Abstract
Melatonin, a hormone secreted at night by the pineal gland, has been touted as a treatment for disorders as diverse as ‘jet lag’ and breast cancer. Much has been made of the putative anti-ageing properties of the compound, while some see it as the ‘natural’ alternative for sleep disturbance. Such claims have produced a plethora of popular volumes with evocative titles such as The Melatonin Miracle [1]. Most of the claims for melatonin's curative properties are based on scant experimental data. The available data have established the diurnal secretion of the hormone, and its role as a marker of circadian rhythms is well recognised. The present volume examines the role of melatonin in a range of psychiatric disorders and neoplastic disease.
Psychiatric and neoplastic disorders make odd bedfellows. On further examination pairing of two of the chapters (‘Melatonin at the cellular level’ and ‘The melatonin rhythm in cancer patients’) remains strange, at least to me, but the final chapter on meditation, melatonin and cancer is relevant to many psychiatrists and psychologists. In any event Part IV of the volume, ‘The role of melatonin in neoplastic disease’, is so little researched that the final three chapters of the volume are highly speculative and are really an add-on.
The first three sections of the volume are an examination of the role of melatonin in psychiatric disorders. Part I of the volume consists of two almost obligatory chapters dealing with the synthesis and changes in melatonin across the life cycle and the minutiae of the anatomy of the pineal gland. Parts II and III deal with the possible role of melatonin in adult and childhood psychiatric disorders. Most evidence exists for an abnormality of melatonin in a particular state being indicative of major depressive disorders. In Part II, Wetterberg, one of the pioneers in this area, provides an extensive review of the literature. As with most of the findings in biological psychiatry the decrease in secretion of melatonin in depression is not a consistent observation across all groups. The chapter is at pains to explain why this may be so, sounding more like the arguments for the defence of a favoured hypothesis than an independent analysis. The nocturnal secretion of melatonin is influenced by many factors. It could be argued that much of the disagreement between individual research groups is due to a lack of understanding of the importance of those factors. Wetterberg discusses some of these: age, gender, light conditions, presence of medications, genetic factors, even the type of tubes into which blood specimens are collected. It would seem that until there is better knowledge of what constitutes normal variation, inconsistent results will bedevil the field.
There follow two interesting chapters on circadian rhythm abnormalities. Lewy et al. provide an overview of the use of melatonin in the treatment of ‘jet lag’, delayed phase sleep syndrome and chronobiological mood disorder (winter depression). The use of melatonin in the latter condition is controversial and, in Australia at least, where melatonin is not an approved substance, would probably be illegal. Furthermore, bright-light therapy has been shown to be effective in all three conditions and provides a reasonable alternative. The possibility that bipolar disorder arises due to a desynchronisation of internal biological rhythms is succinctly addressed by Mayeda and Nurnberger. This short chapter is perhaps the most challenging of the volume offering a number of possibilities for additional research studies attempting to elucidate the biological abnormalities underlying bipolar illness.
A further chapter on the role of melatonin in eating and panic disorders is highly speculative with a dearth of research data to support its inclusion as a separate entity. In panic disorder, for example, the two reported studies show increased nocturnal melatonin secretion but the authors offer no plausible hypotheses why this may occur. Increased sympathetic drive, which could increase melatonin by the action of noradrenaline on pineal beta-receptors, is dismissed on the basis of no increase in urinary metanephrine output. Given the myriad of influences of various neurotransmitters on melatonin secretion, it is surprising that some alternative hypothesis was not forthcoming.
In Part III the studies of nocturnal melatonin secretion in depressed children yield contradictory results: one study showing no abnormality and the other two, both from the same group of researchers, showing an elevation of melatonin. This latter result should be contrasted with the general findings of decreased secretion in adults. How can this be explained? The authors suggest two types of depression in children: high and normal melatonin secretion! This rather astounding conclusion is derived from a database of about 150 subjects. While it is agreed that a hypothesis needs to start somewhere it would surely be more logical to examine the differences between studies. Furthermore why are the results so different from those in adults? What features of depression occurring in adults compared with those in children are likely to make the results so different? The final chapter of this section reports the results of melatonin as a treatment for sleep disturbance in children with neurodevelopmental disabilities such as mental retardation, cerebral palsy, deafness–blindness and epilepsy. Melatonin at an average dose of 5 mg was regarded as successful in 87% of cases. Given the placebo-controlled nature of the study it begs the question of further long-term trials with melatonin itself or one of the more potent melatonin agonists that are in the developmental phase.
In summary this book, like the curate's egg, is good in parts. It is primarily one that researchers focused on melatonin will want to have for the sake of completeness but is not one that would be recommended for the clinician. While a book on the topic of melatonin and psychiatric disorder is warranted, I feel that one with more depth than the present volume can offer is required.