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Melatonin: Genel Özellikleri ve Psikiyatrik Bozukluklardaki Rolü

Yıl 2013, Cilt: 5 Sayı: 2, 179 - 203, 01.06.2013
https://doi.org/10.5455/cap.20130512

Öz

Melatonin hormonu, son yıllarda tüm dünyada gittikçe artan bir ilgiyle araştırılmaktadır. Ana görevi vücudun biyolojik saatini koruyup ritmini ayarlamak olan melatonin, vücudun birçok biyolojik ve fizyolojik süreçlerinde yer alır. Hücrelerin yenilenmesi, bağışıklık siteminin güçlenmesi, uyku ritminin ve vücut ısısının düzenlenmesi diğer önemli görevleri arasındadır. Lipofilik özelliği nedeniyle bilinen en güçlü antioksidandır. Bu özelliği sayesinde tüm vücut alanlarına ulaşabilmekte ve kan-beyin bariyerini geçebilmektedir. Uyku problemi olan kişilerde melatoninin düşük düzeyde bulunması, ilaç olarak kullanımını akla getirmektedir. Yapılan uygulamaların ardından melatoninin uyku total süresini değiştirmeden uyku kalitesini artırdığı belirlenmiştir. Ancak yaygın araştırılmasına rağmen melatoninin işlevleri halen tamamıyla bilinmemektedir. Bu nedenle melatonin ile ilgili mevcut bilgilerin gözden geçirilmesi, bu alanda araştırma yapanlara rehberlik edecektir.

