An Overview of the Heterogeneity of Major Depressive Disorder: Current Knowledge and Future Prospective

Kaipuzha    Venu    Athira; Sikta       Bandopadhyay; Pavan    Kumar    Samudrala; V.G.M.       Naidu; Mangala       Lahkar; Sumana       Chakravarty
doi:10.2174/1570159X17666191001142934
Abstract

Major depressive disorder (MDD) is estimated to impose maximum debilitating effects on the society by 2030, with its critical effects on health, functioning, quality of life and concomitant high levels of morbidity and mortality. Yet, the disease is inadequately understood, diagnosed and treated. Moreover, with the recent drastic rise in the pace of life, stress has materialized as one of the most potent environmental factors for depression. In this scenario, it is important to understand the modern pathogenetic hypotheses and mechanisms, and possibly try to shift from the traditional approaches in depression therapy. These include the elaboration of pathophysiological changes in heterogeneous systems such as genetic, epigenetic, serotonergic, noradrenergic, gammaaminobutyric acid, glutamatergic and endocannabinoid systems, neurotrophic factors, HPA axis, immune system as well as cellular stress mechanisms. These components interact with each other in a complex matrix and further elucidation of their mechanism and cascade pathways are needed. This might aid in the identification of MDD subtypes as well as the development of sophisticated biomarkers. Further, characterization might also aid in developing multitargeted therapies that hold much promise as compared to the conventional monoamine based treatment. New candidate pharmacons, refined psychotherapeutic modalities, advanced neuro-surgical and imaging techniques as well as the implementation of pharmacokinetic, pharmacogenetic prescribing guidelines constitute the emerging expanses of MDD treatment.
Keywords: Stress, MDD, neurotransmitter, neurotrophic factor, hypothalamic-pituitary-adrenal axis, immune system, genetics, epigenetics.
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[1] 
Kessler, R.C.; Berglund, P.; Demler, O.; Jin, R.; Merikangas, K.R.; Walters, E.E. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch. Gen. Psychiatry,  2005, 62(6), 593-602.
[http://dx.doi.org/10.1001/archpsyc.62.6.593] [PMID:  15939837] 
[2] 
Wiles, N.; Thomas, L.; Abel, A.; Ridgway, N.; Turner, N.; Campbell, J.; Garland, A.; Hollinghurst, S.; Jerrom, B.; Kessler, D.; Kuyken, W.; Morrison, J.; Turner, K.; Williams, C.; Peters, T.; Lewis, G. Cognitive behavioural therapy as an adjunct to pharmacotherapy for primary care based patients with treatment resistant depression: results of the CoBalT randomised controlled trial. Lancet,  2013, 381(9864), 375-384.
[http://dx.doi.org/10.1016/S0140-6736(12)61552-9] [PMID:  23219570] 
[3] 
Weissman, M.M.; Bland, R.; Joyce, P.R.; Newman, S.; Wells, J.E.; Wittchen, H-U. Sex differences in rates of depression: cross-national perspectives. J. Affect. Disord.,  1993, 29(2-3), 77-84.
[http://dx.doi.org/10.1016/0165-0327(93)90025-F] [PMID:  8300980] 
[4] 
Wilhelm, K.; Mitchell, P.; Slade, T.; Brownhill, S.; Andrews, G. Prevalence and correlates of DSM-IV major depression in an Australian national survey. J. Affect. Disord.,  2003, 75(2), 155-162.
[http://dx.doi.org/10.1016/S0165-0327(02)00040-X] [PMID:  12798255] 
[5] 
Bijl, R.V.; Ravelli, A. Psychiatric morbidity, service use, and need for care in the general population: results of The Netherlands Mental Health Survey and Incidence Study. Am. J. Public Health,  2000, 90(4), 602-607.
[http://dx.doi.org/10.2105/AJPH.90.4.602] [PMID:  10754976] 
[6] 
Ogłodek, E.; Szota, A.; Just, M.; Moś, D.; Araszkiewicz, A. The role of the neuroendocrine and immune systems in the pathogenesis of depression. Pharmacol. Rep.,  2014, 66(5), 776-781.
[http://dx.doi.org/10.1016/j.pharep.2014.04.009] [PMID:  25149980] 
[7] 
Whiteford, H.A.; Degenhardt, L.; Rehm, J.; Baxter, A.J.; Ferrari, A.J.; Erskine, H.E.; Charlson, F.J.; Norman, R.E.; Flaxman, A.D.; Johns, N.; Burstein, R.; Murray, C.J.; Vos, T. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet,  2013, 382(9904), 1575-1586.
[http://dx.doi.org/10.1016/S0140-6736(13)61611-6] [PMID:  23993280] 
[8] 
Arroll, B.; Elley, C.R.; Fishman, T.; Goodyear-Smith, F.A.; Kenealy, T.; Blashki, G.; Kerse, N.; Macgillivray, S. Antidepressants versus placebo for depression in primary care. Cochrane Database Syst. Rev.,  2009, 3(3) CD007954
[http://dx.doi.org/10.1002/14651858.CD007954] [PMID:  19588448] 
[9] 
Connolly, K.R.; Thase, M.E. Emerging drugs for major depressive disorder. Expert Opin. Emerg. Drugs,  2012, 17(1), 105-126.
[http://dx.doi.org/10.1517/14728214.2012.660146] [PMID:  22339643] 
[10] 
Rush, A.J.; Trivedi, M.H.; Wisniewski, S.R.; Nierenberg, A.A.; Stewart, J.W.; Warden, D.; Niederehe, G.; Thase, M.E.; Lavori, P.W.; Lebowitz, B.D.; McGrath, P.J.; Rosenbaum, J.F.; Sackeim, H.A.; Kupfer, D.J.; Luther, J.; Fava, M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am. J. Psychiatry,  2006, 163(11), 1905-1917.
[http://dx.doi.org/10.1176/ajp.2006.163.11.1905] [PMID:  17074942] 
[11] 
Cassano, P.; Fava, M. Tolerability issues during long-term treatment with antidepressants. Ann. Clin. Psychiatry,  2004, 16(1), 15-25.
[http://dx.doi.org/10.1080/10401230490281618] [PMID:  15147109] 
[12] 
Maletic, V.; Robinson, M.; Oakes, T.; Iyengar, S.; Ball, S.G.; Russell, J. Neurobiology of depression: an integrated view of key findings. Int. J. Clin. Pract.,  2007, 61(12), 2030-2040.
[http://dx.doi.org/10.1111/j.1742-1241.2007.01602.x] [PMID:  17944926] 
[13] 
Hollon, S.D.; Shelton, R.C.; Wisniewski, S.; Warden, D.; Biggs, M.M.; Friedman, E.S.; Husain, M.; Kupfer, D.J.; Nierenberg, A.A.; Petersen, T.J.; Shores-Wilson, K.; Rush, A.J. Presenting characteristics of depressed outpatients as a function of recurrence: preliminary findings from the STAR*D clinical trial. J. Psychiatr. Res.,  2006, 40(1), 59-69.
[http://dx.doi.org/10.1016/j.jpsychires.2005.07.008] [PMID:  16243357] 
[14] 
Gentile, S. Untreated depression during pregnancy: Short- and long-term effects in offspring. A systematic review. Neuroscience,  2017, 342, 154-166.
[http://dx.doi.org/10.1016/j.neuroscience.2015.09.001] [PMID:  26343292] 
[15] 
Rousseau, G. Depression’s forgotten genealogy: notes towards a history of depression. Hist. Psychiatry,  2000, 11(41 Pt 1), 71-106.
[http://dx.doi.org/10.1177/0957154X0001104104] [PMID:  11624608] 
[16] 
Billings, A.G.; Cronkite, R.C.; Moos, R.H. Social-environmental factors in unipolar depression: comparisons of depressed patients and nondepressed controls. J. Abnorm. Psychol.,  1983, 92(2), 119-133.
[http://dx.doi.org/10.1037/0021-843X.92.2.119] [PMID:  6863728] 
[17] 
Allen, N.B.; Badcock, P.B. Darwinian models of depression: a review of evolutionary accounts of mood and mood disorders. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2006, 30(5), 815-826.
[http://dx.doi.org/10.1016/j.pnpbp.2006.01.007] [PMID:  16647176] 
[18] 
Mahar, I.; Bambico, F.R.; Mechawar, N.; Nobrega, J.N. Stress, serotonin, and hippocampal neurogenesis in relation to depression and antidepressant effects. Neurosci. Biobehav. Rev.,  2014, 38, 173-192.
[http://dx.doi.org/10.1016/j.neubiorev.2013.11.009] [PMID:  24300695] 
[19] 
McEwen, B.S. Mood disorders and allostatic load. Biol. Psychiatry,  2003, 54(3), 200-207.
[http://dx.doi.org/10.1016/S0006-3223(03)00177-X] [PMID:  12893096] 
[20] 
Monroe, S.M.; Simons, A.D. Diathesis-stress theories in the context of life stress research: implications for the depressive disorders. Psychol. Bull.,  1991, 110(3), 406-425.
[http://dx.doi.org/10.1037/0033-2909.110.3.406] [PMID:  1758917] 
[21] 
Kendler, K.S.; Gardner, C.O.; Prescott, C.A. Toward a comprehensive developmental model for major depression in women. Am. J. Psychiatry,  2002, 159(7), 1133-1145.
[http://dx.doi.org/10.1176/appi.ajp.159.7.1133] [PMID:  12091191] 
[22] 
Kendler, K.S.; Gardner, C.O.; Prescott, C.A. Toward a comprehensive developmental model for major depression in men. Am. J. Psychiatry,  2006, 163(1), 115-124.
[http://dx.doi.org/10.1176/appi.ajp.163.1.115] [PMID:  16390898] 
[23] 
Kendler, K.S.; Kuhn, J.W.; Prescott, C.A. Childhood sexual abuse, stressful life events and risk for major depression in women. Psychol. Med.,  2004, 34(8), 1475-1482.
[http://dx.doi.org/10.1017/S003329170400265X] [PMID:  15724878] 
[24] 
Gold, P.W. The organization of the stress system and its dysregulation in depressive illness. Mol. Psychiatry,  2015, 20(1), 32-47.
[http://dx.doi.org/10.1038/mp.2014.163] [PMID:  25486982] 
[25] 
Willner, P. Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology,  2005, 52(2), 90-110.
[http://dx.doi.org/10.1159/000087097] [PMID:  16037678] 
[26] 
Karisetty, B.C.; Khandelwal, N.; Kumar, A.; Chakravarty, S. Sex difference in mouse hypothalamic transcriptome profile in stress-induced depression model. Biochem. Biophys. Res. Commun.,  2017, 486(4), 1122-1128.
[http://dx.doi.org/10.1016/j.bbrc.2017.04.005] [PMID:  28385526] 
[27] 
Yang, C.; Shirayama, Y.; Zhang, J-C.; Ren, Q.; Hashimoto, K. Peripheral interleukin-6 promotes resilience versus susceptibility to inescapable electric stress. Acta Neuropsychiatr.,  2015, 27(5), 312-316.
[http://dx.doi.org/10.1017/neu.2015.36] [PMID:  26017899] 
[28] 
Golden, S.A.; Covington, H.E., III; Berton, O.; Russo, S.J. A standardized protocol for repeated social defeat stress in mice. Nat. Protoc.,  2011, 6(8), 1183-1191.
[http://dx.doi.org/10.1038/nprot.2011.361] [PMID:  21799487] 
[29] 
Berton, O.; McClung, C.A.; Dileone, R.J.; Krishnan, V.; Renthal, W.; Russo, S.J.; Graham, D.; Tsankova, N.M.; Bolanos, C.A.; Rios, M.; Monteggia, L.M.; Self, D.W.; Nestler, E.J. Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science,  2006, 311(5762), 864-868.
[http://dx.doi.org/10.1126/science.1120972] [PMID:  16469931] 
[30] 
Veeraiah, P.; Noronha, J.M.; Maitra, S.; Bagga, P.; Khandelwal, N.; Chakravarty, S.; Kumar, A.; Patel, A.B. Dysfunctional glutamatergic and γ-aminobutyric acidergic activities in prefrontal cortex of mice in social defeat model of depression. Biol. Psychiatry,  2014, 76(3), 231-238.
