Circadian rhythm alterations resulting in disturbed sleep and disturbed melatonin secretion are flagship features of depression. Melatonin, known as a hormone of darkness, is secreted by the pineal gland located near to the center of the brain between the two hemispheres. Melatonin has an antidepressant effect by maintaining the body’s circadian rhythm, by regulating the pattern of expression of the clock genes in the suprachiasmatic nucleus (SCN) and modifying the key genes of serotoninergic neurotransmission that are linked with a depressive mood. Melatonin is produced via the metabolism of serotonin in two steps which are catalyzed by serotonin N-acetyltransferase (SNAT) and acetylserotonin-O-methyltransferase (ASMT). Serotonin, SNAT, and ASMT are key melatonin level regulation factors. Melatonin acts mainly on the MT1 and MT2 receptors, which are present in the SCN, to regulate physiological and neuroendocrine functions including circadian entrainment, referred to as a chronobiotic effect. Although melatonin has been known about and refereed to for almost 50 years, the relationship between melatonin and depression is still not clear. In this review, we summarize current knowledge about the genetic and epigenetic regulation of enzymes involved in melatonin synthesis and metabolism as potential features of depression pathophysiology and treatment. Confirmation that melatonin metabolism in peripheral blood partially reflects a disorder in the brain could be a breakthrough in the standardization of measurements of melatonin level for the development of treatment standards, finding new therapeutic targets, and elaborating simple noninvasive clinical tests.

WHO: http://www.who, 2016.
Cohen-Woods S, Craig IW, McGuffin P: The current state of play on the molecular genetics of depression. Psychol Med 2013; 43: 673–687.
Paykel ES: Basic concepts of depression. Dialogues Clin Neurosci 2008; 10: 279–289.
Muneer A (ed): Major Depressive Disorder and Bipolar Disorder: Differentiating Features and Current Treatment Approaches in Understanding Depression. New York, Springer, 2018.
Brunello N, Mendlewicz J, Kasper S, Leonard B, Montgomery S, Nelson J, et al: The role of noradrenaline and selective noradrenaline reuptake inhibition in depression. Eur Neuropsychopharmacol 2002; 12: 461–475.
Lapin IP, Oxenkrug GF: Intensification of the central serotoninergic processes as a possible determinant of the thymoleptic effect. Lancet 1969; 1: 132–136.
Millan MJ: The role of monoamines in the actions of established and “novel” antidepressant agents: a critical review. Eur J Pharmacol 2004; 500: 371–384.
Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW: From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008; 9: 46–56.
Leonard BE: The concept of depression as a dysfunction of the immune system. Curr Immunol Rev 2010; 6: 205–212.
Musselman DL, Nemeroff CB: Depression and endocrine disorders: focus on the thyroid and adrenal system. Br J Psychiatry Suppl 1996; 30: 123–128.
Freeman A, Tyrovolas S, Koyanagi A, Chatterji S, Leonardi M, Ayuso-Mateos JL, et al: The role of socio-economic status in depression: results from the COURAGE (aging survey in Europe). BMC Public Health 2016; 16: 1098.
Kendler KS, Neale MC, Kessler RC, Heath AC, Eaves LJ: A longitudinal twin study of personality and major depression in women. Arch Gen Psychiatry 1993; 50: 853–862.
Kendler KS, Thornton LM, Gardner CO: Stressful life events and previous episodes in the etiology of major depression in women: an evaluation of the “kindling” hypothesis. Am J Psychiatry 2000; 157: 1243–1251.
Vohringer PA, Perlis RH: Discriminating between bipolar disorder and major depressive disorder. Psychiatr Clin North Am 2016; 39: 1–10.
Hansen MV, Danielsen AK, Hageman I, Rosenberg J, Gogenur I: The therapeutic or prophylactic effect of exogenous melatonin against depression and depressive symptoms: a systematic review and meta-analysis. Eur Neuropsychopharmacol 2014; 24: 1719–1728.
Lerner AB, Case JD, Takahashi Y, Lee TH, Mori W: Isolation of melatonin, the pineal gland factor that lightens melanocytes. J Am Chem Soc 1958; 80: 2587.
