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The Validity of Vascular Depression as a Diagnostic Construct

  • Lauren Taylor
  • Adith Mohan
  • Perminder S. SachdevEmail author
Chapter

Abstract

The ‘vascular depression’ (VaD) construct initially proposed a relationship between late-life depression (LLD) and vascular disease and stimulated significant investigation into this nature of this relationship. The construct became synonymous with an aetiological proposition that vascular disease or risk factors are central in the pathogenesis of LLD. Validity of the VaD construct warrants consideration. This chapter reviews strategies that have been used to demonstrate an aetiological relationship between vascular disease and depression and considers the evidence for this association from various perspectives including (i) clinical features and the specificity of a VaD clinical phenotype, (ii) neuroimaging findings, (iii) proposed mechanisms for the aetiological role of vascular disease in depression, (iv) prognostic implications with a focus on treatment response and (v) shared pathomechanisms underlying both depression and vascular pathology. Our review suggests that the evidence in support of a causal relationship between depression and vascular disease, and thus the validity of the VaD construct, is not consistent. Whilst strong associations exist, the agnostic ascription of vascular disease as causative in LLD is potentially misleading, particularly in light of emerging evidence for diverse and interrelated pathomechanisms.

Keywords

White Matter Hyperintensities Small Vessel Disease Uncinate Fasciculus Diffusion Tensor Imaging Study Cerebral Small Vessel Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Ajilore O, Narr K, Rosenthal J, Pham D, Hamilton L, Watari K et al (2010) Regional cortical grey matter thickness differences associated with type 2 diabetes and major depression. Psychiatry Res 184(2):63–70PubMedPubMedCentralCrossRefGoogle Scholar
  2. Alexopoulos GS (2001) ‘The Depression-Executive Dysfunction Syndrome of Late Life’: a specific target for D3 agonists? Am J Geriatr Psychiatry 9(1):22–29PubMedGoogle Scholar
  3. Alexopoulos GS (2005) Depression in the elderly. Lancet 365(9475):1961–1970PubMedCrossRefGoogle Scholar
  4. Alexopoulos GS, Morimoto SS (2011) The inflammation hypothesis in geriatric depression. Int J Geriatr Psychiatry 26(11):1109–1118PubMedPubMedCentralGoogle Scholar
  5. Alexopoulos GS, Meyers BS, Young RC, Kakuma T, Silbersweig D, Charlson M (1997a) Clinically defined vascular depression. Am J Psychiatry 154(4):562–565PubMedCrossRefGoogle Scholar
  6. Alexopoulos GS, Meyers BS, Young RC, Campbell S, Silbersweig D, Charlson M (1997b) ‘Vascular depression’ hypothesis. Arch Gen Psychiatry 54(10):915–922PubMedCrossRefGoogle Scholar
  7. Alexopoulos GS, Kiosses DN, Klimstra S, Kalayam B, Bruce ML (2002a) Clinical presentation of the “depression-executive dysfunction syndrome” of late life. Am J Geriatr Psychiatry 10(1):98–106PubMedGoogle Scholar
  8. Alexopoulos GS, KIosses DN, Choi SJ, Murphy CF, Lim KO (2002b) Frontal white matter microstructure and treatment response of late-life depression: a preliminary study. Am J Psychiatry 159(11):1929–1932PubMedCrossRefGoogle Scholar
  9. Almeida OP (2008) Vascular depression: myth or reality? Int Psychogeriatr 20(4):645–652PubMedCrossRefGoogle Scholar
  10. Anisman H, Hayley S (2012) Inflammatory factors contribute to depression and its comorbid conditions. Sci Signal 5(244):pe45Google Scholar
  11. Annerbrink K, Jonsson EG, Olsson M, Nilsson S, Sedvall GC, Anckarster H et al (2010) Associations between the angiotensin-converting enzyme insertion/deletion polymorphism and monoamine metabolite concentrations in cerebrospinal fluid. Psychiatry Res 179(2):231–234PubMedCrossRefGoogle Scholar
  12. Bae JN, MacFall, Krishnan KR, Payne ME, Steffens DC, Taylor WD (2006) Dorsolateral prefrontal cortex and anterior cingulate cortex white matter alterations in late-life depression. Biol Psychiatry 60(12):1356–1363PubMedCrossRefGoogle Scholar
  13. Baghai TC, Schule C, Zwanzger P, Minov C, Zill P, Ella R et al (2002) Hypothalamic-pituitary-adrenocortical axis dysregulation in patients with major depression is influenced by the insertion/deletion polymorphism in the angiotensin 1-converting enzyme gene. Neurosci Lett 328(3):299–303PubMedCrossRefGoogle Scholar