[http://dx.doi.org/10.1016/j.biopsych.2013.09.024] [PMID:  24239130] 
[31] 
Martin, A.L.; Brown, R.E. The lonely mouse: verification of a separation-induced model of depression in female mice. Behav. Brain Res.,  2010, 207(1), 196-207.
[http://dx.doi.org/10.1016/j.bbr.2009.10.006] [PMID:  19819265] 
[32] 
Kroes, R.A.; Panksepp, J.; Burgdorf, J.; Otto, N.J.; Moskal, J.R. Modeling depression: social dominance-submission gene expression patterns in rat neocortex. Neuroscience,  2006, 137(1), 37-49.
[http://dx.doi.org/10.1016/j.neuroscience.2005.08.076] [PMID:  16289586] 
[33] 
Varghese, A.K.; Verdú, E.F.; Bercik, P.; Khan, W.I.; Blennerhassett, P.A.; Szechtman, H.; Collins, S.M. Antidepressants attenuate increased susceptibility to colitis in a murine model of depression. Gastroenterology,  2006, 130(6), 1743-1753.
[http://dx.doi.org/10.1053/j.gastro.2006.02.007] [PMID:  16697738] 
[34] 
O’Mahony, S.M.; Marchesi, J.R.; Scully, P.; Codling, C.; Ceolho, A-M.; Quigley, E.M.; Cryan, J.F.; Dinan, T.G. Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol. Psychiatry,  2009, 65(3), 263-267.
[http://dx.doi.org/10.1016/j.biopsych.2008.06.026] [PMID:  18723164] 
[35] 
Saveanu, R.V.; Nemeroff, C.B. Etiology of depression: genetic and environmental factors. Psychiatr. Clin. North Am.,  2012, 35(1), 51-71.
[http://dx.doi.org/10.1016/j.psc.2011.12.001] [PMID:  22370490] 
[36] 
Duclot, F.; Kabbaj, M. Epigenetic mechanisms underlying the role of brain-derived neurotrophic factor in depression and response to antidepressants. J. Exp. Biol.,  2015, 218(Pt 1), 21-31.
[http://dx.doi.org/10.1242/jeb.107086] [PMID:  25568448] 
[37] 
Vialou, V.; Feng, J.; Robison, A.J.; Nestler, E.J. Epigenetic mechanisms of depression and antidepressant action. Annu. Rev. Pharmacol. Toxicol.,  2013, 53, 59-87.
[http://dx.doi.org/10.1146/annurev-pharmtox-010611-134540] [PMID:  23020296] 
[38] 
Tsankova, N.M.; Berton, O.; Renthal, W.; Kumar, A.; Neve, R.L.; Nestler, E.J. Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat. Neurosci.,  2006, 9(4), 519-525.
[http://dx.doi.org/10.1038/nn1659] [PMID:  16501568] 
[39] 
Pathak, S.S.; Maitra, S.; Chakravarty, S.; Kumar, A. Histone Lysine demethylases of JMJD2 or KDM4 family are important epigenetic regulators in reward circuitry in the etiopathology of depression. Neuropsychopharmacology,  2017, 42(4), 854-863.
[http://dx.doi.org/10.1038/npp.2016.231] [PMID:  27711046] 
[40] 
Codocedo, J.F.; Inestrosa, N.C. Environmental control of microRNAs in the nervous system: Implications in plasticity and behavior. Neurosci. Biobehav. Rev.,  2016, 60, 121-138.
[http://dx.doi.org/10.1016/j.neubiorev.2015.10.010] [PMID:  26593111] 
[41] 
Réus, G.Z.; Abelaira, H.M.; dos Santos, M.A.B.; Carlessi, A.S.; Tomaz, D.B.; Neotti, M.V.; Liranço, J.L.G.; Gubert, C.; Barth, M.; Kapczinski, F.; Quevedo, J. Ketamine and imipramine in the nucleus accumbens regulate histone deacetylation induced by maternal deprivation and are critical for associated behaviors. Behav. Brain Res.,  2013, 256, 451-456.
[http://dx.doi.org/10.1016/j.bbr.2013.08.041] [PMID:  24004850] 
[42] 
Yuan, T-F.; Li, A.; Sun, X.; Ouyang, H.; Campos, C.; Rocha, N.B.F.; Arias-Carrión, O.; Machado, S.; Hou, G.; So, K.F. Transgenerational inheritance of paternal neurobehavioral phenotypes: stress, addiction, ageing and metabolism. Mol. Neurobiol.,  2016, 53(9), 6367-6376.
[http://dx.doi.org/10.1007/s12035-015-9526-2] [PMID:  26572641] 
[43] 
Hodes, G.E.; Walker, D.M.; Labonté, B.; Nestler, E.J.; Russo, S.J. Understanding the epigenetic basis of sex differences in depression. J. Neurosci. Res.,  2017, 95(1-2), 692-702.
[http://dx.doi.org/10.1002/jnr.23876] [PMID:  27870456] 
[44] 
Feinberg, A.P. Phenotypic plasticity and the epigenetics of human disease. Nature,  2007, 447(7143), 433-440.
[http://dx.doi.org/10.1038/nature05919] [PMID:  17522677] 
[45] 
Chahrour, M.; Jung, S.Y.; Shaw, C.; Zhou, X.; Wong, S.T.; Qin, J.; Zoghbi, H.Y. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science,  2008, 320(5880), 1224-1229.
[http://dx.doi.org/10.1126/science.1153252] [PMID:  18511691] 
[46] 
Melas, P.A.; Rogdaki, M.; Lennartsson, A.; Björk, K.; Qi, H.; Witasp, A.; Werme, M.; Wegener, G.; Mathé, A.A.; Svenningsson, P.; Lavebratt, C. Antidepressant treatment is associated with epigenetic alterations in the promoter of P11 in a genetic model of depression. Int. J. Neuropsychopharmacol.,  2012, 15(5), 669-679.
[http://dx.doi.org/10.1017/S1461145711000940] [PMID:  21682946] 
[47] 
Chakravarty, S.; Bhat, U.A.; Reddy, R.G.; Gupta, P.; Kumar, A. Histone Deacetylase inhibitors and psychiatric disorders in Epigenetics in Psychiatry; Elsevier, 2014, pp. 515-544.
[48] 
Schroeder, F.A.; Lin, C.L.; Crusio, W.E.; Akbarian, S. Antidepressant-like effects of the histone deacetylase inhibitor, sodium butyrate, in the mouse. Biol. Psychiatry,  2007, 62(1), 55-64.
[http://dx.doi.org/10.1016/j.biopsych.2006.06.036] [PMID:  16945350] 
[49] 
Hsing, C-H.; Hung, S-K.; Chen, Y-C.; Wei, T-S.; Sun, D-P.; Wang, J-J.; Yeh, C-H. Histone deacetylase inhibitor trichostatin a ameliorated endotoxin-induced neuroinflammation and cognitive dysfunction. Mediators of Inflamm.,  2015, 2015, 1-11.
[http://dx.doi.org/10.1155/2015/163140] 
[50] 
Lin, H.; Geng, X.; Dang, W.; Wu, B.; Dai, Z.; Li, Y.; Yang, Y.; Zhang, H.; Shi, J. Molecular mechanisms associated with the antidepressant effects of the class I histone deacetylase inhibitor MS-275 in the rat ventrolateral orbital cortex. Brain Res.,  2012, 1447, 119-125.
[http://dx.doi.org/10.1016/j.brainres.2012.01.053] [PMID:  22341874] 
[51] 
Meylan, E.M.; Halfon, O.; Magistretti, P.J.; Cardinaux, J-R. The HDAC inhibitor SAHA improves depressive-like behavior of CRTC1-deficient mice: Possible relevance for treatment-resistant depression. Neuropharmacology,  2016, 107, 111-121.
[http://dx.doi.org/10.1016/j.neuropharm.2016.03.012] [PMID:  26970016] 
[52] 
Kv, A.; Madhana, R.M.; Js, I.C.; Lahkar, M.; Sinha, S.; Naidu, V.G.M. Antidepressant activity of vorinostat is associated with amelioration of oxidative stress and inflammation in a corticosterone-induced chronic stress model in mice. Behav. Brain Res.,  2018, 344, 73-84.
[http://dx.doi.org/10.1016/j.bbr.2018.02.009] [PMID:  29452193] 
[53] 
Hek, K.; Demirkan, A.; Lahti, J.; Terracciano, A.; Teumer, A.; Cornelis, M.C.; Amin, N.; Bakshis, E.; Baumert, J.; Ding, J.; Liu, Y.; Marciante, K.; Meirelles, O.; Nalls, M.A.; Sun, Y.V.; Vogelzangs, N.; Yu, L.; Bandinelli, S.; Benjamin, E.J.; Bennett, D.A.; Boomsma, D.; Cannas, A.; Coker, L.H.; de Geus, E.; De Jager, P.L.; Diez-Roux, A.V.; Purcell, S.; Hu, F.B.; Rimma, E.B.; Hunter, D.J.; Jensen, M.K.; Curhan, G.; Rice, K.; Penman, A.D.; Rotter, J.I.; Sotoodehnia, N.; Emeny, R.; Eriksson, J.G.; Evans, D.A.; Ferrucci, L.; Fornage, M.; Gudnason, V.; Hofman, A.; Illig, T.; Kardia, S.; Kelly-Hayes, M.; Koenen, K.; Kraft, P.; Kuningas, M.; Massaro, J.M.; Melzer, D.; Mulas, A.; Mulder, C.L.; Murray, A.; Oostra, B.A.; Palotie, A.; Penninx, B.; Petersmann, A.; Pilling, L.C.; Psaty, B.; Rawal, R.; Reiman, E.M.; Schulz, A.; Shulman, J.M.; Singleton, A.B.; Smith, A.V.; Sutin, A.R.; Uitterlinden, A.G.; Völzke, H.; Widen, E.; Yaffe, K.; Zonderman, A.B.; Cucca, F.; Harris, T.; Ladwig, K.H.; Llewellyn, D.J.; Räikkönen, K.; Tanaka, T.; van Duijn, C.M.; Grabe, H.J.; Launer, L.J.; Lunetta, K.L.; Mosley, T.H., Jr; Newman, A.B.; Tiemeier, H.; Murabito, J. A genome-wide association study of depressive symptoms. Biol. Psychiatry,  2013, 73(7), 667-678.
[http://dx.doi.org/10.1016/j.biopsych.2012.09.033] [PMID:  23290196] 
[54] 
Dunn, E.C.; Wiste, A.; Radmanesh, F.; Almli, L.M.; Gogarten, S.M.; Sofer, T.; Faul, J.D.; Kardia, S.L.; Smith, J.A.; Weir, D.R.; Zhao, W.; Soare, T.W.; Mirza, S.S.; Hek, K.; Tiemeier, H.; Goveas, J.S.; Sarto, G.E.; Snively, B.M.; Cornelis, M.; Koenen, K.C.; Kraft, P.; Purcell, S.; Ressler, K.J.; Rosand, J.; Wassertheil-Smoller, S.; Smoller, J.W. Genome‐wide association study (GWAS) and genome‐wide by environment interaction study (GWEIS) of depressive symptoms in African American and Hispanic/Latina women. Depress. Anxiety,  2016, 33(4), 265-280.
[http://dx.doi.org/10.1002/da.22484] [PMID:  27038408] 
[55] 
Wray, N.; Sullivan, P. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nature Genetics,  2018, 50, 668-681.bioRxiv, URL. https://www biorxiv org/content/early/2017/07/24/167577
[56] 
Bunney, B.G.; Li, J.Z.; Walsh, D.M.; Stein, R.; Vawter, M.P.; Cartagena, P.; Barchas, J.D.; Schatzberg, A.F.; Myers, R.M.; Watson, S.J.; Akil, H.; Bunney, W.E. Circadian dysregulation of clock genes: clues to rapid treatments in major depressive disorder. Mol. Psychiatry,  2015, 20(1), 48-55.
[http://dx.doi.org/10.1038/mp.2014.138] [PMID:  25349171] 
[57] 
Benedetti, F.; Serretti, A.; Colombo, C.; Barbini, B.; Lorenzi, C.; Campori, E.; Smeraldi, E. Influence of CLOCK gene polymorphism on circadian mood fluctuation and illness recurrence in bipolar depression. Am. J. Med. Genet. B. Neuropsychiatr. Genet.,  2003, 123B(1), 23-26.
