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Diagnosis of Major Depressive Disorders: Clinical and Biological Perspectives

  • Marc Fakhoury
Chapter

Abstract

Major depressive disorder (MDD) is a serious, debilitating mental illness of very high prevalence. It is characterized by a wide array of clinical symptoms that can have devastating impacts on the affected individual, including inability to work and even suicide. With the additional burden of severe social stigma, MDD constitutes a major financial weight for the health-care system worldwide. Although findings from genetic, molecular, and neuroimaging studies have helped decipher some of the underlying neurobiological mechanisms of MDD, the identification of causal mechanisms and treatment allocation has largely been hindered by the symptomatic diversity of this mental illness. Variability in clinical presentation may also interfere with the recognition of this disorder in primary care setting, making decisions regarding diagnosis and treatment plan rather difficult. A variety of biological markers have been shown to contribute to the etiology of MDD, however, the extent to which these biomarkers could help improve the reliability of diagnosis in clinical settings is still uncertain. This chapter discusses the clinical implications of using standardized diagnostic criteria such as those outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), and presents several key biological markers that could be used to increase the recognition and effective management of depression.

Keywords

Biomarkers Classification Diagnosis DSM-5 Major depressive disorders Pathophysiology 

References

  1. Ahdidan J, Hviid LB, Chakravarty MM, Ravnkilde B, Rosenberg R, Rodell A, Stodkilde-Jorgensen H, Videbech P. Longitudinal MR study of brain structure and hippocampus volume in major depressive disorder. Acta Psychiatr Scand. 2011;123:211–9.PubMedCrossRefGoogle Scholar
  2. Albert PR, Benkelfat C, Descarries L. The neurobiology of depression—revisiting the serotonin hypothesis. I. Cellular and molecular mechanisms. Philos Trans R Soc Lond Ser B Biol Sci. 2012;367:2378–81.CrossRefGoogle Scholar
  3. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington: American Psychiatric Association; 1994.Google Scholar
  4. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Association; 2013.CrossRefGoogle Scholar
  5. Austin MC, Janosky JE, Murphy HA. Increased corticotropin-releasing hormone immunoreactivity in monoamine-containing pontine nuclei of depressed suicide men. Mol Psychiatry. 2003;8:324–32.PubMedCrossRefGoogle Scholar
  6. Aydemir O, Deveci A, Taneli F. The effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patients: a preliminary study. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29:261–5.PubMedCrossRefGoogle Scholar
  7. Aydemir C, Yalcin ES, Aksaray S, Kisa C, Yildirim SG, Uzbay T, Goka E. Brain-derived neurotrophic factor (BDNF) changes in the serum of depressed women. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:1256–60.PubMedCrossRefGoogle Scholar
  8. Basterzi AD, Aydemir C, Kisa C, Aksaray S, Tuzer V, Yazici K, Goka E. IL-6 levels decrease with SSRI treatment in patients with major depression. Hum Psychopharmacol. 2005;20:473–6.PubMedCrossRefGoogle Scholar
  9. Beck AT, Brown G, Steer RA. Prediction of eventual suicide in psychiatric inpatients by clinical ratings of hopelessness. J Consult Clin Psychol. 1989;57:309–10.PubMedCrossRefGoogle Scholar
  10. Beck AT, Brown G, Berchick RJ, Stewart BL, Steer RA. Relationship between hopelessness and ultimate suicide: a replication with psychiatric outpatients. Am J Psychiatry. 1990;147:190–5.PubMedCrossRefGoogle Scholar
  11. Beck AT, Steer RA, Beck JS, Newman CF. Hopelessness, depression, suicidal ideation, and clinical diagnosis of depression. Suicide Life Threat Behav. 1993;23:139–45.PubMedPubMedCentralGoogle Scholar
  12. Beneyto M, Kristiansen LV, Oni-Orisan A, McCullumsmith RE, Meador-Woodruff JH. Abnormal glutamate receptor expression in the medial temporal lobe in schizophrenia and mood disorders. Neuropsychopharmacology. 2007;32:1888–902.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Bernard R, Kerman IA, Thompson RC, Jones EG, Bunney WE, Barchas JD, Schatzberg AF, Myers RM, Akil H, Watson SJ. Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression. Mol Psychiatry. 2011;16:634–46.PubMedCrossRefGoogle Scholar
  14. Bocchio-Chiavetto L, Bagnardi V, Zanardini R, Molteni R, Nielsen MG, Placentino A, Giovannini C, Rillosi L, Ventriglia M, Riva MA, Gennarelli M. Serum and plasma BDNF levels in major depression: a replication study and meta-analyses. World J Biol Psychiatry. 2010;11:763–73.PubMedCrossRefGoogle Scholar
  15. Bremner JD, Vythilingam M, Vermetten E, Nazeer A, Adil J, Khan S, Staib LH, Charney DS. Reduced volume of orbitofrontal cortex in major depression. Biol Psychiatry. 2002;51:273–9.PubMedCrossRefGoogle Scholar
  16. Britton PC, Duberstein PR, Conner KR, Heisel MJ, Hirsch JK, Conwell Y. Reasons for living, hopelessness, and suicide ideation among depressed adults 50 years or older. Am J Geriatr Psychiatry. 2008;16:736–41.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Brothers BM, Andersen BL. Hopelessness as a predictor of depressive symptoms for breast cancer patients coping with recurrence. Psychooncology. 2009;18:267–75.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Brown TA, Barlow DH. Dimensional versus categorical classification of mental disorders in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders and beyond: comment on the special section. J Abnorm Psychol. 2005;114:551–6.PubMedCrossRefGoogle Scholar