  14. Baldwin RC (2005) Is vascular depression a distinct sub-type of depressive disorder? A review of causal evidence. Int J Geriatr Psychiatry 20(1):1–11PubMedCrossRefGoogle Scholar
  15. Baldwin RC, Tomenson B (1995) Depression in later life. A comparison of symptoms and risk factors in early and late onset cases. Br J Psychiatry 167(5):649–652PubMedCrossRefGoogle Scholar
  16. Baune B, Stuart M, Gilmour A, Wersching H, Arolt V, Berger K (2012) Moderators of the relationship between depression and cardiovascular disorders: a systematic review. Gen Hosp Psychiatry 34(5):478–492PubMedCrossRefGoogle Scholar
  17. Bhogal SK, Teasell R, Foley N, Speechley M (2004) Lesion location and poststroke depression: systematic review of the methodological limitations of the literature. Stroke 35(3):794–802PubMedCrossRefGoogle Scholar
  18. Breitner C, Husain MM, Figiel GS, Krishnan KR, Koyko OB (1990) Cerebral white matter disease in late-onset paranoid psychosis. Biol Psychiatry 28(3):266–274PubMedCrossRefGoogle Scholar
  19. Brodaty H, Luscombe G, Parker G, Wilhelm K, Hickie I, Austin MP, Mitchell P (2001) Early and late onset depression in old age: different aetiologies, same phenomenology. J Affect Disord 66(2–3):225–236PubMedCrossRefGoogle Scholar
  20. Brodaty H, Cullen B, Thompson C, Mitchell P, Parker G, Wilhelm K, Austin MP, Mahli G (2005) Age and gender in the phenomenology of depression. Am J Geriatr Psychiatry 13(7):589–596PubMedCrossRefGoogle Scholar
  21. Brodaty H, Withall A, Altendorf A, Sachdev PS (2007) Rates of depression at 3 and 15 months poststroke and their relationship with cognitive decline: the Sydney Stroke Study. Am J Geriatr Psychiatry 15(6):477–486PubMedCrossRefGoogle Scholar
  22. Brookes RL, Herbert VH, Lawrence AJ, Morris RG, Markus HS (2014) Depression in small-vessel disease relates to white matter ultrastructural damage, not disability. Neurology 83(16):1417–1423PubMedPubMedCentralCrossRefGoogle Scholar
  23. Carney RM, Rich WM, Tevelde A, Saini J, Clark K, Jaffe AS (1987) Major depressive disorder in coronary artery disease. Am J Cardiol 140(16):1072–1074Google Scholar
  24. Carvalho AF, Miskowiak KK, Hyphantis TN et al (2014) Cognitive dysfunction in depression – pathophysiology and novel targets. CNS Neurol Disord Drug Targets 13(10):1819–1835PubMedCrossRefGoogle Scholar
  25. Chavhan GB, Babyn PS, Thomas B, Shroff MM, Haacke EM (2009) Principles, techniques, and applications of T2-based MR imaging and its special applications. Radiographics 29(5):1433–1449PubMedPubMedCentralCrossRefGoogle Scholar
  26. Coffey CE, Figiel GS, Djang WT, Sullivan DC, Herfkens RJ, Weiner RD (1988) Effects of ECT on brain structure: a pilot prospective magnetic resonance imaging study. Am J Psychiatry 17(8):701–706Google Scholar
  27. Coffey CE, Figiel GS, Djang WT, Weiner RD (1990) Subcortical hyperintensity on magnetic resonance imaging: a comparison of normal and depressed elderly subjects. Am J Pyschiatry 147(2):187–189CrossRefGoogle Scholar
  28. Corruble E, Gorwood P, Falissard B (2008) Association between age of onset and symptom profiles in late-life depression. Act Psychiatr Scand 118(5):389–394CrossRefGoogle Scholar
  29. Dalby RB, Chakravarty MM, Ahdidan J et al (2010) Localisation of white-matter lesions and effect of vascular risk factors in late-onset major depression. Psychol Med 40(8):1389–1399PubMedCrossRefGoogle Scholar
  30. Dantzer R, O’Connor JC, Lawson MA, Kelley KW (2011) Inflammation-associated depression: from serotonin to kynurenine. Psychoneuroendocrinology 36(3):426–436PubMedCrossRefGoogle Scholar
  31. Deisseroth K, Schnitzer MJ (2013) Engineering approaches to illuminating brain structure and dynamics. Neuron 80(3):568–577PubMedCrossRefGoogle Scholar
  32. Devanand DP, Adorno E, Cheng J, Burt T, Pelton GH, Roose SP, Sackheim HA (2004) Late onset dysthymic disorder and major depression differ from early onset dysthymic disorder and major depression in elderly outpatients. J Affect Disord 78(3):259–267PubMedCrossRefGoogle Scholar