Kaynakça

  • Claustrat B, Brun J, Chazot G. The basic physiology and pathophisology of melatonin. Sleep Med Rev 2005; 9:11-24.
  • Macchi MM, Bruce JN. Human pineal physiology and functional significance of melatonin. Front Neuroendocrinol 2004; 25:177-195.
  • Ratzburg, C. Melatonin–the myths and facts. http://www.vanderbilt.edu/ AnS/psychology/ health_psychology/melatonin.htm (retrieved on Jan 01, 2013).
  • Lerner AB. Hormones and skin color. Sci Am. 1961; 205:98-108.
  • Çam A, Erdoğan MF. Melatonin. Ankara Üniversitesi Tıp Fakültesi Mecmuası 2003; 56:103-112.
  • Mollaoğlu H, Özgüner MF. Yaşlanma sürecinde melatoninin rolü. Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi 2005; 12:52-56.
  • Webb SM, Domingo MP. Role of melatonin in health and disease. Clin Endocrinol 1995; 42:221-234.
  • Maksimovich AA. Structure and function of the pineal gland in the vertebrates, Zh Evol Biokhim Fiziol 2002; 38:3-13.
  • Djeridane Y, Touitou Y. Melatonin synthesis in the rat Harderian gland: age and time related effects. Exp Eye Res. 2001; 72:487-492.
  • Bourne RS, Mills GH. Melatonin: possible implications for the postoperative and critically ill patient. Intensive Care Med 2006; 32:371-379.
  • Cardinali DP, Pévet P. Basic aspects of melatonin action. Sleep Med Rev 1998; 2:175-190.
  • Rahman MK, Nagatsu T, Sakurai T, Hori S, Abe M, Matsuda M. Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-DOPA and L-5-hydroxytryptophan as substrates in rats. Jpn J Pharmacol. 1982; 32:803-811. Bouchard S, Bousquet C, Roberge AG. Characteristics of dihydroxyphenylalanine/5hydroxytryptophan decarboxylase activity in brain and liver of cat. Journal of Neurochem 1981; 37:781-787.
  • Gomes P, Soares-da-Silva P. L-DOPA transport properties in an immortalised cell line of rat capillary cerebral endothelial cells, RBE 4. Brain Res. 1999; 829:143-150.
  • Bouchard S, Roberge AG. Biochemical properties and kinetic parameters of dihydroxyphenylalanine--5-hydroxytryptophan decarboxylase in brain, liver, and adrenals of cat. Can. J. Biochem 1979; 57:1014-1018.
  • Amamoto T, Sarai K. On the tryptophan-serotonin metabolism in manic-depressive disorders: changes in plasma 5-HT and 5-HIAA levels and urinary 5-HIAA excretion following oral loading of L-5HTP in patients with depression. Hiroshima J Med Sci 1976; 25:135-140.
  • Palaoğlu S, Beşkonaklı E. Pineal bez ve yaşlanma. Turkish Journal of Geriatrics 1998; 1:13Touitou Y. Human aging and melatonin: clinical relevance. Exp Gerontol 2001; 36:1083-1100.
  • Rohr UD, Herold J. Melatonin deficiencies in women. Maturitas 2002; 41:S85S
  • Nowak JZ, Zawilska JB. Melatonin and its physiological and therapeutic properties. Pharm World Sci 1998; 20:18-27.
  • Bountin JA, Aedinot V, Ferry G. Delagrange P. Molecular tools to study melatonin pathways and actions. Trends Pharmacol Sci 2005; 26:412-419.
  • Özgüner F, Özcankaya R, Delibaş N, Koyu A, Çalışkan S. Melatonin ve klinik önemi. Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi 1995; 2:1-6.
  • Klein DC. Photoneural regulation of the mammalian pineal gland. In Photoperiodism, Melatonin and The Pineal (Eds D Evered, S Clark):38-56. London, Pitman Pub, 1985.
  • Stoschitzky K, Sakotnik A, Lercher P, Zweiker R, Maier R, Liebmann P et al. Influence of beta-blockers on melatonin release. Eur J Clin Pharmacol 1999; 55:111
  • Reppert SM. Melatonin receptors: molecular biology of a new family of G proteincoupled receptors. J. Biol. Rhythms 1997; 12:528-531.
  • Sugden D, Davidson K, Hough KA, Teh MT. Melatonin, melatonin receptors and melanophores: a moving story. Pigment Cell Res 2004; 17:454-460.
  • Moğulkaç R, Baltacı AK. Hipertiroidi oluşturulan ratlarda intraperitoneal melatonin uygulamasının tiroid hormonları ve testesteron salınmasına etkisi. Genel Tıp Dergisi 2002; 12:129-132.
  • Reiter RJ. The pineal gland and melatonin relation to aging: a summary of the theories and of the data. Exp Gerontol 1995; 30:199-212.
  • Lee P, Shiu SY, Chow PH. Regional and diurnal studies of melatonin and melatonin binding sites in the duck gastrointestinal tract. Biol Signals 1995; 4:212-224.
  • Siu AW, Reiter RJ, To CH. The efficacy of vitamin E and melatonin as antioxidants against lipid peroxidation in rat retinal homogenates. J Pineal Res 1998; 24:239-244. Arendt J. Melatonin, circadian rhythms and sleep. New Engl J Med 2000; 343:11141
  • Attele AS, Xie JT, Yuan CS. Treatment of insomnia: an alternative approach. Altern Med Rev. 2000; 5:249-259.
  • Smits MG, Nagtegaal EE, van der Heijden J, Coenen AM, Kerkhof GA. Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial. J Child Neurol 2001; 16:86-92.
  • Bendz LM, Scates AC. Melatonin treatment for insomnia in pediatric patients with attention-deficit/hyperactivity disorder. Ann Pharmacother. 2010; 44:185-191.
  • Baskett JJ, Wood PC, Broad JB, Duncan JR, English J, Arendt J. Melatonin in older people with age-related sleep maintenance problems: a comparison with age matched normal sleepers. Sleep. 2001; 24:418-424.
  • Bazil CW, Short D, Crispin D, Zheng W. Patients with intractable epilepsy have low melatonin, which increases following seizures. Neurology. 2000; 55:1746-1748.
  • Tsuzuki K, Okamoto-Miunu K, Mizuno K. Effects of humid heat exposure on sleep, thermoregulation, melatonin and microclimate. J Therm Biol 2004; 29:31-34.
  • Scheer F, Czeisler CA. Melatonin, sleep, and circadian rhythms. Sleep Med Rev 2005; 9:5-9.
  • Russel R. Melatonin: clinical relevance. Best Pract Res Clin Endocrinol Metab 2003; 17:273-285.
  • Folkard S, Arendt J, Clark M. Can melatonin improve shift workers’ tolerance of the night shift? some preliminary findings. Chronobiol Int 1993; 10:315-320.
  • Shigeta H, Yasui A, Nimura Y, Machida N, Kageyama M, Miur M et al. Postoperative delirium and melatonin levels in elderly patients. Am J Surg 2001; 182:449-454.
  • Garfunkel D, Laundon M, Nof D, Zisapel N. Improvement of sleep quality in elderly people by controlled release of melatonin. Lancet 1990; 346:541-543.
  • Haimov I, Lavie P, Laudon M, Herer P, Vigder C, Zisapel N. Melatonin replacement therapy of elderly insomniacs. Sleep. 1995; 18:598-603.
  • Haimov I, Laudon M, Zisapel N, Souroujon M, Nof D, Schlitner A et al. Sleep disorders and melatonin rhythms in elderly people. BMJ. 1994; 309:167.
  • Cornelissen G, Halberg F, Burioka N, Perfetto F, Tarquini R, Bakken EE. Do plasma melatonin concentrations decline with age? Am J Med 2000; 109:343-345.
  • Commentz JC, Helmkek.Precocious puberty and decreased melatonin secretion due to a hypothalamic hamartoma. Horm Res 1995; 44:271-275.