  19. Brunoni AR, Machado-Vieira R, Zarate CA Jr, Vieira EL, Vanderhasselt MA, Nitsche MA, Valiengo L, Bensenor IM, Lotufo PA, Gattaz WF, Teixeira AL. BDNF plasma levels after antidepressant treatment with sertraline and transcranial direct current stimulation: results from a factorial, randomized, sham-controlled trial. Eur Neuropsychopharmacol. 2014;24:1144–51.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Burrows GD, Maguire KP, Norman TR. Antidepressant efficacy and tolerability of the selective norepinephrine reuptake inhibitor reboxetine: a review. J Clin Psychiatry. 1998;59(Suppl 14):4–7.PubMedGoogle Scholar
  21. Byers AL, Vittinghoff E, Lui LY, Hoang T, Blazer DG, Covinsky KE, Ensrud KE, Cauley JA, Hillier TA, Fredman L, Yaffe K. Twenty-year depressive trajectories among older women. Arch Gen Psychiatry. 2012;69:1073–9.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Caetano SC, Kaur S, Brambilla P, Nicoletti M, Hatch JP, Sassi RB, Mallinger AG, Keshavan MS, Kupfer DJ, Frank E, Soares JC. Smaller cingulate volumes in unipolar depressed patients. Biol Psychiatry. 2006;59:702–6.PubMedCrossRefGoogle Scholar
  23. Callado LF, Meana JJ, Grijalba B, Pazos A, Sastre M, Garcia-Sevilla JA. Selective increase of alpha2A-adrenoceptor agonist binding sites in brains of depressed suicide victims. J Neurochem. 1998;70:1114–23.PubMedCrossRefGoogle Scholar
  24. Chen YW, Lin PY, Tu KY, Cheng YS, Wu CK, Tseng PT. Significantly lower nerve growth factor levels in patients with major depressive disorder than in healthy subjects: a meta-analysis and systematic review. Neuropsychiatr Dis Treat. 2015;11:925–33.PubMedPubMedCentralGoogle Scholar
  25. Clark-Raymond A, Halaris A. VEGF and depression: a comprehensive assessment of clinical data. J Psychiatr Res. 2013;47:1080–7.PubMedCrossRefGoogle Scholar
  26. Cole J, Costafreda SG, McGuffin P, Fu CH. Hippocampal atrophy in first episode depression: a meta-analysis of magnetic resonance imaging studies. J Affect Disord. 2011;134:483–7.PubMedCrossRefGoogle Scholar
  27. Copeland WE, Angold A, Costello EJ, Egger H. Prevalence, comorbidity, and correlates of DSM-5 proposed disruptive mood dysregulation disorder. Am J Psychiatry. 2013;170:173–9.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Cotter D, Mackay D, Landau S, Kerwin R, Everall I. Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Arch Gen Psychiatry. 2001;58:545–53.PubMedCrossRefGoogle Scholar
  29. Cotter D, Mackay D, Chana G, Beasley C, Landau S, Everall IP. Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder. Cereb Cortex. 2002;12:386–94.PubMedCrossRefGoogle Scholar
  30. Cowen PJ, Parry-Billings M, Newsholme EA. Decreased plasma tryptophan levels in major depression. J Affect Disord. 1989;16:27–31.PubMedCrossRefGoogle Scholar
  31. Cross-Disorder Group of the Psychiatric Genomics Consortium, et al. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat Genet. 2013;45:984–94.CrossRefPubMedCentralGoogle Scholar
  32. Cuellar AK, Johnson SL, Winters R. Distinctions between bipolar and unipolar depression. Clin Psychol Rev. 2005;25:307–39.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Davis L, Uezato A, Newell JM, Frazier E. Major depression and comorbid substance use disorders. Curr Opin Psychiatry. 2008;21:14–8.PubMedCrossRefGoogle Scholar
  34. De Paermentier F, Mauger JM, Lowther S, Crompton MR, Katona CL, Horton RW. Brain alpha-adrenoceptors in depressed suicides. Brain Res. 1997;757:60–8.PubMedCrossRefGoogle Scholar
  35. Delgado PL. Depression: the case for a monoamine deficiency. J Clin Psychiatry. 2000;61(Suppl 6):7–11.PubMedGoogle Scholar
  36. Deschwanden A, Karolewicz B, Feyissa AM, Treyer V, Ametamey SM, Johayem A, Burger C, Auberson YP, Sovago J, Stockmeier CA, Buck A, Hasler G. Reduced metabotropic glutamate receptor 5 density in major depression determined by [(11)C]ABP688 PET and postmortem study. Am J Psychiatry. 2011;168:727–34.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Diniz BS, Teixeira AL, Talib L, Gattaz WF, Forlenza OV. Interleukin-1beta serum levels is increased in antidepressant-free elderly depressed patients. Am J Geriatr Psychiatry. 2010;18:172–6.PubMedCrossRefGoogle Scholar
  38. Dome P, Teleki Z, Rihmer Z, Peter L, Dobos J, Kenessey I, Tovari J, Timar J, Paku S, Kovacs G, Dome B. Circulating endothelial progenitor cells and depression: a possible novel link between heart and soul. Mol Psychiatry. 2009;14:523–31.PubMedCrossRefGoogle Scholar
  39. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010;67:446–57.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Drevets WC, Price JL, Simpson JR Jr, Todd RD, Reich T, Vannier M, Raichle ME. Subgenual prefrontal cortex abnormalities in mood disorders. Nature. 1997;386:824–7.PubMedCrossRefGoogle Scholar
  41. Drevets WC, Price JL, Furey ML. Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Struct Funct. 2008;213:93–118.PubMedPubMedCentralCrossRefGoogle Scholar
  42. Drysdale AT, et al. Resting-state connectivity biomarkers define neurophysiological subtypes of depression. Nat Med. 2017;23:28–38.PubMedCrossRefGoogle Scholar
  43. Du X, Pang TY. Is dysregulation of the HPA-axis a core pathophysiology mediating co-morbid depression in neurodegenerative diseases? Front Psych. 2015;6:32.Google Scholar
  44. Dunbar JA, Reddy P, Davis-Lameloise N, Philpot B, Laatikainen T, Kilkkinen A, Bunker SJ, Best JD, Vartiainen E, Kai Lo S, Janus ED. Depression: an important comorbidity with metabolic syndrome in a general population. Diabetes Care. 2008;31:2368–73.PubMedPubMedCentralCrossRefGoogle Scholar
