Depressive Disorders: Prevalence, Costs, and Theories

  • Clara Grosso
  • Patrícia Valentão
  • Paula B. AndradeEmail author


The estimated global cost of mental health conditions, including depressive disorders, was US$2.5 trillion in 2010. According to the World Health Organization (WHO), more than 350 million people of all ages suffer from depression, 10–40 % of them not improving their condition with the current drug therapies, thus contributing to the increased burden of mental disorders. Indeed, prognostics are not encouraging since it is predicted that unipolar depressive disorders will be the first cause of disability-adjusted life years (DALYs) by the year 2030. For these reasons, it is urgent to find new antidepressant drugs that act on other targets rather than the conventional one (monoamine transmission). Having this in mind, this chapter provides a critical review of the theories available to explain the pathogenesis of depressive disorders, namely, those focusing on disturbances of monoamine, glutamate and GABA transmission, changes in the hypothalamic-pituitary-adrenal (HPA) axis, neuroinflammation, neurogenesis and neurotrophic factors, glial pathology, epigenetic mechanisms, and disturbance of the circadian rhythm.


Neurotransmitters Neuroinflammation Hypothalamic-pituitary-adrenal axis Neuroplasticity Epigenetics Glial cells Circadian rhythm 



This work was financed through project UID/QUI/50006/2013, receiving financial support from FCT/MEC through national funds, and co-financed by FEDER, under the Partnership Agreement PT2020. To all financing sources the authors are greatly indebted. Clara Grosso thanks FCT for the FCT Investigator (IF/01332/2014).


  1. Ağargün MY, Cilli AS, Kara H, Tarhan N, Kincir F, Oz H. Repetitive and frightening dreams and suicidal behavior in patients with major depression. Compr Psychiatry. 1998;39(4):198–202.PubMedCrossRefGoogle Scholar
  2. Akhondzadeh S, Jafari S, Raisi F, Nasehi AA, Ghoreishi A, Salehi B, Mohebbi-Rasa S, Raznahan M, Kamalipour A. Clinical trial of adjunctive celecoxib treatment in patients with major depression: a double blind and placebo controlled trial. Depress Anxiety. 2009;26(7):607–11.PubMedCrossRefGoogle Scholar
  3. Al-Harbi KS. Treatment-resistant depression: therapeutic trends, challenges, and future directions. Patient Prefer Adherence. 2012;6:369–88.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Altman J. Autoradiographic and histological studies of postnatal neurogenesis. III. Dating the time of production and onset of differentiation of cerebellar microneurons in rats. J Comp Neurol. 1969;136(3):269–93.PubMedCrossRefGoogle Scholar
  5. Altman J, Das GD. Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol. 1965;124(3):319–35.PubMedCrossRefGoogle Scholar
  6. Altman J, Das GD. Autoradiographic and histological studies of postnatal neurogenesis. I. A longitudinal investigation of the kinetics, migration and transformation of cells incorporating tritiated thymidine in neonate rats, with special reference to postnatal neurogenesis in some brain regions. J Comp Neurol. 1966;126(3):337–89.PubMedCrossRefGoogle Scholar
  7. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, fifth edition (DSM-5). Washington, DC: American Psychiatric Association; 2013.Google Scholar
  8. Anacker C, Zunszain PA, Carvalho LA, Pariante CM. The glucocorticoid receptor: pivot of depression and of antidepressant treatment? Psychoneuroendocrinology. 2011;36(3):415–25.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Aston C, Jiang L, Sokolov BP. Microarray analysis of postmortem temporal cortex from patients with schizophrenia. J Neurosci Res. 2004;77(6):858–66.PubMedCrossRefGoogle Scholar
  10. Ataka T, Gu JG. Relationship between tonic inhibitory currents and phasic inhibitory activity in the spinal cord lamina II region of adult mice. Mol Pain. 2006;2:36.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Auer DP, Putz B, Kraft E, Lipinski B, Schill J, Holsboer F. Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry. 2000;47(4):305–13.PubMedCrossRefGoogle Scholar
  12. Bachis A, Mallei A, Cruz MI, Wellstein A, Mocchetti I. Chronic antidepressant treatments increase basic fibroblast growth factor and fibroblast growth factor-binding protein in neurons. Neuropharmacology. 2008;55(7):1114–20.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Baldessarini RJ. Biogenic amines and behavior. Annu Rev Med. 1972;23(5):343–54.PubMedCrossRefGoogle Scholar
  14. Barden N. Implication of the hypothalamic–pituitary–adrenal axis in the physiopathology of depression. J Psychiatry Neurosci. 2004;29(3):185–93.PubMedPubMedCentralGoogle Scholar
  15. Baudry A, Mouillet-Richard S, Schneider B, Launay JM, Kellermann O. MiR-16 targets the serotonin transporter: a new facet for adaptive responses to antidepressants. Science. 2010;329(5998):1537–41.PubMedCrossRefGoogle Scholar
  16. Beasley CL, Honer WG, Bergmann K, Falkai P, Lütjohann D, Bayer TA. Reductions in cholesterol and synaptic markers in association cortex in mood disorders. Bipolar Disord. 2005;7(5):449–55.PubMedCrossRefGoogle Scholar
  17. Beaurepaire R. Questions raised by the cytokine hypothesis of depression. Brain Behav Immun. 2002;16:610–7.PubMedCrossRefGoogle Scholar
  18. Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47(4):351–4.PubMedCrossRefGoogle Scholar