  • Sato S, Yinc C, Teramoto A, Sakuma Y, Kato M. Sexually dimorphic modulation of GABA(A) receptor currents by melatonin in rats gonadotropin–releasing hormone neurons. J Physiol Sci 2008; 58:317-322.
  • Valcavi R, Zini M, Maestroni GJ, Conti A, Portioli I. Melatonin stimulates growth hormone secretion trough pathway other than the growth hormone-releasing hormone. Clin Endocrinol (Oxf) 1993; 39:193-199.
  • Kerman M, Cirak B, Özgüner MF. Dağtekin A. Does melatonin protect or treat brain damage from traumatic oxidative stres? Exp Brain Res 2005; 163:406-410.
  • Voordouw BC, Euser R, Verdonk RE, Alberda BT, de Jong FH, Drogendijk AC et al. Melatonin and melatoninprogestin combination after pituitary-ovulation function in women and can inhibit ovulation.J Clin Endocrinol Metab 1992; 74:108-117.
  • Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wideranging implications in tissue kinetics. Br J Cancer 1972; 26:239-257.
  • Searle J, Kerr JF, Bishop CJ. Necrosis and apoptosis distinct modes death with fundamentally different significance. Pathol Annu 1982; 17: 229-259.
  • Evan G, Littlewood T. A matter of life and cell death. Science 1998; 281:1317-1321. Toubi E, Shoenfeld Y. Protective autoimmunity in cancer. Oncol Rep 2007; 17:2452
  • García-Santos G, Antolín I, Herrera F, Martín V, Rodriguez-Blanco J, del Pilar Carrera M et al. Melatonin induces apoptosis in human neuroblastoma cancer cells. J Pineal Res 2006; 41:130-135.
  • Sun FY, Lin X, Mao LZ, Ge WH, Zhang LM, Huang YL et al. Neuroprotection by melatonin against ischemic neuronal injury associated with modulation of DNA damage and repair in the rat following a transient cerebral ischemia. J Pineal Res 2002; 33:48-56.
  • Yoo YM, Yim SV, Kim SS, Jang HY, Lea HZ, Hwang GC et al. Melatonin suppresses NO-induced apoptosis via induction of Bcl-2 expression in PGT-β immortalized pineal cells. J Pineal Res 2002; 33:146-150.
  • Eck-Enriquez K, Kiefer TL, Spriggs LL, Hill SM. Pathways through which a regimen of melatonin and retinoic acid induces apoptosis in MCF-7 human breast cancer cells. Breast Cancer Res Treat 2000; 61:229-239.
  • Yönel EE, Yaprak M, Yıldız Y. Yüksek ve düşük doz eksojen melatoninin erkek ratlarda vücut ısısına etkileri. Trakya Üniversitesi Tıp Fakültesi Dergisi 1996; 13:1-4. Nakahara K, Kawana T, Shiota K. Effect of microenjection of melatonin into various brain regions of Japanase quail on locomotor activity and body temperature. Neurosci Lett 2003; 345:117-120.
  • Cagnacci A. Melatonin in relation to physiology in adult humans. J Pineal Res 1996; 21:200-213.
  • Marino FE. Methods, advantages and limitations of body cooling for exercise performance. Br J Sport Med 2002; 36:89-94.
  • Herxheimer A, Petrie KJ. Melatonin for preventing and treating jet lag. Cochrane Database Syst Rev. 2001; 1:CD001520.
  • Poon AM, Pang SF. Pineal melatonin-immune system interactions. In Melatonin: A Universal Photoperiodic Signal with Diverse Actions (Eds PL Tang, SF Pang, RJ Reiter):71-83. Basel, Karger, 1996.
  • Guerrero JM, Garcia-Maurino S, Pozo D. Mechanisms involved in the immunomodulatory effects of melatonin on the human immune system. In The pineal gland and cancer (Eds C Bartsch, H Bartsch, D Blask):408-416. Heidelberg, Springer-Verlag, 2001.
  • Henshaw DL, Reiter RJ. Do magnetic fields increase risk of childhood leukemia via melatonin disruption? Bioelectromagnetics 2005; 7:S86-S97.
  • Balsalobre A. Clock genes in mammalian peripheral tissues. Cell Tissue Res 2002; 309:193-199.
  • Richards J, Gumz ML. Advances in understanding the peripheral circadian clocks. FASEB J 2012; 26:3602-3613.
  • Korkmaz A, Reiter RJ. Gece ışığa maruz kalma, sirkadiyen melatonin ritmi ve metabolik bozulma. Turkiye Klinikleri J Cardiovasc Sci 2009; 21:434-449.
  • Van Someren EJ, Riemersma-Van Der Lek RF. Live to the rhythm, slave to the rhythm. Sleep Med Rev 2007; 11:465-484.
  • Balsalobre A, Brown SA, Marcacci L, Tronche F, Kellendonk C, Reichardt HM et al. Resetting of circadian time in peripheral tissues by glucocorticoid signaling. Science 2000; 289:2344-2347.
  • Wojtowicz M, Jakill G. Melatonin and its role in human reproduction. Ginekol Pol 2002; 73:1231-1237.
  • Partonen T. Melatonin-dependent infertility. Med Hypothesis 1999; 52:269-270.
  • Dullo P, Chaudhary R. Short review of reproductive physiology of melatonin. Pak J Physiol 2009; 5:46-48.
  • Cos S, González A, Martínez-Campa C, Mediavilla MD, Alonso-González C, Sánchez-Barceló EJ. Estrogen-signaling pathway: a link between breast cancer and melatonin oncostatic actions. Cancer Detect Prev 2006; 30:118-128.
  • Cos S, GonzalezA, Martinez-Campa C, Mediavilla MD, Alonso-Gonzalez C, Sanchez Barcelo EJ. Melatonin as a selective estrogen enzyme modulator. Curr Cancer Drug Targets 2008; 8:691-702.
  • Stevens, Richard G. Circadian disruption and breast cancer: from melatonin to clock genes. Epidemiology 2005; 16:254-258.
  • Regelson W, Pierpaoli MD. Melatonin A rediscovered antitumor hormone? Its relation to surface receptors, sex steroid metabolism, immunologic response, and chronologic factors in tumor growth & therapy. Cancer Invest 1987; 5:379-385.
  • Karasket M, Fraschini F. Is there a role for pineal gland in neoplastic growth? In Role of Melatonin and Pineal Peptides in Neuroimmunomodulation (Eds F Fraschini, RJ Reiter):243-251. New York, Plenum, 1991.
  • Coleman MP, Reiter RJ. Breast cancer, blindness and melatonin. Eur J Cancer Clin Oncol 1992; 28:501-503.
  • Bartsch C, Bartsch H, Fluchter StH, Lippert TH. Depleted pineal melatonin production in primary breast and prostate cancer is connected with circadian disturbances; possible role of melatonin for synchronization of circadian rhythmicity. In: Melatonin and the Pineal Gland–From Basic Science to Clinical Application (Eds Y Touitou, J Arendt, P Pevet):311-316. New York, Elsevier, 1993.
  • Feychting M, Osterlund B, Ahlbom A. Reduced cancer incidence among the blind. Epidemiology 1998; 9:490-494.
  • Verkasalo PK, Pukkala E, Stevens RG, Ojamo M, Rudanko SL. Inverse association between breast cancer incidence and degree of visual impairment in Finland. Br J Cancer 1999; 80:1459-1460.
  • Reiter RJ, Tan DX. Melatonin: a novel protective agent against oxidative injury of the ischemic/reperfused heart. Cardiovasc Res 2003; 58:10-19.
  • Tan DX, Manchester LC, Reiter RJ, Qi W, Kim SJ, El-Sokkary GH. Ischemia/reperfusion-induced arrhythmias in the isolated rat heart: prevention by melatonin. J Pineal Res 1998; 25:184-191.