  45. Dunlop BW, Mayberg HS. Neuroimaging-based biomarkers for treatment selection in major depressive disorder. Dialogues Clin Neurosci. 2014;16:479–90.PubMedPubMedCentralGoogle Scholar
  46. Dunn EC, Brown RC, Dai Y, Rosand J, Nugent NR, Amstadter AB, Smoller JW. Genetic determinants of depression: recent findings and future directions. Harv Rev Psychiatry. 2015;23:1–18.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Escriba PV, Ozaita A, Garcia-Sevilla JA. Increased mRNA expression of alpha2A-adrenoceptors, serotonin receptors and mu-opioid receptors in the brains of suicide victims. Neuropsychopharmacology. 2004;29:1512–21.PubMedCrossRefGoogle Scholar
  48. Evans SJ, Choudary PV, Neal CR, Li JZ, Vawter MP, Tomita H, Lopez JF, Thompson RC, Meng F, Stead JD, Walsh DM, Myers RM, Bunney WE, Watson SJ, Jones EG, Akil H. Dysregulation of the fibroblast growth factor system in major depression. Proc Natl Acad Sci U S A. 2004;101:15506–11.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Fakhoury M. New insights into the neurobiological mechanisms of major depressive disorders. Gen Hosp Psychiatry. 2015;37:172–7.PubMedCrossRefGoogle Scholar
  50. Fakhoury M. Revisiting the serotonin hypothesis: implications for major depressive disorders. Mol Neurobiol. 2016;53:2778–86.PubMedCrossRefGoogle Scholar
  51. Fava M, Rush AJ, Alpert JE, Balasubramani GK, Wisniewski SR, Carmin CN, Biggs MM, Zisook S, Leuchter A, Howland R, Warden D, Trivedi MH. Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. Am J Psychiatry. 2008;165:342–51.PubMedCrossRefGoogle Scholar
  52. Felger JC, Lotrich FE. Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications. Neuroscience. 2013;246:199–229.PubMedPubMedCentralCrossRefGoogle Scholar
  53. Feyissa AM, Chandran A, Stockmeier CA, Karolewicz B. Reduced levels of NR2A and NR2B subunits of NMDA receptor and PSD-95 in the prefrontal cortex in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:70–5.CrossRefPubMedGoogle Scholar
  54. Foley DL, Morley KI, Madden PA, Heath AC, Whitfield JB, Martin NG. Major depression and the metabolic syndrome. Twin Res Hum Genet. 2010;13:347–58.PubMedPubMedCentralCrossRefGoogle Scholar
  55. Galvez-Contreras AY, Campos-Ordonez T, Lopez-Virgen V, Gomez-Plascencia J, Ramos-Zuniga R, Gonzalez-Perez O. Growth factors as clinical biomarkers of prognosis and diagnosis in psychiatric disorders. Cytokine Growth Factor Rev. 2016;32:85–96.PubMedCrossRefGoogle Scholar
  56. Garcia-Sevilla JA, Escriba PV, Ozaita A, La Harpe R, Walzer C, Eytan A, Guimon J. Up-regulation of immunolabeled alpha2A-adrenoceptors, Gi coupling proteins, and regulatory receptor kinases in the prefrontal cortex of depressed suicides. J Neurochem. 1999;72:282–91.PubMedCrossRefGoogle Scholar
  57. Gaughran F, Payne J, Sedgwick PM, Cotter D, Berry M. Hippocampal FGF-2 and FGFR1 mRNA expression in major depression, schizophrenia and bipolar disorder. Brain Res Bull. 2006;70:221–7.PubMedCrossRefGoogle Scholar
  58. Gecici O, Kuloglu M, Atmaca M, Tezcan AE, Tunckol H, Emul HM, Ustundag B. High serum leptin levels in depressive disorders with atypical features. Psychiatry Clin Neurosci. 2005;59:736–8.PubMedCrossRefGoogle Scholar
  59. Gerner RH, Hare TA. CSF GABA in normal subjects and patients with depression, schizophrenia, mania, and anorexia nervosa. Am J Psychiatry. 1981;138:1098–101.PubMedCrossRefGoogle Scholar
  60. Gerner RH, Fairbanks L, Anderson GM, Young JG, Scheinin M, Linnoila M, Hare TA, Shaywitz BA, Cohen DJ. CSF neurochemistry in depressed, manic, and schizophrenic patients compared with that of normal controls. Am J Psychiatry. 1984;141:1533–40.PubMedCrossRefGoogle Scholar
  61. Gittins RA, Harrison PJ. A morphometric study of glia and neurons in the anterior cingulate cortex in mood disorder. J Affect Disord. 2011;133:328–32.PubMedCrossRefGoogle Scholar
  62. Godlewska BR, Near J, Cowen PJ. Neurochemistry of major depression: a study using magnetic resonance spectroscopy. Psychopharmacology. 2015;232:501–7.PubMedCrossRefGoogle Scholar
  63. Gold BI, Bowers MB Jr, Roth RH, Sweeney DW. GABA levels in CSF of patients with psychiatric disorders. Am J Psychiatry. 1980;137:362–4.PubMedPubMedCentralCrossRefGoogle Scholar
  64. Gonul AS, Akdeniz F, Taneli F, Donat O, Eker C, Vahip S. Effect of treatment on serum brain-derived neurotrophic factor levels in depressed patients. Eur Arch Psychiatry Clin Neurosci. 2005;255:381–6.PubMedCrossRefGoogle Scholar
  65. Gonzalez-Maeso J, Rodriguez-Puertas R, Meana JJ, Garcia-Sevilla JA, Guimon J. Neurotransmitter receptor-mediated activation of G-proteins in brains of suicide victims with mood disorders: selective supersensitivity of alpha(2A)-adrenoceptors. Mol Psychiatry. 2002;7:755–67.PubMedCrossRefGoogle Scholar
  66. Greene SM. The relationship between depression and hopelessness. Implications for current theories of depression. Br J Psychiatry. 1989;154:650–9.PubMedCrossRefGoogle Scholar
  67. Greene SM, O’Mahony PD, Rungasamy P. Levels of measured hopelessness in physically-ill patients. J Psychosom Res. 1982;26:591–3.PubMedCrossRefGoogle Scholar
  68. Greicius MD, Flores BH, Menon V, Glover GH, Solvason HB, Kenna H, Reiss AL, Schatzberg AF. Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biol Psychiatry. 2007;62:429–37.PubMedPubMedCentralCrossRefGoogle Scholar