  19. 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(6):634–46.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Berton O, McClung CA, Dileone RJ, Krishnan V, Renthal W, Russo SJ, Graham D, Tsankova NM, Bolanos CA, Rios M, Monteggia LM, Self DW, Nestler EJ. Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science. 2006;311(5762):864–8.PubMedCrossRefGoogle Scholar
  21. Bloom DE, Cafiero ET, Jané-Llopis E, Abrahams-Gessel S, Bloom LR, Fathima S, Feigl AB, Gaziano T, Mowafi M, Pandya A, Prettner K, Rosenberg L, Seligman B, Stein AZ, Weinstein C. The global economic burden of noncommunicable diseases. Geneva: World Economic Forum; 2011.Google Scholar
  22. Bouwer C, Claassen J, Dinan TG, Nemeroff CB. Prednisone augmentation in treatment-resistant depression with fatigue and hypocortisolaemia: a case series. Depress Anxiety. 2000;12(1):44–50.PubMedCrossRefGoogle Scholar
  23. Bowley MP, Drevets WC, Ongür D, Price JL. Low glial numbers in the amygdala in major depressive disorder. Biol Psychiatry. 2002;52(5):404–12.PubMedCrossRefGoogle Scholar
  24. 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.PubMedCrossRefGoogle Scholar
  25. Brezun JM, Daszuta A. Depletion in serotonin decreases neurogenesis in the dentate gyrus and the subventricular zone of adult rats. Neuroscience. 1999;89(4):999–1002.PubMedCrossRefGoogle Scholar
  26. Büttner N, Johnsen SA, Kügler S, Vogel T. Af9/Mllt3 interferes with Tbr1 expression through epigenetic modification of histone H3K79 during development of the cerebral cortex. Proc Natl Acad Sci U S A. 2010;107(15):7042–7.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Calabrese F, Guidotti G, Racagni G, Riva MA. Reduced neuroplasticity in aged rats: a role for the neurotrophin brain-derived neurotrophic factor. Neurobiol Aging. 2013;34(12):2768–76.PubMedCrossRefGoogle Scholar
  28. Calabrese F, Rossetti AC, Racagni G, Gass P, Riva MA, Molteni R. Brain-derived neurotrophic factor: a bridge between inflammation and neuroplasticity. Front Cell Neurosci. 2014;8:430.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Cardinali DP, Srinivasan V, Brzezinski A, Brown GM. Melatonin and its analogs in insomnia and depression. J Pineal Res. 2012;52(4):365–75.PubMedCrossRefGoogle Scholar
  30. Carlsson A, Lindqvist M, Magnusson T, Waldeck B. On the presence of 3-hydroxytyramine in brain. Science. 1958;127(3296):471.PubMedCrossRefGoogle Scholar
  31. Carroll BJ, Martin FIR, Davies B. Resistance to suppression by dexamethasone of plasma 11-O.H.C.S. levels in severe depressive illness. Br Med J. 1968;3:285.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Carroll BJ, Feinberg M, Greden JF, Tarika J, Albala AA, Haskett RF, James NM, Kronfol Z, Lohr N, Steiner M, de Vigne JP, Young E. A specific laboratory test for the diagnosis of melancholia. Standardization, validation, and clinical utility. Arch Gen Psychiatry. 1981;38(1):15–22.PubMedCrossRefGoogle Scholar
  33. Chan JP, Unger TJ, Byrnes J, Rios M. Examination of behavioral deficits triggered by targeting BDNF in fetal or postnatal brains of mice. Neuroscience. 2006;142:49–58.PubMedCrossRefGoogle Scholar
  34. Chana G, Landau S, Beasley C, Everall IP, Cotter D. Two-dimensional assessment of cytoarchitecture in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia: evidence for decreased neuronal somal size and increased neuronal density. Biol Psychiatry. 2003;53(12):1086–98.PubMedCrossRefGoogle Scholar
  35. Chessin M, Dubnick B, Kramer ER, Scott CC. Modifications of pharmacology of reserpine and serotonin by iproniazid. J Pharmacol Exp Ther. 1957;119(4):453–60.PubMedGoogle Scholar
  36. Choudary PV, Molnar M, Evans SJ, Tomita H, Li JZ, Vawter MP, Myers RM, Bunney Jr WE, Akil H, Watson SJ, Jones EG. Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression. Proc Natl Acad Sci U S A. 2005;102(43):15653–8.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Chourbaji S, Hellweg R, Brandis D, Zörner B, Zacher C, Lang UE, Henn FA, Hörtnagl H, Gass P. Mice with reduced brain-derived neurotrophic factor expression show decreased choline acetyltransferase activity, but regular brain monoamine levels and unaltered emotional behavior. Mol Brain Res. 2004;121(1-2):28–36.PubMedCrossRefGoogle Scholar
  38. Cinini SM, Barnabe GF, Galvão-Coelho N, de Medeiros MA, Perez-Mendes P, Sousa MB, Covolan L, Mello LE. Social isolation disrupts hippocampal neurogenesis in young non-human primates. Front Neurosci. 2014;8:45.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Coppen A. The biochemistry of affective disorders. Br J Psychiatry. 1967;113(504):1237–64.PubMedCrossRefGoogle Scholar
  40. 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(6):545–53.PubMedCrossRefGoogle Scholar
  41. 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(4):386–94.PubMedCrossRefGoogle Scholar
  42. Cotter D, Hudson L, Landau S. Evidence for orbitofrontal pathology in bipolar disorder and major depression, but not in schizophrenia. Bipolar Disord. 2005;7(4):358–69.PubMedCrossRefGoogle Scholar
  43. Covington HE, Maze I, LaPlant QC, Vialou VF, Ohnishi YN, Berton O, Fass DM, Renthal W, Rush AJ, Wu EY, Ghose S, Krishnan V, Russo SJ, Tamminga C, Haggarty SJ, Nestler EJ. Antidepressant actions of histone deacetylase inhibitors. J Neurosci. 2009;29(37):11451–60.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Craddock N, Jones L, Jones IR, Kirov G, Green EK, Grozeva D, Moskvina V, Nikolov I, Hamshere ML, Vukcevic D, Caesar S, Gordon-Smith K, Fraser C, Russell E, Norton N, Breen G, St Clair D, Collier DA, Young AH, Ferrier IN, Farmer A, McGuffin P, Holmans PA, Wellcome Trust Case Control Consortium (WTCCC), Donnelly P, Owen MJ, O'Donovan MC. Strong genetic evidence for a selective influence of GABA(A) receptors on a component of the bipolar disorder phenotype. Mol Psychiatry. 2010;15(2):146–53.PubMedPubMedCentralCrossRefGoogle Scholar