  • Lee YM, Chen HR, Hsiao G, Sheu JR, Wang JJ, Yen MH. Protective effects of melatonin on myocardial ischemia/reperfusion injury in vivo. J Pineal Res 2002; 33:72
  • Yildiz M, Akdemir O. Assessment of the effects of physiological release of melatonin on arterial distensibility and blood pressure. Cardiol Young 2009; 19:198-203.
  • Nawar WW. Lipids. In Food Chemistry (Ed OR Fennema):225-319. New York, Marcel Dekker, 1996.
  • Kaur C, Kapoor HC. Antioxidants in fruits and vegetables-the millennium’s health. Int J Food Sci Tech 2001; 36:703-725.
  • Duthie GG, Wahle KWJ, James WPT. Oxidants, antioxidants and cardiovascular disease. Nutr Res Rev 1989; 2:51-62.
  • Meydani M. Antioxidants and cognitive function. Nutr Rev 2001; 59:S75-S82.
  • Foote CS. Chemistry of reactive oxygen species. In, Chemical Changes in Food During Processing (Eds T Richardson, JW Finley):17-32. New York, Van Nostrand Rainhold Company, 1985.
  • Lavelli V, Peri C, Rizzola A. Antioxidant activity of tomato products as studied by model reactions using xanthine oxidase, myeloperoxidase, and copper-induced lipid peroxidation. J Agric Food Chem 2000; 48:1442-1448.
  • Hardeland R, Balzer I, Poeggeler B, Fuhrberg B, Uría H, Behrmann G et al. On the primary function of melatonin in evolution: mediation of photoperiodic signals in a unicells, photoxidation and scavenging of free radicals. J Pineal Res 1995; 18:104
  • Reiter RJ, Tan DX, Manchester LC, Qi W. Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence. Cell Biochem Biophys 2001; 34:237-256.
  • Tan DX, Reiter RJ, Manchester LC, Yan MT, El-Sawi M, Sainz RM et al. Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. Curr Topics Med Chem 2002; 2:181-198.
  • Allegra M, Reiter RJ, Tan DX, Gentile C, Tesoriere L, Livrea MA. The chemistry of melatonin's interaction with reactive species. J Pineal Res 2003; 34:1-10.
  • Reiter RJ. Functional aspects of the pineal hormone melatonin in combating cell and tissue damage induced by free radicals. Eur J Endocrinol 1996; 134:412-420.
  • Reiter RJ. Antioxidant actions of melatonin. Adv Pharmacol 1997; 38:103-116.
  • Şahna E, Deniz E, Aksulu HE. Miyokardiyal iskemi-perfüzyon hasarı ve melatonin. Anadolu Kardiyol Derg 2006; 6:163-168.
  • Tan DX, Chen LD, Poeggeler B. Melatonin: A potent endogenous hydroxyl radical scavenger.Endocr J 1993; 1:57-60.
  • Reiter RJ. Cytoprotective properties of melatonin: presumed association with oxidative damage and aging. Nutrition 1998; 14:691-696.
  • Reiter RJ. Functional diversty of the pineal hormone melatonin: its role as an antioxidant. Exp Clin Endocrinol 1996;104:10-16.
  • Lerner AB, Nordlund JJ. Melatonin: clinical pharmacology. J Neural Transm Suppl 1978; 13:339-347.
  • Pail G, Huf W, Pjrek E, Winkler D, Willeit M, Praschak-Rieder N et al. Bright-light therapy in the treatment of mood disorders. Neuropsychobiology. 2011; 64:152-162. Annagür BB, Savaş HA. Depresyonda ekhastalık, ekhastalık olarak depresyon: Türkiye’de yapılmış çalışmaların gözden geçirilmesi. Journal of Mood Disorders 2011; 1:87Lewy AJ, Emens JS, Songer JB, Sims N, Laurie AL, Fiala SC et al. Winter depression: integrating mood, circadian rhythms, and the sleep/wake and light/dark cycles into a bio-psycho-social-environmental model. Sleep Med Clin 2009; 4:2852
  • Roecklein KA, Rohan KJ, Postolache TT. Is seasonal affective disorder a bipolar variant? Curr Psychiatr 2010; 9:42-54.
  • Arendt J. Melatonin and the Mammalian Pineal Gland. London, Chapman&Hall, 19 Şener G. Karanlığın hormonu: melatonin. Marmara Eczacılık Dergisi 2010; 14:112
  • Khaleghipour S, Masjedi M, Ahade H, Enayate M, Pasha G, Nadery F et al. 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.
  • Sher L, Oquendo MA, Galfalvy HC, Zalsman G, Cooper TB, Mann JJ. Higher cortisol levels in spring and fall in patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29:529-534.
  • Challet E. Mini review: Entrainment of the suprachiasmatic clockwork in diurnal and nocturnal mammals. Endocrinology 2007; 148:5648-5655.
  • Lam RW, Bercowitz AL, Berga SL, Clark CM, Kripke DP, Gillin JC. Melatonin suppression in bipolar and unipolar mood disorders. Psychiatry Res 1990; 33:1291
  • Pacchierotti CL, Iapichino L, Bossini L, Pieraccini F, Castrogiovanni P. Melatonin in psychiatric disorders: a review on the melatonin involvement in psychiatry. Front Neuroendocrinol 2001; 22:18-23.
  • Lewy AJ, Wehr TA, Goodwin FK, Newsome DA, Rosenthal NE. Manic-depressive patients may be supersensitive to light. Lancet 1981; 1:383-384.
  • Suresh Kumar PN, Andrade C, Bhakta SG, Singh NM. Melatonin in schizophrenic outpatients with insomnia: a double-blind, placebo-controlled study. J Clin Psychiatry 2007; 68:237-241.
  • Shamir E, Rotenberg VS, Laudon M, Zisapel N, Elizur A. Firts-night effects of melatonin treatment in patients with chronic schizophrenia. J Clin Psychopharmacol 2000; 20:691-694.
  • Blazejova K, Illnerova H, Hajek I, Nevsimalova S. Circadian rhythm in salivary melatonin in narcoleptic patients: Neurosci Lett 2008; 437:162-164.
  • Penttinen J. Hypothesis: low serum cholesterol, suicide and interleukin 2. Am J Epidemiol 1995; 141:711-718. 1 Aydın N, Çayköylü A, Aktaş E, Şahin A, Kırpınar İ. İntihar girişiminde bulunan kişilerde plazma-solubl interlökin-2r ve lipid düzeyleri. Klinik Psikofarmakoloji Bülteni 2001; 11:11-16. 1 Catapano F, Monteleone P, Fuschino A, Maj M, Kemali D. Melatonin and cortisol secretion in patients with primary obsessive-compulsive disorder. Psychiatry Res 1992; 44:217-225. 1 Monteleone P, Catapano F, Tortorella A, Di Martino S, Maj M. Plasma melatonin and cortisol circadian patterns in patients with obsessive-compulsive disorder before and after fluoxetine treatment. Psychoneuroendocrinology 1995;20 :763-770. 1 Cameron OG, Nesse RM. Systemic hormonal and physiological abnormalities in anxiety disorders. Psychoneuroendocrinology 1988; 13:287-307. Fatih Özçelik, Uzm Dr., Erzincan Asker Hastanesi,Erzincan; Murat Erdem, Yrd. Doç. Dr., GATA Ruh Sağlığı ve Hastalıkları ABD, Ankara; Abdullah Bolu, Uzm. Dr. Eskişehir Hava Hastanesi, Eskişehir; Murat Gülsün, Doç. Dr., GATA Ruh Sağlığı ve Hastalıkları ABD, Ankara Yazışma Adresi/Correspondence: Fatih Özçelik, Erzincan Asker Hastanesi, Erzincan, Turkey. E-mail: 68ozcelik@mynet.com Yazarlar bu makale ile ilgili herhangi bir çıkar çatışması bildirmemişlerdir. The authors reported no conflict of interest related to this article. Çevrimiçi adresi / Available online at: www.cappsy.org/archives/vol5/no2/ Çevrimiçi yayım / Published online 04 Şubat/February 04, 2013; doi:10.5455/cap.20130512

