, Anderle MJ, Kalin NH. The neural substrates of affective processing in depressed patients treated with venlafaxine. Am J Psychiatry. 2003;160(1):64–75.PubMedCrossRefGoogle Scholar
  25. 25.
    Lorenzetti V, Allen NB, Fornito A, Yucel M. Structural brain abnormalities in major depressive disorder: a selective review of recent MRI studies. J Affect Disord. 2009;117(1–2):1–17.PubMedCrossRefGoogle Scholar
  26. 26.
    MacQueen GM, Yucel K, Taylor VH, Macdonald K, Joffe R. Posterior hippocampal volumes are associated with remission rates in patients with major depressive disorder. Biol Psychiatry. 2008;64(10):880–3.PubMedCrossRefGoogle Scholar
  27. 27.
    Kronmuller KT, Pantel J, Kohler S, Victor D, Giesel F, Magnotta VA, et al. Hippocampal volume and 2-year outcome in depression. Br J Psychiatry. 2008;192(6):472–3.PubMedCrossRefGoogle Scholar
  28. 28.
    Sheline YI, Gado MH, Price JL. Amygdala core nuclei volumes are decreased in recurrent major depression. Neuroreport. 1998;9(9):2023–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Bremner JD, Narayan M, Anderson ER, Staib LH, Miller HL, Charney DS. Hippocampal volume reduction in major depression. Am J Psychiatry. 2000;157(1):115–8.PubMedGoogle Scholar
  30. 30.
    Bremner JD, Randall P, Scott TM, Bronen RA, Seibyl JP, Southwick SM, et al. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry. 1995;152(7):973–81.PubMedGoogle Scholar
  31. 31.
    Vythilingam M, Heim C, Newport J, Miller AH, Anderson E, Bronen R, et al. Childhood trauma associated with smaller hippocampal volume in women with major depression. Am J Psychiatry. 2002;159(12):2072–80.PubMedCrossRefGoogle Scholar
  32. 32.
    Duman RS. Synaptic plasticity and mood disorders. Mol Psychiatr. 2002;7 Suppl 1:S29–34.CrossRefGoogle Scholar
  33. 33.
    Anand A, Charney DS. Norepinephrine dysfunction in depression. J Clin Psychiatr. 2000;61 Suppl 10:16–24.Google Scholar
  34. 34.
    Drevets WC. Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Curr Opin Neurobiol. 2001;11(2):240–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Ketter TA. Functional brain imaging, limbic function, and affective disorders. Neuroscientist. 1996;2:55–65.Google Scholar
  36. 36.
    Soares JC, Mann JJ. The functional neuroanatomy of mood disorders. J Psychiatr Res. 1997;31(4):393–432.PubMedCrossRefGoogle Scholar
  37. 37.
    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(3):431–47.PubMedCrossRefGoogle Scholar
  38. 38.
    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(9):651–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Thomas KM, Drevets WC, Dahl RE, Ryan ND, Birmaher B, Eccard CH, et al. Amygdala response to fearful faces in anxious and depressed children. Arch Gen Psychiatry. 2001;58(11):1057–63.PubMedCrossRefGoogle Scholar
  40. 40.
    Siegle GJ, Steinhauer SR, Thase ME, Stenger VA, Carter CS. Can't shake that feeling: event-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals. Biol Psychiatry. 2002;51(9):693–707.PubMedCrossRefGoogle Scholar
  41. 41.
    Kumari V, Mitterschiffthaler MT, Teasdale JD. Neural abnormalities during cognitive generation of affect in treatment resistant depression. Biol Psychiatry. 2003;54:777–91.PubMedCrossRefGoogle Scholar
  42. 42.
    Fu CHY, Williams SCR, Cleare AJ, Brammer MJ, Walsh ND, Kim J, et al. Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study. Arch Gen Psychiatry. 2004;61(9):877–89.PubMedCrossRefGoogle Scholar
  43. 43.
