This paper is only available as a PDF. To read, Please Download here.
Abstract
The pineal methoxyindole melatonin remains the most widely studied of the “pineal
principles,” and in subhuman species, the neuroendocrine status of this hormone is
now generally acknowledged. In humans, however, no definitive functional activity
for melatonin has yet been convincingly demonstrated, despite the description in recent
years of marked changes in the metabolism of this hormone in several clinical categories.
Currently, much interest is focused on the role that melatonin may play in various
psychiatric disorders, and pineal research now represents one of the active areas
of current psychiatry research. Investigators in this field have encountered many
technical and practical difficulties, but the advent of the impressively sensitive
and specific assay systems for melatonin has done much to facilitate the progress
of research. Present ideas suggest a positive involvement of melatonin in affective
disorders, possible involvement in the schizophrenic psychosis, and potential involvement
of this hormone in other psychiatric categories. The present review discusses the
etiological significance, diagnostic potential, and clinical utility of melatonin
in psychiatry.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Some effects of aqueous extracts of acetone extracts of acetone dried beef pineal substance in chronic schizophrenia.N Engl J Med. 1957; 257: 919-922
- On the effects of melatonin upon human brain: Its possible therapeutic implications.Life Sci. 1971; 10: 841-850
- Reproducibility of the overnight melatonin secretion pattern in healthy men.in: Brown G.M Wainwright S.D Advances in the Bio-sciences: The Pineal Gland: Endocrine Aspects. Pergamon Press, Oxford1985: 277-282
- The effects of chronic small doses of melatonin given in the late afternoon on fatigue in man: A preliminary study.Neurosci Lett. 1984; 45: 317-321
- The pineal gland: A neurochemical transducer.Science. 1974; 184: 1341-1348
- Enzymatic O-methylation of N-acetylserotonin to melatonin.Science. 1960; 131: 1312
- Increased N-acetylserotonin and melatonin formation induced by d-amphetamine in rat pineal gland organ culture via β-adrenergic receptor mechanism.Acta Physiol Scand. 1973; 87: 113-120
- A marker for pineal tumours?.Lancet. 1978; ii: 372-373
- Acute pharmacology of melatonin.Nature. 1967; 214: 919-920
- Urinary melatonin levels in human breast cancer patients.J Neural Transm. 1981; 52: 281
- Epiglandol bei Dementia Praecox.Therapeut Halbmonatscher. 1920; 34: 667-668
- Hormonal changes in acute depression.in: Perris C Struwe G Jansson B Biological Psychiatry. Elsevier/North Holland Biomedical Press, Amsterdam1981: 1244-1248
- Serum melatonin in relation to clinical variables in patients with major depressive disorders: a hypothesis of a low melatonin syndrome.Acta Psychiatr Scand. 1985; 71: 319-330
- Melatonin immunoreactivity in cerebrospinal fluid of schizophrenic patients and healthy controls.Psychiatry Res. 1984; 11: 107-110
- The daily light-dark cycle and rhythmic metabolism in the photoreceptor pigment epithelial complex.Prog Retinal Res. 1982; 1: 81-124
- Mitotic activity in the adenohypophysis of rats after pinealectomy.J Endocrinol. 1968; 41: 451
- Low nocturnal melatonin serum concentrations in anorexia nervosa—further evidence for body weight influence.IRCS Med Sci (Psychol Psychiatry). 1984; 12: 477
- 6-Sulphatoxymelatonin in melancholia.Am J Psychiatry. 1985; 142: 125-127
- Melatonin action in the midbrain can regulate forebrain dopamine function both behaviourally and biochemically.in: Brown G.M Wainwright S.D Advances in the Biosciences: The Pineal Gland: Endocrine Aspects. Pergamon Press, New York1985: 327-332
- Simultaneous study of 24 hr patterns of melatonin and cortisol secretion in depressed patients.Neuropsychobiology. 1982; 8: 225-232
- Nocturnal serum melatonin in major depressive disorder before and after desmethylimipramine treatment.Psychopharmacol Bull. 1985; 21: 579-581