  45. Czéh B, Welt T, Fischer AK, Erhardt A, Schmitt W, Müller MB, Toschi N, Fuchs E, Keck ME. Chronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation: effects on stress hormone levels and adult hippocampal neurogenesis. Biol Psychiatry. 2002;52(11):1057–65.PubMedCrossRefGoogle Scholar
  46. Danilenko KV, Ivanova IA. Dawn simulation vs. bright light in seasonal affective disorder: Treatment effects and subjective preference. J Affect Disord. 2015;180:87–9.PubMedCrossRefGoogle Scholar
  47. Davis S, Thomas A, Perry R, Oakley A, Kalaria RN, O’Brien JT. Glial fibrillary acidic protein in late life major depressive disorder: an immunocytochemical study. J Neurol Neurosurg Psychiatry. 2002;73(5):556–60.PubMedPubMedCentralCrossRefGoogle Scholar
  48. de Bellis MD, Gold PW, Geracioti Jr TD, Listwak SJ, Kling MA. Association of fluoxetine treatment with reductions in CSF concentrations of corticotropin-releasing hormone and arginine vasopressin in patients with major depression. Am J Psychiatry. 1993;150(4):656–7.PubMedCrossRefGoogle Scholar
  49. de Bodinat C, Guardiola-Lemaitre B, Mocaër E, Renard P, Muñoz C, Millan MJ. Agomelatine, the first melatonergic antidepressant: discovery, characterization and development. Nat Rev Drug Discov. 2010;9(8):628–42.PubMedGoogle Scholar
  50. Dias BG, Banerjee SB, Duman RS, Vaidya VA. Differential regulation of brain derived neurotrophic factor transcripts by antidepressant treatments in the adult rat brain. Neuropharmacology. 2003;45:553–63.PubMedCrossRefGoogle Scholar
  51. Dias BG, Maddox SA, Klengel T, Ressler KJ. Epigenetic mechanisms underlying learning and the inheritance of learned behaviors. Trends Neurosci. 2015;38(2):96–107.Google Scholar
  52. Drew MR, Hen R. Adult hippocampal neurogenesis as target for the treatment of depression. CNS Neurol Disord Drug Targets. 2007;6(3):205–18.PubMedCrossRefGoogle Scholar
  53. Eisch AJ, Bolaños CA, de Wit J, Simonak RD, Pudiak CM, Barrot M, Verhaagen J, Nestler EJ. Brain-derived neurotrophic factor in the ventral midbrain-nucleus accumbens pathway: a role in depression. Biol Psychiatry. 2003;54(10):994–1005.PubMedCrossRefGoogle Scholar
  54. Elliott E, Ezra-Nevo G, Regev L, Neufeld-Cohen A, Chen A. Resilience to social stress coincides with functional DNA methylation of the Crf gene in adult mice. Nat Neurosci. 2010;13(11):1351–3.PubMedCrossRefGoogle Scholar
  55. Emrich HM, Zerssen DV, Kissling W, Möller H-J, Windorfer A. Effect of sodium valproate on mania: the GABA-hypothesis of affective disorders. Arch Psychiatry Neurol Sci. 1980;229(1):1–16.Google Scholar
  56. Eriksson PS, Perfilieva E, Björk-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH. Neurogenesis in the adult human hippocampus. Nat Med. 1998;4(11):1313–7.PubMedCrossRefGoogle Scholar
  57. Ernst C, Nagy C, Kim S, Yang JP, Deng X, Hellstrom IC, Choi KH, Gershenfeld H, Meaney MJ, Turecki G. Dysfunction of astrocyte connexins 30 and 43 in dorsal lateral prefrontal cortex of suicide completers. Biol Psychiatry. 2011;70(4):312–9.PubMedCrossRefGoogle Scholar
  58. Gallagher PJ, Castro V, Fava M, Weilburg JB, Murphy SN, Gainer VS, Churchill SE, Kohane IS, Iosifescu DV, Smoller JW, Perlis RH. Antidepressant response in patients with major depression exposed to NSAIDs: a pharmacovigilance study. Am J Psychiatry. 2012;169(10):1065–72.PubMedPubMedCentralCrossRefGoogle Scholar
  59. Gao J, Wang WY, Mao YW, Gräff J, Guan JS, Pan L, Mak G, Kim D, Su SC, Tsai LH. A novel pathway regulates memory and plasticity via SIRT1 and miR-134. Nature. 2010;466(7310):1105–9.PubMedPubMedCentralCrossRefGoogle Scholar
  60. Gerner RH, Hare TA. CSF GABA in normal subjects and patients with depression, schizophrenia, mania, and anorexia nervosa. Am J Psychiatry. 1981;138(8):1098–101.PubMedCrossRefGoogle Scholar
  61. Gillin JC, Duncan W, Pettigrew KD, Frankel BL, Snyder F. Successful separation of depressed, normal and insomniac subjects by EEG sleep data. Arch Gen Psychiatry. 1979;36(1):85–90.PubMedCrossRefGoogle Scholar
  62. Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386(9995):743–800.PubMedCentralCrossRefGoogle Scholar
  63. Goel N, Innala L, Viau V. Sex differences in serotonin (5-HT) 1A receptor regulation of HPA axis and dorsal raphe responses to acute restraint. Psychoneuroendocrinology. 2014;40:232–41.PubMedCrossRefGoogle Scholar
  64. Gould E, Woolley CS, McEwen BS. Adrenal steroids regulate postnatal development of the rat dentate gyrus: I. Effects of glucocorticoids on cell death. J Comp Neurol. 1991;313(3):479–85.PubMedCrossRefGoogle Scholar
  65. Gould E, Cameron HA, Daniels DC, Woolley CS, McEwen BS. Adrenal hormones suppress cell division in the adult rat dentate gyrus. J Neurosci. 1992;12(9):3642–50.PubMedGoogle Scholar
  66. Govindarajan A, Rao BS, Nair D, Trinh M, Mawjee N, Tonegawa S, Chattarji S. Transgenic brain-derived neurotrophic factor expression causes both anxiogenic and antidepressant effects. Proc Natl Acad Sci U S A. 2006;103(35):13208–13.PubMedPubMedCentralCrossRefGoogle Scholar