Melatonin: General Features and its Role in Psychiatric Disorders

Yıl 2013, Cilt: 5 Sayı: 2, 179 - 203, 01.06.2013
https://doi.org/10.5455/cap.20130512

Öz

In recent years, there is a growing interest in melatonin all over the world. The main task of protecting the body's biological clock, which set the rhythm of melatonin, involves many biological and physiological processes of the body. Cell renewal, strengthening of the immune system and body temperature regulation are other tasks of melatonin. Melatonin, with its lipophilic property, is the most powerful antioxidant as it can reach all body areas and can easily pass the blood-brain barrier. The fact that individuals with low levels of melatonin have sleep problems lead to the consideration of melatonin as a therapeutic medicine in this field. The detailed researches have shown that melatonin can improve sleep quality without changing the total duration of sleep. Nevertheless, despite high number of researches done, the functions of melatonin have not yet fully understood. Therefore, review of the available information related to melatonin will be guide for researchers in the field.

Kaynakça

  • Claustrat B, Brun J, Chazot G. The basic physiology and pathophisology of melatonin. Sleep Med Rev 2005; 9:11-24.
  • Macchi MM, Bruce JN. Human pineal physiology and functional significance of melatonin. Front Neuroendocrinol 2004; 25:177-195.
  • Ratzburg, C. Melatonin–the myths and facts. http://www.vanderbilt.edu/ AnS/psychology/ health_psychology/melatonin.htm (retrieved on Jan 01, 2013).
  • Lerner AB. Hormones and skin color. Sci Am. 1961; 205:98-108.
  • Çam A, Erdoğan MF. Melatonin. Ankara Üniversitesi Tıp Fakültesi Mecmuası 2003; 56:103-112.
  • Mollaoğlu H, Özgüner MF. Yaşlanma sürecinde melatoninin rolü. Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi 2005; 12:52-56.
  • Webb SM, Domingo MP. Role of melatonin in health and disease. Clin Endocrinol 1995; 42:221-234.
  • Maksimovich AA. Structure and function of the pineal gland in the vertebrates, Zh Evol Biokhim Fiziol 2002; 38:3-13.
  • Djeridane Y, Touitou Y. Melatonin synthesis in the rat Harderian gland: age and time related effects. Exp Eye Res. 2001; 72:487-492.
  • Bourne RS, Mills GH. Melatonin: possible implications for the postoperative and critically ill patient. Intensive Care Med 2006; 32:371-379.
  • Cardinali DP, Pévet P. Basic aspects of melatonin action. Sleep Med Rev 1998; 2:175-190.
  • Rahman MK, Nagatsu T, Sakurai T, Hori S, Abe M, Matsuda M. Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-DOPA and L-5-hydroxytryptophan as substrates in rats. Jpn J Pharmacol. 1982; 32:803-811. Bouchard S, Bousquet C, Roberge AG. Characteristics of dihydroxyphenylalanine/5hydroxytryptophan decarboxylase activity in brain and liver of cat. Journal of Neurochem 1981; 37:781-787.
  • Gomes P, Soares-da-Silva P. L-DOPA transport properties in an immortalised cell line of rat capillary cerebral endothelial cells, RBE 4. Brain Res. 1999; 829:143-150.
  • Bouchard S, Roberge AG. Biochemical properties and kinetic parameters of dihydroxyphenylalanine--5-hydroxytryptophan decarboxylase in brain, liver, and adrenals of cat. Can. J. Biochem 1979; 57:1014-1018.
  • Amamoto T, Sarai K. On the tryptophan-serotonin metabolism in manic-depressive disorders: changes in plasma 5-HT and 5-HIAA levels and urinary 5-HIAA excretion following oral loading of L-5HTP in patients with depression. Hiroshima J Med Sci 1976; 25:135-140.
  • Palaoğlu S, Beşkonaklı E. Pineal bez ve yaşlanma. Turkish Journal of Geriatrics 1998; 1:13Touitou Y. Human aging and melatonin: clinical relevance. Exp Gerontol 2001; 36:1083-1100.
  • Rohr UD, Herold J. Melatonin deficiencies in women. Maturitas 2002; 41:S85S
  • Nowak JZ, Zawilska JB. Melatonin and its physiological and therapeutic properties. Pharm World Sci 1998; 20:18-27.
  • Bountin JA, Aedinot V, Ferry G. Delagrange P. Molecular tools to study melatonin pathways and actions. Trends Pharmacol Sci 2005; 26:412-419.
  • Özgüner F, Özcankaya R, Delibaş N, Koyu A, Çalışkan S. Melatonin ve klinik önemi. Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi 1995; 2:1-6.
  • Klein DC. Photoneural regulation of the mammalian pineal gland. In Photoperiodism, Melatonin and The Pineal (Eds D Evered, S Clark):38-56. London, Pitman Pub, 1985.
  • Stoschitzky K, Sakotnik A, Lercher P, Zweiker R, Maier R, Liebmann P et al. Influence of beta-blockers on melatonin release. Eur J Clin Pharmacol 1999; 55:111
  • Reppert SM. Melatonin receptors: molecular biology of a new family of G proteincoupled receptors. J. Biol. Rhythms 1997; 12:528-531.
  • Sugden D, Davidson K, Hough KA, Teh MT. Melatonin, melatonin receptors and melanophores: a moving story. Pigment Cell Res 2004; 17:454-460.
  • Moğulkaç R, Baltacı AK. Hipertiroidi oluşturulan ratlarda intraperitoneal melatonin uygulamasının tiroid hormonları ve testesteron salınmasına etkisi. Genel Tıp Dergisi 2002; 12:129-132.
  • Reiter RJ. The pineal gland and melatonin relation to aging: a summary of the theories and of the data. Exp Gerontol 1995; 30:199-212.
  • Lee P, Shiu SY, Chow PH. Regional and diurnal studies of melatonin and melatonin binding sites in the duck gastrointestinal tract. Biol Signals 1995; 4:212-224.