[http://dx.doi.org/10.1002/ajmg.b.20038] [PMID:  14582141] 
[58] 
Soria, V.; Martínez-Amorós, E.; Escaramís, G.; Valero, J.; Pérez-Egea, R.; García, C.; Gutiérrez-Zotes, A.; Puigdemont, D.; Bayés, M.; Crespo, J.M.; Martorell, L.; Vilella, E.; Labad, A.; Vallejo, J.; Pérez, V.; Menchón, J.M.; Estivill, X.; Gratacòs, M.; Urretavizcaya, M. Differential association of circadian genes with mood disorders: CRY1 and NPAS2 are associated with unipolar major depression and CLOCK and VIP with bipolar disorder. Neuropsychopharmacology,  2010, 35(6), 1279-1289.
[http://dx.doi.org/10.1038/npp.2009.230] [PMID:  20072116] 
[59] 
Utge, S.J.; Soronen, P.; Loukola, A.; Kronholm, E.; Ollila, H.M.; Pirkola, S.; Porkka-Heiskanen, T.; Partonen, T.; Paunio, T. Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance. PLoS One,  2010, 5(2)e9259
[http://dx.doi.org/10.1371/journal.pone.0009259] [PMID:  20174623] 
[60] 
Garriock, H.A.; Kraft, J.B.; Shyn, S.I.; Peters, E.J.; Yokoyama, J.S.; Jenkins, G.D.; Reinalda, M.S.; Slager, S.L.; McGrath, P.J.; Hamilton, S.P. A genomewide association study of citalopram response in major depressive disorder. Biol. Psychiatry,  2010, 67(2), 133-138.
[http://dx.doi.org/10.1016/j.biopsych.2009.08.029] [PMID:  19846067] 
[61] 
Smith, E.N.; Bloss, C.S.; Badner, J.A.; Barrett, T.; Belmonte, P.L.; Berrettini, W.; Byerley, W.; Coryell, W.; Craig, D.; Edenberg, H.J.; Eskin, E.; Foroud, T.; Gershon, E.; Greenwood, T.A.; Hipolito, M.; Koller, D.L.; Lawson, W.B.; Liu, C.; Lohoff, F.; McInnis, M.G.; McMahon, F.J.; Mirel, D.B.; Murray, S.S.; Nievergelt, C.; Nurnberger, J.; Nwulia, E.A.; Paschall, J.; Potash, J.B.; Rice, J.; Schulze, T.G.; Scheftner, W.; Panganiban, C.; Zaitlen, N.; Zandi, P.P.; Zöllner, S.; Schork, N.J.; Kelsoe, J.R. Genome-wide association study of bipolar disorder in European American and African American individuals. Mol. Psychiatry,  2009, 14(8), 755-763.
[http://dx.doi.org/10.1038/mp.2009.43] [PMID:  19488044] 
[62] 
Terracciano, A.; Tanaka, T.; Sutin, A.R.; Sanna, S.; Deiana, B.; Lai, S.; Uda, M.; Schlessinger, D.; Abecasis, G.R.; Ferrucci, L.; Costa, P.T., Jr Genome-wide association scan of trait depression. Biol. Psychiatry,  2010, 68(9), 811-817.
[http://dx.doi.org/10.1016/j.biopsych.2010.06.030] [PMID:  20800221] 
[63] 
Landgraf, D.; McCarthy, M.J.; Welsh, D.K. Circadian clock and stress interactions in the molecular biology of psychiatric disorders. Curr. Psychiatry Rep.,  2014, 16(10), 483.
[http://dx.doi.org/10.1007/s11920-014-0483-7] [PMID:  25135782] 
[64] 
Mukherjee, S.; Coque, L.; Cao, J-L.; Kumar, J.; Chakravarty, S.; Asaithamby, A.; Graham, A.; Gordon, E.; Enwright, J.F., III; DiLeone, R.J.; Birnbaum, S.G.; Cooper, D.C.; McClung, C.A. Knockdown of Clock in the ventral tegmental area through RNA interference results in a mixed state of mania and depression-like behavior. Biol. Psychiatry,  2010, 68(6), 503-511.
[http://dx.doi.org/10.1016/j.biopsych.2010.04.031] [PMID:  20591414] 
[65] 
López León, S.; Croes, E.A.; Sayed-Tabatabaei, F.A.; Claes, S.; Van Broeckhoven, C.; van Duijn, C.M. The dopamine D4 receptor gene 48-base-pair-repeat polymorphism and mood disorders: a meta-analysis. Biol. Psychiatry,  2005, 57(9), 999-1003.
[http://dx.doi.org/10.1016/j.biopsych.2005.01.030] [PMID:  15860340] 
[66] 
Jesulola, E.; Micalos, P.; Baguley, I.J. Understanding the pathophysiology of depression: From monoamines to the neurogenesis hypothesis model - are we there yet? Behav. Brain Res.,  2018, 341, 79-90.
[http://dx.doi.org/10.1016/j.bbr.2017.12.025] [PMID:  29284108] 
[67] 
Poon, D.C-H.; Ho, Y-S.; Chiu, K.; Chang, R.C-C. Cytokines: how important are they in mediating sickness? Neurosci. Biobehav. Rev.,  2013, 37(1), 1-10.
[http://dx.doi.org/10.1016/j.neubiorev.2012.11.001] [PMID:  23153795] 
[68] 
Pralong, E.; Magistretti, P.; Stoop, R. Cellular perspectives on the glutamate-monoamine interactions in limbic lobe structures and their relevance for some psychiatric disorders. Prog. Neurobiol.,  2002, 67(3), 173-202.
[http://dx.doi.org/10.1016/S0301-0082(02)00017-5] [PMID:  12169296] 
[69] 
Hurst, R.; Rollema, H.; Bertrand, D. Nicotinic acetylcholine receptors: from basic science to therapeutics. Pharmacol. Ther.,  2013, 137(1), 22-54.
[http://dx.doi.org/10.1016/j.pharmthera.2012.08.012] [PMID:  22925690] 
[70] 
Holmes, A. Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease. Neurosci. Biobehav. Rev.,  2008, 32(7), 1293-1314.
[http://dx.doi.org/10.1016/j.neubiorev.2008.03.006] [PMID:  18439676] 
[71] 
Li, X.; Frye, M.A.; Shelton, R.C. Review of pharmacological treatment in mood disorders and future directions for drug development. Neuropsychopharmacology,  2012, 37(1), 77-101.
[http://dx.doi.org/10.1038/npp.2011.198] [PMID:  21900884] 
[72] 
Micale, V.; Tabiova, K.; Kucerova, J.; Drago, F. Role of the endocannabinoid system in depression: from preclinical to clinical evidence in Cannabinoid modulation of emotion, memory, and motivation; Springer, 2015, pp. 97-129.
[http://dx.doi.org/10.1007/978-1-4939-2294-9_5] 
[73] 
Coppen, A. The biochemistry of affective disorders. Br. J. Psychiatry,  1967, 113(504), 1237-1264.
[http://dx.doi.org/10.1192/bjp.113.504.1237] [PMID:  4169954] 
[74] 
Maes, M. The serotonin hypothesis of depression Psychopharmacology: the fourth generation of progress 1995, 933-944.
[75] 
Blier, P.; de Montigny, C. Serotonin and drug-induced therapeutic responses in major depression, obsessive-compulsive and panic disorders. Neuropsychopharmacology,  1999, 21(2)(Suppl.), 91S-98S.
[http://dx.doi.org/10.1016/S0893-133X(99)00036-6] [PMID:  10432494] 
[76] 
Ressler, K.J.; Nemeroff, C.B. Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress. Anxiety,  2000, 12(Suppl. 1), 2-19.
[http://dx.doi.org/10.1002/1520-6394(2000)12:1+<2:AID-DA2>3.0.CO;2-4] [PMID:  11098410] 
[77] 
Svenningsson, P.; Kim, Y.; Warner-Schmidt, J.; Oh, Y-S.; Greengard, P. p11 and its role in depression and therapeutic responses to antidepressants. Nat. Rev. Neurosci.,  2013, 14(10), 673-680.
[http://dx.doi.org/10.1038/nrn3564] [PMID:  24002251] 
[78] 
Albert, P.R.; Benkelfat, C.; Descarries, L. The neurobiology of depression—revisiting the serotonin hypothesis. I. Cellular and molecular mechanisms. Philos. Trans. R. Soc. Lond. B Biol. Sci.,  2012, 367, 1601.
[http://dx.doi.org/10.1098/rstb.2012.0190] 
[79] 
Hervás, I.; Artigas, F. Effect of fluoxetine on extracellular 5-hydroxytryptamine in rat brain. Role of 5-HT autoreceptors. Eur. J. Pharmacol.,  1998, 358(1), 9-18.
[http://dx.doi.org/10.1016/S0014-2999(98)00579-2] [PMID:  9809863] 
[80] 
Lambert, G.; Johansson, M.; Ågren, H.; Friberg, P. Reduced brain norepinephrine and dopamine release in treatment-refractory depressive illness: evidence in support of the catecholamine hypothesis of mood disorders. Arch. Gen. Psychiatry,  2000, 57(8), 787-793.
[http://dx.doi.org/10.1001/archpsyc.57.8.787] [PMID:  10920468] 
[81] 
Leggio, G.M.; Salomone, S.; Bucolo, C.; Platania, C.; Micale, V.; Caraci, F.; Drago, F. Dopamine D(3) receptor as a new pharmacological target for the treatment of depression. Eur. J. Pharmacol.,  2013, 719(1-3), 25-33.
[http://dx.doi.org/10.1016/j.ejphar.2013.07.022] [PMID:  23872400] 
[82] 
Diaz, M.R.; Chappell, A.M.; Christian, D.T.; Anderson, N.J.; McCool, B.A. Dopamine D3-like receptors modulate anxiety-like behavior and regulate GABAergic transmission in the rat lateral/basolateral amygdala. Neuropsychopharmacology,  2011, 36(5), 1090-1103.
[http://dx.doi.org/10.1038/npp.2010.246] [PMID:  21270771] 
[83] 
Garattini, S. Pharmacology of amineptine, an antidepressant agent acting on the dopaminergic system: a review. Int. Clin. Psychopharmacol.,  1997, 12(Suppl. 3), S15-S19.
[http://dx.doi.org/10.1097/00004850-199707003-00003] [PMID:  9347388] 
[84] 
Foley, K.F.; DeSanty, K.P.; Kast, R.E. Bupropion: pharmacology and therapeutic applications. Expert Rev. Neurother.,  2006, 6(9), 1249-1265.
[http://dx.doi.org/10.1586/14737175.6.9.1249] [PMID:  17009913] 
[85] 
Katz, N.S.; Guiard, B.P.; El Mansari, M.; Blier, P. Effects of acute and sustained administration of the catecholamine reuptake inhibitor nomifensine on the firing activity of monoaminergic neurons. J. Psychopharmacol. (Oxford),  2010, 24(8), 1223-1235.
[http://dx.doi.org/10.1177/0269881109348178] [PMID:  19939862] 
[86] 
Tadori, Y.; Forbes, R.A.; McQuade, R.D.; Kikuchi, T. In vitro pharmacology of aripiprazole, its metabolite and experimental dopamine partial agonists at human dopamine D2 and D3 receptors. Eur. J. Pharmacol.,  2011, 668(3), 355-365.
[http://dx.doi.org/10.1016/j.ejphar.2011.07.020] [PMID:  21816144] 
[87] 
Pae, C-U.; Forbes, A.; Patkar, A.A. Aripiprazole as adjunctive therapy for patients with major depressive disorder: overview and implications of clinical trial data. CNS Drugs,  2011, 25(2), 109-127.
[http://dx.doi.org/10.2165/11538980-000000000-00000] [PMID:  21254788] 
[88] 
Kiss, B.; Horváth, A.; Némethy, Z.; Schmidt, E.; Laszlovszky, I.; Bugovics, G.; Fazekas, K.; Hornok, K.; Orosz, S.; Gyertyán, I.; Agai-Csongor, E.; Domány, G.; Tihanyi, K.; Adham, N.; Szombathelyi, Z. Cariprazine (RGH-188), a dopamine D(3) receptor-preferring, D(3)/D(2) dopamine receptor antagonist-partial agonist antipsychotic candidate: in vitro and neurochemical profile. J. Pharmacol. Exp. Ther.,  2010, 333(1), 328-340.