Emet M, Ozcan H, Ozel L, Yayla M, Halici Z, Hacimuftuoglu A: A review of melatonin, its receptors and drugs. Eurasian J Med 2016; 48: 135–141.
Sandyk R, Awerbuch GI: Nocturnal melatonin secretion in suicidal patients with multiple sclerosis. Int J Neurosci 1993; 71: 173–182.
Scholtens RM, van Munster BC, van Kempen MF, de Rooij SE: Physiological melatonin levels in healthy older people: a systematic review. J Psychosom Res 2016; 86: 20–27.
Arendt J: Melatonin. Clin Endocrinol 1988; 29: 205–229.
Chattoraj A, Liu T, Zhang LS, Huang Z, Borjigin J: Melatonin formation in mammals: in vivo perspectives. Rev Endocr Metab Disord 2009; 10: 237–243.
Danilenko KV, Putilov AA, Russkikh GS, Duffy LK, Ebbesson SO: Diurnal and seasonal variations of melatonin and serotonin in women with seasonal affective disorder. Arctic Med Res 1994; 53: 137–145.
Pereira JC, Jr, Pradella Hallinan M, Alves RC: Secondary to excessive melatonin synthesis, the consumption of tryptophan from outside the blood-brain barrier and melatonin over-signaling in the pars tuberalis may be central to the pathophysiology of winter depression. Med Hypotheses 2017; 98: 69–75.
Kalsbeek A, Garidou ML, Palm IF, Van Der Vliet J, Simonneaux V, Pevet P, Buijs RM: Melatonin sees the light: Blocking GABA-ergic transmission in the paraventricular nucleus induces daytime secretion of melatonin. Eur J Neurosci 2000; 12: 3146–3154.
Okamoto-Mizuno K, Mizuno K: Effects of thermal environment on sleep and circadian rhythm. J Physiol Anthropol 2012; 31: 14.
Kandalepas PC, Mitchell JW, Gillette MU: Melatonin signal transduction pathways require E-box-mediated transcription of Per1 and Per2 to reset the SCN clock at dusk. PLoS One 2016; 11:e0157824.
Weaver DR, Reppert SM: The mel1a melatonin receptor gene is expressed in human suprachiasmatic nuclei. Neuroreport 1996; 8: 109–112.
Wu YH, Ursinus J, Zhou JN, Scheer FA, Ai-Min B, Jockers R, et al: Alterations of melatonin receptors MT1 and MT2 in the hypothalamic suprachiasmatic nucleus during depression. J Affect Disord 2013; 148: 357–367.
Dubocovich ML, Delagrange P, Krause DN, Sugden D, Cardinali DP, Olcese J: International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol Rev 2010; 62: 343–380.
Dubocovich ML, Markowska M: Functional MT1 and MT2 melatonin receptors in mammals. Endocrine 2005; 27: 101–110.
Dubocovich ML, Yun K, Al-Ghoul WM, Benloucif S, Masana MI: Selective mt2 melatonin receptor antagonists block melatonin-mediated phase advances of circadian rhythms. FASEB J 1998; 12: 1211–1220.
Jockers R, Delagrange P, Dubocovich ML, Markus RP, Renault N, Tosini G, Cecon E, Zlotos DP: Update on melatonin receptors: IUPHAR Review 20. Br J Pharmacol 2016; 173: 2702–2725.
Dubocovich ML, Rivera-Bermudez MA, Gerdin MJ, Masana MI: Molecular pharmacology, regulation and function of mammalian melatonin receptors. Front Biosci 2003; 8:d1093–d1108.
Cecon E, Oishi A, Jockers R: Melatonin receptors: molecular pharmacology and signalling in the context of system bias. Br J Pharmacol 2017, DOI: 10.1111/bph.
Pandi-Perumal SR, Trakht I, Srinivasan V, Spence DW, Maestroni GJ, Zisapel N, Cardinali DP: Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Progr Neurobiol 2008; 85: 335–353.
Nagy AD, Iwamoto A, Kawai M, Goda R, Matsuo H, Otsuka T, et al: Melatonin adjusts the expression pattern of clock genes in the suprachiasmatic nucleus and induces antidepressant-like effect in a mouse model of seasonal affective disorder. Chronobiol Int 2015; 32: 447–457.