  • Siu AW, Reiter RJ, To CH. The efficacy of vitamin E and melatonin as antioxidants against lipid peroxidation in rat retinal homogenates. J Pineal Res 1998; 24:239-244. Arendt J. Melatonin, circadian rhythms and sleep. New Engl J Med 2000; 343:11141
  • Attele AS, Xie JT, Yuan CS. Treatment of insomnia: an alternative approach. Altern Med Rev. 2000; 5:249-259.
  • Smits MG, Nagtegaal EE, van der Heijden J, Coenen AM, Kerkhof GA. Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial. J Child Neurol 2001; 16:86-92.
  • Bendz LM, Scates AC. Melatonin treatment for insomnia in pediatric patients with attention-deficit/hyperactivity disorder. Ann Pharmacother. 2010; 44:185-191.
  • Baskett JJ, Wood PC, Broad JB, Duncan JR, English J, Arendt J. Melatonin in older people with age-related sleep maintenance problems: a comparison with age matched normal sleepers. Sleep. 2001; 24:418-424.
  • Bazil CW, Short D, Crispin D, Zheng W. Patients with intractable epilepsy have low melatonin, which increases following seizures. Neurology. 2000; 55:1746-1748.
  • Tsuzuki K, Okamoto-Miunu K, Mizuno K. Effects of humid heat exposure on sleep, thermoregulation, melatonin and microclimate. J Therm Biol 2004; 29:31-34.
  • Scheer F, Czeisler CA. Melatonin, sleep, and circadian rhythms. Sleep Med Rev 2005; 9:5-9.
  • Russel R. Melatonin: clinical relevance. Best Pract Res Clin Endocrinol Metab 2003; 17:273-285.
  • Folkard S, Arendt J, Clark M. Can melatonin improve shift workers’ tolerance of the night shift? some preliminary findings. Chronobiol Int 1993; 10:315-320.
  • Shigeta H, Yasui A, Nimura Y, Machida N, Kageyama M, Miur M et al. Postoperative delirium and melatonin levels in elderly patients. Am J Surg 2001; 182:449-454.
  • Garfunkel D, Laundon M, Nof D, Zisapel N. Improvement of sleep quality in elderly people by controlled release of melatonin. Lancet 1990; 346:541-543.
  • Haimov I, Lavie P, Laudon M, Herer P, Vigder C, Zisapel N. Melatonin replacement therapy of elderly insomniacs. Sleep. 1995; 18:598-603.
  • Haimov I, Laudon M, Zisapel N, Souroujon M, Nof D, Schlitner A et al. Sleep disorders and melatonin rhythms in elderly people. BMJ. 1994; 309:167.
  • Cornelissen G, Halberg F, Burioka N, Perfetto F, Tarquini R, Bakken EE. Do plasma melatonin concentrations decline with age? Am J Med 2000; 109:343-345.
  • Commentz JC, Helmkek.Precocious puberty and decreased melatonin secretion due to a hypothalamic hamartoma. Horm Res 1995; 44:271-275.
  • Sato S, Yinc C, Teramoto A, Sakuma Y, Kato M. Sexually dimorphic modulation of GABA(A) receptor currents by melatonin in rats gonadotropin–releasing hormone neurons. J Physiol Sci 2008; 58:317-322.
  • Valcavi R, Zini M, Maestroni GJ, Conti A, Portioli I. Melatonin stimulates growth hormone secretion trough pathway other than the growth hormone-releasing hormone. Clin Endocrinol (Oxf) 1993; 39:193-199.
  • Kerman M, Cirak B, Özgüner MF. Dağtekin A. Does melatonin protect or treat brain damage from traumatic oxidative stres? Exp Brain Res 2005; 163:406-410.
  • Voordouw BC, Euser R, Verdonk RE, Alberda BT, de Jong FH, Drogendijk AC et al. Melatonin and melatoninprogestin combination after pituitary-ovulation function in women and can inhibit ovulation.J Clin Endocrinol Metab 1992; 74:108-117.
  • Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wideranging implications in tissue kinetics. Br J Cancer 1972; 26:239-257.
  • Searle J, Kerr JF, Bishop CJ. Necrosis and apoptosis distinct modes death with fundamentally different significance. Pathol Annu 1982; 17: 229-259.
  • Evan G, Littlewood T. A matter of life and cell death. Science 1998; 281:1317-1321. Toubi E, Shoenfeld Y. Protective autoimmunity in cancer. Oncol Rep 2007; 17:2452
  • García-Santos G, Antolín I, Herrera F, Martín V, Rodriguez-Blanco J, del Pilar Carrera M et al. Melatonin induces apoptosis in human neuroblastoma cancer cells. J Pineal Res 2006; 41:130-135.
  • Sun FY, Lin X, Mao LZ, Ge WH, Zhang LM, Huang YL et al. Neuroprotection by melatonin against ischemic neuronal injury associated with modulation of DNA damage and repair in the rat following a transient cerebral ischemia. J Pineal Res 2002; 33:48-56.
  • Yoo YM, Yim SV, Kim SS, Jang HY, Lea HZ, Hwang GC et al. Melatonin suppresses NO-induced apoptosis via induction of Bcl-2 expression in PGT-β immortalized pineal cells. J Pineal Res 2002; 33:146-150.
  • Eck-Enriquez K, Kiefer TL, Spriggs LL, Hill SM. Pathways through which a regimen of melatonin and retinoic acid induces apoptosis in MCF-7 human breast cancer cells. Breast Cancer Res Treat 2000; 61:229-239.
  • Yönel EE, Yaprak M, Yıldız Y. Yüksek ve düşük doz eksojen melatoninin erkek ratlarda vücut ısısına etkileri. Trakya Üniversitesi Tıp Fakültesi Dergisi 1996; 13:1-4. Nakahara K, Kawana T, Shiota K. Effect of microenjection of melatonin into various brain regions of Japanase quail on locomotor activity and body temperature. Neurosci Lett 2003; 345:117-120.
  • Cagnacci A. Melatonin in relation to physiology in adult humans. J Pineal Res 1996; 21:200-213.
  • Marino FE. Methods, advantages and limitations of body cooling for exercise performance. Br J Sport Med 2002; 36:89-94.
  • Herxheimer A, Petrie KJ. Melatonin for preventing and treating jet lag. Cochrane Database Syst Rev. 2001; 1:CD001520.
  • Poon AM, Pang SF. Pineal melatonin-immune system interactions. In Melatonin: A Universal Photoperiodic Signal with Diverse Actions (Eds PL Tang, SF Pang, RJ Reiter):71-83. Basel, Karger, 1996.