- Dif-ferences in nocturnal melatonin secretion between melancholic depressed patients and control subjects.Am J Psychiatry. 1985; 142: 811-816
- Immunohistological localization of N-acetyl-indole—alkylamines in pineal gland, retina and cerebellum.Brain Res. 1974; 81: 223
- Immunohistological localization of melatonin in the rat digestive tract.Experentia. 1977; 33: 662
- A suspension culture of pinealocytes. Regulation of N-acetyltransferase activity.Endocrinology. 1978; 103: 1483
- Melatonin.Endocrinol Rev. 1981; 2: 327
- Binding of melatonin to human and rat plasma proteins.Endocrinology. 1972; 91: 1213-1218
- Negative effects of melatonin on depression.Am J Psychiatry. 1976; 133: 1181-1186
- A chronobiological study of melatonin and cortisol secretion in depressed subjects: plasma melatonin, a biochemical marker in major depression.Biol Psychiatry. 1984; 19: 1215-1228
- Plasma melatonin during des-methylimipramine treatment; evidence for changes in noradrenergic transmission.Br. J Clin Pharmacol. 1985; 19: 799-805
- On the effects of melatonin on sleep and behaviour in man.in: Serotonin: New Vistas, Biochemistry and Behavioural and Clinical Studies. Advances in Biochemical Psychopharmacology. vol II. Raven Press, New York1974: 187-191
- Dopamine receptor binding predicts clinical and pharma-cological potencies of antischizophrenic drugs.Science. 1976; 192: 481-483
- Effect of hydrocortisone on rat brain 5-hydroxytryptamine.Life Sci. 1968; 7: 657
- Profils journaliers de la melatonine, du cortisol et des gonadotrophines chez 8 adolescentes porteuses d'une anorexie mentale.Encephale. 1985; 11: 25-28
- Evidence for the existence of a pineal-adrenal and pineal-thyroidal axis.Acta Endocrinol. 1972; 70: 31-42
- Effect of pinealectomy on the electrical responses of hypothalamic neurones to the application of melatonin.in: Advances in the Bio-sciences: Melatonin: Current Status and Perspectives. vol 29. Pergamon Press, Oxford1980: 123-128
Descartes R (1662 posthumous): De Homine Figuris et Latinitate donatus a F. Schuyl Lugduni Batavorum.
- Hormonal changes after jet lag in normal men.Adv Biol Psychiatry. 1983; 11: 60-63
- Evidence for a serotonin uptake system in isolated bovine pinealocyte suspensions.Mol Pharmacol. 1980; 18: 438
- A pilot study comparing the effects of pineal extract and a placebo in patients with chronic schizophrenia.N Engl J Med. 1961; 263: 1330-1335
- Epileptogenic action of intraventricularly injected anti-melatonin antibody.Neurology. 1977; 27: 567-570
- Reduced nocturnal secretion of melatonin in chronic schizophrenia: Relationship to body weight.Clin Endocrinol. 1982; 17: 181-187
- Melatonin/cortisol ratio in psychiatric illness.Lancet. 1982; i: 1070
- Influence of acute and chronic treatment with desmethylimpramine on catecholamine effects in the rat.J Pharmacol Exp Ther. 1978; 206: 311-319
- Antidepressant drugs with varying pharmacological profiles alter rat pineal β-adrenergic mediated function.J Pharmacol Exp Ther. 1984; 228: 545-550
- Serotonin and antidepressant drugs antagonize melatonin induced behavioural changes after injection into the nucleus accumbens of rats.Neuropharmacology. 1985; 24: 237-244
- Evidence for a brain site of melatonin action in the white footed mouse Peromyscus leucopsus.Neuroendocrinology. 1982; 34: 1-6
- A new marker for noradrenergic function in man? Presented at the American Psychiatric Association Annual meeting, Los Angeles, CA1984 (abstr)
- An inverse correlation between serum levels of desmethylimipramine and melatonin-like immunoreactivity in DMI responsive depressives.Psychiatry Res. 1981; 4: 109-113
- Propranolol in schizophrenia: Clinical, metabolic and pharmacological findings.Arch Gen Psychiatry. 1980; 37: 685
- The activation of pineal hydroxyindole, O-methyltransferase by psychotomimetic drugs.J Pharm Pharmacol. 1973; 25: 751-752
- The inhibition of pineal hydroxyindole, O-methyltrans-ferase by haloperidol and fluphenazine.J Pharm Pharmacol. 1972; 24: 100-103
- Melatonin: Daily cycle in plasma and cerebrospinal fluid of calves.Science. 1977; 195: 686
- Inhibitory effects of a pineal extract on adrenal cortex; lack of competition with ACTH.Horm Res. 1980; 12: 104-112