[http://dx.doi.org/10.1124/jpet.109.160432] [PMID:  20093397] 
[89] 
Willner, P.; Hale, A.S.; Argyropoulos, S. Dopaminergic mechanism of antidepressant action in depressed patients. J. Affect. Disord.,  2005, 86(1), 37-45.
[http://dx.doi.org/10.1016/j.jad.2004.12.010] [PMID:  15820269] 
[90] 
Gobert, A.; Rivet, J.M.; Cistarelli, L.; Melon, C.; Millan, M.J. α2-adrenergic receptor blockade markedly potentiates duloxetine- and fluoxetine-induced increases in noradrenaline, dopamine, and serotonin levels in the frontal cortex of freely moving rats. J. Neurochem.,  1997, 69(6), 2616-2619.
[http://dx.doi.org/10.1046/j.1471-4159.1997.69062616.x] [PMID:  9375697] 
[91] 
Dremencov, E.; Gispan-Herman, I.; Rosenstein, M.; Mendelman, A.; Overstreet, D.H.; Zohar, J.; Yadid, G. The serotonin-dopamine interaction is critical for fast-onset action of antidepressant treatment: in vivo studies in an animal model of depression. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2004, 28(1), 141-147.
[http://dx.doi.org/10.1016/j.pnpbp.2003.09.030] [PMID:  14687868] 
[92] 
Guillin, O.; Diaz, J.; Carroll, P.; Griffon, N.; Schwartz, J-C.; Sokoloff, P. BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization. Nature,  2001, 411(6833), 86-89.
[http://dx.doi.org/10.1038/35075076] [PMID:  11333982] 
[93] 
Leggio, G.M.; Bucolo, C.; Platania, C.B.M.; Salomone, S.; Drago, F. Current drug treatments targeting dopamine D3 receptor. Pharmacol. Ther.,  2016, 165, 164-177.
[http://dx.doi.org/10.1016/j.pharmthera.2016.06.007] [PMID:  27343365] 
[94] 
Sanacora, G.; Treccani, G.; Popoli, M. Towards a glutamate hypothesis of depression: an emerging frontier of neuropsychopharmacology for mood disorders. Neuropharmacology,  2012, 62(1), 63-77.
[http://dx.doi.org/10.1016/j.neuropharm.2011.07.036] [PMID:  21827775] 
[95] 
Luscher, B.; Shen, Q.; Sahir, N. The GABAergic deficit hypothesis of major depressive disorder. Mol. Psychiatry,  2011, 16(4), 383-406.
[http://dx.doi.org/10.1038/mp.2010.120] [PMID:  21079608] 
[96] 
Miller, A.H. Conceptual confluence: the kynurenine pathway as a common target for ketamine and the convergence of the inflammation and glutamate hypotheses of depression. Neuropsychopharmacology,  2013, 38(9), 1607-1608.
[http://dx.doi.org/10.1038/npp.2013.140] [PMID:  23857540] 
[97] 
Luscher, B.; Fuchs, T. GABAergic control of depression-related brain states in Advances in pharmacology; Elsevier, 2015, pp. 97-144.
[98] 
Zarate, C.A., Jr; Singh, J.B.; Carlson, P.J.; Brutsche, N.E.; Ameli, R.; Luckenbaugh, D.A.; Charney, D.S.; Manji, H.K. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch. Gen. Psychiatry,  2006, 63(8), 856-864.
[http://dx.doi.org/10.1001/archpsyc.63.8.856] [PMID:  16894061] 
[99] 
Li, N.; Liu, R-J.; Dwyer, J.M.; Banasr, M.; Lee, B.; Son, H.; Li, X-Y.; Aghajanian, G.; Duman, R.S. Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol. Psychiatry,  2011, 69(8), 754-761.
[http://dx.doi.org/10.1016/j.biopsych.2010.12.015] [PMID:  21292242] 
[100] 
Harraz, M.M.; Tyagi, R.; Cortés, P.; Snyder, S.H. Antidepressant action of ketamine via mTOR is mediated by inhibition of nitrergic Rheb degradation. Mol. Psychiatry,  2016, 21(3), 313-319.
[http://dx.doi.org/10.1038/mp.2015.211] [PMID:  26782056] 
[101] 
Preskorn, S.; Macaluso, M.; Mehra, D.O.; Zammit, G.; Moskal, J.R.; Burch, R.M. Randomized proof of concept trial of GLYX-13, an N-methyl-D-aspartate receptor glycine site partial agonist, in major depressive disorder nonresponsive to a previous antidepressant agent. J. Psychiatr. Pract.,  2015, 21(2), 140-149.
[http://dx.doi.org/10.1097/01.pra.0000462606.17725.93] [PMID:  25782764] 
[102] 
Hillard, C.J.; Liu, Q.S. Endocannabinoid signaling in the etiology and treatment of major depressive illness. Curr. Pharm. Des.,  2014, 20(23), 3795-3811.
[http://dx.doi.org/10.2174/13816128113196660735] [PMID:  24180398] 
[103] 
Häring, M.; Marsicano, G.; Lutz, B.; Monory, K. Identification of the cannabinoid receptor type 1 in serotonergic cells of raphe nuclei in mice. Neuroscience,  2007, 146(3), 1212-1219.
[http://dx.doi.org/10.1016/j.neuroscience.2007.02.021] [PMID:  17383106] 
[104] 
Oropeza, V.C.; Mackie, K.; Van Bockstaele, E.J. Cannabinoid receptors are localized to noradrenergic axon terminals in the rat frontal cortex. Brain Res.,  2007, 1127(1), 36-44.
[http://dx.doi.org/10.1016/j.brainres.2006.09.110] [PMID:  17113043] 
[105] 
Marsicano, G.; Lutz, B. Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain. Eur. J. Neurosci.,  1999, 11(12), 4213-4225.
[http://dx.doi.org/10.1046/j.1460-9568.1999.00847.x] [PMID:  10594647] 
[106] 
Navarria, A.; Tamburella, A.; Iannotti, F.A.; Micale, V.; Camillieri, G.; Gozzo, L.; Verde, R.; Imperatore, R.; Leggio, G.M.; Drago, F.; Di Marzo, V. The dual blocker of FAAH/TRPV1 N-arachidonoylserotonin reverses the behavioral despair induced by stress in rats and modulates the HPA-axis. Pharmacol. Res.,  2014, 87, 151-159.
[http://dx.doi.org/10.1016/j.phrs.2014.04.014] [PMID:  24861565] 
[107] 
Carney, R.M.; Freedland, K.E.; Miller, G.E.; Jaffe, A.S. Depression as a risk factor for cardiac mortality and morbidity: a review of potential mechanisms. J. Psychosom. Res.,  2002, 53(4), 897-902.
[http://dx.doi.org/10.1016/S0022-3999(02)00311-2] [PMID:  12377300] 
[108] 
Pittenger, C.; Duman, R.S. Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology,  2008, 33(1), 88-109.
[http://dx.doi.org/10.1038/sj.npp.1301574] [PMID:  17851537] 
[109] 
Duman, R.S.; Monteggia, L.M. A neurotrophic model for stress-related mood disorders. Biol. Psychiatry,  2006, 59(12), 1116-1127.
[http://dx.doi.org/10.1016/j.biopsych.2006.02.013] [PMID:  16631126] 
[110] 
Monteggia, L.M.; Barrot, M.; Powell, C.M.; Berton, O.; Galanis, V.; Gemelli, T.; Meuth, S.; Nagy, A.; Greene, R.W.; Nestler, E.J. Essential role of brain-derived neurotrophic factor in adult hippocampal function. Proc. Natl. Acad. Sci. USA,  2004, 101(29), 10827-10832.
[http://dx.doi.org/10.1073/pnas.0402141101] [PMID:  15249684] 
[111] 
Krishnan, V.; Nestler, E.J. The molecular neurobiology of depression. Nature,  2008, 455(7215), 894-902.
[http://dx.doi.org/10.1038/nature07455] [PMID:  18923511] 
[112] 
Zhang, X.; Li, J.; Sha, W.; Bu, R. Neurotrophic factors and major
depressive disorder, Major Depressive Disorder-Cognitive and
Neurobiological Mechanisms, IntechOpen 2015.Available from. https://www.intechopen.com/books/major-depressive-disorder-cognitive-and-neurobiological-mechanisms/neurotrophic-factors-and-major-depressive-disorder
[113] 
Kotyuk, E.; Keszler, G.; Nemeth, N.; Ronai, Z.; Sasvari-Szekely, M.; Szekely, A. Glial cell line-derived neurotrophic factor (GDNF) as a novel candidate gene of anxiety. PLoS One,  2013, 8(12) e80613
[http://dx.doi.org/10.1371/journal.pone.0080613] [PMID:  24324616] 
[114] 
Ambrée, O.; Bergink, V.; Grosse, L.; Alferink, J.; Drexhage, H.A.; Rothermundt, M.; Arolt, V.; Birkenhäger, T.K. S100B serum levels predict treatment response in patients with melancholic depression. Int. J. Neuropsychopharmacol.,  2015, 19(3)pyv103
[http://dx.doi.org/10.1093/ijnp/pyv103] [PMID:  26364276] 
[115] 
Numakawa, T.; Adachi, N.; Richards, M.; Chiba, S.; Kunugi, H. Brain-derived neurotrophic factor and glucocorticoids: reciprocal influence on the central nervous system. Neuroscience,  2013, 239, 157-172.
[http://dx.doi.org/10.1016/j.neuroscience.2012.09.073] [PMID:  23069755] 
[116] 
Ichim, G.; Tauszig-Delamasure, S.; Mehlen, P. Neurotrophins and cell death. Exp. Cell Res.,  2012, 318(11), 1221-1228.
[http://dx.doi.org/10.1016/j.yexcr.2012.03.006] [PMID:  22465479] 
[117] 
Numakawa, T.; Richards, M.; Nakajima, S.; Adachi, N.; Furuta, M.; Odaka, H.; Kunugi, H. The role of brain-derived neurotrophic factor in comorbid depression: possible linkage with steroid hormones, cytokines, and nutrition. Front. Psychiatry,  2014, 5, 136.
[http://dx.doi.org/10.3389/fpsyt.2014.00136] [PMID:  25309465] 
[118] 
Calabrese, F.; Rossetti, A.C.; Racagni, G.; Gass, P.; Riva, M.A.; Molteni, R. Brain-derived neurotrophic factor: a bridge between inflammation and neuroplasticity. Front. Cell. Neurosci.,  2014, 8, 430.
[http://dx.doi.org/10.3389/fncel.2014.00430] [PMID:  25565964] 
[119] 
Takebayashi, M.; Hisaoka, K.; Nishida, A.; Tsuchioka, M.; Miyoshi, I.; Kozuru, T.; Hikasa, S.; Okamoto, Y.; Shinno, H.; Morinobu, S.; Yamawaki, S. Decreased levels of whole blood glial cell line-derived neurotrophic factor (GDNF) in remitted patients with mood disorders. Int. J. Neuropsychopharmacol.,  2006, 9(5), 607-612.
[http://dx.doi.org/10.1017/S1461145705006085] [PMID:  16191208] 
[120] 
Hosang, G.M.; Shiles, C.; Tansey, K.E.; McGuffin, P.; Uher, R. Interaction between stress and the BDNF Val66Met polymorphism in depression: a systematic review and meta-analysis. BMC Med.,  2014, 12, 7.
[http://dx.doi.org/10.1186/1741-7015-12-7] [PMID:  24433458] 
[121] 
Klinedinst, N.J.; Resnick, B.; Yerges-Armstrong, L.M.; Dorsey, S.G. The interplay of genetics, behavior, and pain with depressive symptoms in the elderly. Gerontologist,  2015, 55(Suppl. 1), S67-S77.
[http://dx.doi.org/10.1093/geront/gnv015] [PMID:  26055783] 
[122] 
Bramham, C.R.; Messaoudi, E. BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis. Prog. Neurobiol.,  2005, 76(2), 99-125.
[http://dx.doi.org/10.1016/j.pneurobio.2005.06.003] [PMID:  16099088] 
[123] 
Chen, A.; Xiong, L-J.; Tong, Y.; Mao, M. The neuroprotective roles of BDNF in hypoxic ischemic brain injury. Biomed. Rep.,  2013, 1(2), 167-176.