  69. Gurguis GN, Vo SP, Griffith JM, Rush AJ. Platelet alpha2A-adrenoceptor function in major depression: Gi coupling, effects of imipramine and relationship to treatment outcome. Psychiatry Res. 1999;89:73–95.PubMedCrossRefGoogle Scholar
  70. Gururajan A, Clarke G, Dinan TG, Cryan JF. Molecular biomarkers of depression. Neurosci Biobehav Rev. 2016;64:101–33.PubMedPubMedCentralCrossRefGoogle Scholar
  71. Hamilton JP, Chen G, Thomason ME, Schwartz ME, Gotlib IH. Investigating neural primacy in major depressive disorder: multivariate Granger causality analysis of resting-state fMRI time-series data. Mol Psychiatry. 2011;16:763–72.PubMedCrossRefGoogle Scholar
  72. Hannestad J, Della Gioia N, Bloch M. The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology. 2011;36:2452–9.PubMedPubMedCentralCrossRefGoogle Scholar
  73. Hare DL, Toukhsati SR, Johansson P, Jaarsma T. Depression and cardiovascular disease: a clinical review. Eur Heart J. 2014;35:1365–72.PubMedCrossRefGoogle Scholar
  74. Hastings RS, Parsey RV, Oquendo MA, Arango V, Mann JJ. Volumetric analysis of the prefrontal cortex, amygdala, and hippocampus in major depression. Neuropsychopharmacology. 2004;29:952–9.PubMedCrossRefGoogle Scholar
  75. Heiskanen TH, Niskanen LK, Hintikka JJ, Koivumaa-Honkanen HT, Honkalampi KM, Haatainen KM, Viinamaki HT. Metabolic syndrome and depression: a cross-sectional analysis. J Clin Psychiatry. 2006;67:1422–7.PubMedCrossRefGoogle Scholar
  76. Himmerich H, Milenovic S, Fulda S, Plumakers B, Sheldrick AJ, Michel TM, Kircher T, Rink L. Regulatory T cells increased while IL-1beta decreased during antidepressant therapy. J Psychiatr Res. 2010;44:1052–7.PubMedCrossRefGoogle Scholar
  77. Hock C, Heese K, Muller-Spahn F, Huber P, Riesen W, Nitsch RM, Otten U. Increased cerebrospinal fluid levels of neurotrophin 3 (NT-3) in elderly patients with major depression. Mol Psychiatry. 2000;5:510–3.PubMedCrossRefGoogle Scholar
  78. Honig A, Bartlett JR, Bouras N, Bridges PK. Amino acid levels in depression: a preliminary investigation. J Psychiatr Res. 1988;22:159–64.PubMedCrossRefGoogle Scholar
  79. Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677–736.PubMedPubMedCentralCrossRefGoogle Scholar
  80. Huang TL, Lee CT, Liu YL. Serum brain-derived neurotrophic factor levels in patients with major depression: effects of antidepressants. J Psychiatr Res. 2008;42:521–5.PubMedCrossRefGoogle Scholar
  81. Iacob E, Tadler SC, Light KC, Weeks HR, Smith KW, White AT, Hughen RW, Van Haitsma TA, Bushnell LA, Light AR. Leukocyte gene expression in patients with medication refractory depression before and after treatment with ECT or isoflurane anesthesia: a pilot study. Depress Res Treat. 2014;2014:582380.PubMedPubMedCentralGoogle Scholar
  82. Ivleva EI, Morris DW, Osuji J, Moates AF, Carmody TJ, Thaker GK, Cullum M, Tamminga CA. Cognitive endophenotypes of psychosis within dimension and diagnosis. Psychiatry Res. 2012;196:38–44.PubMedPubMedCentralCrossRefGoogle Scholar
  83. Jaiswal SV, Faye AD, Gore SP, Shah HR, Kamath RM. Stressful life events, hopelessness, and suicidal intent in patients admitted with attempted suicide in a tertiary care general hospital. J Postgrad Med. 2016;62:102–4.PubMedPubMedCentralCrossRefGoogle Scholar
  84. Joiner TE Jr, Steer RA, Abramson LY, Alloy LB, Metalsky GI, Schmidt NB. Hopelessness depression as a distinct dimension of depressive symptoms among clinical and non-clinical samples. Behav Res Ther. 2001;39:523–36.PubMedPubMedCentralCrossRefGoogle Scholar
  85. Kahl KG, Bens S, Ziegler K, Rudolf S, Dibbelt L, Kordon A, Schweiger U. Cortisol, the cortisol-dehydroepiandrosterone ratio, and pro-inflammatory cytokines in patients with current major depressive disorder comorbid with borderline personality disorder. Biol Psychiatry. 2006;59:667–71.PubMedCrossRefGoogle Scholar
  86. Kahl KG, Bens S, Ziegler K, Rudolf S, Kordon A, Dibbelt L, Schweiger U. Angiogenic factors in patients with current major depressive disorder comorbid with borderline personality disorder. Psychoneuroendocrinology. 2009;34:353–7.PubMedCrossRefGoogle Scholar
  87. Karege F, Bondolfi G, Gervasoni N, Schwald M, Aubry JM, Bertschy G. Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity. Biol Psychiatry. 2005;57:1068–72.PubMedCrossRefGoogle Scholar
  88. Karolewicz B, Maciag D, O’Dwyer G, Stockmeier CA, Feyissa AM, Rajkowska G. Reduced level of glutamic acid decarboxylase-67 kDa in the prefrontal cortex in major depression. Int J Neuropsychopharmacol. 2010;13:411–20.PubMedCrossRefGoogle Scholar
  89. Kendell SF, Krystal JH, Sanacora G. GABA and glutamate systems as therapeutic targets in depression and mood disorders. Expert Opin Ther Targets. 2005;9:153–68.PubMedCrossRefGoogle Scholar
  90. Kessler RC. Epidemiology of women and depression. J Affect Disord. 2003;74:5–13.PubMedCrossRefGoogle Scholar
  91. Kessler RC. The costs of depression. Psychiatr Clin North Am. 2012;35:1–14.PubMedCrossRefGoogle Scholar
  92. Kim YK, Lee HP, Won SD, Park EY, Lee HY, Lee BH, Lee SW, Yoon D, Han C, Kim DJ, Choi SH. Low plasma BDNF is associated with suicidal behavior in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:78–85.PubMedCrossRefGoogle Scholar
  93. Klimek V, Rajkowska G, Luker SN, Dilley G, Meltzer HY, Overholser JC, Stockmeier CA, Ordway GA. Brain noradrenergic receptors in major depression and schizophrenia. Neuropsychopharmacology. 1999;21:69–81.PubMedCrossRefGoogle Scholar
  94. Kotan Z, Sarandol E, Kirhan E, Ozkaya G, Kirli S. Serum brain-derived neurotrophic factor, vascular endothelial growth factor and leptin levels in patients with a diagnosis of severe major depressive disorder with melancholic features. Ther Adv Psychopharmacol. 2012;2:65–74.PubMedPubMedCentralCrossRefGoogle Scholar