- Effects of darkness and of desmethylimipramine on pineal gland concentrations of adenosine 3, 5-monophosphate.Biochem Pharmacol. 1979; 29: 1341-1346
- Do tricyclic antidepressants enhance adrenergic trans-mission? An update.Am J Psychiatry. 1980; 137: 113-114
- In vitro and in vivo formation of two new metabolites of melatonin.J Biol Chem. 1974; 249: 1311-1313
- Stimulation of serotonin N-acetyltransferase in pineal organ culture by drugs.J Neurochem. 1974; 22: 205-209
- Urinary melatonin rhythms during sleep deprivation in depressed patients and normals.Life Sci. 1977; 20: 1501-1508
- Metabolism of exogenous melatonin in schizophrenic and non-schizophrenic volunteers.Clin Chim Acta. 1969; 26: 281-286
- The Pineal Gland.Harvard University Press, Cambridge MA1954
- Indole metabolism in the pineal gland: A arcadian rhythm in N-acetyltransferase.Science. 1970; 169: 1093-1095
- Pineal gland in organ culture.Mol Pharmacol. 1970; 6: 164-171
- The fate of melatonin in animals.J Biol Chem. 1961; 236: 3072
- Evidence for the presence of melatonin in the human brain.Neurosci Lett. 1980; 19: 237-242
- Effect of melatonin on l-tryptophan and apomorphine stimulated growth hormone secretion in man.J Endocrinol Metab. 1979; 49: 70-72
- Photoperiodic mechanisms for depression and its treatment.in: Penis C Struwe G Jansson B Biological Psychiatry. Elsevier, Amsterdam1981: 1249
- Therapeutic effects of bright light in depressed patients.Ann NY Acad Sci. 1986; 453: 270-281
- Crcadian disorders in manic-depressives.Biol Psychiatry. 1978; 13: 335-351
- Bright white light alleviates depression.Psychiatry Res. 1983; 10: 105-112
- Melatonin.in: Fed Proc. 19. 1960: 590-592
- Isolation of melatonin, the pineal factor that lightens melanocytes.J Am Chem Soc. 1958; 80: 2587
- Structure of melatonin.J Am Chem Soc. 1959; 81: 6085
- Effects of light on human melatonin production and the human circadian system.Prog Neuropsychopharmacol Biol Psychiatry. 1983; 7: 551-556
- Human melatonin secretion: A marker for the circadian system and the effects of light.in: Post RN Ballender JC Neurobiology of Mood Disorders. William & Wilkins, Baltimore1984: 215-226
- Analysis of melatonin in human plasma by gas chromatography negative ionization mass spectrometry.Science. 1978; 201: 741
- Plasma melatonin in manic-depressive illness.in: Catecholamines: Basic and Clinical Frontiers. vol II. Pergamon Press, Oxford1979: 1173-1175
- Manic-depressive patients may be supersensitive to light.Lancet. 1981; i: 383-384
- Bright artificial light treatment of a manic-depressive patient with a seasonal mood cycle.Am J Psychiatry. 1982; 139: 1496-1498
- Melatonin rhythm in some idiopathic hypothalamic-hypophyseal diseases.in: Brown GM Wainwright SD Advances in the Biosciencesx; The Pineal Gland: Endocrine Aspects. Pergamon Press, Oxford1985: 307-312
- Increase in rat pineal melatonin content following L-dopa administration.Life Sci. 1973; 12: 145-151
- Sleep induced by the administration of melatonin to the hypothalamus in unrestrained cats.Experentia. 1964; 20: 435-437
- Lithium delays biochemical circadian rhythms in rats.Neuropsychobiology. 1982; 8: 12-29
- A biochemical concept of mental disease.Postgrad Med. 1961; 30: 111-118
- Abnormal 24 hr pattern of melatonin secretion in depression.Lancet. 1979; ii: 1362
- The 24 hr pattern of plasma melatonin in depressed patients before and after treatment.Commun Psychopharmacol. 1980; 4: 49-55
- Melatonin: Perspectives in laboratory medicine and clinical re-search.in: CRC Reviews in Clinical Laboratory Sciences. CRC Press, Boca Raton, FL1987 (in press).
- Direct radioimmunoassay of melatonin in saliva.Clin Chem. 1985; 31: 1412-1413
- Salivary melatonin estimation in clinical research,.Clin Chem. 1985; 31: 2041-2042
- Diagnostic potential of melatonin analysis in pineal tumours.New Engl J Med. 1985; 313: 329-330
- Melatonin—A diagnostic marker in laboratory medicine?.in: Miles A Philbrick DRS Thompson C Melatonin: Clinical Perspectives. Oxford University Press, Oxford1987 (in press).