[http://dx.doi.org/10.3892/br.2012.48] [PMID:  24648914] 
[124] 
Fargali, S.; Sadahiro, M.; Jiang, C.; Frick, A.L.; Indall, T.; Cogliani, V.; Welagen, J.; Lin, W-J.; Salton, S.R. Role of neurotrophins in the development and function of neural circuits that regulate energy homeostasis. J. Mol. Neurosci.,  2012, 48(3), 654-659.
[http://dx.doi.org/10.1007/s12031-012-9790-9] [PMID:  22581449] 
[125] 
Pruunsild, P.; Kazantseva, A.; Aid, T.; Palm, K.; Timmusk, T. Dissecting the human BDNF locus: bidirectional transcription, complex splicing, and multiple promoters. Genomics,  2007, 90(3), 397-406.
[http://dx.doi.org/10.1016/j.ygeno.2007.05.004] [PMID:  17629449] 
[126] 
Groves, J.O. Is it time to reassess the BDNF hypothesis of depression? Mol. Psychiatry,  2007, 12(12), 1079-1088.
[http://dx.doi.org/10.1038/sj.mp.4002075] [PMID:  17700574] 
[127] 
Ibáñez, C.F. Neurotrophic factors: from structure-function studies to designing effective therapeutics. Trends Biotechnol.,  1995, 13(6), 217-227.
[http://dx.doi.org/10.1016/S0167-7799(00)88949-0] [PMID:  7598845] 
[128] 
Clelland, C.D.; Choi, M.; Romberg, C.; Clemenson, G.D., Jr; Fragniere, A.; Tyers, P.; Jessberger, S.; Saksida, L.M.; Barker, R.A.; Gage, F.H.; Bussey, T.J. A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science,  2009, 325(5937), 210-213.
[http://dx.doi.org/10.1126/science.1173215] [PMID:  19590004] 
[129] 
Sahay, A.; Scobie, K.N.; Hill, A.S.; O’Carroll, C.M.; Kheirbek, M.A.; Burghardt, N.S.; Fenton, A.A.; Dranovsky, A.; Hen, R. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature,  2011, 472(7344), 466-470.
[http://dx.doi.org/10.1038/nature09817] [PMID:  21460835] 
[130] 
Denny, C.A.; Kheirbek, M.A.; Alba, E.L.; Tanaka, K.F.; Brachman, R.A.; Laughman, K.B.; Tomm, N.K.; Turi, G.F.; Losonczy, A.; Hen, R. Hippocampal memory traces are differentially modulated by experience, time, and adult neurogenesis. Neuron,  2014, 83(1), 189-201.
[http://dx.doi.org/10.1016/j.neuron.2014.05.018] [PMID:  24991962] 
[131] 
Ming, G.L.; Song, H. Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron,  2011, 70(4), 687-702.
[http://dx.doi.org/10.1016/j.neuron.2011.05.001] [PMID:  21609825] 
[132] 
Banasr, M.; Soumier, A.; Hery, M.; Mocaër, E.; Daszuta, A. Agomelatine, a new antidepressant, induces regional changes in hippocampal neurogenesis. Biol. Psychiatry,  2006, 59(11), 1087-1096.
[http://dx.doi.org/10.1016/j.biopsych.2005.11.025] [PMID:  16499883] 
[133] 
Dranovsky, A.; Hen, R. Hippocampal neurogenesis: regulation by stress and antidepressants. Biol. Psychiatry,  2006, 59(12), 1136-1143.
[http://dx.doi.org/10.1016/j.biopsych.2006.03.082] [PMID:  16797263] 
[134] 
Fava, M.; Johe, K.; Ereshefsky, L.; Gertsik, L.G.; English, B.A.; Bilello, J.A.; Thurmond, L.M.; Johnstone, J.; Dickerson, B.C.; Makris, N.; Hoeppner, B.B.; Flynn, M.; Mischoulon, D.; Kinrys, G.; Freeman, M.P. A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients. Mol. Psychiatry,  2016, 21(10), 1372-1380.
[http://dx.doi.org/10.1038/mp.2015.178] [PMID:  26643541] 
[135] 
Perera, T.D.; Coplan, J.D.; Lisanby, S.H.; Lipira, C.M.; Arif, M.; Carpio, C.; Spitzer, G.; Santarelli, L.; Scharf, B.; Hen, R.; Rosoklija, G.; Sackeim, H.A.; Dwork, A.J. Antidepressant-induced neurogenesis in the hippocampus of adult nonhuman primates. J. Neurosci.,  2007, 27(18), 4894-4901.
[http://dx.doi.org/10.1523/JNEUROSCI.0237-07.2007] [PMID:  17475797] 
[136] 
Ueyama, E.; Ukai, S.; Ogawa, A.; Yamamoto, M.; Kawaguchi, S.; Ishii, R.; Shinosaki, K. Chronic repetitive transcranial magnetic stimulation increases hippocampal neurogenesis in rats. Psychiatry Clin. Neurosci.,  2011, 65(1), 77-81.
[http://dx.doi.org/10.1111/j.1440-1819.2010.02170.x] [PMID:  21265939] 
[137] 
Glasper, E.R.; Llorens-Martin, M.V.; Leuner, B.; Gould, E.; Trejo, J.L. Blockade of insulin-like growth factor-I has complex effects on structural plasticity in the hippocampus. Hippocampus,  2010, 20(6), 706-712.
[PMID:  19603528] 
[138] 
Kiuchi, T.; Lee, H.; Mikami, T. Regular exercise cures depression-like behavior via VEGF-Flk-1 signaling in chronically stressed mice. Neuroscience,  2012, 207, 208-217.
[http://dx.doi.org/10.1016/j.neuroscience.2012.01.023] [PMID:  22306286] 
[139] 
Brunoni, A.R.; Machado-Vieira, R.; Zarate, C.A., Jr; Vieira, E.L.; Valiengo, L.; Benseñor, I.M.; Lotufo, P.A.; Gattaz, W.F.; Teixeira, A.L. Assessment of non-BDNF neurotrophins and GDNF levels after depression treatment with sertraline and transcranial direct current stimulation in a factorial, randomized, sham-controlled trial (SELECT-TDCS): an exploratory analysis. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2015, 56, 91-96.
[http://dx.doi.org/10.1016/j.pnpbp.2014.08.009] [PMID:  25172025] 
[140] 
Autry, A.E.; Monteggia, L.M. Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol. Rev.,  2012, 64(2), 238-258.
[http://dx.doi.org/10.1124/pr.111.005108] [PMID:  22407616] 
[141] 
Lupien, S.J.; McEwen, B.S.; Gunnar, M.R.; Heim, C. Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat. Rev. Neurosci.,  2009, 10(6), 434-445.
[http://dx.doi.org/10.1038/nrn2639] [PMID:  19401723] 
[142] 
Carroll, B.J. Dexamethasone suppression test in depression in Handbook of Psychiatric Diagnostic Procedures; Springer, 1980. 
[143] 
Hauger, R.L.; Dautzenberg, F.M. Regulation of the stress response by corticotropin-releasing factor receptors in Neuroendocrinology in physiology and medicine; Springer, 2000, pp. 261-286.
[144] 
Herbert, J.; Goodyer, I.M.; Grossman, A.B.; Hastings, M.H.; de Kloet, E.R.; Lightman, S.L.; Lupien, S.J.; Roozendaal, B.; Seckl, J.R. Do corticosteroids damage the brain? J. Neuroendocrinol.,  2006, 18(6), 393-411.
[http://dx.doi.org/10.1111/j.1365-2826.2006.01429.x] [PMID:  16684130] 
[145] 
Gutman, D.A.; Musselman, D.L.; Nemeroff, C.B. Neuropeptide alterations in depression and anxiety disorders. Medical Psychiatry,  2003, 21, 229-266.
[146] 
Aguilera, G.; Subburaju, S.; Young, S.; Chen, J. The parvocellular vasopressinergic system and responsiveness of the hypothalamic pituitary adrenal axis during chronic stress. Prog. Brain Res.,  2008, 170, 29-39.
[http://dx.doi.org/10.1016/S0079-6123(08)00403-2] [PMID:  18655869] 
[147] 
Ranabir, S.; Reetu, K. Stress and hormones. Indian J. Endocrinol. Metab.,  2011, 15(1), 18-22.
[http://dx.doi.org/10.4103/2230-8210.77573] [PMID:  21584161] 
[148] 
Smith, S.M.; Vale, W.W. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin. Neurosci.,  2006, 8(4), 383-395.
[PMID:  17290797] 
[149] 
Reul, J.M.; de Kloet, E.R. Two receptor systems for corticosterone in rat brain: microdistribution and differential occupation. Endocrinology,  1985, 117(6), 2505-2511.
[http://dx.doi.org/10.1210/endo-117-6-2505] [PMID:  2998738] 
[150] 
Reul, J.M.; de Kloet, E.R.; van Sluijs, F.J.; Rijnberk, A.; Rothuizen, J. Binding characteristics of mineralocorticoid and glucocorticoid receptors in dog brain and pituitary. Endocrinology,  1990, 127(2), 907-915.
[http://dx.doi.org/10.1210/endo-127-2-907] [PMID:  2164924] 
[151] 
Stavreva, D.A.; Wiench, M.; John, S.; Conway-Campbell, B.L.; McKenna, M.A.; Pooley, J.R.; Johnson, T.A.; Voss, T.C.; Lightman, S.L.; Hager, G.L. Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription. Nat. Cell Biol.,  2009, 11(9), 1093-1102.
[http://dx.doi.org/10.1038/ncb1922] [PMID:  19684579] 
[152] 
Palazidou, E. The neurobiology of depression. Br. Med. Bull.,  2012, 101, 127-145.
[http://dx.doi.org/10.1093/bmb/lds004] [PMID:  22334281] 
[153] 
Pariante, C.M.; Lightman, S.L. The HPA axis in major depression: classical theories and new developments. Trends Neurosci.,  2008, 31(9), 464-468.
[http://dx.doi.org/10.1016/j.tins.2008.06.006] [PMID:  18675469] 
[154] 
Carroll, B.J. The dexamethasone suppression test for melancholia. Br. J. Psychiatry,  1982, 140, 292-304.
[http://dx.doi.org/10.1192/bjp.140.3.292] [PMID:  7093598] 
[155] 
Nemeroff, C.B.; Vale, W.W. The neurobiology of depression: inroads to treatment and new drug discovery. J. Clin. Psychiatry,  2005, 66(Suppl. 7), 5-13.
[PMID:  16124836] 
[156] 
Schatzberg, A.F.; Keller, J.; Tennakoon, L.; Lembke, A.; Williams, G.; Kraemer, F.B.; Sarginson, J.E.; Lazzeroni, L.C.; Murphy, G.M. HPA axis genetic variation, cortisol and psychosis in major depression. Mol. Psychiatry,  2014, 19(2), 220-227.
[http://dx.doi.org/10.1038/mp.2013.129] [PMID:  24166410] 
[157] 
Lee, S.; Ng, K.L.; Tsang, A. Prevalence and correlates of depression with atypical symptoms in Hong Kong. Aust. N. Z. J. Psychiatry,  2009, 43(12), 1147-1154.
[http://dx.doi.org/10.3109/00048670903279895] [PMID:  20001414] 
[158] 
Zhao, Y.; Ma, R.; Shen, J.; Su, H.; Xing, D.; Du, L. A mouse model of depression induced by repeated corticosterone injections. Eur. J. Pharmacol.,  2008, 581(1-2), 113-120.
[http://dx.doi.org/10.1016/j.ejphar.2007.12.005] [PMID:  18184609] 
[159] 
Ali, S.H.; Madhana, R.M. K v, A.; Kasala, E.R.; Bodduluru, L.N.; Pitta, S.; Mahareddy, J.R.; Lahkar, M. Resveratrol ameliorates depressive-like behavior in repeated corticosterone-induced depression in mice. Steroids,  2015, 101, 37-42.
[http://dx.doi.org/10.1016/j.steroids.2015.05.010] [PMID:  26048446] 
[160] 
Freitas, A.E.; Egea, J.; Buendia, I.; Gómez-Rangel, V.; Parada, E.; Navarro, E.; Casas, A.I.; Wojnicz, A.; Ortiz, J.A.; Cuadrado, A.; Ruiz-Nuño, A.; Rodrigues, A.L.S.; Lopez, M.G. Agmatine, by improving neuroplasticity markers and inducing Nrf2, prevents corticosterone-induced depressive-like behavior in mice. Mol. Neurobiol.,  2016, 53(5), 3030-3045.