    Krishnan KR, McDonald WM, Escalona PR, Doraiswamy PM, Na C, Husain MM, et al. Magnetic resonance imaging of the caudate nuclei in depression. Preliminary observations. Arch Gen Psychiatry. 1992;49(7):553–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Knutson B, Bhanji JP, Cooney RE, Atlas LY, Gotlib IH. Neural responses to monetary incentives in major depression. Biol Psychiatry. 2008;63(7):686–92.PubMedCrossRefGoogle Scholar
  45. 45.
    Remijnse PL, Nielen MMA, van Balkom AJLM, Hendriks G-J, Hoogendijk WJ, Uylings HBM, et al. Differential frontal-striatal and paralimbic activity during reversal learning in major depressive disorder and obsessive-compulsive disorder. Psychol Med. 2009;39(09):1503–18.PubMedCrossRefGoogle Scholar
  46. 46.
    Kumari V, Mitterschiffthaler MT, Teasdale JD, Malhi GS, Brown RG, Giampietro V, et al. Neural abnormalities during cognitive generation of affect in treatment-resistant depression. Biol Psychiatry. 2003;54(8):777–91.PubMedCrossRefGoogle Scholar
  47. 47.
    Surguladze S, Brammer MJ, Keedwell P, Giampietro V, Young AW, Travis MJ, et al. A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder. Biol Psychiatry. 2005;57(3):201–9.PubMedCrossRefGoogle Scholar
  48. 48.
    Malison RT, Price LH, Berman R, van Dyck CH, Pelton GH, Carpenter L, et al. Reduced brain serotonin transporter availability in major depression as measured by [123I]-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane and single photon emission computed tomography. Biol Psychiatry. 1998;44(11):1090–8.PubMedCrossRefGoogle Scholar
  49. 49.
    Kugaya A, Seneca NM, Snyder PJ, Williams SA, Malison RT, Baldwin RM, et al. Changes in human in vivo serotonin and dopamine transporter availabilities during chronic antidepressant administration. Neuropsychopharmacology. 2003;28(2):413–20.PubMedCrossRefGoogle Scholar
  50. 50.
    Anand A, Shekhar A. Brain imaging studies in mood and anxiety disorders: special emphasis on the amygdala. Ann N Y Acad Sci. 2003;985:370–88.PubMedCrossRefGoogle Scholar
  51. 51.
    Drevets WC, Videen TO, Price JL, Preskorn SH, Carmichael ST, Raichle ME. A functional anatomical study of unipolar depression. J Neurosci. 1992;12(9):3628–41.PubMedGoogle Scholar
  52. 52.
    Andreasen NC, Paradiso S, O'Leary DS. "Cognitive dysmetria" as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical-cerebellar circuitry? Schizophr Bull. 1998;24(2):203–18.PubMedCrossRefGoogle Scholar
  53. 53.
    McIntosh AR, Gonzalez-Lima F. Large-scale functional connectivity in associative learning: interrelations of the rat auditory, visual, and limbic systems. J Neurophysiol. 1998;80(6):3148–62.PubMedGoogle Scholar
  54. 54.
    Lawrie SM, Buechel C, Whalley HC, Frith CD, Friston KJ, Johnstone EC. Reduced frontotemporal functional connectivity in schizophrenia associated with auditory hallucinations. Biol Psychiatry. 2002;51(12):1008–11.PubMedCrossRefGoogle Scholar
  55. 55.
    Friston K. Beyond phrenology: what can neuroimaging tell us about distributed circuitry? Annu Rev Neurosci. 2002;25:221–50.PubMedCrossRefGoogle Scholar
  56. 56.
    Anand A, Mathews VP, Bukhari L, Wang Y, Shirely JA, Lightfoot J, et al. Functional connectivity within the mood regulating circuit in depression - an fMRI study. Biol Psychiatry. 2003;53(8S):95S.Google Scholar
  57. 57.
