Melatonin: hormone of the night

Melatonin is phylogenetically an ancient animal is active at night or during the amplitude of secretion (and therefore
biological signalling system and has been daylight. Actions of melatonin are most total amount of melatonin secreted) tends
identified as present in all major likely mediated through a set of membrane to be lower in depressed patients than
organisms, including bacteria, plants, receptors, MT1 and MT2 (5). These matched controls (10). Antidepressant
invertebrate and vertebrate species (1). It belong to the G-protein coupled seven treatment tends to restore concentrations
appears to be a molecule with a multitude trans-membrane spanning domain class of towards normal values (11). There are
of biological functions, signalling not only receptors. Each of the receptors may have two fundamental difficulties with these
the time of day and of the year but, particular functions such as induction of findings. Many medications can decrease
perhaps, possessing immunomodulatory phase shifts (MT2) or suppression of melatonin concentrations by interference
and cytoprotective effects (2). It is neuronal firing (MT1). In addition to with synthesis. Most importantly
certainly among the first biological signals central effects some peripheral actions, benzodiazepines are well-recognised
to appear on earth (3). e.g. vasoconstriction (MT1) and suppressors (12). Thus, findings need to
Melatonin is nocturnally derived by vasodilation (MT2), may also be mediated account for the presence of these agents as
synthesis from tryptophan via serotonin, by melatonin receptors (5). Thus, several well as a range of other medications (e.g.
principally in the pineal gland, but physiological functions have been β-blockers), which can also suppress
extra-pineal sources of melatonin are also proposed for melatonin. melatonin secretion. Secondly many drugs
recognised, e.g. in the retina and Melatonin has been used as a marker of can increase melatonin concentration by
gastrointestinal (GI) tract (2). The circadian phase, and plays an important interference with liver metabolism of the
physiological and pharmacological role in the setting of circadian hormone. Melatonin is principally
mechanisms controlling the secretion of rhythms (6). Perhaps one of the better metabolised by CYP1A2 and CYP1A1
the hormone, at least in mammals, have known uses of melatonin is its purported leading to a hydroxylated form of the
been recognised for several decades (4). efficacy as a reliever of the symptoms of compound, which is subsequently
Regulation of synthesis is mediated by the ‘jet lag’ (7). Antioxidant properties of conjugated and excreted in urine (3).
retinohypothalamic tract, which projects melatonin have attracted attention, and its Clearly inhibitors of these enzymes
from the retina to the suprachiasmatic role as an oncostatic agent has also been (including some antidepressants such as
nucleus (SCN), the major circadian examined (2,8). In psychiatric research, fluvoxamine) will increase circulating
oscillator in the body. Fibres pass from the melatonin is of some interest, principally concentrations of the hormone,
SCN to the paraventricular nucleus, medial because of apparent circadian rhythm independent of fundamental changes in the
forebrain and reticular formation to disturbances in major depressive biochemistry or physiology of the
influence the interomedial dorsal horn cells disorder (9). The role of melatonin in synthetic system. Thus, the diagnostic or
of the spinal cord where preganglionic sleep, as a probable signal for sleep onset, prognostic value of the measurement of
sympathetic neurons innervate the superior has clear implications for the treatment of melatonin plasma concentrations is
cervical ganglion (SCG). The fibres of the psychiatric patients. unlikely to be clinically useful.
SCG terminate on pinealocytes and The nocturnal secretion of melatonin is
regulate melatonin synthesis by releasing dose dependently suppressed by full
noradrenaline on to β-receptors (4). The spectrum white light (13). In patients with
Melatonin and mood disorders
absence of light decreases activity in the bipolar I disorder and seasonal affective
SCN, while pinealocyte activity is The interrelatedness of melatonin and disorder, it has been demonstrated that this
increased, particularly the production of circadian rhythms has been the impetus for sensitivity is increased compared to
the synthesis limiting enzyme N-acetyl studies in patients with major depression, healthy controls (14). While not a
transferase (4). Melatonin concentrations examining both the absolute universal finding, it may suggest
in plasma rise with the onset of darkness concentrations of melatonin and variations dysregulation of the melatonin system in
and begin to decline again in the early in circadian secretion patterns. With these disorders, as well as an alteration of
morning. This circadian rhythm persists in respect to melatonin concentrations circadian phase in patients where the
vertebrates irrespective of whether the findings have been mixed, but generally abnormality is observed. More

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controversially light sensitivity has been phase can be useful for exploiting the Acta Neuropsychiatrica 2009: 21:263–265
proposed as an endophenotype of bipolar phase shifting ability of bright white light. © 2009 John Wiley & Sons A/S
disorder (14). At present, data are lacking Both melatonin and light are capable of DOI: 10.1111/j.1601-5215.2009.0411.x
with respect to the sensitivity and shifting phase but in opposite directions.
specificity of the findings in bipolar Thus, it is possible to use melatonin at
disorder compared to other psychiatric night or light in the early morning to
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