  33. Dickens C, McGowan L, Clark-Carter D, Creed F (2002) Depression in rheumatoid arthritis: a systematic review of the literature with meta-analysis. Psychosom Med 64(1):52–60PubMedCrossRefGoogle Scholar
  34. Dieguez S, Staub F, Brugginmann L, Bogousslavsky J (2004) Is poststroke depression a vascular depression? J Neurol Sci 226(1–2):53–58PubMedCrossRefGoogle Scholar
  35. Diniz BS, Butters MA, Albert SM, Dew MA, Reynolds CF (2013) Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies. Br J Psychiatry 202(5):329–335PubMedPubMedCentralCrossRefGoogle Scholar
  36. Doyle T, Halaris A, Rao M (2014) Shared neurobiological pathways between type 2 diabetes and depressive symptoms: a review of morphological and neurocognitive findings. Curr Diabet Rep 14(12):560. doi: 10.1007/s11892-014-0560-7 CrossRefGoogle Scholar
  37. Egeto P, Fischer CE, Ismail Z, Smith EE, Schweizer TA (2014) Lacunar stroke, deep white matter disease and depression: a meta-analysis. Int Psychogeriatr 26(7):1101–1109PubMedCrossRefGoogle Scholar
  38. Figiel GS, Krishnan KR, Doraiswamy PM (1990) Subcortical structural changes in ECT-induced delirium. J Geriatr Psychiatry Neurol 3(3):172–176PubMedCrossRefGoogle Scholar
  39. Figiel GS, Krishnan KRR, Doraiswamy PM, Rao VP, Nemeroff CB, Boyko OB (1991) Subcortical hyperintensities on brain magnetic resonance imaging: a comparison between late age onset and early onset elderly depressed subjects. Neurobiol Aging 12(3):245–247PubMedCrossRefGoogle Scholar
  40. Ford DE, Mead LA, Chang PP, Cooper-Patrick L, Wang NY, Klag MJ (1998) Depression is a risk factor for coronary artery disease in men: the precursors study. Arch Intern Med 158(13):1422–1426PubMedCrossRefGoogle Scholar
  41. Franklin TB, Saab BJ, Mansuy IM (2012) Neural mechanisms of stress resilience and vulnerability. Neuron 75(5):747–761PubMedCrossRefGoogle Scholar
  42. Fujikawa T, Yamawaki S, Touhouda Y (1994) Background factors and clinical symptoms of major depression with silent cerebral infarction. Stroke 25(4):798–801PubMedCrossRefGoogle Scholar
  43. Godin O, Dufouil C, Maillard P, Delcroix N, Mazoyer B, Crivello F, Alpérovitch A, Tzourio C (2008) White matter lesions as a predictor of depression in the elderly: the 3C-Dijon study. Biol Psychiatry 63(7):663–669PubMedCrossRefGoogle Scholar
  44. Greenwald BS, Kramer-Ginsberg E (1988) Age at onset in geriatric depression: relationship to clinical variables. J Affect Disord 15(1):61–68PubMedCrossRefGoogle Scholar
  45. Greenwald BS, Kramer-Ginsberg E, Krishnan KR, Ashtari M, Auerback C, Patel M (1998) Neuroanatomic localisation of magnetic resonance imaging signal hyperintensities in geriatric depression. Stroke 29(3):613–617PubMedCrossRefGoogle Scholar
  46. Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Crtichley HD (2009) Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol Psychiatry 66(5):407–414PubMedPubMedCentralCrossRefGoogle Scholar
  47. Herrmann IL, Le Masurier M, Ebmeier KP (2008) White matter hyperintensities in late life depression: a systematic review. J Neurol Neurosurg Psychiatry 79(6):619–624PubMedCrossRefGoogle Scholar
  48. Hickie I, Scott E, Mitchell P et al (1995) Subcortical hyperintensities on magnetic resonance imaging: clinical correlates and prognostic significance in patients with severe depression. Biol Psychiatry 37(3):151–160PubMedCrossRefGoogle Scholar
  49. Hickie I, Scott E, Naismith S, Ward PB, Turner K, Parker G, Mitchell P, Wilhelm K (2001) Late-onset depression: genetic, vascular and clinical contributions. Psychol Med 31(8):1403–1412PubMedCrossRefGoogle Scholar
  50. Hickie I, Naismith S, Ward PB et al (2005) Reduced hippocampal volumes and memory loss in patients with early- and late-onset depression. Br J Psychiatry 186:197–202PubMedCrossRefGoogle Scholar
  51. Ikram MA, Luijendijk HJ, Vernooij MW, Hofman A, Niessen WJ, van der Lujt A, Tiemeier H, Breteler MM (2010) Vascular brain disease and depression in the elderly. Epidemiology 21(1):78–81PubMedCrossRefGoogle Scholar
  52. Janssen J, Beekman AT, Comijs HC, Deeg DJ, Heeren TJ (2006) Late-life depression: the differences between early- and late-onset illness in a community-based sample. Int J Geriatr Psychiatry 21(1):86–93PubMedCrossRefGoogle Scholar