  • Guerrero JM, Garcia-Maurino S, Pozo D. Mechanisms involved in the immunomodulatory effects of melatonin on the human immune system. In The pineal gland and cancer (Eds C Bartsch, H Bartsch, D Blask):408-416. Heidelberg, Springer-Verlag, 2001.
  • Henshaw DL, Reiter RJ. Do magnetic fields increase risk of childhood leukemia via melatonin disruption? Bioelectromagnetics 2005; 7:S86-S97.
  • Balsalobre A. Clock genes in mammalian peripheral tissues. Cell Tissue Res 2002; 309:193-199.
  • Richards J, Gumz ML. Advances in understanding the peripheral circadian clocks. FASEB J 2012; 26:3602-3613.
  • Korkmaz A, Reiter RJ. Gece ışığa maruz kalma, sirkadiyen melatonin ritmi ve metabolik bozulma. Turkiye Klinikleri J Cardiovasc Sci 2009; 21:434-449.
  • Van Someren EJ, Riemersma-Van Der Lek RF. Live to the rhythm, slave to the rhythm. Sleep Med Rev 2007; 11:465-484.
  • Balsalobre A, Brown SA, Marcacci L, Tronche F, Kellendonk C, Reichardt HM et al. Resetting of circadian time in peripheral tissues by glucocorticoid signaling. Science 2000; 289:2344-2347.
  • Wojtowicz M, Jakill G. Melatonin and its role in human reproduction. Ginekol Pol 2002; 73:1231-1237.
  • Partonen T. Melatonin-dependent infertility. Med Hypothesis 1999; 52:269-270.
  • Dullo P, Chaudhary R. Short review of reproductive physiology of melatonin. Pak J Physiol 2009; 5:46-48.
  • Cos S, González A, Martínez-Campa C, Mediavilla MD, Alonso-González C, Sánchez-Barceló EJ. Estrogen-signaling pathway: a link between breast cancer and melatonin oncostatic actions. Cancer Detect Prev 2006; 30:118-128.
  • Cos S, GonzalezA, Martinez-Campa C, Mediavilla MD, Alonso-Gonzalez C, Sanchez Barcelo EJ. Melatonin as a selective estrogen enzyme modulator. Curr Cancer Drug Targets 2008; 8:691-702.
  • Stevens, Richard G. Circadian disruption and breast cancer: from melatonin to clock genes. Epidemiology 2005; 16:254-258.
  • Regelson W, Pierpaoli MD. Melatonin A rediscovered antitumor hormone? Its relation to surface receptors, sex steroid metabolism, immunologic response, and chronologic factors in tumor growth & therapy. Cancer Invest 1987; 5:379-385.
  • Karasket M, Fraschini F. Is there a role for pineal gland in neoplastic growth? In Role of Melatonin and Pineal Peptides in Neuroimmunomodulation (Eds F Fraschini, RJ Reiter):243-251. New York, Plenum, 1991.
  • Coleman MP, Reiter RJ. Breast cancer, blindness and melatonin. Eur J Cancer Clin Oncol 1992; 28:501-503.
  • Bartsch C, Bartsch H, Fluchter StH, Lippert TH. Depleted pineal melatonin production in primary breast and prostate cancer is connected with circadian disturbances; possible role of melatonin for synchronization of circadian rhythmicity. In: Melatonin and the Pineal Gland–From Basic Science to Clinical Application (Eds Y Touitou, J Arendt, P Pevet):311-316. New York, Elsevier, 1993.
  • Feychting M, Osterlund B, Ahlbom A. Reduced cancer incidence among the blind. Epidemiology 1998; 9:490-494.
  • Verkasalo PK, Pukkala E, Stevens RG, Ojamo M, Rudanko SL. Inverse association between breast cancer incidence and degree of visual impairment in Finland. Br J Cancer 1999; 80:1459-1460.
  • Reiter RJ, Tan DX. Melatonin: a novel protective agent against oxidative injury of the ischemic/reperfused heart. Cardiovasc Res 2003; 58:10-19.
  • Tan DX, Manchester LC, Reiter RJ, Qi W, Kim SJ, El-Sokkary GH. Ischemia/reperfusion-induced arrhythmias in the isolated rat heart: prevention by melatonin. J Pineal Res 1998; 25:184-191.
  • Lee YM, Chen HR, Hsiao G, Sheu JR, Wang JJ, Yen MH. Protective effects of melatonin on myocardial ischemia/reperfusion injury in vivo. J Pineal Res 2002; 33:72
  • Yildiz M, Akdemir O. Assessment of the effects of physiological release of melatonin on arterial distensibility and blood pressure. Cardiol Young 2009; 19:198-203.
  • Nawar WW. Lipids. In Food Chemistry (Ed OR Fennema):225-319. New York, Marcel Dekker, 1996.
  • Kaur C, Kapoor HC. Antioxidants in fruits and vegetables-the millennium’s health. Int J Food Sci Tech 2001; 36:703-725.
  • Duthie GG, Wahle KWJ, James WPT. Oxidants, antioxidants and cardiovascular disease. Nutr Res Rev 1989; 2:51-62.
  • Meydani M. Antioxidants and cognitive function. Nutr Rev 2001; 59:S75-S82.
  • Foote CS. Chemistry of reactive oxygen species. In, Chemical Changes in Food During Processing (Eds T Richardson, JW Finley):17-32. New York, Van Nostrand Rainhold Company, 1985.
  • Lavelli V, Peri C, Rizzola A. Antioxidant activity of tomato products as studied by model reactions using xanthine oxidase, myeloperoxidase, and copper-induced lipid peroxidation. J Agric Food Chem 2000; 48:1442-1448.
  • Hardeland R, Balzer I, Poeggeler B, Fuhrberg B, Uría H, Behrmann G et al. On the primary function of melatonin in evolution: mediation of photoperiodic signals in a unicells, photoxidation and scavenging of free radicals. J Pineal Res 1995; 18:104
  • Reiter RJ, Tan DX, Manchester LC, Qi W. Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence. Cell Biochem Biophys 2001; 34:237-256.
  • Tan DX, Reiter RJ, Manchester LC, Yan MT, El-Sawi M, Sainz RM et al. Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. Curr Topics Med Chem 2002; 2:181-198.