  95. Koukopoulos A, Sani G, Ghaemi SN. Mixed features of depression: why DSM-5 is wrong (and so was DSM-IV). Br J Psychiatry. 2013;203:3–5.PubMedCrossRefGoogle Scholar
  96. Kraus T, Haack M, Schuld A, Hinze-Selch D, Pollmacher T. Low leptin levels but normal body mass indices in patients with depression or schizophrenia. Neuroendocrinology. 2001;73:243–7.PubMedCrossRefGoogle Scholar
  97. Krishnan R, Cella D, Leonardi C, Papp K, Gottlieb AB, Dunn M, Chiou CF, Patel V, Jahreis A. Effects of etanercept therapy on fatigue and symptoms of depression in subjects treated for moderate to severe plaque psoriasis for up to 96 weeks. Br J Dermatol. 2007;157:1275–7.PubMedCrossRefGoogle Scholar
  98. Kruijshaar ME, Barendregt J, Vos T, de Graaf R, Spijker J, Andrews G. Lifetime prevalence estimates of major depression: an indirect estimation method and a quantification of recall bias. Eur J Epidemiol. 2005;20:103–11.PubMedCrossRefGoogle Scholar
  99. Lacerda AL, Nicoletti MA, Brambilla P, Sassi RB, Mallinger AG, Frank E, Kupfer DJ, Keshavan MS, Soares JC. Anatomical MRI study of basal ganglia in major depressive disorder. Psychiatry Res. 2003;124:129–40.PubMedCrossRefGoogle Scholar
  100. Lamers F, van Oppen P, Comijs HC, Smit JH, Spinhoven P, van Balkom AJ, Nolen WA, Zitman FG, Beekman AT, Penninx BW. Comorbidity patterns of anxiety and depressive disorders in a large cohort study: the Netherlands Study of Depression and Anxiety (NESDA). J Clin Psychiatry. 2011;72:341–8.PubMedCrossRefGoogle Scholar
  101. Lamers F, Vogelzangs N, Merikangas KR, de Jonge P, Beekman AT, Penninx BW. Evidence for a differential role of HPA-axis function, inflammation and metabolic syndrome in melancholic versus atypical depression. Mol Psychiatry. 2013;18:692–9.PubMedCrossRefGoogle Scholar
  102. Lasic D, Bevanda M, Bosnjak N, Uglesic B, Glavina T, Franic T. Metabolic syndrome and inflammation markers in patients with schizophrenia and recurrent depressive disorder. Psychiatr Danub. 2014;26:214–9.PubMedGoogle Scholar
  103. Lee BH, Kim YK. Increased plasma VEGF levels in major depressive or manic episodes in patients with mood disorders. J Affect Disord. 2012;136:181–4.PubMedCrossRefGoogle Scholar
  104. Lee BH, Kim H, Park SH, Kim YK. Decreased plasma BDNF level in depressive patients. J Affect Disord. 2007;101:239–44.PubMedPubMedCentralCrossRefGoogle Scholar
  105. Lehto SM, Hintikka J, Niskanen L, Tolmunen T, Koivumaa-Honkanen H, Honkalampi K, Viinamaki H. Low HDL cholesterol associates with major depression in a sample with a 7-year history of depressive symptoms. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32:1557–61.PubMedCrossRefGoogle Scholar
  106. Levine J, Barak Y, Chengappa KN, Rapoport A, Rebey M, Barak V. Cerebrospinal cytokine levels in patients with acute depression. Neuropsychobiology. 1999;40:171–6.PubMedCrossRefGoogle Scholar
  107. Levitan RD, Vaccarino FJ, Brown GM, Kennedy SH. Low-dose dexamethasone challenge in women with atypical major depression: pilot study. J Psychiatry Neurosci. 2002;27:47–51.PubMedPubMedCentralGoogle Scholar
  108. Li Y, et al. Patterns of co-morbidity with anxiety disorders in Chinese women with recurrent major depression. Psychol Med. 2012;42:1239–48.PubMedCrossRefGoogle Scholar
  109. Lichtenstein P, Yip BH, Bjork C, Pawitan Y, Cannon TD, Sullivan PF, Hultman CM. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet. 2009;373:234–9.PubMedPubMedCentralCrossRefGoogle Scholar
  110. Lindqvist D, Janelidze S, Hagell P, Erhardt S, Samuelsson M, Minthon L, Hansson O, Bjorkqvist M, Traskman-Bendz L, Brundin L. Interleukin-6 is elevated in the cerebrospinal fluid of suicide attempters and related to symptom severity. Biol Psychiatry. 2009;66:287–92.PubMedCrossRefGoogle Scholar
  111. Lohoff FW. Overview of the genetics of major depressive disorder. Curr Psychiatry Rep. 2010;12:539–46.PubMedPubMedCentralCrossRefGoogle Scholar
  112. Lopez-Figueroa AL, Norton CS, Lopez-Figueroa MO, Armellini-Dodel D, Burke S, Akil H, Lopez JF, Watson SJ. Serotonin 5-HT1A, 5-HT1B, and 5-HT2A receptor mRNA expression in subjects with major depression, bipolar disorder, and schizophrenia. Biol Psychiatry. 2004;55:225–33.PubMedCrossRefGoogle Scholar
  113. Lopresti AL, Maker GL, Hood SD, Drummond PD. A review of peripheral biomarkers in major depression: the potential of inflammatory and oxidative stress biomarkers. Prog Neuropsychopharmacol Biol Psychiatry. 2014;48:102–11.PubMedCrossRefGoogle Scholar
  114. Lotrich F. Inflammatory cytokines, growth factors, and depression. Curr Pharm Des. 2012;18:5920–35.PubMedCrossRefGoogle Scholar
  115. Maes M, Van Gastel A, Delmeire L, Meltzer HY. Decreased platelet alpha-2 adrenoceptor density in major depression: effects of tricyclic antidepressants and fluoxetine. Biol Psychiatry. 1999;45:278–84.PubMedCrossRefGoogle Scholar
  116. Malykhin NV, Carter R, Seres P, Coupland NJ. Structural changes in the hippocampus in major depressive disorder: contributions of disease and treatment. J Psychiatry Neurosci. 2010;35:337–43.PubMedPubMedCentralCrossRefGoogle Scholar
  117. Marazziti D, Rutigliano G, Baroni S, Landi P, Dell’Osso L. Metabolic syndrome and major depression. CNS Spectr. 2014;19:293–304.PubMedCrossRefGoogle Scholar
  118. Maurer-Spurej E, Pittendreigh C, Misri S. Platelet serotonin levels support depression scores for women with postpartum depression. J Psychiatry Neurosci. 2007;32:23–9.PubMedPubMedCentralGoogle Scholar