  67. Greenberg PE, Fournier A-A, Sisitsky T, Pike CT, Kessler RC. The economic burden of adults with major depressive disorder in the United States (2005 and 2010). J Clin Psychiatry. 2015;76(2):155–62.PubMedCrossRefGoogle Scholar
  68. Groves JO. Is it time to reassess the BDNF hypothesis of depression? Mol Psychiatry. 2007;12:1079–88.PubMedCrossRefGoogle Scholar
  69. Grunbaum-Novak N, Taler M, Gil-Ad I, Weizman A, Cohen H, Weizman R. Relationship between antidepressants and IGF-1 system in the brain: possible role in cognition. Eur Neuropsychopharmacol. 2008;18(6):431–8.PubMedCrossRefGoogle Scholar
  70. Gu B, Lee MG. Histone H3 lysine 4 methyltransferases and demethylases in self-renewal and differentiation of stem cells. Cell Biosci. 2013;3(1):39.PubMedPubMedCentralCrossRefGoogle Scholar
  71. Guan Z, Fang J. Peripheral immune activation by lipopolysaccharide decreases neurotrophins in the cortex and hippocampus in rats. Brain Behav Immun. 2006;20(1):64–71.PubMedCrossRefGoogle Scholar
  72. Gwinn RP, Kondratyev A, Gale K. Time-dependent increase in basic fibroblast growth factor protein in limbic regions following electroshock seizures. Neuroscience. 2002;114(2):403–9.PubMedCrossRefGoogle Scholar
  73. Hamidi M, Drevets WC, Price JL. Glial reduction in amygdala in major depressive disorder is due to oligodendrocytes. Biol Psychiatry. 2004;55(6):563–9.PubMedCrossRefGoogle Scholar
  74. Hashimoto K, Sawa A, Iyo M. Increased levels of glutamate in brains from patients with mood disorders. Biol Psychiatry. 2007;62(11):1310–6.PubMedCrossRefGoogle Scholar
  75. Hedrich CM, Tsokos GC. Epigenetic mechanisms in systemic lupus erythematosus and other autoimmune diseases. Trends Mol Med. 2011;17(12):714–24.PubMedPubMedCentralCrossRefGoogle Scholar
  76. Hensch TK. Critical period plasticity in local cortical circuits. Nat Rev Neurosci. 2005;6:877–88.PubMedCrossRefGoogle Scholar
  77. Holsboer F, von Bardeleben U, Wiedemann K, Müller OA, Stalla GK. Serial assessment of corticotropin-releasing hormone response after dexamethasone in depression. Implications for pathophysiology of DST nonsuppression. Biol Psychiatry. 1987;22:228–34.PubMedCrossRefGoogle Scholar
  78. Honer WG, Falkai P, Chen C, Arango V, Mann JJ, Dwork AJ. Synaptic and plasticity-associated proteins in anterior frontal cortex in severe mental illness. Neuroscience. 1999;91(4):1247–55.PubMedCrossRefGoogle Scholar
  79. Hu TW. Perspectives: an international review of the national cost estimates of mental illness, 1990–2003. J Ment Health Policy Econ. 2006;9(1):3–13.PubMedGoogle Scholar
  80. Hu TW, He Y, Zhang M, Chen N. Economic costs of depression in China. Soc Psychiatry Psychiatr Epidemiol. 2007;42(2):110–6.PubMedCrossRefGoogle Scholar
  81. Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677–736.PubMedPubMedCentralCrossRefGoogle Scholar
  82. Huang S, Litt M, Felsenfeld G. Methylation of histone H4 by arginine methyltransferase PRMT1 is essential in vivo for many subsequent histone modifications. Genes Dev. 2005;19(16):1885–93.PubMedPubMedCentralCrossRefGoogle Scholar
  83. Hudson JI, Lipinski JF, Frankenburg FR, Grochocinski VJ, Kupfer DJ. Electroencephalographic sleep in mania. Arch Gen Psychiatry. 1988;45(3):267–73.PubMedCrossRefGoogle Scholar
  84. Hudson JI, Lipinski JF, Keck Jr PE, Aizley HG, Lukas SE, Rothschild AJ, Waternaux CM, Kupfer DJ. Polysomnographic characteristics of young manic patients. Comparison with unipolar depressed patients and normal control subjects. Arch Gen Psychiatry. 1992;49(5):378–83.PubMedCrossRefGoogle Scholar
  85. Hunter RG. Epigenetic effects of stress and corticosteroids in the brain. Front Cell Neurosci. 2012;6:article 18.Google Scholar
  86. Hurley LL, Tizabi Y. Neuroinflammation, neurodegeneration, and depression. Neurotox Res. 2013;23:131–44.PubMedPubMedCentralCrossRefGoogle Scholar
  87. Hyland NP, Cryan JF. A gut feeling about GABA: focus on GABA(B) receptors. Front Pharmacol. 2010;1:124.PubMedPubMedCentralCrossRefGoogle Scholar
  88. Iyengar RL, Gandhi S, Aneja A, Thorpe K, Razzouk L, Greenberg J, Mosovich S, Farkouh ME. NSAIDs are associated with lower depression scores in patients with osteoarthritis. Am J Med. 2013;126(11):1017.e11–18.CrossRefGoogle Scholar
  89. Jacobs BL, van Praag H, Gage FH. Adult brain neurogenesis and psychiatry: a novel theory of depression. Mol Psychiatry. 2000;5:262–9.PubMedCrossRefGoogle Scholar
  90. Jernajczyk W. Latency of eye movement and other REM sleep parameters in bipolar depression. Biol Psychiatry. 1986;21(5-6):465–72.PubMedCrossRefGoogle Scholar
  91. Juruena MF, Cleare AJ, Bauer ME, Pariente CM. Molecular mechanisms of glucocorticoid receptor sensitivity and relevance to affective disorders. Acta Neuropsychiatr. 2003;15:354–67.PubMedCrossRefGoogle Scholar
  92. Juruena MF, Cleare AJ, Pariante CM. The hypothalamic pituitary adrenal axis, glucocorticoid receptor function and relevance to depression. Rev Bras Psiquiatr. 2004;26(3):189–201.PubMedCrossRefGoogle Scholar
  93. Kaplan MS, Hinds JW. Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. Science. 1977;197(4308):1092–4.PubMedCrossRefGoogle Scholar
  94. Kee N, Teixeira CM, Wang AH, Frankland PW. Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus. Nat Neurosci. 2007;10(3):355–62.PubMedCrossRefGoogle Scholar
  95. Klempan TA, Sequeira A, Canetti L, Lalovic A, Ernst C, Ffrench-Mullen J, Turecki G. Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depression. Mol Psychiatry. 2009;14(2):175–89.PubMedCrossRefGoogle Scholar