  53. Jonas BS, Mussolino ME (2000) Symptoms of depression as a prospective risk factor for stroke. Psychosom Med 62(4):463–471PubMedCrossRefGoogle Scholar
  54. Jorm AF, Anstey KJ, Christensen H, de Plater G, Kumar R, Wen W, Sachdev P (2005) MRI hyperintensities and depressive symptoms in a community sample of individuals 60–64 years old. Am J Psychiatry 162(4):699–705PubMedCrossRefGoogle Scholar
  55. Kelly RE, Alexopoulos GS (2009) The vascular depression concept and its implications. In: Ellison JM, Kyomen HH, Verma S (eds). Mood disorders in later life. 2nd ed. Informa Healthcare, New York, pp 161–178Google Scholar
  56. Khan U, Porteous L, Hassan A, Markus HS (2007) Risk factor profile of cerebral small vessel disease and its subtypes. J Neurol Neurosurg Psychiatry 78(7):702–706PubMedPubMedCentralCrossRefGoogle Scholar
  57. Khundakar AA, Thomas AJ (2014) Am J Geriatr Psychiatry 22(2):122–132PubMedCrossRefGoogle Scholar
  58. Kivimaki M, Shipley MJ, Allan CL, Sexton CE, Jokela M, Virtanen M et al (2012) Vascular risk status as a predictor of later-life depressive symptoms: a cohort study. Biol Psychiatry 72(4):324–330PubMedPubMedCentralCrossRefGoogle Scholar
  59. Kohler S, Thomas AJ, Lloyd A et al (2010) White matter hyperintensities, cortisol levels, brain atrophy and continuing cognitive deficits in late-life depression. Br J Psychiatry 196(2):143–149PubMedCrossRefGoogle Scholar
  60. Kondo DG, Speer MC, Krishnan KR, McQuoid DR, Slifer SH, Pieper CF, Billups AV, Steffens DC et al (2007) Association of AGTR1 with 18-month treatment outcome in late-life depression. Am J Geriatr Psychiatry 15(7):564–572PubMedCrossRefGoogle Scholar
  61. Koo JW, Duman RS (2008) IL-1 beta is an essential mediator of the antineurogenic and anhedonic effects of stress. Proc Natl Acad Sci U S A 105(2):751–756PubMedPubMedCentralCrossRefGoogle Scholar
  62. Krishnan KRR (1993) Neuroanatomic substrates of depression in the elderly. J Geriatr Psychiatry Neurol 6(1):39–58PubMedCrossRefGoogle Scholar
  63. Krishnan KR (2002) Comorbidity of depression with other medical diseases in the elderly. Biol Psychiatry 15(6):559–588CrossRefGoogle Scholar
  64. Krishnan KR (2005) Psychiatric disease in the genomic era: rational approach. Mol Psychiatry 10(11):978–974PubMedCrossRefGoogle Scholar
  65. Krishnan KRR, McDonald WM (1995) Arteriosclerotic depression. Med Hypotheses 44(2):111–115PubMedCrossRefGoogle Scholar
  66. Krishnan KRR, Goli V, Ellinwood EH, France RD, Blazer DG, Nemeroff CB (1988) Leukoencephalopathy in patients diagnosed as major depressive. Biol Psychiatry 23(5):519–522PubMedCrossRefGoogle Scholar
  67. Krishnan KR, Hays JC, Tupler LA, George LK, Blazer DG (1995) Clinical and phenomenological comparisons of late-onset and early-onset depression. Am J Psychiatry 152(5):785–788PubMedCrossRefGoogle Scholar
  68. Krishnan KR, Hays JC, Blazer DG (1997) MRI-defined vascular depression. Am J Psychiatry 154(4):497–501PubMedCrossRefGoogle Scholar
  69. Krishnan KR, Taylor WD, Dr McQuoid et al (2004) Clinical characteristics of magnetic resonance imaging-defined subcortical ischaemic depression. Biol Psychiatry 55(4):390–397PubMedCrossRefGoogle Scholar
  70. Krishnan MS, O’Brien JT, Firbank MJ, Pantoni L, Carlucci G, Erkinjutti T et al (2006) Relationship between periventricular and deep white matter lesions and depressive symptoms in older people: the LADIS Study. Int J Geriatr Psychiatry 21(10):983–989PubMedCrossRefGoogle Scholar
  71. Lavretsky H, Lesser IM, Wohl M, Miller BL (1998) Relationship of age, age at onset, and sex to depression in older adults. Am J Geriatr Psychiatry 6(3):248–256PubMedCrossRefGoogle Scholar
  72. Li W, Ling S, Yang Y, Hu Z, Davies H, Fang M (2014) Systematic hypothesis for post-stroke depression caused inflammation and neurotransmission and resultant on possible treatments. Neuroendocrinol Lett 35(2):104–109PubMedGoogle Scholar
  73. Lipsey JR, Spencer WC, Rabins PV, Robinson RG (1986) Phenomenological comparison of poststroke depression and functional depression. Am J Psychiatry 143(4):527–529PubMedCrossRefGoogle Scholar
  74. Loubinoux I, Kronenberg G, Endres M, Schumann-Bard P, Freret T, Filipkowski RK, Kaczmarek L, Popa-Wagner A (2012) Poststroke depression: mechanisms, translation and therapy. J Cell Mol Med 16(9):1961–1969PubMedPubMedCentralCrossRefGoogle Scholar