  • Allegra M, Reiter RJ, Tan DX, Gentile C, Tesoriere L, Livrea MA. The chemistry of melatonin's interaction with reactive species. J Pineal Res 2003; 34:1-10.
  • Reiter RJ. Functional aspects of the pineal hormone melatonin in combating cell and tissue damage induced by free radicals. Eur J Endocrinol 1996; 134:412-420.
  • Reiter RJ. Antioxidant actions of melatonin. Adv Pharmacol 1997; 38:103-116.
  • Şahna E, Deniz E, Aksulu HE. Miyokardiyal iskemi-perfüzyon hasarı ve melatonin. Anadolu Kardiyol Derg 2006; 6:163-168.
  • Tan DX, Chen LD, Poeggeler B. Melatonin: A potent endogenous hydroxyl radical scavenger.Endocr J 1993; 1:57-60.
  • Reiter RJ. Cytoprotective properties of melatonin: presumed association with oxidative damage and aging. Nutrition 1998; 14:691-696.
  • Reiter RJ. Functional diversty of the pineal hormone melatonin: its role as an antioxidant. Exp Clin Endocrinol 1996;104:10-16.
  • Lerner AB, Nordlund JJ. Melatonin: clinical pharmacology. J Neural Transm Suppl 1978; 13:339-347.
  • Pail G, Huf W, Pjrek E, Winkler D, Willeit M, Praschak-Rieder N et al. Bright-light therapy in the treatment of mood disorders. Neuropsychobiology. 2011; 64:152-162. Annagür BB, Savaş HA. Depresyonda ekhastalık, ekhastalık olarak depresyon: Türkiye’de yapılmış çalışmaların gözden geçirilmesi. Journal of Mood Disorders 2011; 1:87Lewy AJ, Emens JS, Songer JB, Sims N, Laurie AL, Fiala SC et al. Winter depression: integrating mood, circadian rhythms, and the sleep/wake and light/dark cycles into a bio-psycho-social-environmental model. Sleep Med Clin 2009; 4:2852
  • Roecklein KA, Rohan KJ, Postolache TT. Is seasonal affective disorder a bipolar variant? Curr Psychiatr 2010; 9:42-54.
  • Arendt J. Melatonin and the Mammalian Pineal Gland. London, Chapman&Hall, 19 Şener G. Karanlığın hormonu: melatonin. Marmara Eczacılık Dergisi 2010; 14:112
  • Khaleghipour S, Masjedi M, Ahade H, Enayate M, Pasha G, Nadery F et al. 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.
  • Sher L, Oquendo MA, Galfalvy HC, Zalsman G, Cooper TB, Mann JJ. Higher cortisol levels in spring and fall in patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29:529-534.
  • Challet E. Mini review: Entrainment of the suprachiasmatic clockwork in diurnal and nocturnal mammals. Endocrinology 2007; 148:5648-5655.
  • Lam RW, Bercowitz AL, Berga SL, Clark CM, Kripke DP, Gillin JC. Melatonin suppression in bipolar and unipolar mood disorders. Psychiatry Res 1990; 33:1291
  • Pacchierotti CL, Iapichino L, Bossini L, Pieraccini F, Castrogiovanni P. Melatonin in psychiatric disorders: a review on the melatonin involvement in psychiatry. Front Neuroendocrinol 2001; 22:18-23.
  • Lewy AJ, Wehr TA, Goodwin FK, Newsome DA, Rosenthal NE. Manic-depressive patients may be supersensitive to light. Lancet 1981; 1:383-384.
  • Suresh Kumar PN, Andrade C, Bhakta SG, Singh NM. Melatonin in schizophrenic outpatients with insomnia: a double-blind, placebo-controlled study. J Clin Psychiatry 2007; 68:237-241.
  • Shamir E, Rotenberg VS, Laudon M, Zisapel N, Elizur A. Firts-night effects of melatonin treatment in patients with chronic schizophrenia. J Clin Psychopharmacol 2000; 20:691-694.
  • Blazejova K, Illnerova H, Hajek I, Nevsimalova S. Circadian rhythm in salivary melatonin in narcoleptic patients: Neurosci Lett 2008; 437:162-164.
  • Penttinen J. Hypothesis: low serum cholesterol, suicide and interleukin 2. Am J Epidemiol 1995; 141:711-718. 1 Aydın N, Çayköylü A, Aktaş E, Şahin A, Kırpınar İ. İntihar girişiminde bulunan kişilerde plazma-solubl interlökin-2r ve lipid düzeyleri. Klinik Psikofarmakoloji Bülteni 2001; 11:11-16. 1 Catapano F, Monteleone P, Fuschino A, Maj M, Kemali D. Melatonin and cortisol secretion in patients with primary obsessive-compulsive disorder. Psychiatry Res 1992; 44:217-225. 1 Monteleone P, Catapano F, Tortorella A, Di Martino S, Maj M. Plasma melatonin and cortisol circadian patterns in patients with obsessive-compulsive disorder before and after fluoxetine treatment. Psychoneuroendocrinology 1995;20 :763-770. 1 Cameron OG, Nesse RM. Systemic hormonal and physiological abnormalities in anxiety disorders. Psychoneuroendocrinology 1988; 13:287-307. Fatih Özçelik, Uzm Dr., Erzincan Asker Hastanesi,Erzincan; Murat Erdem, Yrd. Doç. Dr., GATA Ruh Sağlığı ve Hastalıkları ABD, Ankara; Abdullah Bolu, Uzm. Dr. Eskişehir Hava Hastanesi, Eskişehir; Murat Gülsün, Doç. Dr., GATA Ruh Sağlığı ve Hastalıkları ABD, Ankara Yazışma Adresi/Correspondence: Fatih Özçelik, Erzincan Asker Hastanesi, Erzincan, Turkey. E-mail: 68ozcelik@mynet.com Yazarlar bu makale ile ilgili herhangi bir çıkar çatışması bildirmemişlerdir. The authors reported no conflict of interest related to this article. Çevrimiçi adresi / Available online at: www.cappsy.org/archives/vol5/no2/ Çevrimiçi yayım / Published online 04 Şubat/February 04, 2013; doi:10.5455/cap.20130512
Toplam 112 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Derleme
Yazarlar

Fatih Özçelik Bu kişi benim

Murat Erdem Bu kişi benim

Abdullah Bolu Bu kişi benim

Murat Gülsün Bu kişi benim

Yayımlanma Tarihi 1 Haziran 2013
Yayımlandığı Sayı Yıl 2013 Cilt: 5 Sayı: 2

Kaynak Göster

AMA Özçelik F, Erdem M, Bolu A, Gülsün M. Melatonin: Genel Özellikleri ve Psikiyatrik Bozukluklardaki Rolü. Psikiyatride Güncel Yaklaşımlar. Haziran 2013;5(2):179-203. doi:10.5455/cap.20130512

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