  96. Kondratova AA, Kondratov RV. The circadian clock and pathology of the ageing brain. Nat Rev Neurosci. 2012;13:325–35.PubMedPubMedCentralGoogle Scholar
  97. Krishnan KRR, Rayasam K, Reed DR, Smith M, Chappell P, Saunders WB, Ritchie JC, Carroll BJ, Nemeroff CB. The corticotropin releasing factor stimulation test in patients with major depression: Relationship to dexamethasone suppression test results. Depression. 1993;1(3):133–6.CrossRefGoogle Scholar
  98. Lapchak PA, Araujo DM, Beck KD, Finch CE, Johnson SA, Hefti F. BDNF and trkB mRNA expression in the hippocampal formation of aging rats. Neurobiol Aging. 1993;14(2):121–6.PubMedCrossRefGoogle Scholar
  99. Lapin IP, Oxenkrug GF. Intensification of the central serotoninergic processes as a possible determinant of the thymoleptic effect. Lancet. 1969;1(7586):132–6.PubMedCrossRefGoogle Scholar
  100. Lauer CJ, Wiegand M, Krieg JC. All-night electroencephalographic sleep and cranial computed tomography in depression. A study of unipolar and bipolar patients. Eur Arch Psychiatry Clin Neurosci. 1992;242(2-3):59–68.PubMedCrossRefGoogle Scholar
  101. Lavergne F, Jay TM. A new strategy for antidepressant prescription. Front Neurosci. 2010;4:192.PubMedPubMedCentralCrossRefGoogle Scholar
  102. Levine J, Cholestoy A, Zimmerman J. Possible antidepressant effect of minocycline. Am J Psychiatry. 1996;153(4):582.PubMedGoogle Scholar
  103. Loomer HP, Saunders IC, Kline NS. A clinical and pharmacodynamics evaluation of iproniazid as a psychic energizer. Psychiatr Res Rep Am Psychiatr Assoc. 1958;8:129–41.Google Scholar
  104. López-Muñoz F, Alamo C. Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today. Curr Pharm Des. 2009;15(14):1563–86.PubMedCrossRefGoogle Scholar
  105. Lund C, Myer L, Stein DJ, Williams DR, Flisher AJ. Mental illness and lost income among adult South Africans. Soc Psychiatry Psychiatr Epidemiol. 2013;48(5):845–51.PubMedPubMedCentralCrossRefGoogle Scholar
  106. Luscher B, Shen Q, Sahir N. The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry. 2011;16(4):383–406.Google Scholar
  107. Machado, M., Lopera, M.M., Diaz-Rojas, J., Jaramillo, L.E., Einarson, T.R., The Universidad Nacional de Colombia Pharmacoeconomics Group. Pharmacoeconomics of antidepressants in moderate-to-severe depressive disorder in Colombia. Rev Panam Salud Publica. 2008;24(4):233–9.Google Scholar
  108. Maes M, Song C, Lin A, De Jongh R, Van Gastel A, Kenis G, Bosmans E, De Meester I, Benoy I, Neels H, Demedts P, Janca A, Scharpe S, Smith RS. The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a Th1-like response in stress induced anxiety. Cytokine. 1998a;10:313–8.PubMedCrossRefGoogle Scholar
  109. Maes M, Verkerk R, Vandoolaeghe E, Lin A, Scharpe S. Serum levels of excitatory amino acids, serine, glycine, histidine, threonine, taurine, alanine and arginine in treatment-resistant depression: modulation by treatment with antidepressants and prediction of clinical responsivity. Acta Psychiatr Scand. 1998b;97(4):302–8.PubMedCrossRefGoogle Scholar
  110. Maguire J. Stress-induced plasticity of GABAergic inhibition. Front Cell Neurosci. 2014;8:157.Google Scholar
  111. Malberg JE, Duman RS. Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology. 2003;28(9):1562–71.PubMedCrossRefGoogle Scholar
  112. Manicavasagar V. A review of depression diagnosis and management. Melbourne, VIC: The Australian Psychological Society; 2012.Google Scholar
  113. Mauri MC, Ferrara A, Boscati L, Bravin S, Zamberlan F, Alecci M, Invernizzi G. Plasma and platelet amino acid concentrations in patients affected by major depression and under fluvoxamine treatment. Neuropsychobiology. 1998;37(3):124–9.PubMedCrossRefGoogle Scholar
  114. McCarthy DJ, Alexander R, Smith MA, Pathak S, Kanes S, Lee CM, Sanacora G. Glutamate-based depression GBD. Med Hypotheses. 2012;78(5):675–81.PubMedCrossRefGoogle Scholar
  115. McLeod H, Rothberg A, Pels L, Eekhout S, Mubangizi DB, Fish T. The costing of the proposed chronic disease list benefits in South African medical schemes in 2001. Cape Town: Centre for Actuarial Research, University of Cape Town; 2002.Google Scholar
  116. McQuade R, Young AH. Future therapeutic targets in mood disorders: the glucocorticoid receptor. Br J Psychiatry. 2000;177:390–5.PubMedCrossRefGoogle Scholar
  117. McQueen GM, Ramakrishnan K, Croll SD, Siuciak JA, Yu G, Young LT, Fahnestock M. Performance of heterozygous brain-derived neurotrophic factor knockout mice on behavioral analogues of anxiety, nociception, and depression. Behav Neurosci. 2001;115:1145–53.CrossRefGoogle Scholar
  118. Mehl RC, O’Brien LM, Jones JH, Dreisbach JK, Mervis CB, Gozal D. Correlates of sleep and pediatric bipolar disorder. Sleep. 2006;29(2):193–7.PubMedGoogle Scholar
  119. Miguel-Hidalgo JJ, Baucom C, Dilley G, Overholser JC, Meltzer HY, Stockmeier CA, Rajkowska G. Glial fibrillary acidic protein immunoreactivity in the prefrontal cortex distinguishes younger from older adults in major depressive disorder. Biol Psychiatry. 2000;48(8):861–73.PubMedCrossRefGoogle Scholar
  120. 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(1-3):230–40.PubMedPubMedCentralCrossRefGoogle Scholar
  121. Miró X, Pérez-Torres S, Artigas F, Puigdomènech P, Palacios JM, Mengod G. Regulation of cAMP phosphodiesterase mRNAs expression in rat brain by acute and chronic fluoxetine treatment. An in situ hybridization study. Neuropharmacology. 2002;43:1148–57.PubMedCrossRefGoogle Scholar