  75. Lujjendijk HJ, Stricker BH, Wieberdink RG, Koudstaal PJ, Hofman A, Breteler MM, Tiemeier H (2011) Transient ischaemic attack and incident depression. Stroke 42(7):1857–1861CrossRefGoogle Scholar
  76. Lyness JM, Caine ED, Cox C, King DA, Conwell Y, Olivares T (1998) Cerebrovascular risk factors and later-life major depression. Testing a small-vessel brain disease model. Am J Geriatr Psychiatry 6(1):5–13PubMedGoogle Scholar
  77. Lyness JM, King DA, Conwell Y, Cox C, Caine ED (2000) Cerebrovascular risk factors and 1-year depression outcome in older primary care patients. Am J Psychiatry 157(9):1499–1501PubMedCrossRefGoogle Scholar
  78. MacFall JR, Payne ME, Provenzale JM, Krishnan KR (2001) Medial orbital frontal lesions in late-onset depression. Biol Psychiatry 49(9):803–806PubMedCrossRefGoogle Scholar
  79. MacFall JR, Taylor WD, Rex DE, Pieper S, Payne ME, McQuoid D et al (2006) Lobar distribution of lesion volumes in late-life depression: the Biomedical Information Research Network (BIRN). Neuropsychopharmacology 31(7):1500–1507PubMedCrossRefGoogle Scholar
  80. Maes M, Leonard B, Myint A, Kubera M, Verkerk R (2011) The new ‘5-HT’ hypothesis of depression: cell-mediated immune activation induces indoleamine 2, 3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute to the onset of depression. Prog Neuro-Psychopharmacol Biol Psychiatry 35(3):702–721CrossRefGoogle Scholar
  81. McDonald WM, Tupler LA, Marsteller FA, Figiel GS, DiSouza S, Nemeroff CB et al (1999) Hyperintense lesions on magnetic resonance images in bipolar disorder. Biol Psychiatry 45(8):965–971Google Scholar
  82. McDougall F, Brayne C (2007) Systematic review of the depressive symptoms associated with vascular conditions. J Affect Disord 104(1–3):25–35Google Scholar
  83. McLennan SN, Mathias JL (2010) The depression-executive dysfunction (DED) syndrome and response to antidepressants: a meta-analytic review. Int J Geriatr Psychiatry 25(10):933–944PubMedCrossRefGoogle Scholar
  84. Mettenburg JM, Benzinger TL, Shimony JS et al (2012) Diminished performance on neuropsychological testing in late life depression is correlated with microstructural white matter abnormalities. Neuroimage 60(4):2182–2190PubMedPubMedCentralCrossRefGoogle Scholar
  85. Miller AH, Maletic V, Raison CL (2009) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65(9):732–741PubMedPubMedCentralCrossRefGoogle Scholar
  86. Najjar S, Pearlman DM, Devinsky O, Najjar A, Zagzag D (2013) Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence. J Neuroinflammation 10:142PubMedPubMedCentralCrossRefGoogle Scholar
  87. Nucifora PG, Verma R, Lee SK, Melhem ER (2007) Diffusion-tensor MR imaging and tractography: exploring brain microstructure and connectivity. Radiology 245(2):367–384PubMedCrossRefGoogle Scholar
  88. Ovbiagele B, Salver JL (2006) Cerebral white matter hyperintensities on MRI: current concepts and therapeutic implications. Cerebrovasc Dis 22(2–3):83–90Google Scholar
  89. Pace TW, Hu F, Miller AH (2007) Cytokine effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression. Brain Behav Immun 21(1):9–19PubMedCrossRefGoogle Scholar
  90. Pantoni L, Garcia JH (1997) Pathogenesis of leukoaraiosis: a review. Stroke 28(3):652–659PubMedCrossRefGoogle Scholar
  91. Pittenger C, Duman RS (2008) Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology 33(1):88–109PubMedCrossRefGoogle Scholar
  92. Pratt LA, Ford DE, Crum RM, Armenian HK, Gallo JJ, Eaton WW (1996) Depression, psychotropic medication, and risk of myocardial infarction. Prospective data from the Baltimore ECA follow-up. Circulation 94(12):3123–3129PubMedCrossRefGoogle Scholar
  93. Rabkin JG, Charles E, Kass F (1983) Hypertension and DSM-III depression in psychiatric outpatients. Am J Psychiatry 140(8):1072–1074PubMedCrossRefGoogle Scholar
  94. Raison CL, Demetrashvili M, Caproun L, Miller AH (2005) Neuropsychiatric adverse effects of interferon-alpha: recognition and management. CNS Drugs 19(2):105–123PubMedPubMedCentralCrossRefGoogle Scholar
  95. Rapp MA, Dahlman K, Sano M, Grossman HT, Haroutunian V, Gorman JM (2005) Neuropsychological differences between late-onset and recurrent geriatric major depression. Am J Psychiatry 162(4):691–698PubMedCrossRefGoogle Scholar