  119. McCullumsmith CB, Williamson DJ, May RS, Bruer EH, Sheehan DV, Alphs LD. Simple measures of hopelessness and impulsivity are associated with acute suicidal ideation and attempts in patients in psychiatric crisis. Innov Clin Neurosci. 2014;11:47–53.PubMedPubMedCentralGoogle Scholar
  120. McGonigle P, Ruggeri B. Animal models of human disease: challenges in enabling translation. Biochem Pharmacol. 2014;87:162–71.PubMedCrossRefGoogle Scholar
  121. Miguel-Hidalgo JJ, Waltzer R, Whittom AA, Austin MC, Rajkowska G, Stockmeier CA. Glial and glutamatergic markers in depression, alcoholism, and their comorbidity. J Affect Disord. 2010;127:230–40.PubMedPubMedCentralCrossRefGoogle Scholar
  122. Miguel-Hidalgo JJ, Wilson BA, Hussain S, Meshram A, Rajkowska G, Stockmeier CA. Reduced connexin 43 immunolabeling in the orbitofrontal cortex in alcohol dependence and depression. J Psychiatr Res. 2014;55:101–9.PubMedPubMedCentralCrossRefGoogle Scholar
  123. Milne AM, MacQueen GM, Hall GB. Abnormal hippocampal activation in patients with extensive history of major depression: an fMRI study. J Psychiatry Neurosci. 2012;37:28–36.PubMedPubMedCentralCrossRefGoogle Scholar
  124. Mingtian Z, Shuqiao Y, Xiongzhao Z, Jinyao Y, Xueling Z, Xiang W, Yingzi L, Jian L, Wei W. Elevated amygdala activity to negative faces in young adults with early onset major depressive disorder. Psychiatry Res. 2012;201:107–12.PubMedCrossRefGoogle Scholar
  125. Mitchell PB, Frankland A, Hadzi-Pavlovic D, Roberts G, Corry J, Wright A, Loo CK, Breakspear M. Comparison of depressive episodes in bipolar disorder and in major depressive disorder within bipolar disorder pedigrees. Br J Psychiatry. 2011;199:303–9.PubMedCrossRefGoogle Scholar
  126. Muller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Muller B, Spellmann I, Hetzel G, Maino K, Kleindienst N, Moller HJ, Arolt V, Riedel M. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry. 2006;11:680–4.PubMedCrossRefGoogle Scholar
  127. Negele A, Kaufhold J, Kallenbach L, Leuzinger-Bohleber M. Childhood trauma and its relation to chronic depression in adulthood. Depress Res Treat. 2015;2015:650804.PubMedPubMedCentralGoogle Scholar
  128. Nery FG, Monkul ES, Hatch JP, Fonseca M, Zunta-Soares GB, Frey BN, Bowden CL, Soares JC. Celecoxib as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: a double-blind, randomized, placebo-controlled study. Hum Psychopharmacol. 2008;23:87–94.PubMedCrossRefGoogle Scholar
  129. Neumeister A, Drevets WC, Belfer I, Luckenbaugh DA, Henry S, Bonne O, Herscovitch P, Goldman D, Charney DS. Effects of a alpha 2C-adrenoreceptor gene polymorphism on neural responses to facial expressions in depression. Neuropsychopharmacology. 2006;31:1750–6.PubMedCrossRefGoogle Scholar
  130. Nutt DJ. Relationship of neurotransmitters to the symptoms of major depressive disorder. J Clin Psychiatry. 2008;69(Suppl E1):4–7.PubMedGoogle Scholar
  131. Ogawa S, Fujii T, Koga N, Hori H, Teraishi T, Hattori K, Noda T, Higuchi T, Motohashi N, Kunugi H. Plasma L-tryptophan concentration in major depressive disorder: new data and meta-analysis. J Clin Psychiatry. 2014;75:e906–15.PubMedCrossRefGoogle Scholar
  132. Ongur D, Drevets WC, Price JL. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci U S A. 1998;95:13290–5.PubMedPubMedCentralCrossRefGoogle Scholar
  133. Ozsoy S, Besirli A, Abdulrezzak U, Basturk M. Serum ghrelin and leptin levels in patients with depression and the effects of treatment. Psychiatry Invest. 2014;11:167–72.CrossRefGoogle Scholar
  134. Pariante CM, Lightman SL. The HPA axis in major depression: classical theories and new developments. Trends Neurosci. 2008;31:464–8.PubMedCrossRefGoogle Scholar
  135. Parker GF. DSM-5 and psychotic and mood disorders. J Am Acad Psychiatry Law. 2014;42:182–90.PubMedGoogle Scholar
  136. Paul-Savoie E, Potvin S, Daigle K, Normand E, Corbin JF, Gagnon R, Marchand S. A deficit in peripheral serotonin levels in major depressive disorder but not in chronic widespread pain. Clin J Pain. 2011;27:529–34.PubMedCrossRefGoogle Scholar
  137. Petty F, Schlesser MA. Plasma GABA in affective illness. A preliminary investigation. J Affect Disord. 1981;3:339–43.PubMedCrossRefGoogle Scholar
  138. Petty F, Sherman AD. Plasma GABA levels in psychiatric illness. J Affect Disord. 1984;6:131–8.PubMedCrossRefGoogle Scholar
  139. Petty F, Kramer GL, Gullion CM, Rush AJ. Low plasma gamma-aminobutyric acid levels in male patients with depression. Biol Psychiatry. 1992;32:354–63.PubMedCrossRefGoogle Scholar
  140. Piccinni A, Marazziti D, Catena M, Domenici L, Del Debbio A, Bianchi C, Mannari C, Martini C, Da Pozzo E, Schiavi E, Mariotti A, Roncaglia I, Palla A, Consoli G, Giovannini L, Massimetti G, Dell’Osso L. Plasma and serum brain-derived neurotrophic factor (BDNF) in depressed patients during 1 year of antidepressant treatments. J Affect Disord. 2008;105:279–83.PubMedCrossRefGoogle Scholar
  141. Pies RW. The bereavement exclusion and DSM-5: an update and commentary. Innov Clin Neurosci. 2014;11:19–22.PubMedPubMedCentralGoogle Scholar
  142. Piwowarska J, Wrzosek M, Radziwon-Zaleska M, Ryszewska-Pokrasniewicz B, Skalski M, Matsumoto H, Biernacka-Bazyluk A, Szelenberger W, Pachecka J. Serum cortisol concentration in patients with major depression after treatment with clomipramine. Pharmacol Rep. 2009;61:604–11.PubMedCrossRefGoogle Scholar
  143. Piwowarska J, Chimiak A, Matsumoto H, Dziklinska A, Radziwon-Zaleska M, Szelenberger W, Pachecka J. Serum cortisol concentration in patients with major depression after treatment with fluoxetine. Psychiatry Res. 2012;198:407–11.PubMedCrossRefGoogle Scholar