  122. Møldrup C, Oestergaard S. Improving outcomes for patients with depression by enhancing antidepressant therapy with non-pharmacological interventions: a systematic review of reviews. Public Health. 2011;125:357–67.PubMedCrossRefGoogle Scholar
  123. Monteggia LM, Luikart B, Barrot M, Theobold D, Malkovska I, Nef S, Parada LF, Nestler EJ. Brain-derived neurotrophic factor conditional knockouts show gender differences in depression-related behaviors. Biol Psychiatry. 2007;61(2):187–97.PubMedCrossRefGoogle Scholar
  124. Mulinari S. Monoamine theories of depression: historical impact on biomedical research. J Hist Neurosci. 2012;21:366–92.PubMedCrossRefGoogle Scholar
  125. Murphy DL, Garrick NA, Tamarkin L, Taylor PL, Markey SP. Effects of antidepressants and other psychotropic drugs on melatonin release and pineal gland function. J Neural Transm Suppl. 1986;21:291–309.PubMedGoogle Scholar
  126. Nemeroff CB, Bissette G, Akil H, Fink M. Neuropeptide concentrations in the cerebrospinal fluid of depressed patients treated with electroconvulsive therapy: corticotrophin-releasing factor, beta-endorphin and somatostatin. Br J Psychiatry. 1991;158:59–63.PubMedCrossRefGoogle Scholar
  127. Nestler EJ, Peña CJ, Kundakovic M, Mitchell A, Akbarian S. Epigenetic basis of mental illness. Neuroscientist. 2015. doi: 10.1177/1073858415608147.PubMedGoogle Scholar
  128. Newport DJ, Heim C, Owens MJ, Ritchie JC, Ramsey CH, Bonsall R, Miller AH, Nemeroff CB. Cerebrospinal fluid corticotropin-releasing factor (CRF) and vasopressin concentrations predict pituitary response in the CRF stimulation test: a multiple regression analysis. Neuropsychopharmacology. 2003;28(3):569–76.PubMedCrossRefGoogle Scholar
  129. Nibuya M, Morinobu S, Duman RS. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci. 1995;15(11):7539–47.PubMedGoogle Scholar
  130. Niehrs C, Schäfer A. Active DNA demethylation by Gadd45 and DNA repair. Trends Cell Biol. 2012;22(4):220–7.PubMedCrossRefGoogle Scholar
  131. Nowak G, Trullas R, Layer RT, Skolnick P, Paul IA. Adaptive changes in the N-methyl-d-aspartate receptor complex after chronic treatment with imipramine and 1-aminocyclopropanecarboxylic acid. J Pharmacol Exp Ther. 1993;265(3):1380–6.PubMedGoogle Scholar
  132. Olesen J, Gustavsson A, Svensson M, Wittchen H-U, Jönsson B, on behalf of the CDBE2010 study group and the European Brain Council. The economic cost of brain disorders in Europe. Eur J Neurol. 2012;19:155–62.PubMedCrossRefGoogle Scholar
  133. Ongür D, Drevets WC, Price JL. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci U S A. 1998;95(22):13290–5.PubMedPubMedCentralCrossRefGoogle Scholar
  134. Ozbolt LB, Nemeroff CB. Chapter 2: HPA axis modulation in the treatment of mood disorders. In: Schoepf D, editor. Psychiatric disorders – new frontiers in affective disorders. Morn Hill: InTech; 2013.Google Scholar
  135. Pae CU, Marks DM, Han C, Patkar AA. Does minocycline have antidepressant effect? Biomed Pharmacother. 2008;62(5):308–11.PubMedCrossRefGoogle Scholar
  136. Papp M, Moryl E. Similar effects of chronic treatment with imipramine and the NMDA antagonists CGP 37849 and MK-801 in a chronic mild stress model of depression in rats. Eur J Pharmacol. 1993;3(3):348–9.Google Scholar
  137. Papp M, Moryl E. Antidepressant activity of non-competitive and competitive NMDA receptor antagonists in a chronic mild stress model of depression. Eur J Pharmacol. 1994;263(1-2):1–7.PubMedCrossRefGoogle Scholar
  138. Park H, Poo M-m. Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci. 2013;14:7–23.PubMedCrossRefGoogle Scholar
  139. Parker G, McCraw S, Hadzi-Pavlovic D, Fletcher K. Costs of the principal mood disorders: a study of comparative direct and indirect costs incurred by those with bipolar I, bipolar II and unipolar disorders. J Affect Disord. 2013;149(1-3):46–55.PubMedCrossRefGoogle Scholar
  140. Paul IA, Layer RT, Skolnick P, Nowak G. Adaptation of the N-methyl-d-aspartate receptor complex in rat front cortex following chronic treatment with electroconvulsive shock or imipramine. J Pharmacol Exp Ther. 1993;247(3):305–12.Google Scholar
  141. Paul IA, Nowak G, Layer RT, Popik P, Skolnick P. Adaptation of the N-methyl-d-aspartate receptor complex following chronic antidepressant treatments. J Pharmacol Exp Ther. 1994;269(1):95–102.PubMedGoogle Scholar
  142. Petrik D, Lagace D, Eisch AJ. The neurogenesis hypothesis of affective and anxiety disorders: are we mistaking the scaffolding for the building? Neuropharmacology. 2012;62(1):21–34.PubMedPubMedCentralCrossRefGoogle Scholar
  143. Petty F. Plasma concentrations of gamma-aminobutyric acid (GABA) and mood disorders: a blood test for manic depressive disease? Clin Chem. 1994;40(2):296–302.PubMedGoogle Scholar
  144. Petty F, Schiesser MA. Plasma GABA in affective illness. A preliminary investigation. J Affect Disord. 1981;3(4):339–43.PubMedCrossRefGoogle Scholar
  145. Pharm K, Nacher J, Hof PR, McEwen BS. Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrus. Eur J Neurosci. 2003;17:879–86.CrossRefGoogle Scholar
  146. Popper CW. Mood disorders in youth: exercise, light therapy, and pharmacologic complementary and integrative approaches. Child Adolesc Psychiatr Clin N Am. 2013;22(3):403–41.PubMedCrossRefGoogle Scholar
  147. Rajkowska G, Miguel-Hidalgo JJ. Gliogenesis and glial pathology in depression. CNS Neurol Disord Drug Targets. 2007;6(3):219–33.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(9):1085–98.PubMedCrossRefGoogle Scholar