  96. Rickards H (2005) Depression in neurological disorders: Parkinson’s disease, multiple sclerosis, and stroke. J Neurol Neurosurg Psychiatry 76(Suppl.1):i48–i52Google Scholar
  97. Robinson RG (2005) Vascular depression and poststroke depression where do we go from here? Am J Geriatr Psychiatry 13(2):85–87PubMedCrossRefGoogle Scholar
  98. Robinson RG, Spalletta G (2010) Poststroke depression: a review. Can J Psychiatry 55(6):341–349PubMedPubMedCentralGoogle Scholar
  99. Robinson RG, Kubo KL, Starr LB, Rao K, Price TR (1984a) Mood disorders in stroke patients: importance of location of lesion. Brain 107(Pt 1):81–93Google Scholar
  100. Robinson RG, Starr LB, Lipsey JR, Rao K, Price TR (1984b) A two-year longitudinal study of post-stroke mood disorders: dynamic changes in associated variables over the first six months of follow-up. Stroke 15(3):510–517PubMedCrossRefGoogle Scholar
  101. Sachdev PS, Reutens S (2014) Psychiatric consequences of small vessel disease. In: Pantoni L, Gorlick PB (eds) Clinical aspects of cerebral small vessel disease. Cambridge Univ Press, Cambridge, pp 261–272CrossRefGoogle Scholar
  102. Sachdev PS, Brodaty H, Valenzuela MJ, Lorentz L, Looi JC, Wen W, Zagami AS (2004) The neuropsychological profile of vascular cognitive impairment in stroke and TIA patients. Neurology 62(6):912–919PubMedCrossRefGoogle Scholar
  103. Salaycik KJ, Kelly-Hayes M, Beiser A, Nguyen A-H, Brady SM, Kase CS (2007) etal. Depressive symptoms and risk of stroke: the Framingham Study. Stroke 79(6):619–624Google Scholar
  104. Sanders ML, Lyness JM, Eberly S, King DA, Caine ED (2006) Cerebrovascular risk factors, executive dysfunction, and depression in older primary care patients. Am J Geriatr Psychiatry 14(2):145–152PubMedCrossRefGoogle Scholar
  105. Scapagnini G, Davinelli S, Drago F, De Lorenzo A, Oriani G (2012) Antioxidants as antidepressants: fact or fiction? CNS Drugs 26(6):477–490PubMedCrossRefGoogle Scholar
  106. Seminowicz DA, Mayberg HS, McIntosh AR et al (2004) Limbic-frontal circuitry in major depression: a path modeling meta-analysis. NeuroImage 22(1):409–418PubMedCrossRefGoogle Scholar
  107. Serlin Y, Levy J, Shalev H (2011) Vascular pathology and blood-brain barrier disruption in cognitive and psychiatric complications of type 2 diabetes mellitus. Cardiovasc Psychiatry Neurol 2011:609202PubMedPubMedCentralGoogle Scholar
  108. Sexton CE, McDermott L, Kalu UG, Hermann LL, Bradley KM, Allan CL et al (2011) Exploring the pattern and neural correlates of neuropsychological impairment in late-life depression. Psychol Med 42(6):1195–1202PubMedCrossRefGoogle Scholar
  109. Sexton CE, Allan CL, Le Masurier M et al (2012) Magnetic resonance imaging in late-life depression: multimodal examination of network. Arch Gen Psychiatry 69(7):680–689PubMedCrossRefGoogle Scholar
  110. Sheline YI, Price JL, Vaishnavi SN, Mintun MA, Barch DM, Epstein AA et al (2008) Regional white matter hyperintensity burden in automated segmentation distinguishes late-life depressed subjects from comparison subjects matched for vascular risk factors. Am J Psychiatry 165(4):524–532PubMedPubMedCentralCrossRefGoogle Scholar
  111. Simpson SW, Jackson A, Baldwin RC, Burns A (1997) Subcortical hyperintensities in late-life depression: acute response to treatment and neuropsychological impairment. Int Psychogeriatr 9(3):257–275PubMedCrossRefGoogle Scholar
  112. Simpson S, Baldwin RC, Jackson A, Burns AS (1998) Is subcortical disease associated with a poor response to antidepressants? Neurological, neuropsychological and neuroradiological findings in late life depression. Psychol Med 28(5):1015–1026PubMedCrossRefGoogle Scholar
  113. Sneed JR, Culang-Reinlieb (2011) The vascular depression hypothesis: an update. Am J Geriatr Psychiatry 19(2):99–103PubMedPubMedCentralCrossRefGoogle Scholar
  114. Steffens DC, Conway CR, Dombeck CB, Wagner HR, Tupler LA, Weiner RD (2001) Severity of subcortical gray matter hyperintensity predicts ECT response in geriatric depression. J ECT 17(1):45–49PubMedCrossRefGoogle Scholar
  115. Steffens DC, Krishnan KRR, Crump C, Burke GL (2002) Cerebrovascular disease and evolution of depressive symptoms in the cardiovascular health study. Stroke 33(6):1636–1644PubMedCrossRefGoogle Scholar