- Visual pathways and the central neural control of a circadian rhythm in pineal serotonin N-acetyltransferase activity.Brain Res. 1974; 71: 17
- Neural control of pineal function in mammals and birds.J Neural Transm (Suppl). 1978; 13: 47
- Effect of adrenergic stimulation and blockade of melatonin secretion in the human.Prog Brain Res. 1979; 52: 517-521
- Pathological states involving the pineal.in: Martini L Besser GM Clinical Neuroendocrinology. Academic Press, Orlando, FL1977: 503-526
- Opposite effects of acute and repeated administration of desmethylimipramine on adrenergic responsiveness in rat pineal gland.Life Sci. 1979; 24: 2237-2244
- Subsensitivity of the β-adrenergic receptor linked adenylate cyclase system of rat pineal gland following repeated treatment with desme-thylimipramine and nialamide.Mol Pharmacol. 1981; 19: 187-193
- The distribution of haloperidol in rat brain.BrJ Pharmacol. 1959; 36: 208-209
- Melatonin receptors in brain.Eur J Pharmacol. 1979; 55: 219-220
- Melatonin: Daily cycle in plasma and cerebrospinal fluid of calves.Science. 1977; 195: 686
- Effects of melatonin and an aqueous pineal extract on adrenal secretion of reduced steroid metabolites in female rats.Neuroendocrinology. 1977; 23: 113-120
- In vitro effects of melatonin and serotonin on adrenal steroidogenesis.in: Proc Soc Exp Biol Med. 157. 1978: 103-105
Owen F, Ferner IN, Poulter M 91983): Hydroxyindole, O-methyltransferase activity in human pineals: A comparison of controls and schizophrenics. Clin Endocrinol 19:313–317.
- Increase caused by desmethylimipramine in the production of 3H-melatonin by isolated pineal glands.Biochem Pharmacol. 1977; 26: 904-905
- Characterization of pinealectomy induced convulsions in the Mongolian gerbil.Epilepsia. 1978; 19: 485-492
- The pineal gland: Basic implications and clinical correlations.Endocrinol Rev. 1984; 5: 282-308
- The pineal and its hormones in the control of reproduction in mammals.Endocrinol Rev. 1980; 1: 109-131
- Melatonin inhibition of reproduction in the male hamster: Its dependency on time of day of administration and on intact and sympathetically innervated pineal gland.Neuroendocrinology. 1976; 22: 107-116
- Effects of pinealectomy and constant light and darkness on thyrotropin levels in the pituitary and plasma of the rat.Neuroendocrinology. 1972; 10: 46
- Cerebrospinal fluid melatonin.in: Wood JH Neurobiology of Cerebrospinal Fluid. Plenum Press, New York1980: 579-589
- Route of melatonin secretion in sheep.Endocrinology. 1978; 102: 1
- Seasonal affective disorder and phototherapy.Ann NY Acad Sci. 1986; 453: 260-269
- Disrupted patterns of cortisol secretion in psychotic depression.Arch Gen Psychiatry. 1973; 28: 19-24
- Desmethylimipramine treatment increases melatonin production in humans.Biol Psychiatry. 1986; 21: 406-410
- A retinohypothalamic pathway in man—Light mediation of circadian rhythms.Brain Res. 1984; 302: 371-377
- The catecholamine hypothesis of affective disorders: A review of supporting evidence.Am J Psychiatry. 1965; 122: 509
- Chronic lithium treatment and 24 hr rhythms of serum prolactin, growth hormone and melatonin in rats.Prog Neuropharmacol Biol Psychiatry. 1983; 7: 827-830
- Lithium and melatonin rhythms: Implications for depression.in: Brown GM Wainwright SD Advances in the Biosciences: The Pineal Gland: Endocrine Aspects. Pergamon Press, Oxford1985: 333-338
- Melatonin and parkinsonism.Lancet. 1973; i: 271
- Recent progress in schizophrenia research.Lancet. 1976; ii: 136-139
- Melatonin-cortisol ratio and the dexamethasone suppression test in newly admitted psychiatric inpatients.in: Brown GM Wainwright SD Advances in the Biosciences: The Pineal Gland: Endocrine Aspects. Pergamon Press, Oxford1985: 347-353
- Time course and sensitivity of golden hamsters to melatonin injections throughout the day.Biol Reprod. 1983; 29: 432-438
- Changes in regional brain levels of tryptophan, 5-hydroxytryptamine, 5-hydroxyindole acetic acid, dopamine and noradrenaline after pinealectomy in the rat.J Neu-rochem. 1979; 32: 1593-1595
- Psychopharmacological effects of melatonin in mouse and rat.J Pharmacol Exp Ther. 1983; 227: 587-591
- Decreased nocturnal plasma melatonin peak in patients with oestrogen receptor positive breast cancer.Science. 1982; 216: 1003
- Measurement of 6-hydroxymelatonin in human urine, and its clinical variations.Life Sci. 1980; 27: 105
- Melatonin and seasonal affective disorder.in: Miles A Philbrick DRS Thompson C Melatonin: Clinical Perspectives. Oxford University Press, Oxford1987 (in press).