  149. Rajkowska G, Halaris A, Selemon LD. Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder. Biol Psychiatry. 2001;49(9):741–52.PubMedCrossRefGoogle Scholar
  150. Rajkowska G, O'Dwyer G, Teleki Z, Stockmeier CA, Miguel-Hidalgo JJ. GABAergic neurons immunoreactive for calcium binding proteins are reduced in the prefrontal cortex in major depression. Neuropsychopharmacology. 2007;32(2):471–82.PubMedPubMedCentralCrossRefGoogle Scholar
  151. Rastad C, Ulfberg J, Lindberg P. Improvement in fatigue, sleepiness, and health-related quality of life with bright light treatment in persons with seasonal affective disorder and subsyndromal SAD. Depress Res Treat. 2011;2011:543906.PubMedPubMedCentralGoogle Scholar
  152. Rosenberg DR, Macmaster FP, Mirza Y, Smith JM, Easter PC, Banerjee SP, Bhandari R, Boyd C, Lynch M, Rose M, Ivey J, Villafuerte RA, Moore GJ, Renshaw P. Reduced anterior cingulate glutamate in pediatric major depression: a magnetic resonance spectroscopy study. Biol Psychiatry. 2005;58(9):700–4.PubMedCrossRefGoogle Scholar
  153. Roth TL, Sweatt JD. Epigenetic mechanisms and environmental shaping of the brain during sensitive periods of development. J Child Psychol Psychiatry. 2011;52(4):398–408.PubMedPubMedCentralCrossRefGoogle Scholar
  154. Roy A, Dejong J, Ferraro T. CSF GABA in depressed patients and normal controls. Psychol Med. 1991;21(3):613–8.PubMedCrossRefGoogle Scholar
  155. Saarelainen T, Hendolin P, Lucas G, Koponen E, Sairanen M, MacDonald E, Agerman K, Haapasalo A, Nawa H, Aloyz R, Ernfors P, Castrén E. Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects. J Neurosci. 2003;23(1):349–57.PubMedGoogle Scholar
  156. Salgado-Delgado R, Osorio AT, Saderi N, Escobar C. Disruption of circadian rhythms: a crucial factor in the etiology of depression. Depress Res Treat. 2011;2011:839743.PubMedPubMedCentralGoogle Scholar
  157. Sanacora G, Mason GF, Rothman DL, Berman RM, Charney DS, Krystal JH. ECT effects on cortical GABA levels as determined by 1H-MRS. Scientific abstracts from the 37th annual meeting of the American College of Neuropsychopharmacology. San Juan: American College of Neuropsychopharmacology; 1998. p. 200.Google Scholar
  158. 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(11):1043–7.PubMedCrossRefGoogle Scholar
  159. Sanacora G, Mason GF, Rothman DL, Berman RM, Zimolo Z, Krystal JH. Cortical GABA concentrations are increased in depressed patients following treatment with selective serotonin reuptake inhibitors. Scientific abstracts from the 39th annual meeting of the American College of Neuropsychopharmacology. San Juan: American College of Neuropsychopharmacology; 2000. p. 200.Google Scholar
  160. Sanacora G, Zarate CA, Krystal JH, Manji HK. Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov. 2008;7(5):426–37.PubMedPubMedCentralCrossRefGoogle Scholar
  161. Sanai N, Nguyen T, Ihrie RA, Mirzadeh Z, Tsai HH, Wong M, Gupta N, Berger MS, Huang E, Garcia-Verdugo JM, Rowitch DH, Alvarez-Buylla A. Corridors of migrating neurons in the human brain and their decline during infancy. Nature. 2011;478(7369):382–6.PubMedPubMedCentralCrossRefGoogle Scholar
  162. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science. 2003;301:805–9.PubMedCrossRefGoogle Scholar
  163. Schiepers OJG, Wichers MC, Maes M. Cytokines and major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29:201–17.PubMedCrossRefGoogle Scholar
  164. Schildkraut JJ. The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry. 1965;122(5):509–22.PubMedCrossRefGoogle Scholar
  165. Schnydrig S, Korner L, Landweer S, Ernst B, Walker G, Otten U, Kunz D. Peripheral lipopolysaccharide administration transiently affects expression of brain-derived neurotrophic factor, corticotropin and proopiomelanocortin in mouse brain. Neurosci Lett. 2007;429(1):69–73.PubMedCrossRefGoogle Scholar
  166. Schroeder M, Krebs MO, Bleich S, Frieling H. Epigenetics and depression: current challenges and new therapeutic options. Curr Opin Psychiatry. 2010;23(6):588–92.PubMedCrossRefGoogle Scholar
  167. Schroeter ML, Abdul-Khaliq H, Diefenbacher A, Blasig IE. S100B is increased in mood disorders and may be reduced by antidepressive treatment. NeuroReport. 2002;13(13):1675–8.PubMedCrossRefGoogle Scholar
  168. Seckl JR, Fink G. Antidepressants increase glucocorticoid and mineralocorticoid receptor mRNA expression in rat hippocampus in vivo. Neuroendocrinology. 1992;55(6):621–6.PubMedCrossRefGoogle Scholar
  169. Segi-Nishida E, Warner-Schmidt JL, Duman RS. Electroconvulsive seizure and VEGF increase the proliferation of neural stem-like cells in rat hippocampus. Proc Natl Acad Sci U S A. 2008;105(32):11352–7.PubMedPubMedCentralCrossRefGoogle Scholar
  170. Shen Q, Lal R, Luellen BA, Earnheart JC, Andrews AM, Luscher B. Gamma-and antidepressant drug sensitivity reminiscent of melancholic forms of depression. Biol Psychiatry. 2010;68(6):512–20.PubMedPubMedCentralCrossRefGoogle Scholar
  171. Sokolov BP. Oligodendroglial abnormalities in schizophrenia, mood disorders and substance abuse. Comorbidity, shared traits, or molecular phenocopies? Int J Neuropsychopharmacol. 2007;10(4):547–55.PubMedCrossRefGoogle Scholar
  172. Stahl SM, Lee-Zimmerman C, Cartwright S, Morrissette DA. Serotonergic drugs for depression and beyond. Curr Drug Targets. 2013;14(5):578–85.PubMedCrossRefGoogle Scholar