[http://dx.doi.org/10.1007/s12035-015-9182-6] [PMID:  25966970] 
[161] 
McEwen, B.S. Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol. Rev.,  2007, 87(3), 873-904.
[http://dx.doi.org/10.1152/physrev.00041.2006] [PMID:  17615391] 
[162] 
Dekker, M.J.; Tiemeier, H.; Luijendijk, H.J.; Kuningas, M.; Hofman, A.; de Jong, F.H.; Stewart, P.M.; Koper, J.W.; Lamberts, S.W. The effect of common genetic variation in 11β-hydroxysteroid dehydrogenase type 1 on hypothalamic-pituitary-adrenal axis activity and incident depression. J. Clin. Endocrinol. Metab.,  2012, 97(2), E233-E237.
[http://dx.doi.org/10.1210/jc.2011-0601] [PMID:  22112815] 
[163] 
Maes, M.; Bosmans, E.; Suy, E.; Vandervorst, C.; De Jonckheere, C.; Raus, J. Immune disturbances during major depression: upregulated expression of interleukin-2 receptors. Neuropsychobiology,  1990-1991, 24(3), 115-120.
[http://dx.doi.org/10.1159/000119472] [PMID:  2135065] 
[164] 
Maes, M.; Bosmans, E.; Suy, E.; Vandervorst, C.; DeJonckheere, C.; Raus, J. Depression-related disturbances in mitogen-induced lymphocyte responses and interleukin-1 β and soluble interleukin-2 receptor production. Acta Psychiatr. Scand.,  1991, 84(4), 379-386.
[http://dx.doi.org/10.1111/j.1600-0447.1991.tb03163.x] [PMID:  1746291] 
[165] 
Maes, M.; Scharpé, S.; Meltzer, H.Y.; Bosmans, E.; Suy, E.; Calabrese, J.; Cosyns, P. Relationships between interleukin-6 activity, acute phase proteins, and function of the hypothalamic-pituitary-adrenal axis in severe depression. Psychiatry Res.,  1993, 49(1), 11-27.
[http://dx.doi.org/10.1016/0165-1781(93)90027-E] [PMID:  7511248] 
[166] 
Maes, M.; Bosmans, E.; Meltzer, H.Y. Immunoendocrine aspects of major depression. Relationships between plasma interleukin-6 and soluble interleukin-2 receptor, prolactin and cortisol. Eur. Arch. Psychiatry Clin. Neurosci.,  1995, 245(3), 172-178.
[http://dx.doi.org/10.1007/BF02193091] [PMID:  7669825] 
[167] 
Smith, R.S. The macrophage theory of depression. Med. Hypotheses,  1991, 35(4), 298-306.
[http://dx.doi.org/10.1016/0306-9877(91)90272-Z] [PMID:  1943879] 
[168] 
Maes, M. Evidence for an immune response in major depression: a review and hypothesis. Prog. Neuropsychopharmacol. Biol. Psychiatry,  1995, 19(1), 11-38.
[http://dx.doi.org/10.1016/0278-5846(94)00101-M] [PMID:  7708925] 
[169] 
Darko, D.F.; Lucas, A.H.; Gillin, J.C.; Risch, S.C.; Golshan, S.; Hamburger, R.N.; Silverman, M.B.; Janowsky, D.S. Cellular immunity and the hypothalamic-pituitary axis in major affective disorder: a preliminary study. Psychiatry Res.,  1988, 25(1), 1-9.
[http://dx.doi.org/10.1016/0165-1781(88)90152-7] [PMID:  2905815] 
[170] 
Tondo, L.; Pani, P.; Pellegrini-Bettoli, R.; Milia, G. T-lymphocytes in depressive disorder. Med. Sci. Res.,  1988, 16, 867-868.
[171] 
Maes, M.; Lambrechts, J.; Bosmans, E.; Jacobs, J.; Suy, E.; Vandervorst, C.; de Jonckheere, C.; Minner, B.; Raus, J. Evidence for a systemic immune activation during depression: results of leukocyte enumeration by flow cytometry in conjunction with monoclonal antibody staining. Psychol. Med.,  1992, 22(1), 45-53.
[http://dx.doi.org/10.1017/S0033291700032712] [PMID:  1574566] 
[172] 
Liu, Y.; Ho, R.C-M.; Mak, A. Interleukin (IL)-6, tumour necrosis factor alpha (TNF-α) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. J. Affect. Disord.,  2012, 139(3), 230-239.
[http://dx.doi.org/10.1016/j.jad.2011.08.003] [PMID:  21872339] 
[173] 
Maes, M.; Stevens, W.J.; DeClerck, L.S.; Bridts, C.H.; Peeters, D.; Schotte, C.; Cosyns, P. A significantly increased number and percentage of B cells in depressed subjects: results of flow cytometric measurements. J. Affect. Disord.,  1992, 24(3), 127-134.
[http://dx.doi.org/10.1016/0165-0327(92)90060-J] [PMID:  1573121] 
[174] 
Robertson, M.J.; Schacterle, R.S.; Mackin, G.A.; Wilson, S.N.; Bloomingdale, K.L.; Ritz, J.; Komaroff, A.L. Lymphocyte subset differences in patients with chronic fatigue syndrome, multiple sclerosis and major depression. Clin. Exp. Immunol.,  2005, 141(2), 326-332.
[http://dx.doi.org/10.1111/j.1365-2249.2005.02833.x] [PMID:  15996197] 
[175] 
Li, Y.; Xiao, B.; Qiu, W.; Yang, L.; Hu, B.; Tian, X.; Yang, H. Altered expression of CD4(+)CD25(+) regulatory T cells and its 5-HT(1a) receptor in patients with major depression disorder. J. Affect. Disord.,  2010, 124(1-2), 68-75.
[http://dx.doi.org/10.1016/j.jad.2009.10.018] [PMID:  19900711] 
[176] 
Ronaldson, A.; Gazali, A.M.; Zalli, A.; Kaiser, F.; Thompson, S.J.; Henderson, B.; Steptoe, A.; Carvalho, L. Increased percentages of regulatory T cells are associated with inflammatory and neuroendocrine responses to acute psychological stress and poorer health status in older men and women. Psychopharmacology (Berl.),  2016, 233(9), 1661-1668.
[http://dx.doi.org/10.1007/s00213-015-3876-3] [PMID:  25678193] 
[177] 
Musselman, D.L.; Lawson, D.H.; Gumnick, J.F.; Manatunga, A.K.; Penna, S.; Goodkin, R.S.; Greiner, K.; Nemeroff, C.B.; Miller, A.H. Paroxetine for the prevention of depression induced by high-dose interferon alfa. N. Engl. J. Med.,  2001, 344(13), 961-966.
[http://dx.doi.org/10.1056/NEJM200103293441303] [PMID:  11274622] 
[178] 
Capuron, L.; Raison, C.L.; Musselman, D.L.; Lawson, D.H.; Nemeroff, C.B.; Miller, A.H. Association of exaggerated HPA axis response to the initial injection of interferon-alpha with development of depression during interferon-alpha therapy. Am. J. Psychiatry,  2003, 160(7), 1342-1345.
[http://dx.doi.org/10.1176/appi.ajp.160.7.1342] [PMID:  12832253] 
[179] 
Felger, J.C.; Lotrich, F.E. Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications. Neuroscience,  2013, 246, 199-229.
[http://dx.doi.org/10.1016/j.neuroscience.2013.04.060] [PMID:  23644052] 
[180] 
Maes, M. The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuroendocrinol. Lett.,  2008, 29(3), 287-291.
[PMID:  18580840] 
[181] 
Dantzer, R.; O’Connor, J.C.; Freund, G.G.; Johnson, R.W.; Kelley, K.W. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat. Rev. Neurosci.,  2008, 9(1), 46-56.
[http://dx.doi.org/10.1038/nrn2297] [PMID:  18073775] 
[182] 
Capuron, L.; Miller, A.H. Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol. Ther.,  2011, 130(2), 226-238.
[http://dx.doi.org/10.1016/j.pharmthera.2011.01.014] [PMID:  21334376] 
[183] 
Loftis, J.M.; Huckans, M.; Morasco, B.J. Neuroimmune mechanisms of cytokine-induced depression: current theories and novel treatment strategies. Neurobiol. Dis.,  2010, 37(3), 519-533.
[http://dx.doi.org/10.1016/j.nbd.2009.11.015] [PMID:  19944762] 
[184] 
Valentine, A.D.; Meyers, C.A. Neurobehavioral effects of interferon therapy. Curr. Psychiatry Rep.,  2005, 7(5), 391-395.
[http://dx.doi.org/10.1007/s11920-005-0042-3] [PMID:  16216160] 
[185] 
Wichers, M.C.; Kenis, G.; Koek, G.H.; Robaeys, G.; Nicolson, N.A.; Maes, M. Interferon-α-induced depressive symptoms are related to changes in the cytokine network but not to cortisol. J. Psychosom. Res.,  2007, 62(2), 207-214.
[http://dx.doi.org/10.1016/j.jpsychores.2006.09.007] [PMID:  17270579] 
[186] 
Haapakoski, R.; Ebmeier, K.P.; Alenius, H.; Kivimäki, M. Innate and adaptive immunity in the development of depression: An update on current knowledge and technological advances. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2016, 66, 63-72.
[http://dx.doi.org/10.1016/j.pnpbp.2015.11.012] [PMID:  26631274] 
[187] 
Uher, R.; Tansey, K.E.; Dew, T.; Maier, W.; Mors, O.; Hauser, J.; Dernovsek, M.Z.; Henigsberg, N.; Souery, D.; Farmer, A.; McGuffin, P. An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline. Am. J. Psychiatry,  2014, 171(12), 1278-1286.
[http://dx.doi.org/10.1176/appi.ajp.2014.14010094] [PMID:  25017001] 
[188] 
Grosse, L.; Carvalho, L.A.; Birkenhager, T.K.; Hoogendijk, W.J.; Kushner, S.A.; Drexhage, H.A.; Bergink, V. Circulating cytotoxic T cells and natural killer cells as potential predictors for antidepressant response in melancholic depression. Restoration of T regulatory cell populations after antidepressant therapy. Psychopharmacology (Berl.),  2016, 233(9), 1679-1688.
[http://dx.doi.org/10.1007/s00213-015-3943-9] [PMID:  25953327] 
[189] 
Miller, A.H. Depression and immunity: a role for T cells? Brain Behav. Immun.,  2010, 24(1), 1-8.
[http://dx.doi.org/10.1016/j.bbi.2009.09.009] [PMID:  19818725] 
[190] 
Grosse, L.; Carvalho, L.A.; Wijkhuijs, A.J.; Bellingrath, S.; Ruland, T.; Ambrée, O.; Alferink, J.; Ehring, T.; Drexhage, H.A.; Arolt, V. Clinical characteristics of inflammation-associated depression: Monocyte gene expression is age-related in major depressive disorder. Brain Behav. Immun.,  2015, 44, 48-56.
[http://dx.doi.org/10.1016/j.bbi.2014.08.004] [PMID:  25150007] 
[191] 
Grosse, L.; Hoogenboezem, T.; Ambrée, O.; Bellingrath, S.; Jörgens, S.; de Wit, H.J.; Wijkhuijs, A.M.; Arolt, V.; Drexhage, H.A. Deficiencies of the T and natural killer cell system in major depressive disorder: T regulatory cell defects are associated with inflammatory monocyte activation. Brain Behav. Immun.,  2016, 54, 38-44.
[http://dx.doi.org/10.1016/j.bbi.2015.12.003] [PMID:  26674997] 
[192] 
Jansen, R.; Penninx, B.W.; Madar, V.; Xia, K.; Milaneschi, Y.; Hottenga, J.J.; Hammerschlag, A.R.; Beekman, A.; van der Wee, N.; Smit, J.H.; Brooks, A.I.; Tischfield, J.; Posthuma, D.; Schoevers, R.; van Grootheest, G.; Willemsen, G.; de Geus, E.J.; Boomsma, D.I.; Wright, F.A.; Zou, F.; Sun, W.; Sullivan, P.F. Gene expression in major depressive disorder. Mol. Psychiatry,  2016, 21(3), 339-347.
[http://dx.doi.org/10.1038/mp.2015.57] [PMID:  26008736] 
[193] 
Dean, J.; Keshavan, M. The neurobiology of depression: An integrated view. Asian J. Psychiatr.,  2017, 27, 101-111.