Pfeffer M, Rauch A, Korf HW, von Gall C: The endogenous melatonin (MT) signal facilitates reentrainment of the circadian system to light-induced phase advances by acting upon mt2 receptors. Chronobiol Int 2012; 29: 415–429.
Slominski RM, Reiter RJ, Schlabritz-Loutsevitch N, Ostrom RS, Slominski AT: Melatonin membrane receptors in peripheral tissues: distribution and functions. Mol Cell Endocrinol 2012; 351: 152–166.
Tosini G, Owino S, Guillaume JL, Jockers R: Understanding melatonin receptor pharmacology: latest insights from mouse models, and their relevance to human disease. Bioessays 2014; 36: 778–787.
Comai S, Ochoa-Sanchez R, Dominguez-Lopez S, Bambico FR, Gobbi G: Melancholic-like behaviors and circadian neurobiological abnormalities in melatonin mt1 receptor knockout mice. Int J Neuropsychopharmacol 2015; 18:pyu075.
Comai S, Gobbi G: Unveiling the role of melatonin MT2 receptors in sleep, anxiety and other neuropsychiatric diseases: a novel target in psychopharmacology. J Psychiatr Neurosci 2014; 39: 6–21.
Liu J, Clough SJ, Dubocovich ML: Role of the MT1 and MT2 melatonin receptors in mediating depressive- and anxiety-like behaviors in C3H/HeN mice. Genes Brain Behav 2017; 16: 546–553.
Liu J, Clough SJ, Hutchinson AJ, Adamah-Biassi EB, Popovska-Gorevski M, Dubocovich ML: MT1 and MT2 melatonin receptors: a therapeutic perspective. Annu Rev Pharmacol Toxicol 2016; 56: 361–383.
Avery DH, Wildschiodtz G, Rafaelsen OJ: Nocturnal temperature in affective disorder. J Affect Disord 1982; 4: 61–71.
Posener JA, DeBattista C, Williams GH, Chmura Kraemer H, Kalehzan BM, Schatzberg AF: 24-h monitoring of cortisol and corticotropin secretion in psychotic and nonpsychotic major depression. Arch Gen Psychiatry 2000; 57: 755–760.
Wirz-Justice A: Biological rhythms in mood disorders; in Bloom F, Kupfer D (eds): Psychopharmacology: The Fourth Generation of Progress. New York, Raven Press, 1995, pp 999–1017.
Buysse DJ, Nofzinger EA, Germain A, Meltzer CC, Wood A, Ombao H, et al: Regional brain glucose metabolism during morning and evening wakefulness in humans: preliminary findings. Sleep 2004; 27: 1245–1254.
Germain A, Nofzinger EA, Meltzer CC, Wood A, Kupfer DJ, Moore RY, Buysse DJ: Diurnal variation in regional brain glucose metabolism in depression. Biol Psychiatry 2007; 62: 438–445.
Koenigsberg HW, Teicher MH, Mitropoulou V, Navalta C, New AS, Trestman R, et al: 24-h monitoring of plasma norepinephrine, MHPG, cortisol, growth hormone and prolactin in depression. J Psychiatr Res 2004; 38: 503–511.
Leibenluft E, Frank E: Circadian rhythms in affective disorders; in Takahashi J, Turek F, Moore R (eds): Handbook of Behavioral Neurobiology: Circadian Clocks. New York, Kluwer Academic/Plenum, 2001, pp 625–644.
Peeters F, Nicholson NA, Berkhof J: Cortisol responses to daily events in major depressive disorder. Psychosom Med 2003; 65: 836–841.
Crasson M, Kjiri S, Colin A, Kjiri K, L’Hermite-Baleriaux M, Ansseau M, Legros JJ: Serum melatonin and urinary 6-sulfatoxymelatonin in major depression. Psychoneuroendocrinology 2004; 29: 1–12.
Wetterberg L, Aperia B, Beck-Friis J, Kjellman BF, Ljunggren JG, Nilsonne A, et al: Melatonin and cortisol levels in psychiatric illness. Lancet 1982; 2: 100.
Beck-Friis J, von Rosen D, Kjellman BF, Ljunggren JG, Wetterberg L: Melatonin in relation to body measures, sex, age, season and the use of drugs in patients with major affective disorders and healthy subjects. Psychoneuroendocrinology 1984; 9: 261–277.