- Down regulation at pineal β-adrenoreceptors in depressed patients treated with desiprimine?.Lancet. 1983; i: 1101
- Studies with reversible inhibitors of monoamine oxidase: Harmaline and related compounds.Biochem Pharmacol. 1958; 1: 160-165
- Monoamine oxidase activity of the hypothalamus and pituitary: Alter-ations after pinealectomy, changes in photoperiod, or addition of melatonin in vitro.Experentia. 1975; 31: 891
- Effect of melatonin and other pineal indoles on adrenal enlargement produced in female mice by pinealectomy, unilateral adrenalectomy, castration and cold stress.Neuroendocrinology. 1972; 10: 139
- De Humani Corporis Fabrica. Libri Septem. 1551; (Basiliae)
- Testing the TRH hypothesis of pineal function.Med Hypoth. 1978; 4: 376
- Melatonin and thyroid function.in: Miles A Philbrick DRS Thompson C Melatonin: Clinical Perspectives. Oxford University Press, Oxford1987 (in press).
- Status of our knowledge of the pineal gland.in: Brown GM Wainwright SD Advances in the Biosciences: The Pineal Gland: Endocrine Aspects. Pergamon Press, Oxford1985: 355-357
- Fall in nocturnal serum melatonin during prepuberty and pubescence.Lancet. 1984; i: 362
- Desynchronization of circadian rhythms as possible source of manic-depressive cycles.Psychopharmacol Bull. 1980; 16: 19-20
- Biosynthesis of melatonin: Enzymatic conversion of serotonin to N-acetylserotonin.Biochem Biophys Acta. 1960; 43: 352
- Increase in monoamine concentrations in rat brain following melatonin administration.Experentia. 1974; 30: 1167-1168
- Melatonin in humans. Physiological and clinical studies.J Neural Trans (Suppl). 1978; 13: 289-310
- The relationship between the pineal gland and the pituitary-adrenal axis in health, endocrine and psychiatric conditions.Psychoneuroendocrinology. 1983; 8: 75-80
- Melatonin/cortisol ratio in depression.Lancet. 1979; ii: 1361
- Pineal-hypothalamic-pituitary function in patients with depressive illness.in: Fuxe K Gustafsson JA Wetterberg L Steroid Hormone Regulation of the Brain. Pergamon Press, Oxford1981: 397-403
- Melatonin and cortisol levels in psychiatric illness.Lancet. 1982; ii: 100
- Genetic regulation of melatonin excretion in urine. A preliminary report.Clin Genet. 1984; 24: 399-402
- Circadian rhythms in melatonin and cortisol secretion in depression.in: Usdin E Asberg H Bertilsson L Sjoqvist F Frontiers in Biochemical and Pharmacological Research in Depression. Raven Press, New York1984: 197-205
- The synergistic effect of reduced visual input on ketamine action—The possible role of the pineal gland.Neuropharmacology. 1973; 12: 407-416
- Diurnal, menstrual cycle and seasonal rhythms in man and their modification.in: Obiols J Ballus G Gonzales-Monclus E Biological Psychiatry Today. Elsevier/North Holland, Amsterdam1979: 294-302
- Effects of pinealectomy and of a bovine pineal extract in rats.Am J Physiol. 1959; 197: 108
- Interactions of the pineal and exposure to continuous light on organ weights of female rats.Acta Endocrinol. 1961; 36: 617
- Effect of chronic lithium treatment on rat pineal rhythms: N-acetyltransferase, N-acetylserotonin and melatonin.J Pharmacol Exp Ther. 1983; 226: 733-737
- Pineal methoxyindoles in the human.in: The Pineal Gland. vol 3. CRC Press, Boca Raton, FL1981: 189-218
- Effect of oral melatonin administration on melatonin, 5-hydroxyindoleacetic acid, acetic acid and cyclic nucleotides in human cerebrospinal fluid.Neuroendocrinology. 1984; 39: 87-92
- Inhibition by melatonin of dopamine release from rat hypothalamus.Brain Res. 1983; 272: 378-381
Article info
Publication history
Received in revised form:
March 27,
1987
Received:
August 7,
1986
We thank Professor Peter McGuffin and Dr. David M. Shaw for their support; Drs.D. Roger Thomas, Joseph Grey, Alan Wardrop, and Canon David Williams for their interest; and Mrs. Gillian Warren for excellent secretarial assistance.Identification
Copyright
© 1988 Published by Elsevier Inc.