  173. Stelzhammer V, Guest PC, Rothermundt M, Sondermann C, Michael N, Schwarz E, Rahmoune H, Bahn S. Electroconvulsive therapy exerts mainly acute molecular changes in serum of major depressive disorder patients. Eur Neuropsychopharmacol. 2013;23(10):1199–1207.Google Scholar
  174. Stockmeier CA, Mahajan GJ, Konick LC, Overholser JC, Jurjus GJ, Meltzer HY, Uylings HB, Friedman L, Rajkowska G. Cellular changes in the postmortem hippocampus in major depression. Biol Psychiatry. 2004;56(9):640–50.PubMedPubMedCentralCrossRefGoogle Scholar
  175. Stranahan AM, Khalil D, Gould E. Social isolation delays the positive effects of running on adult neurogenesis. Nat Neurosci. 2006;9(4):526–33.PubMedPubMedCentralCrossRefGoogle Scholar
  176. Sun JD, Liu Y, Yuan YH, Li J, Chen NH. Gap junction dysfunction in the prefrontal cortex induces depressive-like behaviors in rats. Neuropsychopharmacology. 2012;37(5):1305–20.PubMedPubMedCentralCrossRefGoogle Scholar
  177. Sun H, Kennedy PJ, Nestler EJ. Epigenetics of the depressed brain: role of histone acetylation and methylation. Neuropsychopharmacology. 2013;38(1):124–37.PubMedPubMedCentralCrossRefGoogle Scholar
  178. Tkachev D, Mimmack ML, Ryan MM, Wayland M, Freeman T, Jones PB, Starkey M, Webster MJ, Yolken RH, Bahn S. Oligodendrocyte dysfunction in schizophrenia and bipolar disorder. Lancet. 2003;362(9386):798–805.PubMedCrossRefGoogle Scholar
  179. Torres GE, Gainetdinov RR, Caron MG. Plasma membrane monoamine transporters: structure, regulation and function. Nat Rev Neurosci. 2003;4(1):13–25.PubMedCrossRefGoogle Scholar
  180. Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM, Ogden KK, Hansen KB, Yuan H, Myers SJ, Dingledine R. Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev. 2010;62(3):405–96.PubMedPubMedCentralCrossRefGoogle Scholar
  181. Trullas R, Skolnick P. Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. Eur J Pharmacol. 1990;185(1):1–10.PubMedCrossRefGoogle Scholar
  182. Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ. Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci. 2006;9(4):519–25.PubMedCrossRefGoogle Scholar
  183. 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.PubMedCrossRefGoogle Scholar
  184. Uranova NA, Vostrikov VM, Orlovskaya DD, Rachmanova VI. Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium. Schizophr Res. 2004;67(2-3):269–75.PubMedCrossRefGoogle Scholar
  185. Varghese BAFP, 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(4):151–5.PubMedPubMedCentralCrossRefGoogle Scholar
  186. Vialou V, Feng J, Robison AJ, Nestler EJ. Epigenetic mechanisms of depression and antidepressant action. Annu Rev Pharmacol Toxicol. 2013;53:59–87.PubMedPubMedCentralCrossRefGoogle Scholar
  187. Vogel GW, Buffenstein A, Minter K, Hennessey A. Drug effects on REM sleep and on endogenous depression. Neurosci Biobehav Rev. 1990;14(1):49–63.PubMedCrossRefGoogle Scholar
  188. Wagner-Smith K, Markou A. Depression: a repair response to stress-induced neuronal microdamage that can grade into chronic neuroinflammatory condition? Neurosci Biobehav Rev. 2011;35:742–64.CrossRefGoogle Scholar
  189. 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(11):4647–52.PubMedPubMedCentralCrossRefGoogle Scholar
  190. Watanabe K, Hashimoto E, Ukai W, Ishii T, Yoshinaga T, Ono T, Tateno M, Watanabe I, Shirasaka T, Saito S, Saito T. Effect of antidepressants on brain-derived neurotrophic factor (BDNF) release from platelets in the rats. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(8):1450–4.PubMedCrossRefGoogle Scholar
  191. Wichers M, Maes M. The psychoneuroimmuno-pathophysiology of cytokine-induced depression in humans. Int J Neuropsychopharmacol. 2002;5:375–88.PubMedCrossRefGoogle Scholar
  192. Wichniak A, Riemann D, Kiemen A, Voderholzer U, Jernajczyk W. Comparison between eye movement latency and REM sleep parameters in major depression. Eur Arch Psychiatry Clin Neurosci. 2000;250(1):48–52.PubMedCrossRefGoogle Scholar
  193. Winokur A, Gary KA, Rodner S, Rae-Red C, Fernando AT, Szuba MP. Depression, sleep physiology, and antidepressant drugs. Depress Anxiety. 2001;14(1):19–28.PubMedCrossRefGoogle Scholar
  194. Wirz-Justice A. Biological rhythm disturbances in mood disorders. Int Clin Psychopharmacol. 2006;21 Suppl 1:S11–5.PubMedCrossRefGoogle Scholar
  195. Wirz-Justice A. Biological rhythms and depression: treatment opportunities. WPA Bull Depress. 2008;12:5–8.Google Scholar
  196. World Health Organization. The global burden of disease. 2004 Update. Geneva: WHO; 2008.Google Scholar
  197. World Health Organization. Depression. Fact sheet N°369; 2015.Google Scholar
  198. Yamada K, Watanabe A, Iwayama-Shigeno Y, Yoshikawa T. Evidence of association between gamma-aminobutyric acid type A receptor genes located on 5q34 and female patients with mood disorders. Neurosci Lett. 2003;349(1):9–12.PubMedCrossRefGoogle Scholar
  199. Young EA, Lopez JF, Murphy-Weinberg V, Watson SJ, Akil H. Mineralocorticoid receptor function in major depression. Arch Gen Psychiatry. 2003;60(1):24–8.PubMedCrossRefGoogle Scholar
  200. Zarate Jr CA, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63(8):856–64.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Clara Grosso
    • 1
  • Patrícia Valentão
    • 2
  • Paula B. Andrade
    • 2
    Email author
  1. 1.REQUIMTE/LAQV, Laboratory of Pharmacognosy, Department of Chemistry, Faculty of PharmacyUniversity of PortoPortoPortugal
  2. 2.REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de FarmáciaUniversidade do PortoPortoPortugal

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