[http://dx.doi.org/10.1016/j.ajp.2017.01.025] [PMID:  28558878] 
[194] 
Fallarino, F.; Grohmann, U.; Vacca, C.; Orabona, C.; Spreca, A.; Fioretti, M.C.; Puccetti, P. T cell apoptosis by kynurenines in Developments in tryptophan and serotonin metabolism; Springer, 2003, pp. 183-190.
[http://dx.doi.org/10.1007/978-1-4615-0135-0_21] 
[195] 
Terness, P.; Bauer, T.M.; Röse, L.; Dufter, C.; Watzlik, A.; Simon, H.; Opelz, G. Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites. J. Exp. Med.,  2002, 196(4), 447-457.
[http://dx.doi.org/10.1084/jem.20020052] [PMID:  12186837] 
[196] 
Morris, G.; Carvalho, A.F.; Anderson, G.; Galecki, P.; Maes, M. The many neuroprogressive actions of tryptophan catabolites (TRYCATs) that may be associated with the pathophysiology of neuro-immune disorders. Curr. Pharm. Des.,  2016, 22(8), 963-977.
[http://dx.doi.org/10.2174/1381612822666151215102420] [PMID:  26667000] 
[197] 
Maes, M.; Leonard, B.E.; Myint, A.M.; Kubera, M.; Verkerk, R. The new ‘5-HT’ hypothesis of depression: cell-mediated immune activation induces indoleamine 2,3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute to the onset of depression. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2011, 35(3), 702-721.
[http://dx.doi.org/10.1016/j.pnpbp.2010.12.017] [PMID:  21185346] 
[198] 
Maes, M.; Galecki, P.; Verkerk, R.; Rief, W. Somatization, but not depression, is characterized by disorders in the tryptophan catabolite (TRYCAT) pathway, indicating increased indoleamine 2,3-dioxygenase and lowered kynurenine aminotransferase activity. Neuroendocrinol. Lett.,  2011, 32(3), 264-273.
[PMID:  21712776] 
[199] 
Maes, M.; Wauters, A.; Verkerk, R.; Demedts, P.; Neels, H.; Van Gastel, A.; Cosyns, P.; Scharpé, S.; Desnyder, R. Lower serum L-tryptophan availability in depression as a marker of a more generalized disorder in protein metabolism. Neuropsychopharmacology,  1996, 15(3), 243-251.
[http://dx.doi.org/10.1016/0893-133X(95)00181-C] [PMID:  8873107] 
[200] 
Maes, M.; Mihaylova, I.; Ruyter, M.D.; Kubera, M.; Bosmans, E. The immune effects of TRYCATs (tryptophan catabolites along the IDO pathway): relevance for depression - and other conditions characterized by tryptophan depletion induced by inflammation. Neuroendocrinol. Lett.,  2007, 28(6), 826-831.
[PMID:  18063923] 
[201] 
Setiawan, E.; Wilson, A.A.; Mizrahi, R.; Rusjan, P.M.; Miler, L.; Rajkowska, G.; Suridjan, I.; Kennedy, J.L.; Rekkas, P.V.; Houle, S.; Meyer, J.H. Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes. JAMA Psychiatry,  2015, 72(3), 268-275.
[http://dx.doi.org/10.1001/jamapsychiatry.2014.2427] [PMID:  25629589] 
[202] 
Réus, G.Z.; Fries, G.R.; Stertz, L.; Badawy, M.; Passos, I.C.; Barichello, T.; Kapczinski, F.; Quevedo, J. The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders. Neuroscience,  2015, 300, 141-154.
[http://dx.doi.org/10.1016/j.neuroscience.2015.05.018] [PMID:  25981208] 
[203] 
Ransohoff, R.M.; Cardona, A.E. The myeloid cells of the central nervous system parenchyma. Nature,  2010, 468(7321), 253-262.
[http://dx.doi.org/10.1038/nature09615] [PMID:  21068834] 
[204] 
Maccioni, R.B.; Rojo, L.E.; Fernández, J.A.; Kuljis, R.O. The role of neuroimmunomodulation in Alzheimer’s disease. Ann. N. Y. Acad. Sci.,  2009, 1153, 240-246.
[http://dx.doi.org/10.1111/j.1749-6632.2008.03972.x] [PMID:  19236346] 
[205] 
Martinon, F.; Burns, K.; Tschopp, J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol. Cell,  2002, 10(2), 417-426.
[http://dx.doi.org/10.1016/S1097-2765(02)00599-3] [PMID:  12191486] 
[206] 
Leemans, J.C.; Cassel, S.L.; Sutterwala, F.S. Sensing damage by the NLRP3 inflammasome. Immunol. Rev.,  2011, 243(1), 152-162.
[http://dx.doi.org/10.1111/j.1600-065X.2011.01043.x] [PMID:  21884174] 
[207] 
Hornung, V.; Latz, E. Critical functions of priming and lysosomal damage for NLRP3 activation. Eur. J. Immunol.,  2010, 40(3), 620-623.
[http://dx.doi.org/10.1002/eji.200940185] [PMID:  20201015] 
[208] 
Martinon, F.; Mayor, A.; Tschopp, J. The inflammasomes: guardians of the body. Annu. Rev. Immunol.,  2009, 27, 229-265.
[http://dx.doi.org/10.1146/annurev.immunol.021908.132715] [PMID:  19302040] 
[209] 
Church, L.D.; Cook, G.P.; McDermott, M.F. Primer: inflammasomes and interleukin 1β in inflammatory disorders. Nat. Clin. Pract. Rheumatol.,  2008, 4(1), 34-42.
[http://dx.doi.org/10.1038/ncprheum0681] [PMID:  18172447] 
[210] 
Walsh, J.G.; Muruve, D.A.; Power, C. Inflammasomes in the CNS. Nat. Rev. Neurosci.,  2014, 15(2), 84-97.
[http://dx.doi.org/10.1038/nrn3638] [PMID:  24399084] 
[211] 
Alcocer-Gómez, E.; de Miguel, M.; Casas-Barquero, N.; Núñez-Vasco, J.; Sánchez-Alcazar, J.A.; Fernández-Rodríguez, A.; Cordero, M.D. NLRP3 inflammasome is activated in mononuclear blood cells from patients with major depressive disorder. Brain Behav. Immun.,  2014, 36, 111-117.
[http://dx.doi.org/10.1016/j.bbi.2013.10.017] [PMID:  24513871] 
[212] 
Raz, E. Organ-specific regulation of innate immunity. Nat. Immunol.,  2007, 8(1), 3-4.
[http://dx.doi.org/10.1038/ni0107-3] [PMID:  17179960] 
[213] 
Marino, F.; Cosentino, M. Adrenergic modulation of immune cells: an update. Amino Acids,  2013, 45(1), 55-71.
[http://dx.doi.org/10.1007/s00726-011-1186-6] [PMID:  22160285] 
[214] 
Amsterdam, A.; Tajima, K.; Sasson, R. Cell-specific regulation of apoptosis by glucocorticoids: implication to their anti-inflammatory action. Biochem. Pharmacol.,  2002, 64(5-6), 843-850.
[http://dx.doi.org/10.1016/S0006-2952(02)01147-4] [PMID:  12213578] 
[215] 
Tracey, K.J. Reflex control of immunity. Nat. Rev. Immunol.,  2009, 9(6), 418-428.
[http://dx.doi.org/10.1038/nri2566] [PMID:  19461672] 
[216] 
Hodes, G.E.; Kana, V.; Menard, C.; Merad, M.; Russo, S.J. Neuroimmune mechanisms of depression. Nat. Neurosci.,  2015, 18(10), 1386-1393.
[http://dx.doi.org/10.1038/nn.4113] [PMID:  26404713] 
[217] 
Manz, M.G.; Boettcher, S. Emergency granulopoiesis. Nat. Rev. Immunol.,  2014, 14(5), 302-314.
[http://dx.doi.org/10.1038/nri3660] [PMID:  24751955] 
[218] 
Belarbi, K.; Arellano, C.; Ferguson, R.; Jopson, T.; Rosi, S. Chronic neuroinflammation impacts the recruitment of adult-born neurons into behaviorally relevant hippocampal networks. Brain Behav. Immun.,  2012, 26(1), 18-23.
[http://dx.doi.org/10.1016/j.bbi.2011.07.225] [PMID:  21787860] 
[219] 
Walter, J.; Honsek, S.D.; Illes, S.; Wellen, J.M.; Hartung, H-P.; Rose, C.R.; Dihné, M. A new role for interferon gamma in neural stem/precursor cell dysregulation. Mol. Neurodegener.,  2011, 6, 18.
[http://dx.doi.org/10.1186/1750-1326-6-18] [PMID:  21371330] 
[220] 
Hritcu, L.; Gorgan, L.D. Intranigral lipopolysaccharide induced anxiety and depression by altered BDNF mRNA expression in rat hippocampus. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2014, 51, 126-132.
[http://dx.doi.org/10.1016/j.pnpbp.2014.01.016] [PMID:  24508447] 
[221] 
Di Filippo, M.; Chiasserini, D.; Gardoni, F.; Viviani, B.; Tozzi, A.; Giampà, C.; Costa, C.; Tantucci, M.; Zianni, E.; Boraso, M.; Siliquini, S.; de Iure, A.; Ghiglieri, V.; Colcelli, E.; Baker, D.; Sarchielli, P.; Fusco, F.R.; Di Luca, M.; Calabresi, P. Effects of central and peripheral inflammation on hippocampal synaptic plasticity. Neurobiol. Dis.,  2013, 52, 229-236.
[http://dx.doi.org/10.1016/j.nbd.2012.12.009] [PMID:  23295855] 
[222] 
Galic, M.A.; Riazi, K.; Pittman, Q.J. Cytokines and brain excitability. Front. Neuroendocrinol.,  2012, 33(1), 116-125.
[http://dx.doi.org/10.1016/j.yfrne.2011.12.002] [PMID:  22214786] 
[223] 
Maes, M.; Galecki, P.; Chang, Y.S.; Berk, M. A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2011, 35(3), 676-692.
[http://dx.doi.org/10.1016/j.pnpbp.2010.05.004] [PMID:  20471444] 
[224] 
Black, C.N.; Bot, M.; Scheffer, P.G.; Cuijpers, P.; Penninx, B.W. Is depression associated with increased oxidative stress? A systematic review and meta-analysis. Psychoneuroendocrinology,  2015, 51, 164-175.
[http://dx.doi.org/10.1016/j.psyneuen.2014.09.025] [PMID:  25462890] 
[225] 
Maes, M.; Mihaylova, I.; Kubera, M.; Uytterhoeven, M.; Vrydags, N.; Bosmans, E. Increased plasma peroxides and serum oxidized low density lipoprotein antibodies in major depression: markers that further explain the higher incidence of neurodegeneration and coronary artery disease. J. Affect. Disord.,  2010, 125(1-3), 287-294.
[http://dx.doi.org/10.1016/j.jad.2009.12.014] [PMID:  20083310] 
[226] 
Katalinic, V.; Modun, D.; Music, I.; Boban, M. Gender differences in antioxidant capacity of rat tissues determined by 2,2′-azinobis (3-ethylbenzothiazoline 6-sulfonate; ABTS) and ferric reducing antioxidant power (FRAP) assays. Comp. Biochem. Physiol. C Toxicol. Pharmacol.,  2005, 140(1), 47-52.
[http://dx.doi.org/10.1016/j.cca.2005.01.005] [PMID:  15792622] 
[227] 
Bakunina, N.; Pariante, C.M.; Zunszain, P.A. Immune mechanisms linked to depression via oxidative stress and neuroprogression. Immunology,  2015, 144(3), 365-373.
[http://dx.doi.org/10.1111/imm.12443] [PMID:  25580634] 
[228] 
Gardner, A.; Johansson, A.; Wibom, R.; Nennesmo, I.; von Döbeln, U.; Hagenfeldt, L.; Hällström, T. Alterations of mitochondrial function and correlations with personality traits in selected major depressive disorder patients. J. Affect. Disord.,  2003, 76(1-3), 55-68.
[http://dx.doi.org/10.1016/S0165-0327(02)00067-8] [PMID:  12943934] 
[229] 
Gong, Y.; Chai, Y.; Ding, J-H.; Sun, X-L.; Hu, G. Chronic mild stress damages mitochondrial ultrastructure and function in mouse brain. Neurosci. Lett.,  2011, 488(1), 76-80.