    Mayberg HS. Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment. Br Med Bull. 2003;65:193–207.PubMedCrossRefGoogle Scholar
  58. 58.
    •• Price JL, Drevets WC. Neurocircuitry of mood disorders. Neuropsychopharmacology. 2009;35(1):192–216. An excellent recent review of basic and clinical studies of neuroanatomy of depression. CrossRefGoogle Scholar
  59. 59.
    Heinz A, Braus DF, Smolka MN, Wrase J, Puls I, Hermann D, et al. Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter. Nat Neurosci. 2005;8(1):20–1.PubMedCrossRefGoogle Scholar
  60. 60.
    Greicius MD, Flores BH, Menon V, Glover GH, Solvason HB, Kenna H, et al. Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biol Psychiatry. 2007;62(5):429–37.PubMedCrossRefGoogle Scholar
  61. 61.
    Greicius M. Resting-state functional connectivity in neuropsychiatric disorders. Curr Opin Neurol. 2008;21(4):424–30. doi: 10.1097/WCO.0b013e328306f2c5.PubMedCrossRefGoogle Scholar
  62. 62.
    •• Lui S, Wu Q, Qiu L, Yang X, Kuang W, Chan RCK, et al. Resting-state functional connectivity in treatment-resistant depression. Am J Psychiatr. 2011;appi.ajp.2010.10101419. This study investigates connectivity of mood related brain regions in treatment responsive and treatment-resistant depression. Google Scholar
  63. 63.
    Sheline YI, Price JL, Yan Z, Mintun MA. Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proc Natl Acad Sci. 2010;107(24):11020–5.PubMedCrossRefGoogle Scholar
  64. 64.
    Cummings JL. Depression and Parkinson's disease: a review. Am J Psychiatry. 1992;149(4):443–54.PubMedGoogle Scholar
  65. 65.
    Benoit M, Robert PH. Imaging correlates of apathy and depression in Parkinson's disease. J Neurol Sci. 2011;310(1–2):58–60.PubMedCrossRefGoogle Scholar
  66. 66.
    Kostic VS, Filippi M. Neuroanatomical correlates of depression and apathy in Parkinson's disease: magnetic resonance imaging studies. J Neurol Sci. 2011;310(1–2):61–3.PubMedCrossRefGoogle Scholar
  67. 67.
    Paulsen JS, Nehl C, Hoth KF, Kanz JE, Benjamin M, Conybeare R, et al. Depression and stages of Huntington's disease. J Neuropsychiatry Clin Neurosci. 2005;17(4):496–502.PubMedCrossRefGoogle Scholar
  68. 68.
    Paulsen JS, Ready RE, Hamilton JM, Mega MS, Cummings JL. Neuropsychiatric aspects of Huntington's disease. J Neurol Neurosurg Psychiatry. 2001;71(3):310–4.PubMedCrossRefGoogle Scholar
  69. 69.
    Hobbs NZ, Pedrick AV, Say MJ, Frost C, Dar Santos R, Coleman A, et al. The structural involvement of the cingulate cortex in premanifest and early Huntington's disease. Mov Disord. 2011;26(9):1684–90.PubMedCrossRefGoogle Scholar
  70. 70.
    Thiruvady DR, Georgiou-Karistianis N, Egan GF, Ray S, Sritharan A, Farrow M, et al. Functional connectivity of the prefrontal cortex in Huntington's disease. J Neurol Neurosurg Psychiatry. 2007;78(2):127–33.PubMedCrossRefGoogle Scholar
  71. 71.
    Mayberg HS, Starkstein SE, Peyser CE, Brandt J, Dannals RF, Folstein SE. Paralimbic frontal lobe hypometabolism in depression associated with Huntington's disease. Neurology. 1992;42(9):1791–7.PubMedCrossRefGoogle Scholar
  72. 72.
    Thieben MJ, Duggins AJ, Good CD, Gomes L, Mahant N, Richards F, et al. The distribution of structural neuropathology in pre-clinical Huntington’s disease. Brain. 2002;125(8):1815–28.PubMedCrossRefGoogle Scholar
  73. 73.