Rubin RT, Heist EK, McGeoy SS, Hanada K, Lesser IM: Neuroendocrine aspects of primary endogenous depression. XI. Serum melatonin measures in patients and matched control subjects. Arch Gen Psychiatry 1992; 49: 558–567.
Sekula LK, Lucke JF, Heist EK, Czambel RK, Rubin RT: Neuroendocrine aspects of primary endogenous depression. XV. Mathematical modeling of nocturnal melatonin secretion in major depressives and normal controls. Psychiatry Res 1997; 69: 143–153.
Souetre E, Salvati E, Belugou JL, Pringuey D, Candito M, Krebs B, Ardisson JL, Darcourt G: Circadian rhythms in depression and recovery: evidence for blunted amplitude as the main chronobiological abnormality. Psychiatry Res 1989; 28: 263–278.
Thompson C, Franey C, Arendt J, Checkley SA: A comparison of melatonin secretion in depressed patients and normal subjects. Br J Psychiatry 1988; 152: 260–265.
Dean J, Keshavan M: The neurobiology of depression: an integrated view. Asian J Psychiatry 2017; 27: 101–111.
Meltzer HY: Role of serotonin in depression. Ann NY Acad Sci 1990; 600: 486–499; discussion 499–500.
Modai I, Malmgren R, Wetterberg L, Eneroth P, Valevski A, Asberg M: Blood levels of melatonin, serotonin, cortisol, and prolactin in relation to the circadian rhythm of platelet serotonin uptake. Psychiatry Res 1992; 43: 161–166.
Chojnacki C, Walecka-Kapica E, Blonska A, Winczyk K, Stepien A, Chojnacki J: Serotonin and melatonin secretion in postmenopausal women with eating disorders. Endokrynol Pol 2016; 67: 299–304.
Rao ML, Muller-Oerlinghausen B, Mackert A, Strebel B, Stieglitz RD, Volz HP: Blood serotonin, serum melatonin and light therapy in healthy subjects and in patients with nonseasonal depression. Acta Psychiatr Scand 1992; 86: 127–132.
Bozhko G, Tsaritsinskii VI, Kostiukovskaia LS, Kulabukhov VM: The effect of an increased intensity of light on changes in the serotonin and melatonin content in patients with depression. Lik Sprava 1994; 7: 88–90.
Uz T, Manev H: Prolonged swim-test immobility of serotonin N-acetyltransferase (AANAT)-mutant mice. J Pineal Res 2001; 30: 166–170.
Melke J, Goubran Botros H, Chaste P, Betancur C, Nygren G, Anckarsater H, et al: Abnormal melatonin synthesis in autism spectrum disorders. Mol Psychiatry 2008; 13: 90–98.
Kripke DF, Nievergelt CM, Tranah GJ, Murray SS, McCarthy MJ, Rex KM, Parimi N, Kelsoe JR: Polymorphisms in melatonin synthesis pathways: possible influences on depression. J Circadian Rhythms 2011; 9: 8.
Kessing LV: Gender differences in the phenomenology of bipolar disorder. Bipolar Disord 2004; 6: 421–425.
Benazzi F: Gender differences in bipolar ii and unipolar depressed outpatients: a 557-case study. Ann Clin Psychiatry 1999; 11: 55–59.
Oakley Browne MA, Wells JE, Scott KM, McGee MA; New Zealand Mental Health Survey Research Team: Lifetime prevalence and projected lifetime risk of DSM-IV disorders in Te Rau Hinengaro: the New Zealand Mental Health Survey. Aust NZ J Psychiatry 2006; 40: 865–874.
Parker G, Brotchie H: Gender differences in depression. Int Rev Psychiatry 2010; 22: 429–436.
Forlani C, Morri M, Ferrari B, Dalmonte E, Menchetti M, De Ronchi D, Atti AR: Prevalence and gender differences in late-life depression: a population-based study. Am J Geriatr Psychiatry 2014; 22: 370–380.
Gunn PJ, Middleton B, Davies SK, Revell VL, Skene DJ: Sex differences in the circadian profiles of melatonin and cortisol in plasma and urine matrices under constant routine conditions. Chronobiol Int 2016; 33: 39–50.