[http://dx.doi.org/10.1016/j.neulet.2010.11.006] [PMID:  21070835] 
[230] 
Gandhi, S.; Abramov, A.Y. Mechanism of oxidative stress in neurodegeneration. Oxid. Med. and Cell. Longev.,  2012, 2012, 1-11.
[http://dx.doi.org/10.1155/2012/428010] 
[231] 
Bakunina, N.; Pariante, C.; Zunszain, P. Modulation of oxidative stress in human hippocampal progenitor cells: a model to study underlying mechanisms of depression. Free Radic. Biol. Med.,  2015, 86, S19.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.07.077] 
[232] 
Djordjevic, J.; Djordjevic, A.; Adzic, M.; Mitic, M.; Lukic, I.; Radojcic, M.B. Alterations in the Nrf2-Keap1 signaling pathway and its downstream target genes in rat brain under stress. Brain Res.,  2015, 1602, 20-31.
[http://dx.doi.org/10.1016/j.brainres.2015.01.010] [PMID:  25598205] 
[233] 
Neurauter, G.; Schröcksnadel, K.; Scholl-Bürgi, S.; Sperner-Unterweger, B.; Schubert, C.; Ledochowski, M.; Fuchs, D. Chronic immune stimulation correlates with reduced phenylalanine turnover. Curr. Drug Metab.,  2008, 9(7), 622-627.
[http://dx.doi.org/10.2174/138920008785821738] [PMID:  18781914] 
[234] 
Kitagishi, Y.; Kobayashi, M.; Kikuta, K.; Matsuda, S. Roles of PI3K/AKT/GSK3/mTOR pathway in cell signaling of mental illnesses. Depress. Res. Treat.,  2012, 2012, 1-8.
[235] 
Hayashi, T. Conversion of psychological stress into cellular stress response: roles of the sigma-1 receptor in the process. Psychiatry Clin. Neurosci.,  2015, 69(4), 179-191.
[http://dx.doi.org/10.1111/pcn.12262] [PMID:  25495202] 
[236] 
Hotamisligil, G.S. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell,  2010, 140(6), 900-917.
[http://dx.doi.org/10.1016/j.cell.2010.02.034] [PMID:  20303879] 
[237] 
Gold, P.W.; Licinio, J.; Pavlatou, M.G. Pathological parainflammation and endoplasmic reticulum stress in depression: potential translational targets through the CNS insulin, klotho and PPAR-γ systems. Mol. Psychiatry,  2013, 18(2), 154-165.
[http://dx.doi.org/10.1038/mp.2012.167] [PMID:  23183489] 
[238] 
Schröder, M.; Kaufman, R.J. The mammalian unfolded protein response. Annu. Rev. Biochem.,  2005, 74, 739-789.
[http://dx.doi.org/10.1146/annurev.biochem.73.011303.074134] [PMID:  15952902] 
[239] 
Smith, M.H.; Ploegh, H.L.; Weissman, J.S. Road to ruin: targeting proteins for degradation in the endoplasmic reticulum. Science,  2011, 334(6059), 1086-1090.
[http://dx.doi.org/10.1126/science.1209235] [PMID:  22116878] 
[240] 
Nevell, L.; Zhang, K.; Aiello, A.E.; Koenen, K.; Galea, S.; Soliven, R.; Zhang, C.; Wildman, D.E.; Uddin, M. Elevated systemic expression of ER stress related genes is associated with stress-related mental disorders in the Detroit Neighborhood Health Study. Psychoneuroendocrinology,  2014, 43, 62-70.
[http://dx.doi.org/10.1016/j.psyneuen.2014.01.013] [PMID:  24703171] 
[241] 
Timberlake, M.A., II; Dwivedi, Y. Altered expression of endoplasmic reticulum stress associated genes in hippocampus of learned helpless rats: relevance to depression pathophysiology. Front. Pharmacol.,  2016, 6, 319.
[http://dx.doi.org/10.3389/fphar.2015.00319] [PMID:  26793110] 
[242] 
Gardner, A.; Boles, R.G. Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2011, 35(3), 730-743.
[http://dx.doi.org/10.1016/j.pnpbp.2010.07.030] [PMID:  20691744] 
[243] 
Karry, R.; Klein, E.; Ben Shachar, D. Mitochondrial complex I subunits expression is altered in schizophrenia: a postmortem study. Biol. Psychiatry,  2004, 55(7), 676-684.
[http://dx.doi.org/10.1016/j.biopsych.2003.12.012] [PMID:  15038995] 
[244] 
Shao, L.; Martin, M.V.; Watson, S.J.; Schatzberg, A.; Akil, H.; Myers, R.M.; Jones, E.G.; Bunney, W.E.; Vawter, M.P. Mitochondrial involvement in psychiatric disorders. Ann. Med.,  2008, 40(4), 281-295.
[http://dx.doi.org/10.1080/07853890801923753] [PMID:  18428021] 
[245] 
Andreazza, A.C.; Shao, L.; Wang, J-F.; Young, L.T. Mitochondrial complex I activity and oxidative damage to mitochondrial proteins in the prefrontal cortex of patients with bipolar disorder. Arch. Gen. Psychiatry,  2010, 67(4), 360-368.
[http://dx.doi.org/10.1001/archgenpsychiatry.2010.22] [PMID:  20368511] 
[246] 
Réus, G. Z.; Stringari, R. B.; Gonçalves, C. L.; Scaini, G.; Carvalho-Silva, M.; Jeremias, G. C.; Jeremias, I. C.; Ferreira, G. K.; Streck, E. L.; Hallak, J. E. Administration of harmine and imipramine alters creatine kinase and mitochondrial respiratory chain activities in the rat brain. Depression Res. Treat.,  2012, 2012
[http://dx.doi.org/10.1155/2012/987397] 
[247] 
Kormos, V.; Gaszner, B. Role of neuropeptides in anxiety, stress, and depression: from animals to humans. Neuropeptides,  2013, 47(6), 401-419.
[http://dx.doi.org/10.1016/j.npep.2013.10.014] [PMID:  24210138] 
[248] 
Westrich, L.; Sprouse, J. Circadian rhythm dysregulation in bipolar
disorder. Curr. Opinion Investig. Drugs (London, England: 2000),  2010, 11, 779-787.
[249] 
Quera, A.; Salva, M.; Hartley, S.; Barbot, F.; C. Alvarez, J.; Lofaso, F.; Guilleminault, C. Circadian rhythms, melatonin and depression. Curr. Pharm. Des.,  2011, 17, 1459-1470.
[250] 
Orozco-Solis, R.; Montellier, E.; Aguilar-Arnal, L.; Sato, S.; Vawter, M.P.; Bunney, B.G.; Bunney, W.E.; Sassone-Corsi, P. A circadian genomic signature common to ketamine and sleep deprivation in the anterior cingulate cortex. Biol. Psychiatry,  2017, 82(5), 351-360.
[http://dx.doi.org/10.1016/j.biopsych.2017.02.1176] [PMID:  28395871] 
[251] 
Grosso, G.; Pajak, A.; Marventano, S.; Castellano, S.; Galvano, F.; Bucolo, C.; Drago, F.; Caraci, F. Role of omega-3 fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials. PLoS One,  2014, 9(5)e96905
[http://dx.doi.org/10.1371/journal.pone.0096905] [PMID:  24805797] 
[252] 
Grosso, G.; Galvano, F.; Marventano, S.; Malaguarnera, M.; Bucolo, C.; Drago, F.; Caraci, F. Omega-3 fatty acids and depression: scientific evidence and biological mechanisms. Oxid. Med. and Cell. Longev.,  2014, 2014, 1-16.
[http://dx.doi.org/10.1155/2014/313570] 
[253] 
Karisetty, B.C.; Joshi, P.C.; Kumar, A.; Chakravarty, S. Sex differences in the effect of chronic mild stress on mouse prefrontal cortical BDNF levels: A role of major ovarian hormones. Neuroscience,  2017, 356, 89-101.
[http://dx.doi.org/10.1016/j.neuroscience.2017.05.020] [PMID:  28527954] 
[254] 
Papakostas, G.I.; Ionescu, D.F. Towards new mechanisms: an update on therapeutics for treatment-resistant major depressive disorder. Mol. Psychiatry,  2015, 20(10), 1142-1150.
[http://dx.doi.org/10.1038/mp.2015.92] [PMID:  26148812] 
[255] 
Ramaker, M.J.; Dulawa, S.C. Identifying fast-onset antidepressants using rodent models. Mol. Psychiatry,  2017, 22(5), 656-665.
[http://dx.doi.org/10.1038/mp.2017.36] [PMID:  28322276] 
[256] 
Kocsis, J.H.; Gelenberg, A.J.; Rothbaum, B.O.; Klein, D.N.; Trivedi, M.H.; Manber, R.; Keller, M.B.; Leon, A.C.; Wisniewski, S.R.; Arnow, B.A.; Markowitz, J.C.; Thase, M.E. Cognitive behavioral analysis system of psychotherapy and brief supportive psychotherapy for augmentation of antidepressant nonresponse in chronic depression: the REVAMP Trial. Arch. Gen. Psychiatry,  2009, 66(11), 1178-1188.
[http://dx.doi.org/10.1001/archgenpsychiatry.2009.144] [PMID:  19884606] 
[257] 
Bewernick, B.H.; Kayser, S.; Sturm, V.; Schlaepfer, T.E. Long-term effects of nucleus accumbens deep brain stimulation in treatment-resistant depression: evidence for sustained efficacy. Neuropsychopharmacology,  2012, 37(9), 1975-1985.
[http://dx.doi.org/10.1038/npp.2012.44] [PMID:  22473055] 
[258] 
McGrath, C.L.; Kelley, M.E.; Holtzheimer, P.E.; Dunlop, B.W.; Craighead, W.E.; Franco, A.R.; Craddock, R.C.; Mayberg, H.S. Toward a neuroimaging treatment selection biomarker for major depressive disorder. JAMA Psychiatry,  2013, 70(8), 821-829.
[http://dx.doi.org/10.1001/jamapsychiatry.2013.143] [PMID:  23760393] 
[259] 
Nassan, M.; Nicholson, W.T.; Elliott, M.A.; Vitek, C.R.R.; Black, J.L.; Frye, M.A. Pharmacokinetic pharmacogenetic prescribing guidelines for antidepressants: a template for psychiatric precision medicine. Mayo Clin. Proc.,  2016, 91, 897-907.
[http://dx.doi.org/10.1016/j.mayocp.2016.02.023] 
[260] 
Sanchez, C.; Asin, K.E.; Artigas, F. Vortioxetine, a novel antidepressant with multimodal activity: review of preclinical and clinical data. Pharmacol. Ther.,  2015, 145, 43-57.
[http://dx.doi.org/10.1016/j.pharmthera.2014.07.001] [PMID:  25016186] 
[261] 
Ribas, L.A.A.; de Aguiar, P.H.P.; dos Santos Camargo, A.T.; Ferreira, J.J.C.; Lopes, V.H.; Simis, A.; Cottin, S.C.; Galani, N.; Simis, S. Deep brain stimulation versus vagus nerve stimulation in the treatment of therapy-resistant depression: A systematic review and meta-analysis. Revista Chilena de Neurocirugia,  2018, 44, 69.
[262] 
Khan, A.M.; Ahmed, R.; Kotapati, V.P.; Dar, S.K.; Qamar, I.; Jafri, A.; Ibrahim, M.; Kumar, P.; Begum, G. Vagus Nerve Stimulation (VNS) vs. Deep Brain Stimulation (DBS) Treatment for Major Depressive Disorder and Bipolar Depression: A Comparative Meta-analytic Review. Int. J. Med. Public Health,  2018, 8.
[http://dx.doi.org/10.5530/ijmedph.2018.3.26] 
[263] 
Elliott, W.; Chan, J. Esketamine Nasal Spray (Spravato) CIII; Internal Medicine Alert, 2019, p. 41.
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DOI https://dx.doi.org/10.2174/1570159X17666191001142934	Print ISSN 1570-159X
Publisher Name Bentham Science Publisher	Online ISSN 1875-6190
Current Neuropharmacology

An Overview of the Heterogeneity of Major Depressive Disorder: Current Knowledge and Future Prospective

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