    Singh A, Herrmann N, Black SE. The importance of lesion location in poststroke depression: a critical review. Can J Psychiatr. 1998;43(9):921–7.Google Scholar
  74. 74.
    Starkstein SE, Robinson RG, Honig MA, Parikh RM, Joselyn J, Price TR. Mood changes after right-hemisphere lesions. Br J Psychiatry. 1989;155:79–85.PubMedCrossRefGoogle Scholar
  75. 75.
    Santos M, Kovari E, Gold G, Bozikas VP, Hof PR, Bouras C, et al. The neuroanatomical model of post-stroke depression: towards a change of focus? J Neurol Sci. 2009;283(1–2):158–62.PubMedCrossRefGoogle Scholar
  76. 76.
    Provinciali L, Coccia M. Post-stroke and vascular depression: a critical review. Neurol Sci. 2002;22(6):417–28.PubMedCrossRefGoogle Scholar
  77. 77.
    Ferro JM, Caeiro L, Santos C. Poststroke emotional and behavior impairment: a narrative review. Cerebrovasc Dis. 2009;27 Suppl 1:197–203.PubMedCrossRefGoogle Scholar
  78. 78.
    Alexopoulos GS. The vascular depression hypothesis: 10 years later. Biol Psychiatry. 2006;60(12):1304–5.PubMedCrossRefGoogle Scholar
  79. 79.
    Kanner AM. Mood disorder and epilepsy: a neurobiologic perspective of their relationship. Dialogues Clin Neurosci. 2008;10(1):39–45.PubMedGoogle Scholar
  80. 80.
    Paradiso S, Hermann BP, Blumer D, Davies K, Robinson RG. Impact of depressed mood on neuropsychological status in temporal lobe epilepsy. J Neurol Neurosurg Psychiatry. 2001;70(2):180–5.PubMedCrossRefGoogle Scholar
  81. 81.
    Archer J, Hutchison I, Korszun A. Mood and malignancy: head and neck cancer and depression. J Oral Pathol Med. 2008;37(5):255–70.PubMedCrossRefGoogle Scholar
  82. 82.
    Litofsky NS, Resnick AG. The relationships between depression and brain tumors. J Neurooncol. 2009;94(2):153–61.PubMedCrossRefGoogle Scholar
  83. 83.
    Rooney AG, Carson A, Grant R. Depression in cerebral glioma patients: a systematic review of observational studies. J Natl Canc Inst. 2010;103(1):61–76.Google Scholar
  84. 84.
    George MS. New methods of minimally invasive brain modulation as therapies in psychiatry: TMS, MST, VNS and DBS. 2002;349–60, 2002 Aug.Google Scholar
  85. 85.
    Carpenter LL, Janicak PG, Aaronson ST, Boyadjis T, Brock DG, Cook IA, et al. Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of acute treatment outcomes in clinical practice. Depress Anxiety. 2012;29(7):587–96.PubMedCrossRefGoogle Scholar
  86. 86.
    Connolly RK, Helmer A, Cristancho MA, Cristancho P, O'Reardon JP. Effectiveness of transcranial magnetic stimulation in clinical practice post-FDA approval in the United States: results observed with the first 100 consecutive cases of depression at an academic medical center. J Clin Psychiatr. 2012;73(4):e567–73.CrossRefGoogle Scholar
  87. 87.
    Schutter DJLG. Quantitative review of the efficacy of slow-frequency magnetic brain stimulation in major depressive disorder. Psychol Med. 2010;40(11):1789–95.PubMedCrossRefGoogle Scholar
  88. 88.
    Fox MD, Buckner RL, White MP, Greicius MD, Pascual-Leone A. Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate. Biol Psychiatr. 2012.Google Scholar
  89. 89.