  144. Portella MJ, de Diego-Adelino J, Gomez-Anson B, Morgan-Ferrando R, Vives Y, Puigdemont D, Perez-Egea R, Ruscalleda J, Enric A, Perez V. Ventromedial prefrontal spectroscopic abnormalities over the course of depression: a comparison among first episode, remitted recurrent and chronic patients. J Psychiatr Res. 2011;45:427–34.PubMedCrossRefGoogle Scholar
  145. Pulkki-Raback L, Elovainio M, Kivimaki M, Mattsson N, Raitakari OT, Puttonen S, Marniemi J, Viikari JS, Keltikangas-Jarvinen L. Depressive symptoms and the metabolic syndrome in childhood and adulthood: a prospective cohort study. Health Psychol. 2009;28:108–16.PubMedPubMedCentralCrossRefGoogle Scholar
  146. Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, Haroon E, Miller AH. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiat. 2013;70:31–41.CrossRefGoogle Scholar
  147. Rajkowska G, Stockmeier CA. Astrocyte pathology in major depressive disorder: insights from human postmortem brain tissue. Curr Drug Targets. 2013;14:1225–36.PubMedPubMedCentralCrossRefGoogle Scholar
  148. Rajkowska G, Miguel-Hidalgo JJ, Wei J, Dilley G, Pittman SD, Meltzer HY, Overholser JC, Roth BL, Stockmeier CA. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry. 1999;45:1085–98.PubMedCrossRefGoogle Scholar
  149. Reiff M, Schwartz S, Northridge M. Relationship of depressive symptoms to hypertension in a household survey in Harlem. Psychosom Med. 2001;63:711–21.PubMedCrossRefGoogle Scholar
  150. Rial D, Lemos C, Pinheiro H, Duarte JM, Goncalves FQ, Real JI, Prediger RD, Goncalves N, Gomes CA, Canas PM, Agostinho P, Cunha RA. Depression as a Glial-based synaptic dysfunction. Front Cell Neurosci. 2015;9:521.PubMedGoogle Scholar
  151. Ristevska-Dimitrovska G, Shishkov R, Gerazova VP, Vujovik V, Stefanovski B, Novotni A, Marinov P, Filov I. Different serum BDNF levels in depression: results from BDNF studies in FYR Macedonia and Bulgaria. Psychiatr Danub. 2013;25:123–7.PubMedGoogle Scholar
  152. Rocc P, De Leo C, Eva C, Marchiaro L, Milani AM, Musso R, Ravizza L, Zanalda E, Bogetto F. Decrease of the D4 dopamine receptor messenger RNA expression in lymphocytes from patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26:1155–60.PubMedPubMedCentralCrossRefGoogle Scholar
  153. Roy A, Dejong J, Ferraro T. CSF GABA in depressed patients and normal controls. Psychol Med. 1991;21:613–8.PubMedPubMedCentralCrossRefGoogle Scholar
  154. Ruhe HG, Booij J, Veltman DJ, Michel MC, Schene AH. Successful pharmacologic treatment of major depressive disorder attenuates amygdala activation to negative facial expressions: a functional magnetic resonance imaging study. J Clin Psychiatry. 2012;73:451–9.PubMedCrossRefGoogle Scholar
  155. Sanacora G, Mason GF, Rothman DL, Behar KL, Hyder F, Petroff OA, Berman RM, Charney DS, Krystal JH. Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy. Arch Gen Psychiatry. 1999;56:1043–7.PubMedCrossRefGoogle Scholar
  156. Schilling C, Gilles M, Blum WF, Daseking E, Colla M, Weber-Hamann B, Lederbogen F, Krumm B, Heuser I, Wudy SA, Kopf D, Deuschle M. Leptin plasma concentrations increase during antidepressant treatment with amitriptyline and mirtazapine, but not paroxetine and venlafaxine: leptin resistance mediated by antihistaminergic activity? J Clin Psychopharmacol. 2013;33:99–103.PubMedCrossRefGoogle Scholar
  157. Schmidt HD, Shelton RC, Duman RS. Functional biomarkers of depression: diagnosis, treatment, and pathophysiology. Neuropsychopharmacology. 2011;36:2375–94.PubMedPubMedCentralCrossRefGoogle Scholar
  158. Serra-Millas M, Lopez-Vilchez I, Navarro V, Galan AM, Escolar G, Penades R, Catalan R, Fananas L, Arias B, Gasto C. Changes in plasma and platelet BDNF levels induced by S-citalopram in major depression. Psychopharmacology. 2011;216:1–8.PubMedCrossRefGoogle Scholar
  159. Shah PJ, Glabus MF, Goodwin GM, Ebmeier KP. Chronic, treatment-resistant depression and right fronto-striatal atrophy. Br J Psychiatry. 2002;180:434–40.PubMedCrossRefGoogle Scholar
  160. Shapero BG, Black SK, Liu RT, Klugman J, Bender RE, Abramson LY, Alloy LB. Stressful life events and depression symptoms: the effect of childhood emotional abuse on stress reactivity. J Clin Psychol. 2014;70:209–23.PubMedCrossRefGoogle Scholar
  161. Shelton RC, Sanders-Bush E, Manier DH, Lewis DA. Elevated 5-HT 2A receptors in postmortem prefrontal cortex in major depression is associated with reduced activity of protein kinase A. Neuroscience. 2009;158:1406–15.PubMedCrossRefGoogle Scholar
  162. Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C, Nakazato M, Watanabe H, Shinoda N, Okada S, Iyo M. Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry. 2003;54:70–5.PubMedCrossRefGoogle Scholar
  163. Si X, Miguel-Hidalgo JJ, O’Dwyer G, Stockmeier CA, Rajkowska G. Age-dependent reductions in the level of glial fibrillary acidic protein in the prefrontal cortex in major depression. Neuropsychopharmacology. 2004;29:2088–96.PubMedPubMedCentralCrossRefGoogle Scholar
  164. 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;44:894–902.PubMedPubMedCentralCrossRefGoogle Scholar
  165. Thompson M, Weickert CS, Wyatt E, Webster MJ. Decreased glutamic acid decarboxylase(67) mRNA expression in multiple brain areas of patients with schizophrenia and mood disorders. J Psychiatr Res. 2009;43:970–7.PubMedCrossRefGoogle Scholar
  166. Tschudin S, Bertea PC, Zemp E. Prevalence and predictors of premenstrual syndrome and premenstrual dysphoric disorder in a population-based sample. Arch Womens Ment Health. 2010;13:485–94.PubMedCrossRefGoogle Scholar