Galecki P, Szemraj J, Bartosz G, Bienkiewicz M, Galecka E, Florkowski A, et al: Single-nucleotide polymorphisms and mRNA expression for melatonin synthesis rate-limiting enzyme in recurrent depressive disorder. J Pineal Res 2010; 48: 311–317.
Geoffroy PA, Boudebesse C, Henrion A, Jamain S, Henry C, Leboyer M, et al: An ASMT variant associated with bipolar disorder influences sleep and circadian rhythms: a pilot study. Genes Brain Behav 2014; 13: 299–304.
Soria V, Martinez-Amoros E, Escaramis G, Valero J, Crespo JM, Gutierrez-Zotes A, et al: Resequencing and association analysis of arylalkylamine N-acetyltransferase (AANAT) gene and its contribution to major depression susceptibility. J Pineal Res 2010; 49: 35–44.
Park HJ, Park JK, Kim SK, Cho AR, Kim JW, Yim SV, Chung JH: Association of polymorphism in the promoter of the melatonin receptor 1A gene with schizophrenia and with insomnia symptoms in schizophrenia patients. J Mol Neurosci 2011; 45: 304–308.
Galecka E, Szemraj J, Florkowski A, Galecki P, Bienkiewicz M, Karbownik-Lewinska M, Lewinski A: Single nucleotide polymorphisms and mRNA expression for melatonin MT2 receptor in depression. Psychiatry Res 2011; 189: 472–474.
Braam W, Keijzer H, Struijker Boudier H, Didden R, Smits M, Curfs L: CYP1A2 polymorphisms in slow melatonin metabolisers: a possible relationship with autism spectrum disorder? J Intellect Disabil Res 2013; 57: 993–1000.
Tiwari AK, Deshpande SN, Lerer B, Nimgaonkar VL, Thelma BK: Genetic susceptibility to tardive dyskinesia in chronic schizophrenia subjects: V. Association of CYP1A2 1545 C>T polymorphism. Pharmacogenomics J 2007; 7: 305–311.
Mahmood D, Muhammad BY, Alghani M, Anwar J, el-Lebban N, Haider M: Advancing role of melatonin in the treatment of neuropsychiatric disorders. EJBAS 2016; 3: 203–218.
Pozo D, Garcia-Maurino S, Guerrero JM, Calvo JR: mRNA expression of nuclear receptor RZR/RORα, melatonin membrane receptor MT, and hydroxindole-O-methyltransferase in different populations of human immune cells. J Pineal Res 2004; 37: 48–54.
Talarowska M, Szemraj J, Zajaczkowska M, Galecki P: ASMT gene expression correlates with cognitive impairment in patients with recurrent depressive disorder. Med Sci Monit 2014; 20: 905–912.
Millan MJ: On ‘polypharmacy’ and multi-target agents, complementary strategies for improving the treatment of depression: a comparative appraisal. Int J Neuropsychopharmacol 2014; 17: 1009–1037.
Byrne EM, Carrillo-Roa T, Henders AK, Bowdler L, McRae AF, Heath AC, Martin NG, Montgomery GW, Krause L, Wray NR: Monozygotic twins affected with major depressive disorder have greater variance in methylation than their unaffected co-twin. Transl Psychiatry 2013; 3:e269.
Murphy TM, O’Donovan A, Mullins N, O’Farrelly C, McCann A, Malone K: Anxiety is associated with higher levels of global DNA methylation and altered expression of epigenetic and interleukin-6 genes. Psychiatr Genet 2015; 25: 71–78.
Tseng PT, Lin PY, Lee Y, Hung CF, Lung FW, Chen CS, Chong MY: Age-associated decrease in global DNA methylation in patients with major depression. Neuropsychiatr Dis Treat 2014; 10: 2105–2114.
Soeiro-de-Souza MG, Andreazza AC, Carvalho AF, Machado-Vieira R, Young LT, Moreno RA: Number of manic episodes is associated with elevated DNA oxidation in bipolar I disorder. Int J Neuropsychopharmacol 2013; 16: 1505–1512.
Germain A, Kupfer DJ: Circadian rhythm disturbances in depression. Hum Psychopharmacol 2008; 23: 571–585.