    George MS, Nahas Z, Bohning DE, Kozel FA, Anderson B, Chae JH, et al. Vagus nerve stimulation therapy: a research update. Neurology. 2002;59(6 Suppl 4):S56–61.PubMedCrossRefGoogle Scholar
  90. 90.
    Ko D, Heck C, Grafton S, Apuzzo ML, Couldwell WT, Chen T, et al. Vagus nerve stimulation activates central nervous system structures in epileptic patients during PET H2(15)O blood flow imaging. Neurosurgery. 1996;39(2):426–30. discussion 30–1.PubMedCrossRefGoogle Scholar
  91. 91.
    Chae JH, Nahas Z, Lomarev M, Denslow S, Lorberbaum JP, Bohning DE, et al. A review of functional neuroimaging studies of vagus nerve stimulation (VNS). J Psychiatr Res. 2003;37(6):443–55.PubMedCrossRefGoogle Scholar
  92. 92.
    Conway CR, Sheline YI, Chibnall JT, George MS, Fletcher JW, Mintun MA. Cerebral blood flow changes during vagus nerve stimulation for depression. Psychiatr Res. 2006;146(2):179–84. 2006 Mar 31.CrossRefGoogle Scholar
  93. 93.
    •• Malone DA Jr, Dougherty DD, Rezai AR, Carpenter LL, Friehs GM, Eskandar EN, et al. Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression. Biological Psychiatry. 2009;65(4):267–75. An important study of deep brain stimulation in a specific region for treatment of depression. PubMedCrossRefGoogle Scholar
  94. 94.
    Schlaepfer TE, Cohen MX, Frick C, Kosel M, Brodesser D, Axmacher N, et al. Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression. Neuropsychopharmacology. 2007;33(2):368–77.PubMedCrossRefGoogle Scholar
  95. 95.
    Kennedy SH, Giacobbe P, Rizvi SJ, Placenza FM, Nishikawa Y, Mayberg HS, et al. Deep brain stimulation for treatment-resistant depression: follow-up after 3 to 6 years. Am J Psychiatry. 2011;168(5):502–10.PubMedCrossRefGoogle Scholar
  96. 96.
    Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, et al. Deep brain stimulation for treatment-resistant depression. Neuron. 2005;45(5):651–60.PubMedCrossRefGoogle Scholar
  97. 97.
    Anderson RJ, Frye MA, Abulseoud OA, Lee KH, McGillivray J, Berk M, et al. Deep brain stimulation for treatment-resistant depression: efficacy, safety and mechanisms of action. Neurosci Biobehav Rev. 2012.Google Scholar
  98. 98.
    Lozano AM, Mayberg HS, Giacobbe P, Hamani C, Craddock RC, Kennedy SH. Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression. Biol Psychiatry. 2008;64(6):461–7.PubMedCrossRefGoogle Scholar
  99. 99.
    Baker KB, Kopell BH, Malone D, Horenstein C, Lowe M, Phillips MD, et al. Deep brain stimulation for obsessive-compulsive disorder: using functional magnetic resonance imaging and electrophysiological techniques: technical case report. Neurosurgery. 2007;61(5):E367–8. doi: 10.1227/01.neu.0000303995.66902.36.PubMedCrossRefGoogle Scholar
  100. 100.
    Bewernick BH, Hurlemann R, Matusch A, Kayser S, Grubert C, Hadrysiewicz B, et al. Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression. Biol Psychiatry. 2010;67(2):110–6.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Mayur Pandya
    • 1
  • Murat Altinay
    • 1
  • Donald A. MaloneJr.
    • 1
  • Amit Anand
    • 2
    • 3
  1. 1.Department of Psychiatry and Center for Behavioral HealthNeurological Institute, Cleveland ClinicClevelandUSA
  2. 2.Department of RadiologyIndiana University Center for NeuroimagingIndianapolisUSA
  3. 3.Adult Outpatient Clinic, Department of PsychiatryIndiana University School of MedicineIndianapolisUSA

Personalised recommendations