Where in the Brain Is Depression?

Abstract

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.

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

References

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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    Article  CAS  Google Scholar 

  6. 6.

    George MS. Transcranial magnetic stimulation for the treatment of depression. Expert Rev Neurother. 2010;10(11):1761–72.

    PubMed  Article  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    Article  CAS  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  CAS  Google 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.

    CAS  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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Deen B, Pitskel NB, Pelphrey KA. Three systems of insular functional connectivity identified with cluster analysis. Cerebr Cortex. 2010.

  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.

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Modinos G, Ormel J, Aleman A. Activation of anterior insula during self-reflection. PLoS One. 2009;4(2):e4618.

    PubMed  Article  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  Google 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.

    Article  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  CAS  Google 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.

    PubMed  CAS  Google 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.

    PubMed  Article  Google Scholar 

  32. 32.

    Duman RS. Synaptic plasticity and mood disorders. Mol Psychiatr. 2002;7 Suppl 1:S29–34.

    Article  CAS  Google Scholar 

  33. 33.

    Anand A, Charney DS. Norepinephrine dysfunction in depression. J Clin Psychiatr. 2000;61 Suppl 10:16–24.

    CAS  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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  Google 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.

    PubMed  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  CAS  Google 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.

    PubMed  Article  Google Scholar 

  55. 55.

    Friston K. Beyond phrenology: what can neuroimaging tell us about distributed circuitry? Annu Rev Neurosci. 2002;25:221–50.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  Google 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.

    Article  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  Google 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.

  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.

    PubMed  Article  CAS  Google Scholar 

  64. 64.

    Cummings JL. Depression and Parkinson's disease: a review. Am J Psychiatry. 1992;149(4):443–54.

    PubMed  CAS  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    CAS  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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  Google Scholar 

  76. 76.

    Provinciali L, Coccia M. Post-stroke and vascular depression: a critical review. Neurol Sci. 2002;22(6):417–28.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  Google Scholar 

  78. 78.

    Alexopoulos GS. The vascular depression hypothesis: 10 years later. Biol Psychiatry. 2006;60(12):1304–5.

    PubMed  Article  Google Scholar 

  79. 79.

    Kanner AM. Mood disorder and epilepsy: a neurobiologic perspective of their relationship. Dialogues Clin Neurosci. 2008;10(1):39–45.

    PubMed  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  Google Scholar 

  82. 82.

    Litofsky NS, Resnick AG. The relationships between depression and brain tumors. J Neurooncol. 2009;94(2):153–61.

    PubMed  Article  Google 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.

  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.

    PubMed  Article  Google 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.

    Article  Google 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.

    PubMed  Article  CAS  Google 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.

  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.

    PubMed  Article  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  Google 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.

    Article  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  CAS  Google 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.

  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.

    PubMed  Article  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  Google Scholar 

Download references

Disclosure

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

Author information

Affiliations

Authors

Corresponding author

Correspondence to Amit Anand.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Pandya, M., Altinay, M., Malone, D.A. et al. Where in the Brain Is Depression?. Curr Psychiatry Rep 14, 634–642 (2012). https://doi.org/10.1007/s11920-012-0322-7

Download citation

Keywords

  • 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