REVIEW ARTICLE Melatonin: an overlooked factor in schizophrenia and in the inhibition of anti-psychotic side effects George Anderson & Michael Maes Received: 27 February 2012 / Accepted: 11 April 2012 / Published online: 25 April 2012 # Springer Science+Business Media, LLC 2012 Abstract This paper reviews melatonin as an overlooked factor in the developmental etiology and maintenance of schizophrenia; the neuroimmune and oxidative pathophysiol- ogy of schizophrenia; specific symptoms in schizophrenia, including sleep disturbance; circadian rhythms; and side effects of antipsychotics, including tardive dyskinesia and metabolic syndrome. Electronic databases, i.e. PUBMED, Scopus and Google Scholar were used as sources for this review using keywords: schizophrenia, psychosis, tardive dyskinesia, antipsychotics, metabolic syndrome, drug side effects and melatonin. Articles were selected on the basis of relevance to the etiology, course and treatment of schizophre- nia. Melatonin levels and melatonin circadian rhythm are significantly decreased in schizophrenic patients. The adjunc- tive use of melatonin in schizophrenia may augment the efficacy of antipsychotics through its anti-inflammatory and antioxidative effects. Further, melatonin would be expected to improve sleep disorders in schizophrenia and side effects of anti-psychotics, such as tardive dyskinesia, metaboilic syn- drome and hypertension. It is proposed that melatonin also impacts on the tryptophan catabolic pathway via its effect on stress response and cortisol secretion, thereby impacting on cortex associated cognition, amygdala associated affect and striatal motivational processing. The secretion of melatonin is decreased in schizophrenia, contributing to its etiology, path- ophysiology and management. Melatonin is likely to have impacts on the metabolic side effects of anti-psychotics that contribute to subsequent decreases in life-expectancy. Keywords Melatonin . Schizophrenia . Anti-psychotics . Metabolic . Inflammation . Vitamin D Introduction Schizophrenia is associated with a dramatic decrease in life expectancy, not entirely explained by increased suicide rates (Flaum 2010). The effects of anti-psychotics, via the induction of metabolic syndrome, are widely thought to contribute to this. The moral dilemma of containing psychotic symptoms, whilst likely contributing to decreased longevity and longer- term health problems, is arguably the major practical issue faced in the treatment of schizophrenia today. Out with its well-known efficacy in sleep induction and circadian rhythm modulation (Marczynski et al. 1964), melatonin’ s role in the etiology, course and treatment of schizophrenia has received relatively little attention. Melatonin has a number of potential effects relevant to the context of schizophrenia, including in its etiology, pathophysiology and on the prevention of the meta- bolic and other side effects induced by anti-psychotics (Bushe and Leonard 2007; Tardieu et al. 2003). This review aims to highlight the relevance of alterations in melatonin in the etiology and maintenance of schizophre- nia. It is proposed that its adjuvant use will prevent many side effects of typical and atypical antipsychotics that con- tribute to decreased longevity and quality of life. Methods Electronic databases, i.e. PUBMED, Scopus and Google Scholar were used as sources for this review using keywords: G. Anderson (*) CRC, Rm 30, 57 Laurel St., Glasgow G11 7QT, Scotland, UK e-mail: anderson.george@rocketmail.com M. Maes Piyavate Hospital, Bangkok, Thailand Metab Brain Dis (2012) 27:113–119 DOI 10.1007/s11011-012-9307-9