  116. Steinberg EE, Christoffel DJ, Deisseroth K, Malenka RC (2015) Illuminating circuitry relevant to psychiatric disorders with optogenetics. Curr Opin Neurobiol 30:9–16PubMedCrossRefGoogle Scholar
  117. Stewart R, Hirani V (2010) General health status and vascular disorders as correlates of late-life depressive symptoms in a national survey sample. Int J Geriatr Psychiatry 25(5):483–488PubMedCrossRefGoogle Scholar
  118. Stockmeier CA, Mahajan GJ, Konick LC, Overholser JC, Jurjus GJ, Meltzer HY et al (2004) Cellular changes in the post-mortem hippocampus in major depression. Biol Psychiatry 56(9):640–650PubMedPubMedCentralCrossRefGoogle Scholar
  119. Surtees PG, Wainwright NM, Boekholdt SM, Luben RN, Wareham NJ, Khaw KT (2008) Major depression, C-reactive protein, and incident ischaemic heart disease in healthy men and women. Psychosom Med 70(8):850–855PubMedCrossRefGoogle Scholar
  120. Tang WK, Chen YK, Lu JY, Chu WC, Mok VC, Ungvari GS, Wong KS (2011a) Cerebral microbleeds and symptom severity of post-stroke depression: a magnetic resonance imaging study. J Affect Disord 129(1–3):354–358Google Scholar
  121. Tang WK, Lu JY, Chen JK, Chu WC, Mok V, Ungvari GS, Wong KS (2011b) Association of frontal subcortical circuit infarcts in poststroke depression: a magnetic resonance imaging study of 591 Chinese patients with ischaemic stroke. J Geriatr Psychiatry Neurol 24(1):44–49PubMedGoogle Scholar
  122. Taragano FE, Allegri R, Vicario A, Bagnatti P, Lyketsos CG (2001) A double blind, randomised clinical trial assessing the efficacy and safety of augmenting standardised antidepressant therapy with nimodipine in the treatment of “vascular depression”. Int J Geriatr Psychiatry 16(3):254–260PubMedCrossRefGoogle Scholar
  123. Taylor WD, MacFall JR, Steffens DC, Payne ME, Provenzale JM, Krishnan KR (2003a) Localisation of age-associated white matter hyperintensities in late-life depression. Prog Neurospcyhopharmacol Biol Psychiatry 27(3):539–544CrossRefGoogle Scholar
  124. Taylor WD, Steffens DC, MacFall JR, McQuoid DR, Payne ME, Provenzale JM, Krishnan KRR (2003b) White matter hyperintensity progression and late life depression outcomes. Arch Gen Psychiatry 60(11):1090–1096PubMedCrossRefGoogle Scholar
  125. Taylor WD, Steffens DC, Krishnan KR (2006) Psychiatric disease in the twenty-first century: the case for subcortical ischaemic depression. Biol Psychiatry 60(12):1299–1303Google Scholar
  126. Taylor WD, Benjamin S, McQuoid DR, Payne ME, Krishnan RR, MacFall JR et al (2012) AGTR1 gene variation: association with depression and frontotemporal morphology. Psychiatry Res 202(2):104–109PubMedPubMedCentralCrossRefGoogle Scholar
  127. Taylor WD, Aizenstein HJ, Alexopoulos GS (2013a) The vascular depression hypothesis: mechanisms linking vascular disease with depression. Mol Psychiatry 18(9):963–974PubMedPubMedCentralCrossRefGoogle Scholar
  128. Taylor WD, Zhao Z, Ashley-Koch A et al (2013b) Fiber tract specific white matter lesion severity. Findings in late life depression and by AGTR1 A1166C genotype. Hum Brain Mapp 34(2):295–303PubMedCrossRefGoogle Scholar
  129. Teodorczuk A, Firbank MJ, Pantoni L, Pggessi A, Erkinjuntti T, Wallin A et al (2010) Relationship between baseline white-matter changes and development of late-life depressive symptoms:3-year results from the LADIS study. Psychol Med 40(4):603–610PubMedCrossRefGoogle Scholar
  130. Thomas AJ (2013) Vascular depression. In: Ferro FM (ed) Neuropsychiatric symptoms of cerebrovascular diseases. Springer, London, pp 299–305CrossRefGoogle Scholar
  131. Thomas AJ, Ferrier IN, Kalaria RN, Perry RH, Brown A, O’Brien JT (2001) A neuropathological study of vascular factors in late-life depression. J Neurol Neurosurg Psychiatry 70(1):83–87PubMedPubMedCentralCrossRefGoogle Scholar
  132. Thomas AJ, O’Brien JT, Davis S, Ballard C, Barber R, Kalaria RN, Perry RH (2002) Ischaemic basis for deep white matter hyperintensities in major depression: a neuropathological study. Arch Gen Psychiatry 59(9):785–792PubMedCrossRefGoogle Scholar
  133. Thomas AJ, Perry R, Kalaria RN, Oakley A, McMeekin W, O’Brien JT (2003a) Neuropathological evidence for ischaemia in the white matter of the dorsolateral prefrontal cortex in late-life depression. Int J Geriatr Psychiatry 18(1):7–13PubMedCrossRefGoogle Scholar