Quera Salva MA, Hartley S: Mood disorders, circadian rhythms, melatonin and melatonin agonists. J Cent Nerv Syst Dis 2012; 4: 15–26.
Barylnik JB, Filippova NV, Trayber LV: Modern approaches to the synchronization of circadian rhythms in treatment of depression. Zh Nevrol Psikhiatr Im SS Korsakova 2014; 114: 124–128.
Wang RZ, Vashistha V, Kaur S, Houchens NW: Serotonin syndrome: preventing, recognizing, and treating it. Cleve Clin J Med 2016; 83: 810–817.
The Agency for Health Technology Assessment and Tariff System:
Richard DM, Dawes MA, Mathias CW, Acheson A, Hill-Kapturczak N, Dougherty DM: L-tryptophan: basic metabolic functions, behavioral research and therapeutic indications. Int J Tryptophan Res 2009; 2: 45–60.
United States Department of Agriculture Agricultural Research Service USDA Food Composition Databases: 2018.
Lindseth G, Helland B, Caspers J: The effects of dietary tryptophan on affective disorders. Arch Psychiatr Nurs 2015; 29: 102–107.
Meng X, Li Y, Li S, Zhou Y, Gan RY, Xu DP, Li HB: Dietary sources and bioactivities of melatonin. Nutrients 2017; 9:E367.
Sae-Teaw M, Johns J, Johns NP, Subongkot S: Serum melatonin levels and antioxidant capacities after consumption of pineapple, orange, or banana by healthy male volunteers. J Pineal Res 2013; 55: 58–64.
EFSA Panel on Dietetic Products, Nutrition and Allergies: Scientific opinion on the substantiation of a health claim related to melatonin and reduction of sleep onset latency (ID 1698, 1780, 4080) pursuant to Article 13 of Regulation (EC) No. 1924/2006. EFSA J 2011; 9: 2241.
Srinivasan V, Smits M, Spence W, Lowe AD, Kayumov L, Pandi-Perumal SR, Parry B, Cardinali DP: Melatonin in mood disorders. World J Biol Psychiatry 2006; 7: 138–151.
Lewy AJ, Lefler BJ, Emens JS, Bauer VK: The circadian basis of winter depression. Proc Natl Acad Sci USA 2006; 103: 7414–7419.
Saldanha D, Kumar N, Ryali V, Srivastava K, Pawar AA: Serum serotonin abnormality in depression. Med J Armed Forces India 2009; 65: 108–112.
Akpinar Z, Tokgoz S, Gokbel H, Okudan N, Uguz F, Yilmaz G: The association of nocturnal serum melatonin levels with major depression in patients with acute multiple sclerosis. Psychiatry Res 2008; 161: 253–257.
Khaleghipour S, Masjedi M, Ahade H, Enayate M, Pasha G, Nadery F, Ahmadzade G: Morning and nocturnal serum melatonin rhythm levels in patients with major depressive disorder: an analytical cross-sectional study. Sao Paulo Med J 2012; 130: 167–172.
Oglodek EA, Just MJ, Szromek AR, Araszkiewicz A: Melatonin and neurotrophins NT-3, BDNF, NGF in patients with varying levels of depression severity. Pharmacol Rep 2016; 68: 945–951.
Shroff KE, Sainis KB, Sengupta SR, Kamat RS: Major histocompatibility complex restriction of T-cell suppression of immune response to mycobacteria. Int J Lepr Other Mycobact Dis 1991; 59: 49–57.
Quirion A, Boisvert P, Brisson GR, DeCarufel D, Laurencelle L, Dulac S, et al: Effects of selective cooling of the facial area on physiological and metabolic output during graded maximal or prolonged submaximal exercise. Int J Biometeorol 1989; 33: 82–84.
Laika B, Leucht S, Heres S, Schneider H, Steimer W: Pharmacogenetics and olanzapine treatment: CYP1A2*1F and serotonergic polymorphisms influence therapeutic outcome. Pharmacogenomics J 2010; 10: 20–29.
Kravitz HM, Janssen I, Lotrich FE, Kado DM, Bromberger JT: Sex steroid hormone gene polymorphisms and depressive symptoms in women at midlife. Am J Med 2006; 119:S87–S93.
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