  167. Tuncel OK, Akbas S, Bilgici B. Increased ghrelin levels and unchanged adipocytokine levels in major depressive disorder. J Child Adolesc Psychopharmacol. 2016;26:733–9.PubMedCrossRefGoogle Scholar
  168. Uher R, Perlis RH, Henigsberg N, Zobel A, Rietschel M, Mors O, Hauser J, Dernovsek MZ, Souery D, Bajs M, Maier W, Aitchison KJ, Farmer A, McGuffin P. Depression symptom dimensions as predictors of antidepressant treatment outcome: replicable evidence for interest-activity symptoms. Psychol Med. 2012;42:967–80.PubMedPubMedCentralCrossRefGoogle Scholar
  169. Uher R, Payne JL, Pavlova B, Perlis RH. Major depressive disorder in DSM-5: implications for clinical practice and research of changes from DSM-IV. Depress Anxiety. 2014;31:459–71.PubMedPubMedCentralCrossRefGoogle Scholar
  170. Valdizan EM, Diez-Alarcia R, Gonzalez-Maeso J, Pilar-Cuellar F, Garcia-Sevilla JA, Meana JJ, Pazos A. Alpha(2)-adrenoceptor functionality in postmortem frontal cortex of depressed suicide victims. Biol Psychiatry. 2010;68:869–72.PubMedPubMedCentralCrossRefGoogle Scholar
  171. Van Den Eede F, Van den Bossche B, Hulstijn W, Sabbe BG, Cosyns P, Claes SJ. Combined dexamethasone/CRF test in remitted outpatients with recurrent major depressive disorder. J Affect Disord. 2006;93:259–63.CrossRefGoogle Scholar
  172. van der Werf-Eldering MJ, Burger H, Holthausen EA, Aleman A, Nolen WA. Cognitive functioning in patients with bipolar disorder: association with depressive symptoms and alcohol use. PLoS One. 2010;5Google Scholar
  173. van Londen L, Goekoop JG, van Kempen GM, Frankhuijzen-Sierevogel AC, Wiegant VM, van der Velde EA, De Wied D. Plasma levels of arginine vasopressin elevated in patients with major depression. Neuropsychopharmacology. 1997;17:284–92.PubMedCrossRefGoogle Scholar
  174. Varghese FP, Brown ES. The hypothalamic-pituitary-adrenal axis in major depressive disorder: a brief primer for primary care physicians. Prim Care Companion J Clin Psychiatry. 2001;3:151–5.PubMedPubMedCentralCrossRefGoogle Scholar
  175. von Gunten A, Fox NC, Cipolotti L, Ron MA. A volumetric study of hippocampus and amygdala in depressed patients with subjective memory problems. J Neuropsychiatry Clin Neurosci. 2000;12:493–8.CrossRefGoogle Scholar
  176. Vreeburg SA, Hoogendijk WJ, van Pelt J, Derijk RH, Verhagen JC, van Dyck R, Smit JH, Zitman FG, Penninx BW. Major depressive disorder and hypothalamic-pituitary-adrenal axis activity: results from a large cohort study. Arch Gen Psychiatry. 2009;66:617–26.PubMedCrossRefGoogle Scholar
  177. Warner-Schmidt JL, Duman RS. VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants. Proc Natl Acad Sci U S A. 2007;104:4647–52.PubMedPubMedCentralCrossRefGoogle Scholar
  178. Watson S, Gallagher P, Del-Estal D, Hearn A, Ferrier IN, Young AH. Hypothalamic-pituitary-adrenal axis function in patients with chronic depression. Psychol Med. 2002;32:1021–8.PubMedCrossRefGoogle Scholar
  179. Weissman MM, Bland RC, Canino GJ, Faravelli C, Greenwald S, Hwu HG, Joyce PR, Karam EG, Lee CK, Lellouch J, Lepine JP, Newman SC, Rubio-Stipec M, Wells JE, Wickramaratne PJ, Wittchen H, Yeh EK. Cross-national epidemiology of major depression and bipolar disorder. JAMA. 1996;276:293–9.PubMedCrossRefGoogle Scholar
  180. Wetzel RD, Margulies T, Davis R, Karam E. Hopelessness, depression, and suicide intent. J Clin Psychiatry. 1980;41:159–60.PubMedGoogle Scholar
  181. Wu Z, Chen J, Yuan C, Hong W, Peng D, Zhang C, Cao L, Fang Y. Difference in remission in a Chinese population with anxious versus nonanxious treatment-resistant depression: a report of OPERATION study. J Affect Disord. 2013;150:834–9.PubMedCrossRefGoogle Scholar
  182. Wysokinski A. Serum levels of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in depressed patients with schizophrenia. Nord J Psychiatry. 2016;70:267–71.PubMedCrossRefGoogle Scholar
  183. Xiang L, Szebeni K, Szebeni A, Klimek V, Stockmeier CA, Karolewicz B, Kalbfleisch J, Ordway GA.  Dopamine receptor gene expression in human amygdaloid nuclei: elevated D4 receptor mRNA in major depression. Brain Res. 2008;1207:214–24.PubMedPubMedCentralCrossRefGoogle Scholar
  184. Yoshimura R, Mitoma M, Sugita A, Hori H, Okamoto T, Umene W, Ueda N, Nakamura J. Effects of paroxetine or milnacipran on serum brain-derived neurotrophic factor in depressed patients. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:1034–7.PubMedCrossRefGoogle Scholar
  185. Zhao G, Ford ES, Li C, Tsai J, Dhingra S, Balluz LS. Waist circumference, abdominal obesity, and depression among overweight and obese U.S. adults: National Health and Nutrition Examination Survey 2005-2006. BMC Psychiatry. 2011;11:130.PubMedPubMedCentralCrossRefGoogle Scholar
  186. Zisook S, Kendler KS. Is bereavement-related depression different than non-bereavement-related depression? Psychol Med. 2007;37:779–94.PubMedCrossRefGoogle Scholar
  187. Zisook S, Shear K, Kendler KS. Validity of the bereavement exclusion criterion for the diagnosis of major depressive episode. World Psychiatry. 2007;6:102–7.PubMedPubMedCentralGoogle Scholar
  188. Zisook S, Corruble E, Duan N, Iglewicz A, Karam EG, Lanouette N, Lebowitz B, Pies R, Reynolds C, Seay K, Katherine Shear M, Simon N, Young IT. The bereavement exclusion and DSM-5. Depress Anxiety. 2012;29:425–43.PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of Neurosciences, Faculty of MedicineUniversité de MontréalMontrealCanada

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