  134. Thomas AJ, Kalaria RN, O’Brien JT (2004) Depression and vascular disease: what is the relationship? J Affect Disord 79(1–3):81–95PubMedCrossRefGoogle Scholar
  135. Tonkonogy JM, Geller JL (1999) Late-onset paranoid psychosis as a distinct clinicopathologic entity: magnetic resonance imaging data in elderly patients with paranoid psychosis of late onset and schizophrenia of early onset. Neuropsychiatry Neuropsychol Behav Neurol 12(4):230–235PubMedGoogle Scholar
  136. Tsopelas C, Stewart R, Sawa GM et al (2011) Neuropathological correlates of late-life depression in older people. Br J Psychiatry 198(2):109–114PubMedCrossRefGoogle Scholar
  137. Turnbull AV, Rivier CL (1999) Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action. Physiol Rev 79(1):1–71PubMedGoogle Scholar
  138. Valenti R, Poggesi A, Pescini F, Inzitari D, Pantoni L (2008) Psychiatric disturbances in CADASIL: a brief review. Acta Neurol Scand 118(5):291–295PubMedCrossRefGoogle Scholar
  139. Valkanova V, Ebmeier K (2013) Vascular risk factors and depression in later life: a systematic review and meta-analysis. Biol Psychiatry 73(5):406–413PubMedCrossRefGoogle Scholar
  140. Vataja R, Leppavuori A, Pohjasvaara T, Mantyla R, Aronen HJ, Salonen O, Kaste M, Erkinjuntti T (2004) Poststroke depression and lesion location revisited. J Neuropsychiatry Clin Neurosci 16(2):156–162PubMedCrossRefGoogle Scholar
  141. Verslius CE, van der Mast RC, van Buchem MA, Bollen MA, Bollen EL, Blauw GJ, Eekhof JA et al (2006) Progression of cerebral white matter lesions is not associated with development of depressive symptoms in elderly subjects at risk of cardiovascular disease: the PROSPER study. In J Geriatr Psychiatry 21(4):375–381CrossRefGoogle Scholar
  142. Vu NQ, Aizenstein HJ (2013) Depression in the elderly: brain correlates, neuropsychological findings, and role of vascular lesion load. Curr Opin Neurol 26(6):656–661PubMedCrossRefGoogle Scholar
  143. Wade DT, Legh-Smith J, Hewer RA (1987) Depressed mood after stroke. A community study of its frequency. Br J Psychiatry 151:200–205PubMedCrossRefGoogle Scholar
  144. Wen W, Sachdev PS (2004) The topography of white matter hyperintensities on brain MRI in healthy 60- to 64-year-old individuals. Neuroimage 22(1):144–154PubMedCrossRefGoogle Scholar
  145. Wen W, Sachdev PS, Li JJ, Chen X, Anstey KJ (2009) White matter hyperintensities in the forties: their prevalence and topography in an epidemiological sample aged 44–48. Hum Brain Mapp 30(4):1155–1167PubMedCrossRefGoogle Scholar
  146. Whyte EM, Mulsant BH (2003) Poststroke depression: prevalence, diagnosis, treatment, and disease progression. Biol Psychiatry 54(3):376–387CrossRefGoogle Scholar
  147. Wright L, Simpson W, Van Lieshout RJ (2014) Steiner. Depression and cardiovascular disease in women: is there a common immunological basis? A theoretical synthesis. Ther Adv Cardiovasc Dis 8(2):56–69PubMedCrossRefGoogle Scholar
  148. Xiong YY, Wong A, Mok VC, Tang WK, Lam WW, Kwok TC, Chu WC, Chan AY, Wong LK (2011) Frequency and predictors of proxy-confirmed post-stroke cognitive complaints in lacunar stroke patients without major depression. Int J Geriatr Psychiatry 26:1144–1151Google Scholar
  149. Zill P, Baghai TC, Schule C, Born C, Frustuck C, Buttner A et al (2012) DNA methylation analysis of the angiotensin converting enzyme (ACE) in major depression. PLoS ONE 7(7):e40479PubMedPubMedCentralCrossRefGoogle Scholar
  150. Zou K, Huang X, Li T, Gong Q, Li Z, Ou-yang L et al (2008) Alterations of white matter integrity on adults with major depressive disorder: a magnetic resonance imaging study. Psychiatry Neurosci 33(6):525–530Google Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Lauren Taylor
    • 1
    • 2
  • Adith Mohan
    • 3
    • 1
    • 2
  • Perminder S. Sachdev
    • 3
    • 1
    • 2
    Email author
  1. 1.School of PsychiatryUniversity of New South Wales MedicineRandwickAustralia
  2. 2.Neuropsychiatric Institute (NPI), Euroa Centre Prince of Wales HospitalSydneyAustralia
  3. 3.Centre for Healthy Brain Ageing (CHeBA)RandwickAustralia

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